key: cord-0052075-n4i9p2rk
authors: nan
title: Proceedings of the 26th European Paediatric Rheumatology Congress: part 1: Virtual. 23 - 26 September 2020
date: 2020-10-28
journal: Pediatr Rheumatol Online J
DOI: 10.1186/s12969-020-00469-y
sha: 53ec420ba5e359c6163159708b9da40afdc39e17
doc_id: 52075
cord_uid: n4i9p2rk

nan

Introduction: STING-Associated Vasculopathy with Onset in Infancy (SAVI) is a rare autoinflammatory interferonopathy caused by gain-offunction mutations in STING1, characterized by peripheral vasculopathy and interstitial lung disease Objectives: Describe the clinical and immunological manifestations of SAVI Methods: Clinical information on 30 patients with SAVI, based on NIH evaluation (n=15) or on records and samples provided by collaborators (n=15), were retrospectively reviewed. All patients were enrolled in an IRB-approved natural history protocol. The IFN score was calculated as previously described [1] . Features of lung inflammation and damage on Computed Tomography (CT) were scored by a single radiologist (LF) Results: 11/30 (37%) patients were female. SAVI was sporadic in 77% and familial in 23%. It was due to heterozygous mutations in 80%; only one mutation, p.R281W, present in 6 patients from 4 families, needs homozygosity to be disease-causing. The p.N154S and p.V155M mutations were most common (27% each). Disease symptoms presented in the first year of life (78%), with rash (14/27), respiratory symptoms (11/ 27) and fever (10/27). Median age at last evaluation was 12.6 years (range 0.4-54), 4 patients had no peripheral vasculopathy and 4 had no lung involvement. Compared to the other genotypes, the p.V155M mutation was more commonly associated with severe lung involvement (100% vs 47.6%, p=0.01). Table 1 lists clinical and laboratory features in SAVI. Patients failed a mean of 2.2 DMARDs or biologic, 73% received steroids; 7 patients died at a mean age of 7 years, mostly due to respiratory failure. 23 patients were treated with a JAK-inhibitor (baricitinib n=14, tofacitinib n=6, ruxolitinib n=6), for a median of 1.6 years (range 0.1-5.7). Skin ulcers improved in 9/9 patients, but recurred. Over an average of 2.6 years (range 1.1-3.9), chest CT inflammatory features improved in 6/7, with stable/improved damage in 6/7. Conclusion: SAVI is a severe early-onset interferonopathy, that is sporadic in 77%. SAVI can present with isolated pulmonary involvement and should be suspected in patients with interstitial lung disease even in the absence of vasculopathy. The p.V155M mutation is associated with severe lung disease. Rarely, the IFN score can be negative in whole blood and positive in PBMCs. Treatment with JAK inhibitors halted progression of lung damage over an average of 2. Introduction: Chronic nonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO) predominantly affects children and young adults. Classification criteria are not available and diagnostic criteria that were suggested have not been validated. We previously identified candidate items for the development of classification criteria.

Objectives: To refine candidate items for pediatric classification criteria for CNO by comparing clinical, laboratory and imaging features of CNO against mimicking conditions. Methods: International multicentre collection of clinical and investigational features of cases with CNO or mimicker diseases with at least 12 months follow-up was conducted through a REDCap online database. Prevalence ratios of each collected item between CNO and mimickers were calculated. A p value of <.05 was considered significant.

Results: 450 cases were collected from 20 centers in 7 countries and 4 continents. Cases were filtered based on indicated confidence levels of diagnosis for CNO or mimickers using a cut-off of +/-2 (moderately confident). 264 (59%) CNO cases and 145 (32%) mimicker controls were used for analysis. 41 (9%) cases were excluded. When compared to mimicker diagnoses, CNO patients were predominantly female, more frequently exhibited intermittent versus continued pain (especially of neck, back and upper torso), but less commonly had fever. Clavicular swelling was more common in CNO, while active arthritis was less common as compared to controls. CNO patients more frequently had whole body imaging (usually whole-body MRI). Symmetric patterns of bone lesions were more common in CNO. CNO frequently involved the thoracic spine, clavicle, sternum/manubrium, pelvic bones, bilateral femur, bilateral tibia, unilateral fibula, and foot bones. Imaging features concerning for infection or malignancy were less common in CNO. Lastly, complete and sustained response to antibiotic treatment is less frequent in CNO patients.

Conclusion: Using a case-based approach, key features of CNO were identified to support the development of classification criteria. Next steps will include expert panel discussions and a 1000Minds exercise. patients (5%) had kidney transplantation and two patients (2%) were on dialysis. All patients had used colchicine but only 72 patients (71.3%) are on colchicine treatment currently. Twenty-eight patients were treated with biologic DMARDs (Anakinra in 12 patients (11.9%), Canakinumab in 16 patients (15.8%). Conclusion: To the best of our knowledge, our cohort is the largest number of childhood onset FMF patients who developed AA amyloidosis. The positive family history of FMF and amyloidosis, presence of arthritis, high M694V allele frequency and elevated hs-CRP level are the most prominent findings in our cohort. FMF related AA amyloidosis is still major problem especially in the countries where the disease has high prevalence such as Turkey, Israel.

Introduction: Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is characterized by regularly recurrent fever flares of early onset, accompanied by pharyngitis, cervical lymphadenopathy and oral aphthous ulcers. The diagnosis was based on the modified Marshall's criteria proposed in 1999. PFAPA is not a well-defined disease and shows a clinical overlap with inherited periodic fevers (IPF), such as Familial Mediterranean Fever (FMF), Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and Mevalonate kinase deficiency (MVK) and Cryopyrine associated periodic syndrome (CAPS), for which a causative gene is well established. Recently new classification criteria for PFAPA and IPF have been developed during a consensus conference in Genoa in March 2017.

Objectives: To evaluate the performance of the new clinical criteria for PFAPA, FMF, MDK, TRAPS and CAPS on our cohort of patients with recurrent fever. Methods: In the first part, we selected all patients with PFAPA, FMF, MDK, TRAPS, CAPS and UPF from 5 participating centers, and applied the new classification criteria for PFAPA. In the second part, we applied the five new sets of clinical criteria on a population of PFAPA and UPF patients from 2 centers. In the last part, we considered the 121 patients from our Swiss consultation and evaluated the clinical outcome.

Results: In the first part, we included 417 patients (187 PFAPA, 63 UPF, 12 MKD, 114 FMF, 29 TRAPS, 12 CAPS): 42% of them met 7 out of the 8 criteria to be classified as PFAPA. Based on these results, we calculated for the new PFAPA criteria a sensitivity of 80.2% and a specificity of 89.1%, and a good positive predictive value (85.7%). In the second part, we evaluated the overlap between PFAPA and the monogenic AID. We applied the five sets of criteria to 288 patients, classified by the clinician as PFAPA (n= 195) and UPF (n=93). In the third part, we evaluated the outcome in 121 patients followed in Lausanne for PFAPA (n=85) or UPF (n=36). In the PFAPA group, 88.1% had a remission of flares, 7.1% were stable and 4.8% had a flare increase. In the UPF group, 85.2% had a remission of flares, 7.4% were stable and 7.4% had a flare increase. Among all the different groups defined by the classification criteria there were no significant difference of the evolution. Conclusion: The new criteria for PFAPA syndrome showed, when applied to a cohort of real-life patients, good sensitivity and specificity, and a good predictive value. However, when applying the 5 sets of clinical criteria to PFAPA and UPF patients, we found a large diagnostic overlap mainly between PFAPA and MKD. In the second part, we prove that when applied to patients of our cohort, the new clinical criteria were unable to distinguish PFAPA from MKD in about a third of our cohort. Clinical progression in patients with recurrent non-monogenic fever is generally favorable and is not different between the clusters. Introduction: Chronic non-bacterial osteomyelitis (CNO) is classified among autoinflammatory bone disorders but the exact etiology and pathogenesis are currently under investigation. The interplay between genetics, immunological and enviromental factors has been recognized as a possible causative factor so far. Emerging studies are suggesting that an altered ecology and function of microbiota (known as dysbiosis) can contribute to the occurrence or progression of a range of inflammatory diseases, affecting the balance between pro and anti-inflammatory immune responses. In a mouse model of CNO (cmo) dietary manipulation was accompanied with significant alterations of gut microbiome and significantly decreased of pro-IL-1β expression by distant neutrophils, thus resulting in protection from bone inflammation (gut-microbiota axis inflammasome). Objectives: To assess the composition of gut microbiota in a cohort of CNO patients compared to healthy controls in order to assess its potential contribution to the pathogenesis of the disease. Methods: In an observational cohort study, fecal samples were collected during follow up from 15 CNO patients (9 males) with a median age of 14.1 years (IQR 11.7-17. 3 ). Four of them presented active disease at time of microbiota analysis. Microbiome maps were compared to samples from geographically-and age-matched healthy children. Gut microbiota ecology was determined by 16S ribosomal RNA-based metagenomics. Data were analyzed for their αand βdiversity and differences in bacterial distribution were investigated by Mann Whitney and LEfSe assays.

Results: Microbiota richness, in terms of rare operational taxonomic units (OTUs), measured by the Shannon index, showed increased richness compared to healthy controls. In particular, ecological analysis revealed the presence of two distinct subjects' clusters, represented by CNO patients and healthy controls. The CNO group was characterized by a decrease of Verrucomicrobia and an increase of Actinobacteria. Especially, Bacteroides, Odoribacter and Flavobacterium were identified as potential microbial biomarkers for CNOs. Remarkably, the presence of Prevotella was only associated to the CTRL group.

Conclusion: This is the first study regarding the microbiome in CNO patients and our findings show evidence for clear dysbiosis and a distinct beta-diversity profile in the CNO patients. The dysbiosis could actually lead to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

Introduction: A new classification of pathogenicity of genetic variants associated to hereditary recurrent fevers 1 is available. The new Eurofever/PRINTO classification criteria (EPCC) 2 combine clinical manifestations with genotype.

Objectives: To describe the baseline characteristics of a longitudinal international cohort of familial Mediterranean fever (FMF) patients (pts) enrolled in the Eurofever registry and to evaluate the impact of EPCC criteria and new classification criteria for the pathogenicity of MEFV variants Methods: We reviewed baseline demographic, genetic and clinical data of FMF pts included in the Eurofever registry. EPCC criteria were applied to the population. All MEFV variants were classified according to ref. 1 .

Results: Since November 2009, 1175 FMF pts from 119 centers were enrolled in the registry. Clinical information was available for 1012 pts (532 males/480 females, 827 children/185 adults). For 125 pts clinical and genetic data mandatory for the application of EPCC were missing. Among the 887 remaining pts 623 (70.2%) satisfied EPCC (EPPC+), while 264 (29.8%) did not (EPPC-). Most of the EPCC-pts (172, 65.1%) displayed negative or non-informative genetics (monoallelic or biallelic benign variants, monoallelic VOUS). Eighty-nine (33.7%) and 3 (1.1%) pts with monoallelic and biallelic pathogenic variants respectively lacked FMF-associated clinical manifestations for EPCC The differences in clinical manifestations between the EPCC+ and EPCC-pts are shown in Table 1 . In EPPC+ group, the frequency of South-east Mediterranean ethnicity was higher. At baseline 68.5% pts were treated with colchicine (438 EPCC+, 212 EPCC-). NSAIDs and steroids on demand were used in 30.8% and 16.9% in EPCC-and in 21.1% and 8.3% in EPPC+ pts respectively. Anti-IL1 treatment was used in 41 (4.1%) pts , without significative differences between the two groups.

Conclusion: The combination of EPCC and the new pathogenic variant classification criteria captured the majority of FMF pts in the Eurofever cohort in a homogeneous group. The longitudinal evaluation of EPCC+ and EPCC-pts will provide clues on the overall long-term outcome with particular interest for the efficacy, safety and tolerability of different treatments. Introduction: Whilst, by definition, up-regulation of type I interferon (IFN) signalling is common to the type I interferonopathies (T1Is), disease expression varies across this set of diseases, the basis of which remains unclear.

Objectives: To compare the levels of IFN-alpha in the cerebrospinal fluid (CSF) and serum in distinct IFN-related diseases. Methods: We collected CSF and serum from patients with the known T1Is Aicardi-Goutières syndrome (AGS) and STING-associated vasculopathy with onset in infancy (SAVI), from individuals with presumed monogenic T1Is (pT1I), from cases of childhood-onset neuropsychiatric systemic lupus erythematosus (nSLE), and from children with non-IFN related auto-inflammation (AI) and non-inflammatory hydrocephalus (as controls). We measured IFN-alpha protein using digital-ELISA.

Results: Eighty-four and 60 measurements were recorded respectively in CSF and serum of 42 patients and 6 controls. In an intergroup comparison of the CSF data (taking one sample per analysed individual), the median level of CSF IFN-alpha was elevated in AGS, SAVI, pT1I and nSLE compared to AI and controls, with levels highest in AGS compared to all other groups. In AGS, CSF IFN-alpha concentrations were higher than in paired serum samples. In contrast, serum IFN was consistently higher compared to CSF levels in SAVI, pT1I and nSLE.

Conclusion: Whilst IFN-alpha is present in the CSF and serum of all IFN-related diseases studied here, the primary sites of IFN production in AGS and SAVI are, respectively, the CNS and the periphery. These data likely reflect tissue specificity in the expression, or biological redundancy, of the mutated gene, and/or in the generation of the endogenous self-nucleic acid ligands presumed to trigger the observed IFN response. We thank ImmunoQure AG for sharing antibodies.

Introduction: Autoimmune thyroid diseases is the most frequent organ-specific autoimmune disease. Although it is well-known that autoimmune thyroid diseases are more common in most of the autoimmune connective tissue diseases, the relationship between autoinflammatory diseases like familial Mediterranean fever (FMF) and autoimmune thyroid diseases has not well-evaluated yet and still remains unclear.

Objectives: The objective of this study was to evaluate the frequency of autoimmune diseases of the thyroid gland in children with FMF.

Methods: A total of 133 children aged <18 years with FMF and 70 healthy controls were included in the study. Thyroxine (fT4), thyroid stimulating hormone (TSH), thyroid peroxidase (TPO) and thyroglobulin (TG) antibodies, and thyroid ultrasound findings of all participant were evaluated. Results: One hundred thirty-three patients with FMF [72 female and 61 male] and 70 healthy controls (n=40 female/30 male) were enrolled in the study. The mean free T4 levels of the patients and control groups were 1.25 ± 0.13 ng /ml and 1.35 ± 0.27 ng / mL, respectively (p=0.20). The mean TSH levels were 2.86 ± 1.72 mcU / mL in patients group and 3.1 ± 1.55 mcU / mL in control group. There was no statistical difference in TSH values between two groups (p=0.76) (table1) There were five patients with increased levels of antibodies (2 of them positive for anti TPO and 3 of them positive for both of the antibodies) in patients with FMF and all of them were euthyroid. Four of these patients with high autoantibodies were pubertal and 1 of them were prepubertal. Two cases of control group had positive thyroid antibodies and they were euthyroid, too. Heterogeneity in thyroid parenchyma was observed in 1 of 5 patients with high autoantibodies in patients with FMF and 1 of 2 patients with high autoantibodies of the control. Thus, the frequency of Hashimoto's thyroiditis was 0.7 % in the cases with FMF and 1,2 % in control group.

In the FMF group, one patient had overt hypothyroidism and 5 patients had subclinical hypothyroidism. In the control group, subclinical hypothyroidism was detected in 3 patients and overt hypothyroidism was detected in 2 patients. The antibodies of the patients with overt and subclinical hypothyroidism in both groups were negative and the ultrasound findings were normal. Conclusion: Although the relationship between thyroid abnormalities and FMF has been reported before, we did not find a deterioration in thyroid functions in children with FMF. Our results suggest that there is no need for routine screening of serum thyroid function tests and thyroid antibody levels in patients with FMF in the absence of clinical symptoms or family history.

None declared Introduction: Paediatric sarcoidosis is a multisystemic inflammatory condition characterised by the formation of non-caseating granulomata that may lead to end-organ damage. Diagnosis is challenging as a compatible clinical-radiographic presentation with histopathologic confirmation is needed. Caution must be exercised to exclude granulomata of infectious aetiology as well as those seen in immunodeficiencies associated with immune dysregulation. Little is known about this rare disease's presentation and outcome in children. We report a retrospective cohort of children with biopsy-confirmed sarcoidosis.

Objectives: To describe the phenotype of children with biopsyproven sarcoidosis, their treatment and the course of the disease on various treatments. Methods: Patients' notes were reviewed retrospectively, and multisystem involvement identified. We included patients with biopsies consistent with sarcoidosis or granulomatous inflammation which were performed or reviewed at our centre between 2010 and 2020. Excluded were gut biopsies, samples suggestive of an infectious diagnosis and immunodeficiencies with immune dysregulation.

Results: We identified 42 children with biopsy-proven sarcoidosis. Mean age at diagnosis was 9.4 years; male to female ratio 0.68. Twenty-seven patients were of Afro-Caribbean descent, 7 Asian, 5 Caucasian and 1 of mixed race. Tissues biopsied included lymph node, skin, kidney, liver, lung, submandibular, lacrimal and salivary gland, eye, spleen, bone, brain and synovium. 28 patients had lymphadenopathy, 16 glandular involvement (13 parotid, 16 other glands including submandibular, lacrimal, thyroid), 17 liver, 17 pancreas, 13 renal (including 3 with nephrocalcinosis), 11 spleen, 27 skin, 14 lung involvement, 11 arthritis, 4 tenosynovitis, 3 hearing loss, 2 bone, 1 cerebral, and 25 eye involvement (including 19 with uveitis). Remarkable laboratory findings were as follows: 9 patients had hypercalcaemia, 16 raised amylase, 4 raised lipase and 30 raised ACE levels; 12 patients had abnormal renal function, 13 abnormal liver function. 13 patients were tested for NOD2 mutations, which were present in 5. 38 patients received treatment for sarcoidosis. Of those, 37 received steroids, 16 intravenous followed by oral steroids, 18 oral steroids only and 18 received steroid eye drops; 36 patients received diseasemodifying antirheumatic drugs (DMARDS) including 26 methotrexate, 11 mycophenolate mofetil and 10 azathioprine; 4 patients received hydroxychloroquine, 5 cyclophosphamide; 10 received biologic therapy including 9 anti-TNF, 2 interleukin-1 blockade, one JAK inhibitor, one IL-6 blocker and 1 rituximab. All patients had a good response to steroids, and most responded to methotrexate. The treatment of a subset of patients was escalated to include anti-TNF treatment, owing to grumbling disease activity. Although most of the patients were able to wean off regular steroids, the majority remained on long-term DMARDS to maintain disease control.

Conclusion: Our study suggests that non-necrotizing granulomatous inflammation on biopsy, multiorgan involvement, response to steroids and chronic course appear to be the hallmarks of paediatric sarcoidosis. DMARDs, in particular methotrexate, were used with efficacy. When response was partial, addition of an anti-TNF was efficacious at controlling the disease, particularly in ocular sarcoidosis. Additional organ involvement occurs over time when the disease is not fully controlled. However, no biomarkers are available to assess disease activity apart from ACE, which does not appear sensitive enough. Prospective cohort studies are needed to define this rare paediatric disease.

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children and adolescents. A consistent therapy is required to avoid consequential damage and permanent loss of function. Biologic disease modifying anti-rheumatic drugs (bDMARDs) provide a well-accepted option for treatment of patients with a severe course of JIA. Etanercept (ETA) is still the most commonly prescribed bDMARD for JIA in Germany.

Objectives: To analyze adherence to treatment with ETA with special attention on discontinuation after achieving an inactive disease and recurrence of active disease after ETA withdrawal. Methods: Data from two ongoing prospective, multicenter, noninterventional registries BiKeR and JuMBO were used for the analysis. JuMBO is the follow-up study to BiKeR and follows patients who have reached the age of 18. Both registers provide treatment data, individual trajectories of clinical data and outcomes from childhood into adulthood in JIA patients treated with bDMARDs and csDMARDs. Clinical disease characteristics, such as disease activity, were reported by the rheumatologists in addition to patient-reported outcomes at each six-months follow-up. Start and end dates for DMARDs as well as reasons for discontinuation were reported by the rheumatologists. Remission was defined as inactive disease defined by the Wallace Criteria.

Results: Data from 2,500 patients who were included in BiKeR and had an age ≥18 at the time of analysis were considered. A subset of 1,535 were enrolled in JuMBO. The mean follow-up was 8.6 (SD 4.2) years for the JuMBO patients. The majority of them had polyarthritis (35%), followed by enthesitis-related arthritis (20%). A total of 1,779 (68.8% of 2,584) patients were ever treated with ETA, providing 2,178 ETA treatment courses. There were 1,724 (67%) patients with first, 338 patients with a second and 54 with a third course of ETA treatment course. 710 (41.2%) discontinued ETA by ineffectiveness in the first course with similar rates of discontinuation due to ineffectiveness in the first and second course. A total of 332 (+/-MTX, 19 .3%) discontinued ETA after achieving remission in the first ETA course. Among those, 129 (38.9%) patients did not require treatment with any other bDMARD subsequently until last follow-up (3.9 years, SD 3.5), while 169 (50.9%) re-started treatment with ETA, 14 (4.2%) with adalimumab and 4 with other bDMARDs. The likelihood of discontinuing ETA due to an inactive disease was positively associated with a younger age (hazard ratio (HR) 1.08, p<0.001), persistent oligoarthritis (HR 1.89, p=0.004), a shorter duration between JIA onset and ETA start (HR 1.10, p<0.001) as well as a good response to therapy within the first six months of treatment (HR 1.11, p<0.001). 209 (of 332) had ETA monotherapy at withdrawal. Of those, 77% (n=161) experienced recurrence of disease with a mean time to flare of 12.1 (SD 13.7) months. 129 patients restarted bDMARD therapy (n=117 ETA). We could not identify any correlates for the risk of flare. 70% re-achieved remission and 20% again discontinued therapy thereafter.

Conclusion: The study confirms the good effectiveness of ETA, even in the re-treatment of patients with JIA. Our data highlight the association of an early bDMARD treatment with a higher likelihood to achieve an inactive disease indicating a window of opportunity.

Introduction: Vaccination WP has its first meeting at PRES congress in Athens 2017. Officially it was established in 2018 PRES congress in Lisbon, Portugal. One of the main reasons for establishing this WP was low level of evidence on which recommendation for vaccination in children with rheumatic diseases (RD) was based and it was concluded that in following years we need more solid evidence to answer numerous remaining questions. The first task was to create the platform for future multicentre studies. We gathered data from 25 countries about the variability of vaccination practices across the globe and presented it as the first Vaccination WP poster. There were considerable qualitative and quantitative differences amongst countries in their vaccination programmes, coverage and in parent obligation to vaccinate the child.

Objectives: The group identified many problems in this field including vaccine coverage in children with RD, the attitude of physicians towards vaccinations, the hesitancy of parents to vaccinate their children and among other the main issue was safety and immunogenicity of live attenuated vaccines, in particular MMR and varicella vaccine in children treated with different immunosuppressive and anti-inflammatory drugs including the 'biologics'. Another unanswered question was also long term immunogenicity of vaccines in children with RD. Methods: We created on line data collection on vaccine coverage, on attitude of physicians towards vaccinations in children with RD and on safety of booster MMR/V vaccine in children with RD on immunosuppressive therapy. Results: In the 2019 PRES congress the group presented 2 abstracts: Live attenuated vaccines in pediatric rheumatic diseases are safe: Multicenter, retrospective data collection that was presented in YIM and in the congress plenary session as oral presentation by Veronica Moshe and An international survey on approaches towards immunization in children with rheumatic diseases: a report of the PRES Vaccinations Working Group in YIM and congress as poster presenation by Elena Moraitis. Recently, the article »Live attenuated MMR/V booster vaccines in children with rheumatic diseases on immunosuppressive therapy are safe: Multicenter, retrospective data collection" was published in Vaccine.

In 2020 we collected the data on Influenza vaccine uptake which was low in majority of participating countries. Conclusion: The main task for the future is prospective study on MMR/V safety and immunogenicity in children with RD on immunosuppressive therapy. In conclusion we believe that there are many tasks in front of us. Infections remain the main adverse event of immunosuppressive drugs that we use with great success for treatment of children with RD. And even more so in this terrible time of corona epidemics when we realised again how endanger can we be because of infection and that vaccine can be the only solution to the problem in such times.

Introduction: Enthesitis Related Arhtritis (ERA) is one of the most challenging JIA subtypes in terms of drug management and duration of treatment. Objectives: We present the results of a retrospective study regarding clinical remission sustainment and potential relapse-associated factors in children with ERA treated with TNF-inhibitor (adalimumab -ADA).

Methods: This was a retrospective case study including patients with ERA (based on ILAR criteria) who received ADA from January 2012 to December 2017. All subjects had clinically inactive disease (clinical remission on medication (CRM) and Juvenile Spondylarthritis Disease Activity (JSpADA) remission criteria) for at least 2 years on treatment. Demographics, clinical, laboratory parameters as well data on medication exposure and clinical outcome were documented. Data were analyzed using STATA 15. Results: In a total of 35(17 girls) patients with inactive ERA(median age 12.5 years), ADA treatment was discontinued. Median treatment duration was 2.8 years. Median time to achieve clinically inactive disease was 5.2 months (range 3.8-7.8). Discontinuation was gradual; in 40% of patients we performed gradual dose reduction while dose spacing was performed in 60% of patients. In 29 patients ADA treatment was successfully ceased. Out of these 29 patients, 3 (10%) developed a single episode of peripheral mono-arthritis managed by intra-articular joint injection while 3 (10%) had a flare of anterior uveitis managed with topical steroids; the rest remained in flare-free clinical remission (>2 years). 6(19%) patients considerably flared during the follow-up period and were restarted on ADA. Median duration of remission following ADA withdrawal was 5 months (range 3.6-11.6).

Subgroup analysis showed that patients with unilateral (92%) vs bilateral (74%) sacroiliitis (p=0.06) and patients with shorter disease duration (0.5 vs 1.1 years, p=0.03) had a higher chance of successful withdrawal. In addition, patients with accompanying uveitis were more prone to require drug re-initiation(p=0.04). Time to achieve clinically inactive disease, rise of inflammatory markers at initiation of ADA, presence of enthesitis, peripheral arthritis as well as the tender joint count at diagnosis did not affect the primary outcome. Relapse rate decreased proportionally to time [66.5% relapse(< 6m) vs 33.5%(>6m), p=0.07]. The relapse percentages were identical in the dose-reduction versus gradual spacing mode of discontinuation groups. Age, gender, range of inflammatory markers at diagnosis did not affect clinical outcome.

Conclusion: This was a retrospective study regarding discontinuation of ADA used as monotherapy in patients with ERA (and associated sacroiliitis), following attainment of clinical disease remission, showing optimistic results. TNFi are generally effective in inducing and maintaining remission in ERA and ankylosing spondylitis(AS) patients and therefore long-term therapy is recommended. Overall, biologic-naïve patients demonstrate a swift and sustained response to TNFi; however majority of studies also ensue a synthetic DMARD.

Our study demonstrated that ADA withdrawal is feasible in a significant proportion of ERA patients, provided anti-TNFi is initiated promptly. Patients with shorter disease duration and unilateral sacroiliitis showed a higher chance of attaining long-term remission.

Prolonging the duration of treatment in clinical remission before discontinuation may show favorable results in contrast to other studies endeavoring earlier discontinuation.

Introduction: Treatment with canakinumab (CAN), a selective, human anti-IL-1β monoclonal antibody, has shown sustained therapeutic effect along with corticosteroid dose reduction/discontinuation in patients with systemic juvenile idiopathic arthritis (sJIA), in a long-term extension study (NCT00891046).

Objectives: To evaluate the efficacy and safety of 2 different canakinumab tapering regimens in sJIA patients who were in clinical remission (NCT02296424).

Methods: This Phase 3b/4 study had two parts. In Part I 182 patients, n=84 with inactive disease from the extension study1 (cohort 1) and n=96 CAN-naïve patients (cohort 2) with active disease were administered subcutaneous CAN 4 mg/kg q4w. Per protocol titration off corticosteroids and/or methotrexate was attempted during Part I. Eligible patients (inactive disease for 24 consecutive weeks and being corticosteroid-and methotrexate-free for at least 4 weeks) advanced to Part II. Patients were randomised to either a 3-step CAN dose reduction regimen (2mg/kg/q4w, followed by tapering to 1 mg/kg/ q4w and then discontinuation) or dose interval prolongation regimen (4mg/kg q8w, followed by tapering to 4 mg/kg/q12w and then discontinuation); patients advanced to the next tapering step if inactive disease was maintained for 24 weeks. The primary objective was to evaluate if at least 40% of patients were able to maintain inactive disease status for at least 24 consecutive weeks on either 2mg/kg q4w or 4mg/kg q8w. Results: In Part II, a total of 75 patients were randomised to a dose reduction (n=38) or dose interval prolongation (n=37) CAN tapering regimen. The proportion of patients who maintained inactive disease for 24 consecutive weeks significantly exceeded the predefined threshold of 40% of Step 1 in both treatment arms: CAN reduced dose (71%; 2 mg/kg q4w) and in prolonged dose interval (84%; 4 mg/kg q8w). A total of 68% (26/38) and 79% (30/37) of the dose reduction and interval prolongation arms, respectively were successful in Step 2, while only 33% (25/75) of patients successfully discontinued CAN and maintained inactive disease for 24 consecutive weeks. Adverse events (AEs) and serious AEs observed within the 2 treatment cohorts and across Parts I and II were similar without any specific pattern or relationship to patients' disease status at baseline or treatment regimen. The most frequent AEs were common infections such as nasopharyngitis, upper respiratory tract infection, and pharyngitis followed by sJIA-related events such as rash, pyrexia and arthralgia. Clinical laboratory abnormalities were consistent with expected findings in patients with active sJIA and the known safety profile of CAN. Conclusion: sJIA patients who are able to maintain inactive disease status on CAN monotherapy can successfully taper CAN by either reducing the dose or prolonging the dosing interval. However, only a minority of patients successfully discontinued CAN treatment for 24 weeks. The safety profile for both CAN titration regimens was similar and consistent with other CAN sJIA studies. No new safety signals were identified. Introduction: Systemic juvenile idiopathic arthritis (sJIA) is characterized by extra-articular manifestations, as fever and rash, and rarely associated by a potentially lethal complication as macrophage activation syndrome (MAS). Anakinra is a recombinant human interleukin (IL)-1 receptor antagonist whose efficacy and safety profile has been studied for patients with sJIA.

Objectives: To evaluate the long-term safety profile of anakinra in patients with sJIA in current clinical practice. Methods: Data from patients with sJIA treated with anakinra and enrolled in Pharmachild registry before 30 September 2018 was retrospectively analyzed (EUPAS28378). The study endpoints were the occurrence of non-serious adverse events (AEs) of at least moderate severity and serious AEs (SAEs), including MAS; the duration of anakinra treatment and reasons for discontinuation. All endpoints were analyzed overall and stratified by 6 months time windows. Results: 306 patients were enrolled with both genders equally represented. Anakinra was administered at the median age of 8.0 years and after a median of 0.6 years from the disease onset. Almost half of the patients (n=146; 46%) were continuously treated with anakinra for at least 12 months, 34.0% for at least 18 months and 28.1% for at least 24 months. A total of 201 AEs was reported during a total of 509.3 patient years (py) of treatment with an overall incidence rate (IR) of 39.5 (95% CI 30.8-50.6) per 100 py, mostly represented by infections (52 events, 25.9%; IR 10.2/100 py). 56 SAEs were reported (IR 11.0/100 py; 95% CI 7.9-15.2), whereof 13 infections (23.2%; IR 2.6/100 py), and 11 MAS episodes (19.6%; IR 2.2/ 100 py). The IR/100 py of AEs was higher during the first 6 months of treatment and gradually decreased over time. Ten patients (3.3%) had a history of MAS before anakinra start, 9 of these patients did not experience any new MAS episode after anakinra start. 8 patients developed MAS several months after anakinra discontinuation. Discontinuation of treatment occurred at least once in 233 patients (76%) more often during the first 6 months and decreased over time and reasons were overall secondary to inefficacy (43%), remission (31%) or AEs and intolerance (15.0%). No deaths occurred during anakinra treatment while 3 deaths occurred after anakinra discontinuation (5 months, 3 years, and 5 years after discontinuation, respectively). No malignancies were reported neither during treatment with anakinra nor after discontinuation.

The results of the present study confirm the long-term safety profile of anakinra in sJIA patients without any new safety findings. Long-term treatment with anakinra in sJIA patients was well tolerated, with a decreasing overall incidence rate of AEs.

opportunity", for which the evolution of the disease can be modified preventing the onset of chronic arthritis. Despite a good response to anakinra in a high percentage of patients, there is a subset of nonresponders. The early identification of non-responder patients is of primary importance to avoid the progression towards chronic arthritis. Some single nucleotide polymorphisms (SNPs) in IL1RN gene have been found associated with sJIA, and recently, a cluster of SNPs in the IL1RN non-translated region has been suggested as a possible predictor of non-response to anakinra.

Objectives: The aim of this study was to evaluate the impact of early treatment and genetic variants in IL1RN gene on the response to anakinra in sJIA.

Methods: Response to anakinra was considered as clinically inactive disease (CID) at 6 months, without glucocorticoids treatment. Demographic, clinical and laboratory characteristics of 56 patients were analyzed in univariate and multivariate analysis as predictors of response to treatment. Six SNPs in IL1RN gene were genotyped by qPCR or Sanger sequencing. Haplotype mapping was performed with Haploview software and IL1RN mRNA expression in whole blood from patients before anakinra initiation was assessed by qPCR. Results: After 6 months of treatment, 73.2% of patients met the criteria for CID off glucocorticoids. In univariate analysis the variable strongly related with the response was disease duration from onset to anakinra initiation, with an optimal cut-off at 3 months. Patients who started anakinra after 3 months from disease onset had an 8fold higher risk of non-response at 6 months. We confirmed that the 6 IL1RN SNPs were inherited as a common haplotype in our cohort of patients. We found that homozygosity for at least one high expression SNP correlates with higher IL1RN mRNA levels and was associated with a 6 fold higher risk of non-response, independently of disease duration. Conclusion: Our results confirm the important role of early IL-1 inhibition and suggest that genetic IL1RN variants predict non-response to therapy with IL-1 blockade in patients with sJIA. Introduction: Childhood-onset systemic lupus erythematosus (cSLE) is a chronic, autoimmune multisystem inflammatory disease that is associated with sizable morbidity and mortality. Hydroxychloroquine (HCQ) is an antimalarial agent given to patients with systemic lupus erythematosus (SLE) as first-line therapy with accumulating evidence on its role in reducing mortality and morbidity. HCQ is known to alleviate cSLE skin and musculoskeletal disease, along with decreasing disease activity and flare. Despite longstanding use of HCQ in children patients, the effect of HCQ in pediatric population and the potential need for dose adjustments remains unknown.

Objectives: To study the pharmacokinetics/ pharmacodynamics relationships of HCQ in cSLE Methods: We performed a population-pharmacokinetic analysis using samples from patients' medical records in Necker-Enfantsmalades Hospital and Robert-Debré hospital from 2016 to 2018. cSLE flares were defined using the SLE Disease Activity Index (SLEDAI); flare was denoted by a SLEDAI score of > 6. Hydroxychloroquine blood concentration was measured using highperformance liquid chromatography with fluorometric detection. Population pharmacokinetic/pharmacodynamic parameters were estimated using the nonlinear mixed-effects modelling software Monolix (version 2019R2 Introduction: 'Treat to target' (T2T), in which treatment is adjusted or escalated until a specific target is achieved, is now part of routine clinical care in many areas of medicine. It has been proposed as a strategy to improve management of juvenile-onset systemic lupus erythematosus (JSLE), using existing treatments in a more structured way. The TARGET LUPUS research programme; 'Targeting disease, Agreeing Recommendations and reducing Glucocorticoids through Effective Treatment, in LUPUS' has been established in order to develop a JSLE T2T study. There is currently little guidance on JSLE patient/parental views on the concept of T2T.

Objectives: To explore, in-depth, the views of JSLE patients and parents on the treatment targets, outcome measures and study designs for T2T being considered by TARGET LUPUS, in light of their previous treatment and care. Methods: Topic guided semi-structured interviews explored what it means to JSLE patients to be 'well', and their views on potential T2T study targets e.g. Lupus Low Disease Activity State (LLDAS). As part of the interviews, patients and parents completed health-related quality of life (HRQOL) and fatigue tools and were then asked about their views of the tools and how well these captured their experiences. The concept of T2T was also explored, and patient and parental views on the proposed study and potential study designs were sought. Analysis of audio recorded interviews was informed by thematic approaches.

Results: 24 semi-structured interviews were conducted with 12 JSLE patients (aged 9-18 years) and 12 parents from six UK hospitals. Most patients reported feeling very well at the time of the interview, with several commenting that they felt completely back to normal. Most parents also classed their children as feeling well. However, several parents rated their child's wellbeing as worse than their child had themselves. Both patients and parents tended to class joint pain, muscle aches/weakness and rash as consistent with low disease activity. When asked about symptoms/signs that had not previously experienced during their disease course patients and parents often regarded as these signifying high disease activity. Of the three HRQOL questionnaires assessed, both patients and parents favoured the Peds QL Rheumatology Module, as they felt it provided the clearest picture of both wellbeing and functioning. Almost all patients and parents thought it was important to have a specific questionnaire focusing on fatigue. Most families felt that reducing corticosteroids would be a good treatment target. Almost all families liked the idea of a T2T approach to treatment, commenting that it would structure their treatment and enable more frequent clinic visits where needed. However, some were concerned about the impact of increased visits on schooling and parental work and suggested holding monthly visits until medication is stable, and then visits could become less frequent.

Conclusion: This study has provided insights on patient and parental perspectives on treatment targets, outcomes measures and indicated that the concept of T2T is acceptable to families in principle. These findings will be shared with JSLE experts, including patients and families during future international consensus meetings on further defining a treatment target and treatment strategy which is acceptable to both patients, families and clinical teams.

Introduction: Recurrent pericarditis (RP) is a rare cause of morbidity in children. Non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and colchicine are the standard of care in adults. Recently, anakinra has been proven to be effective in patients with steroid-dependence and colchicine resistance.

Objectives: To analyse, in a cohort of paediatric patients with RP undergoing to anti-IL-1 treatment for resistance to standard treatments, the appropriateness of the first line treatments, the long-term efficacy of different IL1-blockers and the percentage of patients achieving a drug-free remission.

Methods: Paediatric patients with RP pericarditis followed by Italian centers of paediatric rheumatology or cardiology and treated with IL1 inhibitors were included in the study. The efficacy of treatment with IL1-blockers was evaluated trough an annualized relapse. A bivariate logistic regression analysis wad used to identify variables associated to an increased probability to withdraw the biological treatment without relapses.

Results: 58 patients were enrolled in the study. Overall, NSAIDS, colchicine and steroids were used in 56, 49 and 48 patients, respectively. 8/18 and 6/38 patients without a complete response to treatment with NSAIDs and colchicine, respectively, were not receiving an adequate dosage according to ESC guidelines. 4/48 patients treated with glucocorticoids were receiving the proper dosage of < 0,5 mg/kg/day of prednisone or equivalent. Steroidaldependence was observed in 45 patients. Anakinra and canakinumab were used in 57 and 6 patients respectively. In 57 patients treated with anakinra the annualized relapse rate (ARR) before treatment was of 3.05 and 0.28 (p <0.0001) during daily treatment; however, an increase in the number of relapses was then observed after the reduction or discontinuation of treatment (ARR=0.83, p<.0001). In the 6 patients treated with canakinumab he ARR was 2.3 and 1.46, before and during treatment, respectively. At last follow-up, only 9 patients had withdrawn all treatment. None of the variables analysed were associated with a statistically significance between the group of these patients and those 49 in which the withdrawal was not possible, due to recurrence of the disease.

Conclusion: This study confirm the effectiveness of IL-1 blockade in paediatric patients with recurrent pericarditis; however, most of the patients require prolonged treatment to maintain relapse-free remission. In our cohort of patients the rate of response was higher for anakinra then for canakinumab.

Objectives: To assess the course of the disease after tapering or stopping BT in a cohort of JIA patients. Tapering strategies and median time to flare were analyzed. Methods: A retrospective, descriptive study was conducted in a cohort of JIA patients followed up in a Pediatric and Introduction: Inflammatory bowel disease is a relatively rare comorbidity in patients with juvenile idiopathic arthritis but is known to have an important negative impact on quality of life. It is suggested that IBD development is associated with use of etanercept but due to its low incidence, thus far this has not been proven.

Objectives: The aim of this study was to determine risk factors for developing IBD in JIA patients and evaluate the possible relationship between medication and IBD development. Methods: In this study, Pharmachild, the largest international JIA registry was used. Enrollment of patients was facilitated by members of the Paediatric Rheumatology INternational Trials Organisation (PRINTO). Risk factors for IBD where identified both before and after adjustment for confounders. A prediction model was developed using multivariable logistic regression analysis in a backward procedure based on likelihood ratio tests. To identify associations between drugs of interest and IBD development, patients who developed IBD were matched to similar controls based on the variables in the prediction model. Odds ratios were calculated using conditional logistic regression analysis. Results: 8,942 patients were included in this study of which 48 (0.5%) developed IBD. Age at JIA onset was significantly higher in patients with IBD (8.94 years vs 5.33 years p=0.000) and there was a lower female predominance in the IBD group (52.1% vs 68.0% p=0.029). Family history was significantly more positive for autoimmune disease in IBD patients (43.8% vs 29.0% p=0.037) and enthesitis-related arthritis (ERA) was more frequently observed (39.6% vs 10.8% p=0.000). The model with the best discriminative performance included the variables age, gender, ERA and the total number of first and second degree relatives with a history of autoimmune disease and had an AUC of 0.721 (95% CI 0.646-0.796). Analyses on IBD patients with available onset date (n =27) matched to non-IBD controls (n = 129) showed that patients treated with ETN had a 6.88 and 7.45 times higher odds for developing IBD within 3 and 6 months respectively, compared to control patients that did not receive ETN at similar disease duration (Table 1 ). In addition, both patients using ETN and MTX dual therapy and patients using ETN without MTX had higher odds for developing IBD. Use of other biologicals and MTX without ETN were not significantly associated with IBD. Conclusion: In this study, ERA patients were at an increased risk of developing IBD. The most important risk factors for developing IBD were age, gender, ERA subtype and family history of autoimmune disease. In addition, patients using ETN had higher odds of developing IBD while we did not find a protective role of MTX for the development of IBD. Therefore, we recommend to prescribe other biologicals than ETN to JIA patients with a higher risk of developing IBD.

None declared Introduction: Biological therapy (BT) has changed the treatment and perspectives of JIA patients but little is known about when is the best moment to start BT and the impact of this prompt initiation. Objectives: To analyse the response to BT of Juvenile Idiopathic Arthritis (JIA) patients according to the time when the BT was started Methods: A retrospective, descriptive study was conducted on JIA patients followed up in a referal hospital that started BT up to 24 months after diagnosis from 2000 to 2018. Disease activity was measured, at 2 years after diagnosis, according to Wallace criteria for remission (absence of: active arthirits, active uveitis, fever, rash or any other manifestation attributable to JIA, normal CRP and ESR, PGA indicating no active disease) for at least 6 months. Results: 55 JIA patients that started BT up to 24 months from diagnosis were analyzed. 69,1% were girls with a median age at diagnosis of 8 years old [IQR(3-13)], median age at the start of BT of 9 years old [IQR (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) ]. Regarding JIA categories: 25,5% were Oligoarticular Persistent (OligP), 18,2% Systemic JIA (sJIA), 16,4% Entesitis related Arthritis (ERA), 12,7% Psoriatic Arthritis (APso) and Polyarticular RF-(PolyRF-), 5,5% Oligoarticular Extended (OligE) and Polyarticular RF+ (PolyRF+), 3,6% Undifferentiated (Und). 20% of patients had uveitis during followup. Conventional DMARD (cDMARD) was indicated in 83,6% of patients (95,7% Methotrexate) at diagnosis [median 0 months IQR(0-2,3)]. At the end of followup (2 years) only 30,9% of patients continued with cDMARDs. The main causes of discontinuation were: adverse events (46,7%), remission (36,7%). TNF inhibitors were precribed in 81,8% of patients and 18,2% of patients recieved two BT during the first 2 years from diagnosis. 54,5% of BT were indicated during the first 6 months from diagnosis, 27,3% from 7 to 12 months, 12,7% from 13 to 18 months, 5,5% from 19 to 24 months. After 2 years from diagnosis, 78,2% of patients were on remission and 21,8% active. Among patients with active disease: 75% had arthritis, 16,7% had uveitis and 8,3% had both. There were no differences regarding disease activity among patients with uveitis and neither taking cDMARDs. Regarding JIA categories: 66,7% of OligE, 57,1% of PolyRF-and 57,1% of APso patients were active at 2 years from diagnosis when compared to the other categories (p= 0.004). Patients on remission at 24 months from diagnosis started sooner the BT than active patients [CI 95% (0,46-8,29) p=0,029]. The time when the BT was started was correlated to the activity at 2 years (K= 0,294 p=0,029). When the BT was prescribed after 7,5months from diagnosis it was correlated, in a COR curve, with a higher probability of active disease at 2 years(S= 0,67 E= 0,63). There was a correlation, among patients on remission at 2 years, between prompt start of BT and less time to reach remission (K= -0,345 p=0,024). Patients with active disease at 2 years, regardless of moment of BT iniciation, required more BT during follow-up (p=0,002). Conclusion: Prompt iniciation of BT was correlated with a better outcome. JIA patients that started BT early after diagnosis had a higher probability of remission after 2 years. Starting BT after 7,5 months was correlated with a higher probability of active disease at 2 years. Active disease at 24 months was correlated with presistent active disease during follow-up. We included pediatric patients from 0 to 16 years with refractory dcSSc and sJIA, whom underwent AHSCT. We carried out a retrospective analysis of these cases. Results: The present study was carried out from January 2018 to December 2019. We report 6 patients. 33% of patients with dcSSc and 67% sJIA. 83% were female. The mean age at the time of diagnosis was 12.8. The median time interval from diagnosis to AHSC T was 52 months. Regarding the dcSSc patients, received an average of 4 nonbiologic disease-modifying antirheumatic drugs (DMARDs) and 1 biologic agent prior to AHSCT. The sJIA patients received an average of 1.5 nonbiologic DMARDs and 2 biologic agents prior to AHSCT. The peripheral stem cells were mobilized with cyclophosphamide (CYC) and granulocyte colony-stimulating factor and harvested by leukapheresis and subsequently selected for CD34+ cells, on day 0 were infused, after compliance with the conditioning adjustment (CYC was given on days -8, -7 and -6 and antithymocyte globulin on days -5, -4, -3, -2 y -1). All patients received acyclovir, cefepime and fluconazole for infection prophylaxis. We follow-up the patients a median of 28.5 weeks. Patients with dcSSc experienced resolution of dyspnea, digital ulcers, decrease 33% the mRss and the number of Raynaud's phenomenon events. There were no significant changes in lung function tests, HRCT of the lungs and EGDS in dcSSc. All patients with JIAs had 0 joints with active arthritis, we documented a decrease of CRP 95% and VSG 64% after AHSCT. The cHAQ score improved 98% and the DAS 28 score 61%. The total of patients with dcSSc are in complete remission. Of the patients with AIJs, 66% have complete remission and 33% partial remission. No mortality has been reported. Conclusion: To our best knowledge, this is the first study in Mexico that describes the use of AHSCT in patients with refractory dcSSc and sJIA. AHSCT is a viable, effective and safe procedure in dcSSc and sJIA. AHSCT can slow the progression of rheumatologic disease, however, it does not reverse established damage. We must investigate poor prognosis factors that allow us to recognize patients with a high probability of rapid disease progression in order to select them for the AHSCT in a timely manner. Introduction: Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease, however there is limited data on other health-related outcomes in JIA patients.

Objectives: The aims of this study were to use publicly available genome-wide association study (GWAS) datasets to interrogate the genetic correlation between JIA and a broad range of health-related traits. We then sought to examine whether JIA was causally associated with any correlated traits. Methods: We used publicly available JIA GWAS data (sample size 15872) and the LDHub platform to implement linkage disequilibrium score regression (LDSC) to explore genetic correlation (r g ) between JIA and 832 other health traits across the life course. Results were adjusted for multiple testing based on the false discovery rate (FDR). For non-autoimmune traits correlated with JIA (FDR-adjusted p value, P adj , <0.05), we then conducted two sample Mendelian randomisation (2SMR) to examine evidence of causality. We employed multiple sensitivity analyses to ensure the evidence was robust. MR estimates for continuous outcomes are reported as beta coefficients and for binary outcomes are transformed onto the odds ratio scale. Results: We found robust evidence of positive genetic correlation between JIA and seven human traits: "rheumatoid arthritis" (r g 0.63, P adj 0.029), "coeliac disease" (r g g 0.58, P adj 0.032), "systemic lupus erythematosus" (r g 0.40, P adj 0.032), "coronary artery disease" (CAD, r g 0.42,P 6.0x10 -3 ), "hypothyroidism/myxoedema" (r g 0.61, P adj 4.1x10 -5 ), "number of non-cancer illnesses" (r g 0.42, P adj 0.016) and "paternal health" (r g 0.57, P adj 0.032). There was robust evidence of negative correlation with "strenuous sports" (r g -0.52, P adj 0.032). In addition, we found some evidence for genetic correlation between JIA and a number of unfavourable cardiometabolic traits. Using 2SMR we identified robust evidence for a causal relationship between genetically predicted JIA and "number of non-cancer illnesses"(2SMR causal estimate beta 0.021, 0.008-0.034). The 2SMR estimate for genetically predicted JIA and CAD (OR 1.05, 95% CI 0.98-1.12), "paternal health" (OR 1.05, 95% CI 0.98-1.13) and "strenuous sports" (OR 0.98, 95% CI 0.96-1.00) provides very little evidence of a causal relationship between these traits and JIA despite their high genetic correlation. Conclusion: We show evidence of genetic correlation between JIA and a several novel and important long-term health outcomes, particularly coronary artery disease and other systemic and organspecific autoimmune disorders. Although 2SMR analysis suggests the association between JIA and CAD is one of correlation rather than causation, our findings support the observational literature regarding the need for cardiovascular risk assessment and management of JIA patients, and the consideration of routine thyroid function monitoring and coeliac screening. Med, 2020), we initially observed, that S100A12-treatment of primary human monocytes did not result in comparable IL18 expression. Broadened analyses of pro-inflammatory and IFN-related gene expression in LPS, S100A12, IFNa or IFNg-treated human PBMCs revealed, that in contrast to LPS, S100A12 -even when far beyond physiological levels -failed in inducing IFI27, IFI44L, IFIT1, ISG15 and RSAD2 expression. IL1A, IL1B, IL1RN and IL6 expression was induced at levels comparable to LPS. When investigating stimulated cells by flow cytometry, we observed no TLR4internalization by S100A12-treated human monocytes. Vice versa, inhibition of LBP, which has been assigned a fundamental role in TLR4-internalization, impaired LPS-induced receptor endocytosis, which resulted in abrogation of T1-IFN-related gene expression as observed with S100A12 treatment. When testing stimulations with other TLR4-dependent DAMPs (S100A8/A9, SAA, ApoA1, HMGB1) alongside with S100A12 we universally observed proinflammatory but no IFIT1, ISG15 and RSAD2 expression compared to LPS. In contrast to LPS, TLR4-dependent DAMPs fail to enable  LBP-driven receptor internalization. In consequence, this restricts  DAMP-signaling to the MyD88-dependent pro-inflammatory pathway  and excludes TRIF-dependent T1-IFN expression. As T1-IFN acts as  natural negative regulator of IL-1, while it is strictly required Objectives: Our primary objective was to examine gene expression patterns in non-lesional skin of human and murine lupus skin. We seek to develop an LC ADAM17-deficient gene expression signature and hypothesize the presence of a prominent IFN signature further demonstrating a potential link between interferon and ADAM17 downregulation.

Methods: Transcriptomics of non-lesional skin from discoid lupus (DLE) and healthy controls and of MRL and MRL/lpr mice were compared. Human data was gathered from unpublished data from Krueger et al (2014) using microarray in DLE lesions compared to psoriasis and healthy skin. We performed RNA seq on non-lesional skin of MRL and MRL/lpr mice. Data were analyzed in R using edgeR. Gene set analyses were performed with QuSAGE and plots were generated using a custom Shiny platform developed by the HSS Genomics Center. To examine whether LCs show an IFN-I regulated gene signature, we are currently sorting LCs from both UVR-exposed and non-exposed WT and Adam 17 fl/fl Langerin Cre mice for RNA seq. Using the IRB approved method of suction blistering to sample immune cells in the skin, our plan is to gather LCs from the skin of SLE patients to determine LC ADAM17 activity and whether this correlates with interferon signature via RNA seq.

Results: IFN-I regulated genes were among the most differentially regulated genes in non-lesional skin in both human and the MRL/lpr lupus mouse model. Many interferon regulated genes were found to be highly expressed in both (Fig 1A, D) . Pathway analysis further showed that IFN-I-regulated genes were among the most differentially regulated pathways in disease vs control skin for both humans and mice (Fig 1B, E) . Preliminary results from the analysis of ADAM17fl/fl Langerin Cre mice are expected in the next several months. Conclusion: Microarray results suggest an elevated IFN signature in non-lesional skin of DLE patients with a similar IFN signature found in MRL/lpr mice via RNA sequencing. We anticipate that we will detect a reduction in ADAM17 activity in non-lesional skin of human SLE patients and find a correlation with IFN signature, supporting a potential role for IFN-I in dysregulating ADAM17 in lupus photosensitivity. These findings could help to understand why type I IFN targeted therapies are having success in SLE skin disease and may lead to targeting of ADAM17 for lupus. In the future, we hope to determine whether the gene signature associated with ADAM17 deficiency can be seen in other inflammatory skin conditions, such as dermatomyositis. Introduction: Resident memory T cells (T RM ) are site-specific memory T cells that take up long-term residence in peripheral tissues and aid in local immune defense. T RM have also been implicated in autoimmune diseases by driving localized recurrent inflammation. Objectives: As chronic arthritis is characterized by recurrent sitespecific joint inflammation, we sought to investigate the role of T RM in joint-specific memory. Methods: We performed 10x genomics droplet-based single cell RNA sequencing and immune repertoire profiling on memory T cells disaggregated from human rheumatoid arthritis synovium to evaluate transcriptomic signature. We also used Mantra multispectral immunofluorescence microscopy to evaluate T cells expressing common T RM protein markers in human arthritic synovial tissue sections. To assess the functional contribution of T RM cells in arthritis in vivo, we generated a novel murine model of joint-specific recurrent synovitis. We utilized adoptive transfer, in vitro metabolic and migration assays, in vivo cell labeling, and localized depletion strategies to characterize T RM cells in the synovium and their functional role in arthritis flare. Results: We identified cells with the phenotypic and transcriptomic signature of T RM within human arthritic synovium. These cells were primarily CD8+ and exhibited restricted T cell receptor clonotypes as well as a pro-inflammatory gene expression profile. Adoptive transfer studies in our animal model of joint-specific recurrent inflammation confirmed that arthritis flares were mediated by antigen-specific CD8+ T cells that remained within previously inflamed joints during remission. These cells were bone fide T RM , as confirmed through surface signature, failure to migrate in vivo or in vitro, preferential uptake of free fatty acids, and long-term residency. Site-specific depletion of synovial T cells during remission markedly ameliorated disease recurrence, confirming a role of synovial T RM in arthritis flares.

Conclusion: Here, we demonstrate that synovial T RM present in human inflamed synovium are a targetable mediator of joint-specific memory in arthritis. Introduction: Inflammation has been associated with a marked increase in the basal levels of NGF in tissues, but how NGF and its immature form proNGF, regulate cell functions and mediator release during inflammatory responses is still largely unknown. In this study, we investigated the effects of proNGF, the biological active NGF precursor, on inflammatory cytokine production in synovial fibroblasts to clarify whether changes in proNGF concentration or in the expression of its specific receptor p75NTR are involved in joint inflammation.

Objectives: To investigate whether proNGF and its specific receptor p75NTR modulate distinct pro-inflammatory pathways in synovial fibroblasts of chronic arthritis patients and whether p75NTR/proNGF axis inhibition dampens inflammatory cytokine production. Methods: NGF expressions, TrkA, p75NTR expression and signaling in synovial fibroblasts from arthritis patients were evaluated by quantitative PCR (qPCR) and Western Blot Analysis. Specific ELISA were used to analyze NGF, proNGF and cytokine production. In vitro inhibition of p75NTR was performed using a synthetic inhibitors (LM11A-31) that blocks the binding site of proNGF.

Results: High amounts of proNGF were detected in the synovial fluid of chronic arthritis patients. In vitro stimulation of patient synoviocytes with recombinant cytokines strongly enhanced the release of proNGF in conditioned media as well as the expression of p75NTR. Inhibition of p75NTR significantly decreased the release of inflammatory mediators as IL-6, IL-1β, IL-8, MCP1. To recreate ex vivo the condition of an inflamed synovia, synovial fibroblasts were cultured in media enriched with 30% synovial fluid (SF) obtained from active Juvenile Idiopathic Arthritis (JIA) patients and that contained high concentration of inflammatory mediators and high proNGF amounts. As expected, synoviocytes cultured in 30% SF significantly enhanced the release of IL-6 and other inflammatory cytokines in the conditioned media. The inhibition of proNGF binding to p75NTR using LM11A-31, strongly decreased inflammatory cytokines release. This reduction was even more substantial of the one obtained using monoclonal antibodies against IL-6 R (tocilizumab), IL-1β (canakinumab) and TNFα (infliximab) commonly used for arthritis treatment. The analysis of the intracellular pathways in LM11A-31 treated synoviocytes showed a decreased phosphorylation of MAPK downstream molecules like p38 and JNK, indicating that inhibition of proNGF binding to p75NTR results in a decreased activity of the proinflammatory cascade response. Conclusion: Inflammatory stimuli induce both p75NTR expression and the release of proNGF in synoviocytes. Blocking the binding of proNGF to its receptor p75NTR, using LM11A-31 inhibitor, strongly reduces in synoviocytes the release of inflammatory mediators, suggesting that enhanced p75NTR expression levels might have a crucial role in the chronicity of the inflammatory response and prospect the use of p75NTR inhibitors as a new therapeutic approach to chronic arthritis. Introduction: Over the past decade, genome-wide association studies (GWAS) have identified TRAF1/C5 locus as a risk locus for rheumatoid diseases including RA and JIA (1, 2) , and TRAF1 negatively regulates Toll-like receptor signaling (3) . However, the exact risk variant within that locus and its underlying mechanism regulating TRAF1 expression is still not known. Objectives: We aim to identify non-coding variant in TRAF1/C5 locus governing the expression of TRAF1 gene and its regulatory pathway. Methods: Single-nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) with the most disease associated SNP in TRAF1/C5 locus from immunochip data (5 thousands JIA patients and 14 thousands health controls) were high-throughput screened by SNP-seq(4). Top candidates' regulatory function were further validated by Electrophoretic mobility shift assay (EMSA) and luciferase reporter assay. Then the transcriptional factor that might binds to the functional variant after validation was tested by CHIP-qPCR, oligo pulldown assay as well as supershift assay. Finally, the association between this transciptional factor and TRAF1 gene expression were analyzed by RNAi knockdown experiment. Results: After screening by SNP-seq, EMSA and luciferase reporter assay, rs7034653 was found to be the best functional non-coding variant in TRAF1/C5 locus that is associated with JIA. EMSA shows that protein from monocyte nuclear extract has a preferential binding to protective allele A than the risk allele G of rs7034653, and that binding preference likely regulates higher gene expression as shown by luciferase reporter assay, which is consistent of existing eQTL data that shows higher expression of TRAF1 in protective allele than risk allele in human monocytes. Furthermore, this variant is found to be able to bind to AP1 transcriptional factor FRA2. Suppressed expression of FRA2 by RNAi leads to lower expression of TRAF1 after LPS stimulation in THP-1 monocytic cell line. Results: Biologicals demonstrated more pathophysiology-directed efficiency than non-biological drugs. IL-1 blockade mainly acts on the innate immune system, while IL-6 signaling blockade has a weaker activity on the innate immunity and rather affects the adaptive immunity ( Table 1 ). The MoA models showed that the IL-1β inhibitor canakinumab is more efficient than the IL-6 receptor inhibiting antibody tocilizumab in the autoinflammatory/systemic phases of Still's disease. MoA models reproduced 67% of the information obtained from expression data. Conclusion: Systems biology-based modelling supported the preferred use of biologics as immunomodulatory treatment strategy for Still's disease. This further encourages early IL-1β blockade in initial autoinflammatory/systemic phases of Still's disease to prevent the development of disease or drug-related complications. Further studies are needed to determine the optimal timeframe of the window of opportunity for canakinumab treatment. Methods: MRI of 502 SIJ in 251 children (132 girls), mean age 12.4 years (range 6.1-18.0), were obtained. Ethics committee approval was obtained, informed consent was signed by all children and parents. 127/251 had asymptomatic joints and were imaged for nonrheumatologic reasons in whom we added semi-coronal T1 and STIR of the SI joints, and 124 had low back pain but no sign of sacroiliitis on initial clinical MRI review. Before the main reading exercise, images of 10 participants (20 SIJ) who had been excluded from the study were used for multi-step calibration exercises. Three calibration rounds were conducted over 8 months. Subchondral high signal ('flaring') was defined as increased signal in subarticular bone on STIR images compared to normal bone marrow in the centre of S1 and S2 vertebral bodies. After calibration, three subspecialist radiologists independently scored subchondral signal changes from 0-3 in 4 locations: vertical sacral (along the lateral apophyses of the sacrum), horizontal sacral (along the intersegmental apophyses), iliac (vertically along iliac side of SIJ), and iliac crest (horizontally along iliac wing upper margin), separately for left and right sides. The degree of closure of sacral segmental apophyses was graded as well. Readers were blinded to demographic, clinical and other imaging findings. Associations between patient age, sex, signal changes and apophyseal closure were analysed. Results: Rimlike subchondral increased T2 signal or 'flaring' was commonly seen in children at the margins of the SI joints, and is far more common on the sacral side (72% vs 16%, p<.001). It was symmetrical in >90% of children. Iliac flaring scores were always lower than sacral, except for 1 child. Signal changes decreased as sacral apophyses closed, and were seen in <20% of subjects with fully closed apophyses. Signal changes were more frequent in boys, and peaked in intensity later than for girls (ages 8-12 vs. 7-10). Subchondral signal in iliac crests was high throughout childhood and did not correlate with other locations. We found no significant difference between left/right side, boys/girls nor between both groups. Conclusion: Rimlike subchondral high T2 signal 'flaring' is commonly observed at MRI of sacroiliac joints in children, and should not be confused with pathology. It is generally sacral-predominant, symmetrical, and seen in less than 1/5 of children after segmental apophyses are closed. Flaring that is asymmetrical, greater in ilium than sacrum, or intense in a teenager with closed apophyses, is unusual for normal children and raises concern for pathologic bone marrow edema. Subchondral signal in iliac crests is high throughout childhood and cannot be used for reference in diagnostic criteria. Accurately distinguishing between normal and pathologic pediatric subchondral sacroiliac joint signal changes requires understanding the patterns of normal variation, to avoid misdiagnosis of sacroiliitis. Our data suggest that, in a treat-to-target concept, attainment of at least JADAS ADA at 3 months may be meaningful.

Introduction: Juvenile idiopathic arthritis (JIA) patients may experience significant adverse effects (AEs) from medications. AEs may negatively affect patients' well-being and reduce treatment compliance, ultimately compromising patient outcomes.

Objectives: 1) To assess the frequency of patient-reported adverse events (AEs) and their effects on well-being, health-related quality of life (HRQoL) and school activity.

2) To investigate treatment non-adherence and its determinants, focusing on the possible impact of AEs.

Methods: Data on 13704 visits of 8402 patients were obtained from two large multi-center international studies, the pharmacovigilance registry Pharmachild and The EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA) cohort. Subjects who were on medications at the time of visit were included. AEs, currently prescribed medications, root of administration, disease-related school problems, self-reported treatment adherence (as a dichotomic variable), reasons for non-compliance, patient overall well-being (PGA), physician global assessment (MD-global) and VAS-rated pain intensity were collected through the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). HRQoL was assessed through a ten items Likert-type HRQoL scale encompassing a physical health (PhH) and psychosocial health (PsH) subscale, with higher scores indicating worse outcomes. The effects of AEs on PGA, PsH scale, school problems, and the determinants of therapy non-compliance were analyzed using General Linear and Generalized Mixed Effects Models with random intercepts per individual. Results: AEs were reported by 29,49% of patients. Experiencing one or more AEs was associated to worse PGA (β 0.377, η 2 0.011, p < 0.001) and PsH score (β 0.618, η 2 0.024, p < 0.001) and school problems (OR 1.82, 95%Cl 1.64-2.01, p < .001) after adjustment for MD-global, PhH and pain levels. Mood swings, sleep problems and weight gain showed the highest impact on PsH; frequency of the main AEs and regression estimates for outcomes are depicted in the table. Treatment non-adherence was reported by 9,27% of subjects. The most frequently cited reasons for non-adherence were drug refusal by the child (n=200) and fear of adverse events (n=142). Self-reported medication adherence was negatively associated to combination treatment with conventional and biologic DMARDs (OR 0.40, 95%Cl 0.26-0.62, p < .001) and subcutaneous administration (OR 0.13, 95%Cl 0.09-0.20, p < .001). Nausea predicted non-compliance due to fear of AEs (OR 13.93, 95%Cl 5.02-38.65, p < .001). Conclusion: AEs have a substantial impact on patients' quality of life, functioning and therapy adherence in JIA. Understanding treatmentrelated burden is vital to achieve good therapeutic compliance and improve outcomes in JIA.

None declared (Table) . At W44, each CHAQ domain had improved from Part 2 BL (W18) by a numerically greater extent with tofacitinib vs PBO (Table) . Mean scores for the 15 CHQ health concepts, and the PhS (Table) , improved from Part 1 BL to W18 with tofacitinib, with these improvements generally sustained with tofacitinib and PBO in Part 2.

The CHQ PsS was within the range of a healthy normative population (ie mean 50 [standard deviation 10]) at Part 1 BL and remained as such throughout the study (Table) .

Conclusion: In pts with pcJIA, tofacitinib demonstrated sustained improvements in PROs, as measured by the CHAQ and CHQ. Objectives: The aim of our study was to evaluate the childhood vaccine responses against hepatitis B and varicella zoster virus of patients with JIA using classical DMARDs and biologic drugs. Methods: Our study included 95 JIA patients who received classical DMARDs (methotrexate,salazopyrin,leflunomide,cyclosporine, hydroxychloroquine), 95 JIA patients who received biological drugs(anti-TNF, anti-IL-6, anti-IL-1 and CTLA4-Ig) and 91 healthy controls between the ages of 2-19 years. All participants were vaccinated according to our country's routine vaccination program in infancy. The anti-HBs and anti-VZV IgG antibody levels of participants were evaluated. Also the patients receiving DMARDs and biologic treatments were assessed within each group separately. Results: Anti-HBs and anti-VZV IgG titers were not different in patients with DMARDs, patients with biologics and healthy controls(p= 0.094), (p=0.22) . The duration of biologic treatment was longer in patients with anti-HBs negative in biologic group(p=0.023), and was found to be a risk factor for anti-HBs negativity (OR:0.978 95%CI 0.961-0.966, p=0.012) in univariate logistic regression. However, the duration of biological treatment did not affect anti-VZV positivity(p= 0,553). Significant relationship was not detected between the duration of DMARDs therapy and anti-HBs(p=0.721) and anti-VZV(p= 0.560) positivity. Conclusion: We found that the anti-HBs and anti-VZV positivity are not different in patients with JIA from healthy controls. However, the duration of biologic therapy is a risk factor for negative anti-HBs titers. Introduction: In the last years, the interest in the assessment of parent-and child-reported outcomes (PCROs) in paediatric rheumatic diseases is gaining increasing importance. These measures reflect the parent and child perception of the disease course and effectiveness of therapeutic interventions and may facilitate concordance with physician's choices, improve adherence to treatment, and participation in a shared decision -making strategy. Moreover, the availability of reliable PCROs could be crucial for remote monitoring of patients when in person clinical evaluation may be difficult or even not possible.

Objectives: Aim of this work is to provide further evidence of validity and reliability for four PCRO measures included in the OMERACT JIA core domain set: the evaluation of the child's pain and of the child's level of disease activity, the assessment of the morning stiffness (MS) duration, and an active joint count for parent/patient proxy or selfassessment.

Methods: Pain and disease activity were rated on a 21-numbered circle scale corresponding to the traditional VAS (0=no pain; 10=extreme pain). MS was measured with a 5-point Likert scale. The proxyand self-assessment of active joints was obtained by rating the presence of pain or swelling in the following joints or joint groups: cervical spine, lumbo-sacral spine, shoulders, elbows, wrists, small hand joints, hips, knees, ankles, and small foot joints. To each joint or joint group, one point was given in case of monolateral involvement, two points in case of bilateral involvement. Patients were included in a multinational dataset of patients enrolled in the Epidemiology Treatment and Outcome of Childhood Arthritis study. Criterion validity was assessed by examining the correlation of the four tested measures with physician centered measures, ESR, and composite disease activity scores. To further assess the validity of the tools correlations of the measure with the cJADAS10 were computed after grouping patients by ILAR category, by geographic area, and by education level. Reliability was assessed in a subset of subjects with Spearman correlations and intraclass correlation coefficients (ICC), comparing two visits 7-14 days apart. Results: A total of 8,848 parents and 6,204 patients had all the evaluations available. Correlations of tested measures were in the moderate range (0.4-0-7) with physician centered measures and in the poor range (< 0.4) with ESR. The level of correlation of the tested parent measures with the cJADAS10 remained stable after grouping patients by ILAR category. In the same analysis with patients grouped in eight geographic areas, correlation levels were similar, although, on average, they were higher in Latin America and slightly lower in North America. The levels of correlation with the cJADAS10 were similar in subjects in which the level of education of the parent filling the questionnaire was elementary or lower, high school, or degree, respectively. In 442 parents and 344 children, correlations between first and second assessment was > 0.7 for all measures; ICC Introduction: It is currently agreed that disease remission should be an over-riding goal in the management of juvenile idiopathic arthritis (JIA), but the existence of multiple ways in which this target can be assessed in the clinical setting makes its definition more challenging. Objectives: To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in JIA, and to seek for factors driving discordance. Methods: The frequency of fulfillment of existing ID and LDA definitions was evaluated in 10186 patients extracted from three cross-sectional datasets. Patients were divided in the "functional phenotypes" of oligoarthritis and polyarthritis. Concordance between criteria was examined through Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. Results: ID criteria were met by 31.2 to 41% of patients with oligoarthritis and by 26.5 to 33% of patients with polyarthritis. LDA criteria were met by 44.8 to 62.4% of patients with oligoarthritis and by 44.6 to 50.4% of patients with polyarthritis. There was a 63.2 to 67.1% overlap between ID criteria and a 67.9 to 85% overlap between LDA criteria. The parent global assessment of child's wellbeing and the physician global assessment of disease activity were responsible for the majority of instances of discordance among ID criteria (9.2-17.5% and 9.6-12%, respectively). Conclusion: We found fair concordance between definitions of ID and LDA in JIA, with the main drivers of discordance being the physician and parent global assessments. This observation highlights the need for further studies aimed to compare the relationship between physician-and parent-perceived remission and remission assessed by objective measures of inflammatory activity. Introduction: Juvenile arthritis (JA) is the most common pediatric rheumatic disease, potentially having permanent functional impacts on patients long after initial diagnosis. There has not been a comprehensive review of these studies to collate and assess the quality of their information. Objectives: The purpose of this systematic review is to summarize clinical outcomes in adults with JA (age >16) and assessing quality of The quality of publications was assessed using QUality In Prognosis Studies (QUIPS) risk-of-bias tool. QUIPS is classified into six domains of bias -study population, attrition, outcome, prognostic factor, confounding factor and statistical analysis. Papers were graded by trained reviewers who assigned a risk-of-bias grading (low/ moderate/ high) to the overall domain. We identified and extracted all statistically significant study outcomes and information related to studies. Statistical modelling was extracted to help determine the significance and validity of the results. Results: 56 of 12 243 papers were included in this study for analysis. The majority (50.8%) of studies were cross-sectional, and the most common study queries were disease (34.9%), functional status/psychosocial (22.2%), temporomandibular joint (11.1%), and uveitis (9.5%) outcomes. 13 publications (21%) were repeat publications of non-unique cohorts, with the majority of these using the same cohort from Norway.

In terms of QUIPS, study confounding (95%), participation (81%) and attrition (82.1%) domains had the largest proportion of studies with moderate to high levels of bias.

In disease outcomes, the most common reported were remission (36%), and use of DMARDs (71%). HAQ functional status was reported with a median score of 0.49, signifying mild disability. VAS pain scale had a median score of 6.51 cm. DMARDs and NSAIDs usage ever were reported with 42.8% and 63.3% respectively. Uveitis was reported in 22.9% patients. Out of 56 papers, 35 performed statistical multivariable modelling. Within each study topic there were no multivariable models of similar outcomes to allow for identification of consistent prognostic factors. Conclusion: Only 2 (3.1%) truly longitudinal studies focused on the adult outcomes of JA patients. We therefore do not know the disease course information of adults with JA. The evidence in the studies had a high risk of bias in confounding factors, population and attrition, thus should be interpreted with caution. One theme that is not as prevalent is the effectiveness of medication and the complications with medication over time.

Limitations in our paper include being consistent in extracting the many categories of information. There are subjective biases in rating QUIPS as well. Another drawback exists in working with already presented results in published articles, which make come with biases in the information that is presented. The majority of the studies have high levels of bias in study designs and outcomes. Future literature should describe the source of patients and report the differences between participants and nonparticipants. Our next step is to categorize outcomes by duration of disease and compare within the same subtype as well as make recommendations on formulating a standard reporting format for future JIA research. [3] , 11% of mid-late adolescents with inactive oligoarthritis and 10% with inactive polyarthritis stated to achieve the minimum amount of PA on at most 2 days per week. In patients aged 10 to 14 years, cJADAS-10 (p = 0.027, η 2 = 0.005), CHAQ (P = 0.001, η 2 = 0.011) and BMI (P < 0.001, η 2 = 0.008) were significantly associated with PA. In comparison, in 15-19-year-olds were sex (P = 0.000, η 2 = 0.015), CHAQ (P = 0.001, η 2 = 0.013) and BMI (P = 0.003, η 2 = 0.006) significantly related to PA. Conclusion: About 80% of adolescence with JIA fail to meet the global recommendations on PA, partly despite of an inactive disease state. In order to promote activities of daily life and to implement adequate interventions, JADAS and CHAQ should be controlled. To clarify both the safety of PA and the health risks associated with inactivity, efforts are needed to improve the quality of information provided for parents, health professionals, teachers and patients. (Table) .The majority of the participants was employed(72%),married(82.5%) and had tertiary education(50.9%). The commonest diagnosis was oligoarticular JIA(28.9%), while 28.6% of caregivers did not know the child's diagnosis.The mean age of children is 10.5years(SD=4.8) with a median disease duration of 4years(IQR:2-7).

Most patients are currently treated systemically(71.4%), mainly with MTX(47%). 13.3% reported previous vaccine side effects;82.2% were fully vaccinated according to national vaccination schedules while 40.9% had received influenza vaccine in the past. A total of 87 children(30.3%) were vaccinated against influenza for this season and 89.7% of them had a stable disease during the immunization.Most of the participants were informed of the recommendation by attending pediatric rheumatologist(33.4%) or pediatrician(28.2%).The highest vaccine uptake was recorded in Greece(70.8%),followed by Israel(41.9%),while none of the JIA patients from Croatia and Slovakia was vaccinated(p< 0.05).Compared to employed caregivers,unemployed ones were more likely to vaccinate their children(25.7%vs53.3%,p< 0.05).Children with sJIA had the highest vaccine uptake(65.4%) while caregivers who did not know the child's diagnosis reported the lowest one(12.2%)(p<0.05).Those who were informed of influenza vaccine recommendations by medical staff and had vaccinated their children in the past were more likely to vaccinate the current season(both p<0.05).However,children who had previously experienced adverse vaccine-related events reported the lowest vaccine uptake(p<0.05). Among non-vaccinators,59.5% did not have the opportunity to discuss their concerns with a specialist.Major reasons for nonvaccination included unawareness of the need(39.7%),fear of side effects(28.4%) and fear of disease flare(17.1%). The decision for nonvaccination was driven mainly by personal beliefs(41.5%),while 17.5% reported it was a doctor's advice.Among suggestions to improve influenza vaccine uptake,"informing families in advance" was the most commonly cited recommendation(59.6%),followed by "campaigns"(32.4%).

Despite the variations among European countries,influenza vaccine uptake remains low among JIA patients.Those previously vaccinated and those aware of the recommendations were more likely to be vaccinated.Informing families,discussing their concerns and organizing campaigns that will address the fears and highlight the importance of the influenza vaccine for this JIA population at risk may increase vaccination rates in children with rheumatic diseases. Introduction: Uveitis is the most common comorbidity in patients with juvenile idiopathic arthritis (JIA) and can lead to sightthreatening complications if not diagnosed and subsequently treated in an early stage. The estimated prevalence of JIA-U varies up to 30%, but the individual risk of acquiring uveitis is unknown. Objectives: To build a clinical prediction model for JIA associated uveitis (JIA-U) providing individual risk estimates that could be used to inform patients/parents and aid physicians in determining screening frequencies.

Methods: Data from the international observational Pharmachild registry were used. For every patient with a follow-up period of at least 4 years, occurrence of JIA-U was determined from retrospective and prospective records since registration into Pharmachild. Multivariable logistic regression analysis was used to determine significant risk factors for JIA-U after correcting for confounding variables and to build a prediction model. Risk factors and confounders concerned were identified based on the existing literature and consensus of the authors, these included: age at JIA onset, gender, JIA subtype, ANA positivity, RF positivity and HLA-B27 positivity. The prediction model was selected based on Akaike information criterion and bootstrap resampling with replacement (n = 200) was used for internal validation and to adjust for model optimism. Results: JIA-U was observed in 1,108 of 5,535 eligible JIA patients (20.0%). After correcting for confounding variables, independent risk factors for JIA-U were ANA positivity (OR: 1.89, 95% CI: 1.55 -2.32), HLA-B27 positivity (OR: 1.47, 95% CI: 1.11 -1.94), undifferentiated arthritis (OR: 1.70, 95% CI: 1.17 -2.43), oligoarthritis (OR: 1.56, 95% CI: 1.27 -1.91) and enthesitis-related arthritis (OR: 1.49, 95% CI: 1.02 -2.14). Older age at JIA onset (continuous variable) was an independent protective factor (OR: 0.84, 0.81 -0.87). Of all variables considered, the combination of age at JIA onset (in years), JIA subtype and ANA status (1 = positive, 0 = negative) performed best in predicting JIA-U (Table 1 ). Following the model, ANA positive patients with a young age at JIA onset and enthesitis-related arthritis run the highest risk of acquiring JIA-U. The prediction model had good Introduction: Idiopathic chronic ANA-positive anterior noninfectious uveitis (CAU) has similar clinical characteristics as juvenile idiopathic arthritis related uveitis (JIAU), except for inflammatory arthritis. A damage and response index has already been developed by a European collaboration of pediatric rheumatologists and ophthalmologists for JIAU (MIWGUC) [1] . As innovative effective treatment options are emerging for pediatric uveitis, it is important to define a response and damage index to assess the effectivity of drugs in preventing ocular damage in children with idiopathic CAU. Objectives: To develop a response and damage and response index to measure ocular damage in children with idiopathic CAU Methods: MIWGUC already agreed on items to evaluate outcome [1] for JIAU. 6 paediatric rheumatologist and 6 uveitis specialized ophthalmologists were asked to score the items, which were derived from the JIAU response and damage index. Regarding relevance for response and damage in CAU (Table 1 ) the items were scored. Items with scores between 1-3 points were discarded, >7 were accepted, and 4-7 were further discussed in the group with nominal group technique. 80% agreement was required to keep the item. Results: The MIWGUC group agreed in a consensus meeting in Barcelona, that idiopathic CAU and JIAU may be managed similarly. Tables one presents the result of the voting. Conclusion: We propose items to assess response to treatment and ocular damage in children with CAU. Validation of these indices is required in clinical cohorts to assess effectivity of a given drug for treating activity and preventing eye damage. This proposal will be evaluated from the MIWGUC group in a prospective study. Results: After excluding 10 poor quality VC, 186 VC were conducted over 41 days for patients world over but largely from a 700 km radius consulted. Age ranges (mean), physician-caregiver satisfaction with VC in differing age groups in new and old patients and their interobserver agreement is shown in Table 1 . 6/7 new and 77/107 old patients and 9/9 physicians gave 5 star rating. 9/107 expressed dissatisfaction with physical examination on VC. Physicians expressed lacunae in the process, coordination and case presentation.

Conclusion: Benefits of VC as a resource saver is applicable to paediatric rheumatology, where perusal of records, meticulous history, and inspection stand crucial. Our study bears this out providing several highlights. However, lacunae like parents missing human connect, better elicitation of signs need to be addressed. VC provides excellent opportunity to partner with and educate referring physicians regarding diagnosis and management. Going forward VC can be proposed initially to selected follow-up patients >5years, alternating with in-person consultations. Educating caregivers on simple examination methods may make VC more conclusive. While structured in-person consultation remains the gold standard, VC can become viable alternative in difficult times or resource challenged situations. VC could plug the gaps in access to paediatric rheumatologists and open the concept of practice to a world without borders. Introduction: Growing up with a chronic disease comes with challenges, such as coping with fatigue. Many adolescents are severely fatigued, thugh its associated factors exhibit considerable interpersonal and longitudinal variation. Objectives: We assessed whether PROfeel, a combination of a smartphone-based ecological momentary assessment (EMA) method using the internet, followed by (face-to-face) patient-tailored treatment advice based on a dynamic network analysis report, was feasible and useful.

Methods: Feasibility study in fatigued outpatient adolescents 12-18 years of age with an autoimmune disease, post-cancer treatment, or with medically unexplained fatigue. Participants were assessed at baseline to personalize EMA questions. EMA was conducted via smartphone notifications five times per day for approximately six weeks. Hereby, data was collected and stored via the internet. The EMA results were translated into a personalized report, discussed with the participant, and subsequently translated into a personalized treatment advice. Afterwards, semi-structured interviews on feasibility and usefulness were held. Results: Fifty-seven adolescents were assessed (mean age 16.2y±1.6, 16% male). Adolescents deemed the smartphonebased EMA feasible, with the app being used for an average of 49 days. Forty-two percent of the notifications were answered and 85% of the participants would recommend the app to other adolescents. The personalized report was deemed useful and comprehensible and 95% recognized themselves in the personalized report, with 64% rating improved insight in their symptoms and subsequent steps towards treatment as good or very good. Conclusion: PROfeel was found to be highly feasible and useful for fatigued adolescents with a chronic condition. This innovative method has clinical relevance through bringing a patient's daily life into the clinical conversation. Personalized treatment advices to cope with fatigue can boost motivation and treatment adherence, and may lead to improved self-management of symptoms, thereby decreasing the need for additional treatment. Introduction: Electronic educational resources (e-resources) have the potential to promote awareness and knowledge about paediatric musculoskeletal (paed MSK) conditions, but if they are to achieve this goal, it is important to understand if and how they may lead to change in clinical practice. This is important and timely, given the current expansion of e-learning within clinical education. Our research group has developed a suite of e-resources with the overall ; reporting areas of impact that included: increased awareness and diagnostic capabilities, increased ease and capability in clinical examination, improved teaching, opportunity to view rare clinical cases, increased awareness in other healthcare providers, and the provision of resources and information to aid teaching and self review. Increased ratings of confidence in MSK medicine or examination were reported after use; 82% (PMM), 90% (pGALS App) and 87% (ELM) reported to be confident or very confident compared to 52%, 68% and 57% before. Suggestions to increase impact and use concerned increased awareness of resources, targeting a wider range of clinicians involved in the care of paed rheumatology patients, integration with local systems or curriculum, and linking in with professional organisations to increase visibility. Lack of awareness, time constraints, costs, potential language barriers and challenges in electronic access were reported as key barriers to use and impact.

Conclusion: E-resources have an increasingly key part to play in clinical education. Our findings suggest our e-resources are fulfilling their role in raising awareness and early recognition of MSK conditions in childhood. Future qualitative work will explore our findings in more depth in particular in relation to developing an evaluation strategy that may be applied to other e-resources.

None declared

A realist approach to eliciting the initial programme theories for the self-and shared-management of juvenile idiopathic arthritis by children, young people, families and professionals involved in their care S. R. Introduction: Enabling children and young people (CYP) with juvenile idiopathic arthritis (JIA) to adopt self-management behaviours early on is likely to benefit their health and wellbeing through childhood and into adulthood. However, there is limited evidence of interventions focused on supporting the self-management of JIA by CYP, and the shared-management by families, and the most appropriate manner in which to deliver such support. Therefore, there was a need to develop a theoretical basis to underpin future self-and shared-management support, across public, private and voluntary sectors, to support CYP living with JIA and their families across the life-course.

Objectives: To elicit initial programme theories (IPTs) as the first stage of a realist evaluation pertaining to the self-and sharedmanagement of JIA by CYP, their families and professionals involved in their care.

Methods: A realist evaluation approach guided the theory elicitation stage of this study. Firstly, information was obtained from an integrative review of self-and shared-management interventions targeted at CYP and families living with long-term conditions. Secondly, a document review of long-term condition self-and shared-management evidence was undertaken. A pragmatic search of JIA self-and shared-management support then followed. A realist evaluation heuristic (context-mechanism-outcome [CMO] ) was used to synthesise information from sources into IPTs and CMO configurations, using retroduction to link theory and causality.

Results: Seven IPTs pertaining to the self-and shared-management of JIA by CYP, their families, and professionals involved in their care were identified. Four IPTs (1) (2) (3) (4) were elicited at the individual and interpersonal level, while three IPTs (5-7) were elicited at the institutional and infrastructural level (Table) . The elicitation process reiterated the argument that causality is located at the individual and interpersonal levelamongst the actions CYP and families take, individually and collaboratively, in response to the resources made available to them through self-and shared-management support interventions.

Conclusion: The IPTs and the initial CMO configurations describe how and why JIA self-and shared-management support is expected to work. By qualitatively testing IPTs with key stakeholders using the realist evaluation approach, the IPTs can be refuted, refined, and consolidated into a refined theory of 'what works, for whom, in what circumstances and why' in the context of JIA self-and sharedmanagement support.

None declared Introduction: Systemic autoinflammatory diseases (SAIDs) encompass clinical entities in which spontaneous inflammation occurs due to dysregulation of the innate immune response. The variability in presentation and rarity frequently lead to a diagnostic delay with potential damage from uncontrolled inflammation and negative impact on quality of life (QOL). Objectives: We aimed to investigate the patient-reported factors underlying this negative impact. Methods: A self-reported 25 question online survey on QOL of patients with SAIDs was developed by the non-profit organizations, the Autoinflammatory Alliance, KAISZ/VAISZ, ENCA and sJIA Foundation in English and Dutch. Respondents were recruited by convenience sampling through online social media posts. Data on triggers, medications, family history, and correlation of symptoms with labs were collected in addition to detailed information on QOL both during and in between flares. Results: Between 2017 and 2019, there were 365 responses (342 in English and 23 in Dutch; Demographics are in the table). The most common diagnosis was undifferentiated SAID (uSAID). Seventy percent was diagnosed by a rheumatologist. Delay in diagnosis was common (5-20 years for 40% of patients). Almost half of the respondents saw 3-8 specialists before receiving their final diagnosis. In addition to the common features such as fever (79%), rash (60%), abdominal pain (70%), and oral ulcers (50%), SAID patients often experienced pain (80%) and fatigue (87%). Fifty percent of patients rated being "severely limited" during flares and "somewhat limited" in between flares. 80% reported negative affect on their studies, job, and career. We categorized open-ended responses into different impact domains of: 1.Physical: lack of understanding of the disease amongst both the medical and lay community, delays in diagnosis, unpredictable symptomatology, unknown long term side effects of medications, 2. Emotional: feelings of anxiety, hopelessness and frustration, feeling doubted about disease severity, constant worry about flares, 3. Social: inability to make plans for vacations/social events due to unpredictability of symptoms, leading to isolation, dependence on others, 4. Financial: insurance not covering specialists/medications, inability to work. Conclusion: Patient engagement in designing survey questions helps to capture the impact of a disease on all aspects of life. In addition to the well-known negative impact of chronic diseases on QOL, the unpredictable nature of the course of SAIDs magnifies the stress of daily living for patients and caretakers. More granular questionnaires paired with clinical and biomarker analyses are needed to identify specific vulnerabilities and risk factors so that preventive measures can be implemented to improve QOL of patients with SAIDs. Introduction: Juvenile Idiopathic Arthritis (JIA) is the umbrella term for a group of childhood, chronic rheumatic arthritides affecting approximately 1 in 1000 children and young people. It is defined as persistence of arthritis for more than 6 weeks of unknown origin, in patients aged under 16 years (1). Whilst much research has been conducted into understanding prognosis and treatment of JIA, there is still much unknown regarding tools to predict outcome, select treatment, or predict response. The Childhood arthritis and its associated uveitis: stratification through endotypes and mechanism to deliver benefit (CLUSTER) Consortium aims to address these research priorities. The role of patient and parent involvement has been key in the creation of the Consortium. To provide two-way fully-integrated involvement and engagement within the programme, we developed a patient and parent working group entitled the CLUSTER Consortium Champions. Objectives: To develop a patient and parent working group that feeds into all aspects of research and management within the Consortium. The goal is for CLUSTER Champions to collate and express the thoughts, interest and ideas of patients, parents and the public. This provides an integrated two-way system of benefit. Methods: A concept document was developed, providing background information on the potential role of CLUSTER Introduction: Vaccination coverage in children and young people (CYP) with rheumatic and auto-inflammatory diseases is reported to be lower than healthy CYP. However, the reasons why vaccinations are declined by parents/carers remain unclear. In September and November 2019 a survey was posted online. Awareness for this survey was raised through social media and patient organisations. Main objective of the survey was to get more insight into the knowledge and awareness of patients with specific diseases (autoimmune and auto inflammatory) and their potential use of certain vaccinations. Objectives: To understand the views of parents/carers regarding vaccinations in CYP with rheumatic and autoinflammatory diseases.

Methods: An electronic survey of parents/carers of CYP with rheumatic and autoinflammatory diseases was distributed in English using the national organisations representing parents/carers and CYP. The survey consisted of 60 questions, and was accessible between September and November 2019. Aside from demographics, we asked respondents for their views on the value of vaccinations, risk/benefit balance, available information/commentary on vaccinations and shared decision-making opportunities with healthcare professionals (HCPs).

Results: A total of 463 responses were received (62% from Europe, 38% from non-European countries). We collected data on a variety of topics such as demographics, diseases, medications and vaccinations. While the majority of respondents recognised the importance of vaccinations (95%) and believed in the value of vaccination programmes (82%), 34% reported postponing vaccinations for personal reasons. Concerns were focussed more on short-term side effects (61%) than long-term side effects (48%); with 42% suggesting that they knew somebody else who had experienced a side effect. The most common vaccination concern was that a disease flare may be triggered. However, most were also concerned about vaccine-preventable diseases (62%). The top three reasons against vaccination were: risk of side effects, advice from HCPs (e.g. against live vaccines while on biologics) and poor information about vaccinations. The influence of media information about vaccinations was inconsistent. Most felt they were able to discuss vaccinations with HCPs (90%). Finally, several respondents called for an independent online resource about vaccinations for CYP with rheumatic and autoinflammatory diseases. Conclusion: Parents/carers of CYP with rheumatic and autoinflammatory diseases generally recognise the importance and value of vaccinations. However, many are concerned about vaccinations triggering a disease flare, resulting in some parents/ carers postponing vaccinations. It is clear that HCPs play an important role in discussing vaccinations with parents/carers as part of the shared decision-making process. An independent online resource about vaccinations, specifically for this population, may need to be developed to support evidence-informed decision-making. Objectives: To develop a patient-led, longitudinal survey to identify the potential risk-factors associated with COVID-19 infection in people with rheumatic, autoimmune and autoinflammatory conditions; to compare outcomes among these patients; and to characterise and understand how they may be differentially affected by COVID-19. Methods: The COVID-19 European Patient Registry (EPR) was developed by parents of children and young people (CYP) representing ENCA, with support and involvement from individuals and organisations across Europe, including adult patients and the Paediatric Rheumatology European Society (PReS). As partners of the Global Rheumatology Alliance, the EPR was specifically created as a longitudinal survey tool. Development was very rapid, allowing data to be collected within 3 days from the start of the project, maximising the potential for capturing vital information through the web-based survey tools at www.jarproject.org/covid. The EPR has two parts: paediatric (to be completed by parent/ caregiver) and adult. It comprises an online survey asking about rheumatic conditions, general health, medication and underlying comorbidities. Each participant is sent a short follow-up survey, weekly, asking about exposure to COVID-19, preventative steps taken to avoid infection, symptoms, diagnosis and outcomes. The EPR was launched on 24 March 2020 and is available in 13 languages. Individuals can join it at any time, on a rolling basis. Each week, data from the initial and follow-up surveys are downloaded, anonymised and combined to generate the longitudinal registry. Consent is provided when enrolling, and confirmed at each follow-up survey. Results: As of 24 May 2020, 3,740 people (603 CYP and 3,137 adults) had joined the EPR. Among the CYP, only 5 reported a COVID-19 infection (0.8%). The follow-up response rate at week 1 was 52%. Table 1 provides a summary of CYP participants to 24 May 2020. Conclusion: The COVID-19 EPR provides an opportunity to develop an understanding of how COVID-19 infection affects paediatric and adult rheumatology patients, to identify risk-factors for infection and/or disease severity. Currently, COVID-19 in CYP has low prevalence and mild outcomes. Updated results will be presented at the PRES Congress.

We are grateful to the team of volunteers who helped translate the surveys, as well as ENCA , PRES and representatives from the rheumatology community for their expertise and support. Introduction: Having a child with a chronic illness has been associated with increased levels of parenting stress across several health conditions. Parenting stress has not been examined in parents of children recently diagnosed with juvenile idiopathic arthritis (JIA). To help support parents, it is important to identify levels of parenting stress and to understand factors that may influence stress levels.

Objectives: To examine the relationship between the health status of children with JIA and illness-related parenting stress experienced by their parents. Methods: Parents of children aged ≤12 years who had been recently diagnosed with JIA (≤6 months) were recruited during clinic appointments at tertiary paediatric rheumatology clinics in England. Participants were recruited to a multicentre randomised controlled trial of a website for parents of children with JIA. This abstract reports data collected prior to randomisation. Parents completed the Pediatric Inventory for Parents (PIP) measure of childhood illness-related parenting stress. The PIP has two scales, measuring the frequency (PIP-F) and difficulty (PIP-D) of illness-related events that parents may face. Each scale provides a total score ranging from 42-210 with higher scores indicating greater stress. Child clinical data collected included: JIA subtype; time since diagnosis; medication; number of active and limited joints; erythrocyte sedimentation rate; Child Health Assessment Questionnaire; parent global rating; physician global rating; presence of comorbid illness. Multiple linear regressions were performed to analyse the relationship of child health status with PIP-F and PIP-D. Results: Parents of 203 children participated; 166 mothers and 37 fathers are included in the analyses. Their mean age was 36.3 (6.5) years. Their children with JIA had an average age of 6.2 (3.4) years; most were female (n=136, 67%) and had oligoarticular (n=107, 52.7%) or polyarticular (n=65, 32.0%) JIA. Sixty-eight (33.5%) had been prescribed methotrexate. Mean (SD) scores on the PIP-F and PIP-D were 108.6 (32.1) and 103.1 (32.6) respectively. This is similar to stress levels reported by parents of children with other health conditions, including type 1 diabetes and sickle cell disease. Regression analysis explained 24% of the variance in PIP-F. Significant independent predictors of higher scores on the PIP-F, representing greater frequency of difficult events were: Female parent gender (B=12.72, p=0.018), systemic JIA subtype (B=26.30, p= 0.038) and presence of a co-morbid illness (B=11.05, p=0.041). Regression analysis explained 20% of the variance in PIP-D. Significant independent predictors of higher scores on the PIP-D, representing greater difficulty experienced were: systemic JIA subtype (B= 43.26, p<0.001) and a poorer parent global rating score (B=2.089, p= 0.037). Conclusion: This research identified levels of parenting stress among parents of children recently diagnosed with JIA that are similar to those of parents of children with other serious health conditions. Parents in this study who were at an increased risk of high stress levels were those whose children have systemic JIA or co-morbid conditions and those who rate their child's overall wellbeing more poorly. The study findings have helped to identify parents who may be at increased need for support to help reduce parenting stress. Introduction: Juvenile idiopathic arthritis (JIA) -combines a diverse group of chronic joint diseases and is one of the most common and disabling rheumatic diseases of childhood. The course of the disease leaves its mark on both the lifestyle and the psychoemotional status of a sick child, which may determine the risk of various psychological changes and disorders of the emotional and motivational sphere.

The study of the psychoemotional status of patients with JIA is an urgent problem of our time, requiring study to form a set of measures of psychological support for a sick child.

Objectives: Assess the psychoemotional status of patients with a verified diagnosis of JIA.

Methods: The study involved 70 patients aged 3.9 years to 16.11 years (mean age 9.6 ± 4.1 years) with an established diagnosis of JIA according to ILAR criteria, no later than 6 months from the start of the study. In the study group there was the following distribution of patients -20 children with a systemic variant of the disease and 50 children with the articular form of JIA (30 patients with an oligoarticular and 20 with a polyarticular variant of the course of JIA).

The comparison group consisted of relatively healthy children (n = 20). Assessment of the psychoemotional status in the main and control groups was carried out using a set of standardized methods: Sachs-Levy test "Method of incomplete sentences" (SSCT method), test M. Kovach "Questionnaire for childhood depression" (CDI) for patients older than 7 years, test L.S. Slavina "Three wishes." Results: Analysis of the Sachs-Levy test "The method of unfinished sentences" showed that almost 75% of the children of the main group had certain fears and concerns associated with the course of the underlying disease, but positive attitudes prevailed in 30.8% of patients in all spheres of life, while while 17.7% of children in the study group had negative attitudes that were not related to the course of the disease, in the control group this indicator was 12%. When analyzing the method of M. Kovach's "Questionnaire for Child Depression," the CDI score on the A scale showed that a general decrease in mood, a negative assessment of their own effectiveness, was generally observed in 45% of children in the study group and only 5% in the control group; on a scale B 19% of children in the main group identified themselves with the role of the bad, in the control group this indicator was 50%; on a scale of C, 27.5% of children showed a high level of conviction of inefficiency at school, in the control group, 2% of respondents; on a scale of D 35% of the respondents in the main group had a high level of exhaustion and a feeling of loneliness; on the E scale: a negative assessment of one's own inefficiency, the presence of suicidal thoughts was noted in 15% of the respondents in the main group and 1% of the control group. Evaluation of the results of the method L.S. Slavina's "Three Wishes" showed that in almost 90% of the children in the study group, at least one desire was associated with the course of the underlying disease, 15% had 2 wishes, and only one patient with a severe course of the systemic variant of JIA had all three wishes illnesses. An analysis of the data obtained indicated a narrowing of the motivational-consumer (MP) sphere in the study group.

Conclusion: A study of the psychoemotional status of patients suffering from JIA showed that, in general, more than half of the children showed changes in the emotional and motivational sphere of life compared with children from the control group. Thus, it is worth talking about the need for dynamic monitoring of the state of the psychoemotional sphere in rheumatological patients, and the need for psychological support, both at the stages of inpatient treatment and on an outpatient basis.

None declared Introduction: Depression is a common mental disorder, the leading cause of disability and makes a significant "contribution" to the global burden of diseases. Besides, depression is an associated condition in rheumatic diseases including arthritis even in childhood. The relevance of this problem is also due to the fact that in children, despite the presence of a chronic disease, high adaptive abilities of the psyche take place. Therefore, it is especially important to reliably determine the presence of the first signs of depressive conditions at earlier stages of the underlying disease.

Objectives: The aim of the study was to identify early signs of depressive states in children with juvenile idiopathic arthritis (JIA) and their relationship with the activity, duration and complex treatment.

Methods: This study included 16 children (8 girls Objectives: The objective of this study was to measure the economic, psychological and social impact that PRD has on the caregivers of Mexican children and the factors associated with these impacts.

Methods: This is a cross-sectional study in which primary caregivers were prospectively included between April and November 2019 in four public hospitals of specialized care. Descriptive statistics used used to the sociodemographic characteristics of the participants and the patients' clinics, a univariate analysis was performed with the interview responses of the CAREGIVERS questionnaire and the sociodemographic, clinical, and health system variables using the Chi square, Mann-Whitney U, and Kruskal-Wallis tests (p <0.05).

Results: 200 participants were included, women (84.5%) with median age of 38 years; 54.5% cared for patients with JIA, 14% with JDM and 31.5% with JSLE. Most of the caregivers felt concern (42.5%) when learning about the diagnosis, which then was modified by tranquility (44%) when the current feeling was questioned; however, 40 expressed sadness when sharing the patient's PRD (20%) and 39 do not like to do so (19.5%).The main cause of concern is pain (41.5%), followed by difficulty in movement (28.5%) and covering the costs of treatment (25%). Eighteen studies were included in the review. The included studies were of a variety of low, moderate and high quality. The synthesis of the data identified pain to be the most common barrier and the modification of physical activities to the need of the individual to be the most common facilitator to physical activity in JIA. Conclusion: Identifying the most common barriers and facilitators to physical activity allows clinicians to apply better management strategies when treating an individual with JIA. Our findings demonstrate the need for further research in this area to assist increasing physical activity participation for children and adolescents who have JIA. [8] . The initial development and validation process was iterative, patient-centred, and consistent with best practices in PRO development. Currently, the LoSQI is the only JLS-specific PRO, and the only PRO that includes both qualitative and quantitative validity evidence. It is currently being utilized within two large American scleroderma registries but will require cross-cultural adaptation for international use.

Objectives: to undertake cross-cultural adaptation and validation of the Localised Scleroderma Quality of Life Instrument (LoSQI) in juvenile localised scleroderma (JLS). Conclusion: Collaboration between PRINTO centres, CARRA and PRES scleroderma working party members in partnership with patients and families will facilitate shared aims and this will be the first multinational study of a disease-specific patient-reported outcome (PRO) in JLS. To allow further validation work of outcome measures, this important step will allow cohorts from multiple countries to combine datasets and results with an overarching aim to embed PRO in routine clinical practice. This is invaluable for a rare disease population, where research is continuously limited by small samples sizes, large geographical dispersion of subjects, and lack of consensus in selection and use of outcome measures. Introduction: Neurologic disturbances (ND) in children with localized scleroderma (LS) occur more frequent in linear scleroderma en coupe de sabre (ECDS). The frequency of Central nervous system involvement in pediatric craniofacial scleroderma is estimated to be 28-38%. Mostly epilepsy, headache, focal symptoms, neuropsychiatric disorders are described. Only several cases of stroke were recorded in adults with ECDS. The origin of ND is still unclear. There is data for neurovasculitis hypothesis with endothelial cell injury, microthrombotic angiopathy. Other data suggests a prenatal malformation of one side of rostral neural tube resulting in hemiatrophy of facial tissue and underlying brain parenchyma. Objectives: To analyze frequency of neurologic involvement ECDS in children, describe 3 cases ischemic stroke (IS). Methods: Retrospective analysis of ND in ECDS childhood cases was done. All children carried out physical and neurologic examination, brain magnetic resonance imaging (MRI), electroencephalography (EEG), rheumatological observation (physical, instrumental and laboratory including homocystein serum level (Hcy), evaluation for genetic thrombophilia (GThr). Results: We observed 115 children with ECDS, aged from 3 to 16 years, the mean age 12,4 years (M ±3,52), 63 girls and 52 boys (girls/ boys = 1.2:1).

ND were found in 52 children (45%), among them: recent-onset headache in 25 patients (pts) (22%), seizures in 14 pts (12%), parasomnias in 5 pts (4,3%), IS in 3 pts (2,6%), cranial neuropathies in 3 pts (2,6%), hearing loss on the side of leisure in 2 pts (1,7%), paraplegic migraine in 1 pt. IS is a casuistic presentation of ECDS. Clinical data on the IS patients is summarized in Table below. 2 of 3 presented cases (Pt.2 and 3) have neurologic signs, while typical skin scleroderma changes appeare in 8 and 12 months after IS. In another case (Pt.1) a patient suffered from LS for 2 years, before IS, received corticosteroids (CS) orally 0.5 mg/kg 10 weeks, methotrexate (MTX) 12 mg/b.sq. for 2 years with decrease of skin process activity. MRI showed local ischemic focus in the region of left middle cerebral artery. In cases of neurologic disease debut (Pt.2 and 3), focal neurologic deficit (hemiplegia, hemiparesis, aphasia, ataxia, and seizures) lasted for less than 24 hours. MRI showed ischemic foci in frontal and temporal brain regions. In both cases vascular brain anomalies were suspected. Pt.2 and 3 also had recurrent ischemic brain attacks. All pts showed mutations in MTHRF gene and elevated Hcy serum level. After the diagnosis of ECDS was clear in Pt.2 and 3, MTX 12 mg/b.sq. started, usage of CS was avoided. Pts received antithrombotic, neurotrophic and metabolic therapy, folic acid, and rehabilitation. Despite complex therapy, our pts have irrepressible changes of brain parenchyma revealed by MRI and serious neurologic sequelae in 2 -7 years follow up. Conclusion: We speculate that IS in observed ECDS children was strongly associated with GThr and possible undiscovered brain vascular malformations, as addition to scleroderma vasculopathy. IS occurs in less than 3 % of ND in our cohort of ECDS children, but, it demands attention of rheumatologists due to life threatened consequences. Pts with ECDS have to be cheked for GThr, as a risk factor for stroke. Introduction: Raynaud's Phenomenon (RP) is an episodic response to cold or emotional stress which causes colour change and symptoms including numbness and pain in the extremities. Primary Raynaud's, due to functional changes in blood vessels, does not cause tissue damage. Secondary Raynaud's, associated and often the first sign of a rheumatological condition e.g. scleroderma or SLE, can cause tissue loss, digital ulcers and gangrene. It is characterised by nailfold capillaroscopic (NFC) abnormalities and autoantibody formation, which appear to be risk factors for CTD progression. Repeat autoantibody profile and NFC is important as they can progress over time.

The PRES scleroderma working group developed recommendations for assessment, monitoring and treatment of Paediatric RP in 2016, including ANA testing in all and the recommendation to screen for SSc-specific antibodies, anti-dsDNA and ENA in ANA positive patients. NFC should be performed in all and classified as 'normal', 'non-specific changes' or 'SSc pattern'. Objectives: To describe UK & Ireland assessment, management and monitoring of paediatric RP, considering PRES working party recommendations. Methods: Electronic Survey sent to Paediatric Rheumatology networks. Results: There were 64 respondents. 60% were unaware of PRES working party recommendations. Definition of primary RP varied. Most defined it as RP in the absence of a definitive/evolving CTD (48%) . Most tested for ANA 'always' (62%) or 'sometimes' (34%) in a new patient. Clinical suspicion of evolving CTD and family history influenced decision. ANA, if positive, was mostly repeated 'sometimes' (50%), rather than 'always' (23%) or 'not repeated' (27%). Titre, clinical condition and symptom evolution influenced decision to repeat. This was mostly done at 6-months (37%) or 12-months (21%). SSc-specific antibodies were mostly measured 'sometimes' (41%)particularly if scleroderma features. 29% tested these only if ANA positive, 13% never did. Other ENA (93%), Scl70/topoisomerase I (82%) and centromere (71%) were most often included. Most performed NFC at diagnosis: 'Yes always' (58%) or 'Sometimes' (28%). Only 14% did not. Ophthalmoscope was most often used (68%), followed by dermatoscope (28%). 3% used a USB microscope. 9% referred to another centre for formal videocapillaroscopy. Half could not access formal video capillaroscopy. The other half could directly or elsewhere. Only 12% of respondents had received formal NFC training, with most receiving informal training (62%) or none (25%). Confidence levels were mixed. 43% of trainees were 'fairly confident' and 50% 'fairly unconfident'. 41% of consultants were fairly confident, 28% confident, 24% neutral and 7% fairly unconfident. 88% used descriptive free text to describe NFC changes. 14% classified as 'normal', 'non-specific' or 'scleroderma-type'. FU of a patient with no risk factors for CTD varied with most choosing not to follow-up (37%) or to follow-up 'sometimes' (22%). Frequency of followup (FU) was 'It depends' (45%), 6-monthly (22%) or annually (24%). At subsequent visits, most would perform neither ANA nor NFC (33%). The vast majority (94%) would FU a patient with clinical and laboratory risk factors for CTD (3-monthly 19%, 6-monthly 28%, annually 12%, 'It depends' 41%). Most would do both ANA and NFC at subsequent visits (41%) The commonest first-line treatment for primary RP was calcium channel blocker (76%), for RP with tissue damage IV prostinoid (34%) and calcium channel blocker (34%). Conclusion: Among UK & Ireland clinicians, there is variation in definition, diagnosis, monitoring and management of paediatric RP. Access to imaging including NFC by video-capillaroscopy was poor. Our survey highlighted a NFC training need and un-warranted variation in practice from PRES working party recommendations. There was high ever-use of hydroxychloroquine (97%) and mycophenolate (84%) across the cohort, while cyclophosphamide (28%) and rituximab (25%) were more varied. In 15 centers with ≥ 5 patients with class III/IV proliferative disease, mycophenolate use ranged from 60-100%, cyclophosphamide use ranged from 0-100%, and rituximab use ranged from 0-100% of patients.

Conclusion: This initial study of patients with pediatric lupus nephritis in the CARRA Registry demonstrates a diverse cohort of patients with predominantly proliferative lupus nephritis. There is substantial variation medication utilization for proliferative nephritis between centers, as well as biopsy reporting practices across the cohort. Further study and implementation of optimal management for cSLE nephritis is needed to improve long-term outcomes. ( 5), other ( 24). Therapy consisted in Anti-TNF (95), anakinra (7), tocilizumab (7), other (14); eighty-one patients were also on a cDMARD. None of them were confirmed cases of COVID-19 . Eight children presented mild respiratory symptoms; three of them were family members of adults with probable COVID-19 infection (i.e. with fever, cough, difficulty to breath but no confirmatory positive SARS-COV-2 Real-Time PCR . No patient stopped ongoing therapy nor needed hospitalization. All patients adopted a preventive strategy against COVID-19 based on social distancing and use of personal protective equipment, but usually only after the beginning of the outbreak.

No definitive conclusions about the incidence of SARS-CoV-2 infection in children with rheumatic diseases, nor on the overall outcome of immunocompromised patients affected by COVID-19 can be drawn from our study. However, in agreement with observations on adult rheumatology patients , our preliminary experience supports the idea that patients with chronic diseases treated with bDMARDs do not seem to be at increased risk of severe or life-threatening complications from SARS-COV-2 compared with the general population. A strict disease control may be of great importance since it is known that disease activity may be a risk factor for the development of infections. Objectives: To evaluate whether routine laboratory parameters at disease onset may predict the development of MAS in patients with sJIA. To define a risk score of MAS using these parameters and to validate the score in a second population. Methods: Laboratory parameters of disease activity and severity were retrospectively evaluated in 99 sJIA patients referred to Bambino Gesù Hospital in the last 10 years with at least 2 years of follow-up. Laboratory parameters were evaluated during active sJIA, without MAS, at disease onset or disease flare, immediately before treatment for sJIA was started or modified. Patients were divided in sJIA patients without MAS in the 2 years of follow-up and sJIA patients with at least one MAS episode. To create the MAS risk score, laboratory parameters with a statistically significant difference between the 2 groups were selected. Results: Thirty patients, that fulfilled the 2016 classification criteria for MAS at time of sampling, were excluded from the analysis. Therefore, we analysed laboratory parameters of 69 sJIA patients, 41 without MAS in the follow-up and 28 with at least one episode of MAS. Levels of ferritin, AST, LDH and triglycerides were significantly higher in patients with MAS during follow-up compared to those without. Their respective cut-off were computed by means of ROC curve analysis. A regression coefficient-based scoring system was used to assign weights to the risk index and the optimal score cutoff was defined by ROC curve analysis (Table1). A MAS risk score >5 identified 27 out of 28 sJIA patients with MAS during the follow-up and 8 out of 41 sJIA patients without MAS. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the score are detailed in table 1. In order to validate the MAS risk score on a different population, we applied the score on 132 sJIA patients from other paediatric Rheumatologic centres, 100 without history of MAS and 32 with at least one episode of MAS. Se, Sp, PPV and NPV of the score are reported in table 1. Conclusion: In conclusion we developed a MAS risk score based on routine laboratory parameters, available worldwide, that can help clinicians to identify early in the disease course sJIA patients with high risk to develop MAS. Introduction: Hemophagocityc lymphohistiocytosis (HLH) is a lifethreatening syndrome characterized by a hyperinflammatory state. HLH is typically caused by biallelic mutations in genes encoding proteins involved in the cytotoxic activity of T lymphocytes and natural killer (NK) cells (primary HLH), but it can also occur, in the absence of known genetic causes, in the context of malignancies, infections and rheumatic diseases (secondary HLH). A constitutive or transient defect in NK cell cytotoxicity is typically occurring in patients with, respectively, primary and secondary HLH and is believed to play a key role in the pathogenesis of the disease. Objectives: HLH has also been reported in patients with inherited primary immunodeficiencies, including those caused by inborn errors of type I IFN-mediated immune responses. Here, we describe a 2 years boy with two previously undescribed frameshift mutations in the interferon (IFN)α/β receptor 2 (IFNAR2) gene presenting with HLH following measles-mumps-rubella (MMR) vaccination. The relation between HLH and defective type I IFN-mediated responses is to date unclear. Methods: Clinical Exome, using a custom panel including 6920 genes known as associated to genetic diseases, was sequenced on NovaSeq6000® platform. In silico analysis was performed on the basis of the patient's clinical phenotype. Peripheral blood mononuclear cells (PBMCs) were isolated from the patient and his family and stimulated with IFNα or IFNγ; phosphorylation of STAT1 and type I and type II IFN signatures were analyzed by flow cytometric and RT-PCR analyses. NK cell degranulation and IFNγ production were analysed by flow cytometry. Results: Here we report the case of a 2 year old Caucasian boy presenting with high fever and lethargy five days after inoculation of live-attenuated MMR vaccine. Laboratory parameters were suggestive for secondary HLH, with progressive decrease in cell blood count, hyperferritinemia, elevation of liver enzymes and lactate Introduction: JDM is a rare childhood autoimmune myositis that presents with proximal muscle weakness and associated skin changes. There is an unmet need to develop targeted treatments for JDM.

Objectives: This study aimed to identify dysregulated biological processes by RNA-sequencing in JDM and develop functional assays to confirm these pathways.

Methods: Peripheral blood samples were obtained from JDM patients and age/sex-matched child healthy controls (CHC). CD4 + , CD8 + , CD14 + and CD19 + cells were sorted by flow-cytometry from PBMC, and RNA was extracted and RNA-sequenced. Total PBMC were taken from JDM and CHC, sub-sets of the CD14+ cell population were analysed by flow cytometry. To measure cytokine expression; CD14+ monocytes were isolated by immunomagnetic positive selection from total PBMC populations from JDM and CHC samples. The monocytes were cultured overnight with and without LPS. Cytokine expression in the culture supernatant was measured by cytometric bead array (CBA). To investigate metabolic function, CD14+ monocytes were isolated by immunomagnetic positive selection from total PBMC populations from JDM and CHC samples. The monocytes were cultured in carbon-13 labeled glucose RPMI-media. Medium was sampled at hourly time points for 6hrs and then at 24hrs over a time course. The metabolism of the 13 C glucose into CO 2 , lactate and ribulose-5-phosphate was measured by gas chromatography-mass spectrometry (GCMS Linear regression showed a trend towards increased disease activity, reflected by a lower MMT8 score, with a higher percentage of intermediate monocytes, therefore, in samples from JDM patients naïve of treatment (R = -0.57, p =0.085). Cytometric bead array (CBA) analysis showed that both pro-inflammatory and anti-inflammatory cytokines were down-regulated in monocytes from JDM compared to CHC (IL-6 (p=0.0152); IL-1β (p=0.0152); IL-10 (p=0.0649). Functionally, 13 C lactate concentration was significantly lower after monocytes had been cultured for 24hrs in 13 C glucose medium from JDM samples compared to CHC (p=0.0063). Ongoing work is being done to assess the expression of glucose transporters and uptake.

Conclusion: This study establishes that in JDM, monocyte metabolism and homeostasis is dysfunctional, identifying an exciting novel pathogenic mechanism. In the future a specific area to investigate is the mechanistic relationship between IFN1 driven inflammation and altered mitochondrial metabolism in monocytes, this has the potential to identify novel therapeutic targets. Introduction: In patients with juvenile dermatomyositis (JDM) objective evaluation of disease activity is challenging but crucial for prevention of both over-and undertreatment. We recently validated galectin-9 and CXCL10 in a multi-center cohort study as sensitive and reliable biomarkers for disease activity in JDM, outperforming creatinine kinase (CK). Implementation of these biomarkers into clinical practice, as tools to monitor disease activity and guide treatment, might enable personalized treatment strategies for patients with JDM.

Objectives: We investigated the additional value of galectin-9 and CXCL10 in the clinical decision-making in JDM patients as assessed by pediatric rheumatologists.

Methods: Galectin-9 and CXCL10 serum levels as measured by multiplex immunoassay were implemented as routine tests in the diagnostic laboratory of a tertiary hospital in June 2017 and June 2018, respectively. Test results generally became available 1-2 weeks after sampling. Pediatric rheumatologists reported for all measurements performed in JDM patients between June 2017 and March 2020 whether, and if so, how the biomarker levels would have affected their clinical-decision making, had the results been available at time of consultation. In addition, they scored the additional value of the biomarker levels semi-quantitatively (decisive, supportive, helpful, no added value (NAD), distracting or "other").

Results: Biomarker measurements from 184 consultations in a total of 39 JDM patients were included (175 galectin-9, 152 CXCL10). Median number of consultations per patient was 4 (range 1-17). In 154 consultations (84%) the galectin-9 and/or CXCL10 results were considered to be of additional value (8 decisive, 31 helpful, 115 supportive). Results were considered to be of NAD, distracting or "other" in 19, 7 and 4 consultations, respectively. Results were most often considered decisive or helpful when increased biomarker levels confirmed clinically active disease while CK remained low, when increased or rising levels indicated bad treatment response, or when low levels confirmed clinically inactive disease in cases with aspecific symptoms or increased CK. Results were most often considered supportive when low levels confirmed clinically inactive disease or when decreasing levels indicated good treatment response. Results were most often reported to be of NAD in patients in long-term drug-free clinical remission. Transient increases in biomarker levels during clinically inactive disease were considered distracting. Also, low levels in cases with evident clinical disease activity were scored as distracting.

Interestingly, the latter was only reported in patients with skin but no muscle disease activity, indicating that the biomarkers do not reflect skin disease well. In 13% of consultations the galectin-9 and/or CXCL10 results would have led to changes in clinical decision making, mostly with regard to MRI requests and medication changes. Conclusion: Galectin-9 and CXCL10 results were of additional value in the clinical decision-making in patients with JDM, as reported by pediatric rheumatologists. The biomarkers were particularly useful in monitoring treatment response and when CK was deemed unreliable. Also, their potential to guide personal treatment strategies and to reduce the use of expensive imaging modalities was shown. We are currently conducting a large prospective cohort study to further validate clinical implementation of these biomarkers, including their prognostic value and tissue specificity, and to develop recommendations for biomarker-guided treatment in JDM.

None declared In a Kaplan-Meier analysis, the larger cluster needed a longer time to achieve clinically inactive disease than the smaller cluster with statistical significance. Importantly, JDM patients in the larger cluster had a significantly higher Siglec-1 expression on CD14+ cells when compared to the other cluster, whereas no significant difference in IFN score between these 2 clusters was found. Conclusion: Siglec-1 could be used as a surrogate biomarker reflecting IFN activity and monitoring disease activity in JDM. Siglec-1 expression at the onset of JDM patients might be a useful tool to define subgroups of JDM patients and identify patients at risk who may benefit from more aggressive treatment. The yield of the criteria in childhood presentations may be improved by including the recently identified myositis-specific antibodies, validated muscle biopsy score tool parameters, and muscle magnetic resonance imaging data. High serum levels of total bilirubin, ALT, AST, GGT, and platelet count less than 300´10 9 /L were associated with IVIG resistance in univariate analysis. Five risk factors were re-evaluated with multivariate analysis; platelet count less than 3001 0 9 /L and GGT serum levels were independent risk factors for IVIG resistance (OR: 3.896; 95%CI: 1.054-14.404; p=0.042 and OR: 1.008; 95%CI: 1.001-1.015; p=0.050). Coronary artery involvement was detected in 44 of 129 patients (34.1%) which was more frequently observed in patients under the age of 1 year and in boys (p=0.01, p=0.02, respectively). The multivariate analysis identified male gender and young age (<1 year of age) as independent risk factors for coronary involvement (OR: 0.399; 95%CI: 0.175-0.908; p=0.029 and OR: 3.802; 95%CI: 1.248-11.582; p=0.019, respectively). Conclusion: The adaptation of the current scoring systems is limited due to lack of sensitivity in our study population. Increased serum GGT levels and low platelet count were risk factors for predicting IVIG resistance.

None declared

Kawanet-score for predicting resistance to first immunoglobulins in Kawasaki disease: confirmation of its good sensitivity and proposal to improve specificity. Introduction: Kawasaki disease (KD) is the leading cause of acquired heart disease in childhood in developed countries. Early identification of these high-risk patients is critical to initiate aggressive therapies, but available scoring systems lack sensitivity in non-Asian populations. In their recent publication in Science Reports, Piram et al. proposed a new scoring system to predict the need for secondary treatment in non-Asian populations, the Kawanet score(sensitivity 77%, specificity 60%). Objectives: To validate the Kawanet score in an independent cohort. Methods: We retrospectively analyzed clinical and epidemiological data from a registry including all successive KD patients followed in our French tertiary center from 2006 to 2019. After exclusion of patients who had participatedin the Kawanetstudy (n=20), 186 children were included in our study. Cardiac abnormalities at the first echocardiography were defined as presence of at least one abnormal echocardiography finding including coronary artery dilatation, aneurysm, zMax ≥2.0, perivascular coronary artery brightness, pericardial effusion, valvular dysfunction. Results: In our cohort the Kawanet score had a sensitivity of 81,4% but a specificity of only 32,7%. Given the low specificity, we tried to implement other parameters to improve the Kawanet score performances. Abnormal findings at the initial echocardiography were observed in 61/186 (32.8%) patients. In multivariate regression analysis adjusted on the Kawanet score, initial cardiac abnormalities at the initial echocardiogram was significantly associated with a need of secondary treatment (OR 3.2, 95% CI [1.4; 7.6], p=0.0060). We built a "modified Kawanet score", including the Kawanet score variables plus cardiac abnormalities (one point per variable). The modified Kawanet score, with a cutoff at >=3, was associated with need for secondary treatment (OR of 3.4, 95% CI [1.4; 8.3], p= 0.0069). Combining the Kawanet score with information on abnormalities observed at the initial echocardiogram allowed to obtain a sensitivity of 71.4% and a specificity of 59.5%. Conclusion: In conclusion, our observations confirm the good sensitivity of the Kawanet score to predict need for secondary treatments in European populations but point out a poor specificity. The specificity of this score can be substantially improved by adding initial echocardiography findings as an additional parameter. Introduction: Henoch-Schönlein purpura nephritis (HSPN) is the main and almost the only cause of morbidity and mortality among children suffering from this most common vasculitis in childhood. Several histological classifications are used in the analysis of renal biopsy findings in HSPN, but it remains unknown which one has the strongest association with the severity and outcome. Objectives: The aim was to compare the four most commonly used histologic classifications for HSPN to determinate which one is the best predictor of disease outcome and to establish which variables of each histological classification have the strongest association with unfavorable outcomes. Methods: The cross-sectional study included 69 patients with HSPN (diagnosed by EULAR/PRES/PRINTO criteria) and available renal biopsy specimens for analysis using the four histological classifications for HSPN (the International Study of Kidney Disease in Children (ISKD C) classification, the Oxford classification, the Haas histologic classification of IgA nephropathy and the modified semi-quantitative classification (SQC), developed by Koskela et al.). The clinical outcome was defined through four categories, graded according to the modified classification of Counahan (physical examination, hematuria, proteinuria, urine albumin-to-creatinine ratio, hypertension and eGFR). The linear relationships between outcome and histological classifications were analysed using ordinal regressions using the first-order of polynomial orthogonal contrasts. Results: The SQC classification proved to be the best, reducing the deviation (of the model-predicted outcome value from the observed value) by 9.5% (Χ 2 1 =13,89, p < 0,001), followed by the Oxford classification with a deviation reduction of 8.0% (Χ 2 1 =11,76, p = 0,001), then the ISKDC classification with a decrease in deviation of 3.3% (Χ 2 1 =4,89, p = 0,027), and the worst was the Haas classification with a decrease in deviation of 2.1% (Χ 2 1 =3,06, p = 0,080). Analysis of individual variables of Oxford and SQC classifications showed that with increasing values in the variables of interstitial fibrosis (t 66 = 3,23, p = 0,002), tubular atrophy (t 66 = 2,94, p = 0,005) and tubular dilatation (t 66 = 2,40, p = 0,019) in the SQC classification, and endocapillary hypercellularity (t 66 = 3,14, p = 0,003) and crescents (t 66 = 2,07, p = 0,043) in the Oxford classification the outcome worsens. Conclusion: The pilot study showed that the SQC classification, developed by Koskela et al., has the strongest association with the severity and outcome of HSPN, followed by the Oxford classification, while other classifications are less related to the outcome of the disease. Although crescents on renal biopsy were considered the most important outcome indicators, this pilot study suggests that tubulointerstitial changes could be even more important as predictors of poor outcome. Histological changes in the interstitium and renal tubules of HSPN patients should be further explored in order to have an even better predictive value in terms of disease outcomes and to be incorporated into existing or new classifications, on the basis of which guidelines for the treatment of patients would be developed. SUPPORT: Croatian Science Foundation project IP-2019-04-8822. Introduction: IgA vasculitis/ Henoch Schönlein Purpura (IgAV/HSP) is the most common vasculitis of childhood, characterized by the IgA1 immune deposits in the small vessels. Although it is very common, the understanding of its molecular pathogenesis is still very limited. Objectives: We aimed to analyse plasma proteomes of IgAV/HSP patients using nano liquid chromatographytandem mass spectrometry (nLC-MS/MS) to investigate the disease pathogenesis. Methods: IgAV/HSP was diagnosed according to the Ankara criteria in 2008 (1). Five active IgAV/HSP patients and two age and gendermatched health controls were enrolled in this pilot study. Serum samples from subjects were collected on the same day of IgAV/HSP diagnosis and before steroid or other immunosuppressive treatment initiated. Sample preparation was carried out using PreOmics İST Kit. We investigated the alteration of serum proteome using the nano LC-MS/MS approach. Bruker raw files were analyzed using the proteomics software Max Quant (1.6.7.0). The human reference proteome set from UniProt was used to identify proteins. Proteomic data were analyzed with Perseus 1.6.7.0. Results: The data file includes peptide and protein identification, accession numbers, protein and gene names, sequence coverage and label free quantification (LFQ) values of each sample. 345 proteins were reported per sample. Identifications from the reverse decoy database, identified by site only and known contaminants were excluded. Data were log transformed. Two sample T-test was performed between groups. We identified 23 significantly different expressed proteins. Mainly the differentially expressed proteins were in the innate immune system, Ig and complement pathway. The levels of Complement C3, Apolipoprotein E, Glyceraldehyde-3phosphate dehydrogenase, Filamin-A, Alpha-1B-glycoprotein, Tubulin beta-1 chain, Lipopolysaccharide-binding protein, Ig mu chain C region were significantly higher in IgAV patients. Objectives: To present the peculiar characteristics of FCAS, through a case report that includes four generations of the same family. To stress the importance of familial history, that together with clinical features, can lead to the hypothesis formulation and to the request of a genetic assessment that will confirm the diagnosis. Methods: We describe a case of FCAS in a 2-years-old child, who came for the first time to our rheumatology clinic because of a history of recurrent fever episodes, associated with urticarial rash and elevations in acute phase reactants, beginning at 6-7 months of life. Both father and paternal grandmother were in follow up for hives rash and arthritis since childhood, diagnosed as seronegative polyarthritis. In addition, father presented conjunctivitis. The episodes of urticarial eruption and fever appeared to be induced by cold exposition. Paternal great-grandmother was reported to have the same clinical situation. The medical and familial history were suggestive for an autoinflammatory disease, therefore genetic analysis was performed and the family was referred to the Autoinflammatory Diseases Centre of the IRCCS Gaslini in Genova. Written informed consent to publication of the case report was obtained by parents.

Results: The genetic analysis found a point mutation on the gene NLRP3 (Ala439Val), thus confirming the diagnosis of FCAS. The same mutation was found on blood samples of father and paternal grandmother, while great-grandmother is still being analyzed. Treatment with Anakinra was promptly initiated in both child and relatives. Conclusion: Cryopyrin-associated periodic syndromes are rare disorders with relatively aspecific manifestations. An infant presenting with recurrent episodes of fever and urticarial rash exacerbated by generalized cold exposure, should be investigated for FCAS. Early diagnosis and rapid initiation of IL-1 inhibition control the inflammation and prevent organ damage with rapid resolution of clinical symptoms. Anti-interleukin-1 treatment with anakinra, rilonacept or canakinumab induces in most cases complete remission and normalization of inflammatory markers. Methods: there were examined 22 children at the age of 7 to 17 years old diagnosed with CAPS-9, TRAPS-8, FMF-5. Among them there were 12 boys and 10 girls. The diagnosis in all the patients was confirmed through detection of pathogenic mutations in the NLRP3, TNFRSF1A and MEFV genes. The following methods were used: a clinical conversation; attention diagnostics (Schulte tables); thinking diagnostics (establishing a sequence of events, "four is a crwod", simple analogies, interpretation of proverbs).

The functions of attention of children suffering from monogenic auto-inflammatory diseases. In the majority of patients with TRAPS and CAPS, indicators of the operational side of thinking were normal (87.5% and 55.5%, respectively).The majority of the examined patients with FMF (80%) had a non-severe violation of establishing causal relationships. Inertia of thinking was more often registered in patients with TRAPS (37.5%). Violations in the motivational sphere of thinking were not detected in any group. Conclusion: Impaired attention functions were observed in the majority of patients with TRAPS and were expressed in them to the maximum extent. Most patients with CAPS and FMF had impaired attention distribution, and all other attention functions were not impaired in most of these patients. Non-rough thinking disorders were registered in the majority of patients with FMF. In the majority of patients with CAPS and TRAPS, indicators of thinking function were within the normal range . In patients with TRAPS, more often than in patients with CAPS and FMF, inertia of thinking was observed. Objectives: In this study, we aimed to evaluate the status of the adaptive immune system in our patients with CAPS. Methods: Nine patients who were diagnosed with CAPS were included in the study. The data were obtained retrospectively from the hospital records. Introduction: We describe a case of a six year old girl who presented with episodes of recurrent abdominal pain and petechial and purpuric rashes affecting the lower limbs. The clinical picture resembled Henoch Schonlein Purpura but following her third episode, we requested additional investigations including genetic analysis and found a homozygous mutation in an exon 2 of gene MEFV, which is associated with a recently reported disease of Pyrin associated autoinflammation with neutrophilic dermatosis (PAAND).

Objectives: To describe the clinical presentation of a child who was found to be homozygous for the MEFV variant c.623G>C.

A six year old girl presented with recurring stereotyped episodes of abdominal pain, joint pain and petechial and purpuric rashes to the lower limbs resembling Henoch-Schönlein purpura. The typical episode lasted for six-eight weeks and resolved spontaneously. She remained systemically well on each occasion with normal urinalysis and vital signs. On the third presentation she was noted to have a petechial rash to the extensor surfaces of her lower limbs and a swollen left ankle. The physical examination was otherwise unremarkable with no organomegaly or lymphadenopathy. She had no history of fever, weight loss or fatigue. She was of Pakistani ethnicity and her parents were consanguineous. There was no family history of note. She attended a mainstream school, there were no developmental concerns. Abdominal ultrasound was normal. Her blood tests showed a mild normocytic anaemia and a mild eosinophilia with maximum 0.82. The rest of the full blood count was unremarkable. She had normal renal and liver function. Her inflammatory markers were mildly elevated with maximum erythrocyte sedimentation rate (ESR) 87 mm/h, CRP 59 mg/L, serum amyloid 13.0 mg/L. Complement factors C3 and C4 were normal. Antinuclear antibody (ANA) and anti C1q antibodies were negative. Atypical p-ANCA antibodies were detected with negative specific ANCA PR3 and MPO antibodies. Skin biopsy showed small vessel leucocytoclastic vasculitis. She was kept under follow up and following her fifth presentation with similar picture, we requested genetic testing focusing on autoinflammatory diseases and she was found to be homozygous for the MEFV mutation c623G>C.

Results: MEFV is a gene associated with recessive Familial Mediterranean Fever (FMF). This specific mutation is known to be associated with a phenotype of Pyrin associated autoinflammatory disease. Another three patients of Pakistani consanguineous background carrying the same mutation have already been described. All patients share a remitting-relapsing course of disease, characterized by raised inflammatory markers, eosinophilia, oral ulceration, intestinal inflammation and lymphadenopathy [1] . Following her fourth flare of rash and joint pain, our patient commenced a short course of oral prednisolone with good response. She remains under regular follow up with a plan to trial colchicine in case of further flare Conclusion: FMF is the most frequent autoinflammatory disease caused by mutations in MEFV gene. Pyrin associated autoinflammation with neutrophilic dermatosis is a recently described condition associated with mutations in exon 2 of the MEFV gene [2, 3] . At admission, clinical examination showed hepatosplenomegaly and enlarged neck and submandibular lymph nodes, but joint assessment was normal. At laboratory investigation, anemia and neutropenia were confirmed and LDH was persistently high. Immunological and autoimmune screening were normal, including the neutrophilic degranulation test. Bone marrow aspiration was negative too. A total-body X-ray was negative while abdomen ultrasound confirmed hepatosplenomegaly. During the following years, the patient presented arthralgias in several districts, responsive to short courses of nonsteroidal antiinflammatory therapy. Joint symptomatology progressively improved during the growth until complete remission after puberty. Since the age of 6 years, she had presented recurrent blepharitis and chalazion episodes, treated first with antibiotic therapy and then with surgery, and a mild form of psoriasis. A relapsing abscess of median cyst of the neck was treated with oral antibiotic therapy. Periodic blood exams showed neutropenia and raised LDH, c-reactive protein and erythrocyte sedimentation rate.

Suspecting an autoinflammatory syndrome, in 2008 and 2016 she underwent genetic investigations (Sanger technique) resulted normal. In August 2018, a new genetic study performed with Next Generation Sequencing highlighted the de novo genomic variant p.E250K (c.748G>A) in heterozygosity of the PSTPIP1 gene, described as a pathogenetic variant associated to PAMI syndrome. The diagnosis was confirmed after the evaluation of serum zinc levels resulted elevated (538 ug/dl). Conclusion: PAMI syndrome is a rare auto-inflammatory disease, genetically determined, with early onset, incomplete penetrance and variable expression. Our patient presented a mild phenotype of PAMI syndrome, since some typical features of the disease, such as poor growth, skin inflammation, thrombocytopenia and arthritis, were absent. PAMI syndrome should be considered in the differential diagnosis of patients with neutropenia and undefined systemic inflammation, even if other clinical manifestations are absent; the dosage of serum zinc may be a useful tool in the differential diagnosis in these cases because high serum zinc values can lead the clinician towards an early diagnosis. Introduction: During the last decade, remarkable progress with massive sequencing has been made in the identification of diseaseassociated genes for AIDs using the next generation sequencing technologies (NGS). International group of experts described the ideal genetic screening method which should give information about SNVs, InDels, Copy Number Variations (CNVs), GC rich regions.

Objectives: Our aim was to develop and validate molecular diagnostic method in conjunction with NGS platform as an inexpensive, extended and uniform coverage and fast screening tool which consist of nine genes known to be associated with various AIDs.

Methods: To validation of four and nine gene containing panels, long range multiplex models were setup on 9 healthy sample without any known variations for MEFV, MVK, TNFRSF1A, NLRP3, PSTPIP1, IL1RN, NOD2, NLRP12 and LPIN2 genes. Ten patients with AIDs who had already known causative genes were sequenced for analytical validation. As a last step, multiplex models validated on 46 patients with pre-diagnosis of AIDs. All sequencing steps were performed on Illumina NGS platform. Validity steps included the selection of related candidate genes, primer design, development of screening methods, validation and verification of the product. GDPE (Gentera) bioinformatics pipeline was followed.

Results: Although there was no non-synonymous variation in 9 healthy samples, 127 synonymous variant alleles and some intronic and UTR variants were detected. In 10 patients who underwent analytical validation, beside the 11 known non-synonymous variant alleles, 9 additional non-synonymous variant alleles and a total of 110 exonic variant alleles were found. In clinical validation phase, 46 patients sequenced with multiplex panels, genetic and clinical findings were combined for diagnosis. Conclusion: In this study, we described the development and validation of NGS-based multiplex array enables the "long-amplicon" approach for targeted sequencing of nine AIDs genes. This screening tool is less expensive and more comprehensive compared to other methods and more informative than traditional sequencing. Our panels have a great advantage compared to WES or hybridization probe equivalents in terms of CNV analysis, high sensitivity and uniformity, GC-rich region sequencing, InDel detection and intron covering. Introduction: Anakinra, a recombinant IL-1 receptorantagonist, is a treatment option that acts byblocking the biological activity of IL-1 in autoinflammatory conditions. The diseases that the IL-1 was over expressed are the potential conditions for this treatment. Such as familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), and hyperimmunglobulin D syndrome (HIDS) with monogenic inheritance, and systemic juvenile idiopathic arthritis (SoJIA) or idiopathic recurrent pericarditis as non-Mendelian polygenic diseases, can be listed as examples of these diseases. Objectives: We aim to report our experiences of pediatric rheumatic diseases treated with anakinra.

The study group consisted of children with pediatric rheumatic diseases followed up in the Pediatric Rheumatology Department of University of Health Sciences and treated with anakinra (anti-IL 1) for at least one month, between 1 July 2016 and 1 January 2020. The data of these patients were collected retrospectively. The disease activity of the patients at 3rd month and 12th month after the treatment were assessed. Results: There were 28 patients treated with anakinra for the different pediatric rheumatic diseases. The diagnoses of these patients were as follows; eight were macrophage activation syndrome (MAS) complicating SoJIA, six were HIDS, four were CAPS, four were FMF, four were idiopathic recurrent pericarditis, one was deficiency of interleukin-36 receptor antagonist (DITRA), and one was undefined systemic autoinflammatory disease. 46.4% of the patients were male and 53.6% were female. The median age of diagnosis of the patients was 6.5 ((interquartile range (IQR): 4-12.7) years. The median follow-up duration of the patients was 14 (IQR: 3.7-28) months. The patients median anakinra treatment duration was 3 (IQR: 1-4) months. Fever reduced and C-reactive protein normalized within median 2 (IQR: 1-3) and 5 (IQR: 5-7) days, respectively. In the 3rd month after treatment; It was observed that 53.6% of patients achieved a complete remission (no attack was seen or MAS was improved). The frequency of attacks were decreased more than 50% in 35.7% of patients and less than 50% in 7.1%. 3.6% of patients were unresponsive to treatment. In the 12th month assessment after the initiation of treatment, it was observed that 28.6% of patients were still under anakinra treatment and in remission, 10.7% of them were in remission without anakinra treatment. In 60.7% of patients, anakinra was switch to other biological treatments for different reasons (35.7% partial response or unresponsiveness, 17.8% injection site reactions and 7.1% daily-injection difficulty). Biologic drug switch to canakinumab and tocilizumab was observed in 88.2% and 11.8% of patients , respectively. One patient developed recurrent MAS episodes when the anakinra dose was tapered, and one another patient was unresponsive to the anakinra and dead due to secondary to MAS. Conclusion: Anakinra seems to be a successful treatment to achieve inactive disease in a significant portion of patients in the early period. The recurrence of disease attacks while drug tapering and injection site reactions were appears the main causes of treatment switch or discontinuation. Introduction: Familial Mediterranean Fever (FMF) and Majeed syndrome are both rare autosomal recessive periodic fever syndromes that are most prevalent in the Eastern Mediterranean population(1). Majeed syndrome is extremely rare and caused by mutations in the LPIN2 gene which encodes phosphatidate phosphatase LPIN2 (Lipin-2), that controls excessive production of pro-Interleukin-1 beta(pro-IL-1β) during inflamasome priming (2). This syndrome associates recurrent fever, congenital dyserythropoetic anemia, chronic recurrent multifocal osteomyelitis (CRMO) and neutrophilic dermatosis and it has a poor long-term outcome (2) . Objectives: We report the association of these 2 rare autoinflammatory diseases in a Lebanese child and the dramatic clinical and biological improvement with IL-1 blockade.

Methods: A now 8-year-old girl born to consanguineous parents, presented with severe anemia since the age of 3 months (Hb=4g/dL). Intermittent high LDH and low neutrophils counts were seen. Repeated Bone Marrow Aspiration (BMA) and bone marrow biopsy came in favor of myelofibrosis with signs of dysmyelopoiesis. The child was successfully treated with long duration oral steroids. She came to our attention at the age of 3 years for intermittent fever and mild arthritis in both ankles with no other abnormality. Her family history was notable for JIA in a paternal cousin. Biology showed normal CRP, WBC, platelets with Hb at 10g/dL. ANA, antiDNA, antiENA, RF and anti-CCP were negative. C3, C4, C1q inhib and C1q were normal. X-rays of ankles showed bilateral unspecific diaphysal and metaphysal osteocendensation. She received NSAID with Methotrexate; ankles normalized but anemia worsened motivating re-use of glucocorticoids. History was then marked with repeated episodes of fever for 3 days with abdominal pain. Genetic testing for FMF showed compound heterozygous mutations (M694I/E148V). Methotrexate was stopped and colchicine was started.

The patient was then lost to follow-up and took colchicine inconsistently due to digestive intolerance. Fever recurred daily and ankle pain was intermittent. Seen again at the age of 7 years, we noted growth delay with normal physical exam. Biology showed anemia(Hb=8.3g/dL) with increased inflammatory markers (CRP=125mg/L, SAA 877mg/L). X-ray of ankles was normal.

Results: Given the atypical association of FMF to probable autoinflammatory myelofibrosis and the atypical osteoarticular findings, genetic testing was performed and revealed a homozygous mutation in LPIN2(c.362delC) confirming the diagnosis of Majeed syndrome. Anakinra treatment was then started. Fever and arthralgia resolved. After 9 months of biotherapy, the patient was still asymptomatic with normal biology and catch-up growth. Conclusion: Majeed syndrome is an extremely rare disease with only few recent reports in literature (3). This is the first report of a Lebanese patient. To the best of our knowledge, there was no previous association of Majeed syndrome and FMF. Based on this clinical presentation, other genetic inflammatory diseases should be considered in case of atypical symptoms or resistant FMF. In this patient who received steroid therapy for years, IL-1 blockade with Anakinra was attempted and showed sustained control of inflammation with correction of anemia and complete resolution of symptoms.

Musculoskeletal symptoms and their impact on health-related quality of life in chronic nonbacterial osteomyelitis patients S. Introduction: NLRP1-associated auto-inflammation with arthritis and dyskeratosis (NAIAD) is a rare, genetic auto-inflammatory and autoimmune disease in childhood. It was first reported in 2016 in three patients from two families with dyskeratosis, arthritis, recurrent fever and increased inflammatory markers.

Objectives: To report a case of a 3-years-old Turkish boy who presented with some clinical features of NAIAD syndrome. Methods: Presentation of clinical and genetic finding of a patient with NAIAD. Results: A 3-years-old boy attended our clinic with progressive joint swelling and limping lasted for six months. In the physical examination; generalized polyarticular joint involvement, mild dyskeratotic lesions of the limbs and trunk, and nail dystrophy on his foot were detected. The level of acute phase reactants was high. He received pulse steroid and IVIG treatment due to severe autoimmune hemolytic anemia (hemoglobin=3.9 g/dl, direct coombs=4+, reticulo-cytes=11%) when he was two years old. The family reported that he had dyskeratotic lesions on his limbs and trunk, and nail dystrophy on his foot since he was two months old and these lesions regressed following the steroid treatment. The patient was scanned in terms of metabolic diseases due to skeletal dysplasia and polyarthralgia. Skeletal radiographs revealed abnormal features such as overgrowth and osteopenia in the epiphysis and metaphysis of distal femoral and proximal tibias. Ultrasonography detected intraarticular effusion and synovitis in hands, feet, knees, ankle and wrists, and these findings were confirmed with magnetic resonance imaging. ANA and rheumatoid factor were negative. C3 and C4 were normal. No signs of uveitis were detected. Subcutaneous methotrexate and oral steroid (2mg/ kg/day) were administered due to an initial diagnosis of polyarticular juvenile idiopathic arthritis. Despite the improvements, steroid could not been tapered. Recurrent episodes of unprovoked fever and systemic inflammation associated with elevated levels of CRP and ESR occurred. Persistent arthritis, presence of skin lesions, history of autoimmune hemolytic anemia, and abnormal features in the skeletal radiographs suggested autoinflammatory diseases. Anti-TNF inhibitor (etanercept) was added to treatment. However, no clinical response was achieved at 6 months. A heterozygous mutation in NLRP1 c.1887 C>A, p. Phe629Leu was detected in the patient. Anti-TNF treatment was ceased and IL-1B inhibitor (canakinumab) and steroid (2mg/kg/ day) were administered. The arthritis dramatically improved. However, steroid treatment could not be reduced below 1mg/kg/day. Eventually, IL-1 inhibitor was ceased and IL-6 inhibitor was started. The patient is currently well under the tocilizumab treatment once in a two week for 6 months. Conclusion: Only four patients with NAIAD were reported worldwide so far. The NLRP1 mutation of the present patient (c.1887 C>A, p. Phe629Leu) was predicted as "probably damaging" according to PolyPhen-2 database. To the best of our knowledge, this patient is the first NAIAD case presenting this mutation. Objectives: to evaluate serum ferritin levels in children and adults with various monogenic AIDs and sJA. Methods: ferritin was detected in 85 samples of blood serum of 74 patients(pts): in 30 children with sJA (female 16, male 14). 17 samples from 13 FMF pts (children -10, adults -3, male -6, female-7). In 4 pts, the study was performed in dynamics before and past the appointment of therapy(in 2 colchicine, in 2 colchicine with biologic (and etanercept). 25 samples of serums were from 22 pts with CAPS pts(children -11, adults -11, male -9, female-13); in 4 pts, the study was performed in dynamics before and past the appointment of canakinumab therapy. 13 serums from 10 pts with TNF-receptorassociated periodic syndrome (TRAPS): (children -9, adults -1, male -5, female-5, including 3 pts in dynamics on the background of canakinumab therapy. Ferritin was determined by enzyme immunoassay with a set of reagents ORGENTEC. The normal value for ferritin varies between 20 and 150 μg/L. Diagnoses of monogenic AIDs (FMF, CAPS, TRAPS) were confirmed by the detection of pathogenic mutations of causal genes. The diagnosis of sJA was based on ILAR criteria. Statistical analysis was performed using standard indicators: median, 25th and 75th quartiles, and the difference between the groups according to the Mann-Whitney criterion. In all patients the same sera values of CRP and SAA were determined using the nephelometric method. In patients with sJA the normal ferritin values were found in 12 (41%) pts; in FMF the normal values were found in 100% of pts; in pts with CAPS normal values in 8 (32%) sera semples; in pts with TRAPS normal values were found in 9 (90%) pts, and only 1 pt showed an increase in ferritin despite treatment with canakinumab. A statistically significant difference was obtained between the groups of sJA and CAPS (p< 0.001), sJA and TRAPS (p=0.03). The correlation between the level of CRP and ferritin was maximal for pts with CAPS: r=0.64(p<0.001) and with sJA: r=0.6 (p<0.001). There was no significant correlation between the level of CRP and ferritin in patients with FMF. The correlation of SAA and ferritin levels was maximal in pts with TRAPS: r=0.7(p=0.0072) and CAPS: r=0.54 (p=0.0051). There was no significant correlation between SAA and ferritin levels in patients with FMF. Conclusion: the maximum sera values of ferritin were observed in pts with sJA, their value was statistically significantly higher than in the CAPS and TRAPS groups. Among pts with mAIDs, the most frequent increase in ferritin was observed in patients with CAPS. In patients with FMF, no elevated ferritin levels were detected; in a patient with TRAPS, a persistent increase in ferritin in dynamics was observed in 1 patient whose phenotype had the similarity to sJA. Ferritin may be used as an additional laboratory differential diagnostic sign between patients with sJA and mAIDs. Introduction: Dermatological findings may be the sole complaints of diseases in pediatric rheumatology practice. It is well-known that evaluating patients with a multi-disciplinary approach may facilitate access to an accurate diagnosis.

Objectives: Herein, we reported our one-year experiences of collaborative pediatric rheumatology-dermatology.

Methods: Patients were initially evaluated separately in pediatric rheumatology-dermatology outpatient clinics. Subsequently, once a week, final diagnoses of patients with suspected skin rash were colloboratively discussed by two pediatric rheumatologists and a dermatologist.

Results: A hundred and one patients were included to the study. Of these patients, 65 attended initially to dermatology outpatient clinic while the remaining 36 applied to pediatric rheumatology outpatient clinic. The most common mucocutaneous finding was squamous lesions in 30 patients, followed by erythematous lesions in 28 and mucosal ulcers in 14. Finally, 69 patients were diagnosed with a rheumatic disease while 32 had differential diagnoses apart from rheumatic diseases. Conclusion: Patients with rheumatologic diseases frequently present with only mucocutaneous findings. So a detailed examination of the mucosa, skin and its attachments is of paramount importance in rheumatology practice. We suggest that a close interaction between pediatric rheumatology-dermatology and formation of consensus clinics are going to assist clinicians to make easier and accurate diagnoses.

None declared P016

The musculoskeletal system manifestations in children with familial mediterranean fever Introduction: Familial Mediterranean fever (FMF) is a monogenic inherited periodic fever syndrome presenting with episodes of selflimiting fever and inflammation of serosal membranes. The attacks emerge with arthritis were defined as one of the major diagnostic criteria besides involvement of serosal membranes. Non-specific musculoskeletal findings such as myalgia, arthralgia, transient synovitis, and more rare manifestations like protracted febrile myalgia can also be seen in FMF patients attacks Objectives: We aim to reveal the frequency and genotype association of musculoskeletal manifestations in children with FMF. Methods: The patients diagnosed with FMF between January 1, 2017 and June 1, 2019, and followed for at least 6 months in our pediatric rheumatology clinic were included in the study. Musculoskeletal manifestations of patients were enrolled. The patients were grouped according to the "Mediterranean Fever" (MEFV) gene variants. vomiting, 10.7% had erysipelas like erythema, and 9.3% had headache. The musculoskeletal symptoms were accompanied by 58.6% (n: 372) of the patients during the attack period. The most common musculoskeletal manifestation was found as arthralgia (32.6%, n: 206). Also, the other musculosceletal manifestations were found as follows during attacks; arthritis in 23.7% (n: 150), myalgia in 20.5% (n: 130), exertional calf pain in 6.5% (n: 41), and protracted febrile myalgia in 1% (n: 7) of the patients. It was observed that the musculoskeletal manifestations were significantly higher in patients with homozygous M694V variant in exon-10 (p=0.017). Also, it was found that the musculoskeletal manifestations are more common in the attack periods of patients carrying the M694V variant in at least one allele (p = 0.019). Conclusion: We found that the musculoskeletal manifestations were accompanied in more than half of FMF patients. M694V variant found as a risk factor for emerge of musculoskeletal manifestations. haploinsufficiency (HA20) that resembles Behcet's disease. The protein A20 encoded by TNFAIP3 is structurally divided into two types of domains, OTU domain and C-terminal domain. It is involved in the negative regulation of nuclear factor-kB (NF-Kb). Dysregulation of A20, due to mutations in both domains, leads to constitutive NF-kB activation and development of inflammation. Patients with HA20 can also show an autoimmune phenotype Objectives: To describe a novel mutation in TNFAIP3 gene leading to a novel phenotype in four patients from an Italian family Methods: Clinical data of the patients were reviewed. Clinical Exome was sequenced on Illumina NovaSeq6000® platform. In silico analysis was performed on the basis of the patient's clinical phenotype. We took into account only variants with an allelic frequency in global population lower than 1%, according with GnomAD database. Production of proinflammatory cytokines following ex vivo stimulation of PBMCs with lipopolysaccharides (LPS) was analysed by ELISA. B and T cell phenotyping were performed. Moreover, B and T cells stimulation were done to follow the ability of the cells to respond to stimuli and the ability to proliferate Results: Patient (Pt) 1 was referred to our hospital because of a severe relapsing remitting form of haemolytic anaemia that was treated with immunoglobulin, glucocorticoids and a course of rituximab. From the age of 5 she suffered from autoimmune thyroiditis. In addition, at 9 years she developed an antinuclearantibody (ANA) negative polyarthritis, treated with intra-articular glucocorticoids and methotrexate. Her mother (Pt2) presented with autoimmune thyroiditis and oral aphtosis. Her elder sister (Pt 3) suffered from type I diabetes and autoimmune thyroiditis; at 20 years, she presented with wrist arthritis and tenosynovitis that required subcutaneous treatment with methotrexate and etanercept. Her younger sister (Pt4) suffered from recurrent febrile episodes associated with cervical lymphoadenopathy not related to infections until the age of 7. All of them were evaluated for short stature; Pt 2 was treated for one year with growth hormone therapy that was dismissed due to inefficacy. Sequencing analysis revealed the heterozygous c.1723_1724insC variant, not described previously in human genetic database. This variant leads to a premature stop codon causing a putative truncation of the protein and segregates with phenotype in the family. Western blot analysis, that could demonstrate the truncation of the protein, is still ongoing. PBMCs obtained from Pt1-4 were stimulated ex vivo with several concentration of LPS releasing significantly higher levels of the pro-inflammatory cytokines IL-1b and IL-6 compared to healthy subjects. Pt1 immunological assay revealed a marked reduction of memory and transitional B cells. The few switched memory B cells present did not express IgG and IgA on the surface. Table 1 shows the clinical features of patients Conclusion: We identified, in four patients of an Italian family, a novel mutation of TNFAIP3 gene that, based on our functional data, seems to be pathogenic. The majority of the patients (3/4) showed autoimmune rather than autoinflammatory features. This study confirms that HA20 is characterized by different phenotypes even among members of the same family carrying the same mutation. Our results expand the phenotype and genotype spectrum of A20 haploinsufficiency. Conclusion: In this study we evaluated the incidence of PPS in a large pediatric cohort of 203 cases and the presence of predictive risk factors associated to the development of PPS. Analyzing the two groups (with or without PPS) no differences were noted in terms of gender, duration of intervention or presence of comorbidities. An older age at the moment of surgery and an higher BMI seem to be associated to an higher risk of development of clinically significant pericardial effusion. The presence of fever and ST segment elevation at ECG following surgery can be predictive for a later development of PPS requiring a closer follow-up of these patients after discharge.

Introduction: Autoinflammatory periodic fever syndromes characterized by excessive interleukin(IL)-1ß release and severe systemic and organ inflammation have been successfully treated with the anti-IL-1ß inhibitor canakinumab (CAN). In clinical trial situations and real life, rapid remission of symptoms and normalization of laboratory parameters were observed in most patients. Objectives: The present study explores long-term effectiveness and safety of CAN under routine clinical practice conditions in pediatric and adult patients with CAPS (cryopyrin-associated periodic syndromes), FMF (familial Mediterranean fever), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency). Methods: RELIANCE is a prospective, non-interventional, multi-center, observational study based in Germany with a 3-year follow-up period. Pediatric (age ≥2 years) and adult patients with clinically confirmed diagnoses of CAPS, FMF, TRAPS and HIDS/MKD that routinely receive CAN are enrolled in order to evaluate effectiveness and safety of CAN under standard clinical practice conditions. Evaluation of disease activity and fatigue by patients' assessment, days absent from school/work due to study indication, inflammatory markers and physician global assessment (PGA) was performed at baseline and will be further assessed at 6monthly intervals within the 3-year observation period of the study. Results: This first interim analysis of a patient subset diagnosed with FMF, HIDS and TRAPS includes baseline data of 41 patients (29 FMF, 10 TRAPS, 2 HIDS) as well as preliminary 6-month data of the FMF subset (N=16). Preliminary results of a first subset of N=16 patients diagnosed with FMF indicate stable remission and disease control upon long-term CAN treatment. Within the first study interval, no major changes were observed regarding the analyzed parameters (table 1) . Physician Global assessments of disease activity (% none-mild/moderatesevere) were for FMF patients at baseline 35-28-7 and 38-44-0 at month 6, for TRAPS patients at baseline 11-67-0 and for HIDS/MKD patients at baseline 100-0-0. Serious adverse events were reported for 2 patients including tonsillectomy and arthritis. Conclusion: Baseline characteristics of the FMF/TRAPS/HIDS-subgroup and first interim data of FMF patients are available from the RELIANCE study, the longest running real-life CAN registry. Further interval data will be analysed to assess efficacy and safety of long-term CANtreatment in patients with autoinflammatory periodic fever syndromes. Skin biopsy of erythematous lesions on the soles of the feet performed in infancy was found consistent with lupus pernio. Physical examination of the patient shown painful and in places ulcerated erythematous plaque lesions on the both ears helix, on both cheeks and dorsal faces of bilateral toes. All laboratory parameters were found in normal range. Brain MRI and echocardiography were performed and found normal. FCL was considered as a preliminary diagnosis in the patient with chilblain-like lesions onset at an early age and triggered by cold. Genetic panel analysis was performed. Homozygous R152H mutation was shown in TREX-1 gene. The patient was diagnosed as FCL due to the presence of just chilblain lesions. Hydroxychloroquine, prednisolone and tofacitinib treatment were started, respectively. All chilblain lesions healed, leaving hyperpigmentation. During the follow-up, prednisolone was tapered and discontinued. The 23-year-old sister of the index patient, who had arthritis and chilblain lesions, had also the same TREX-1 mutation and was diagnosed with FCL.

Conclusion: Familial chilblain lupus should consider in differential diagnosis in patients with chilblain lesions beginning at early age and with a similar family history.

Introduction: The last time was signed by the pandemic diffusion of COVID-19, with an emergency area COVID-19 dedicated and the need to minimize the inflow of children and adolescents affected by chronic diseases into the hospitals. Otherwise, paediatricians had to limit visits and to consider a new setting for febrile children.

Objectives: Patients affected by autoinflammatory diseases were assisted by telephonic consultations guaranteed by the paediatricians of free choice and by the paediatric rheumatologists. However, the patients frequently needed a direct clinical approach and a specialistic evaluation in the case of flares and/or abnormal laboratory parameters and adverse reactions to drugs. Another frequent question was the differential diagnosis of febrile episodes, to distinguish a recurrent fever, linked to autoinflammation, from an infectious disease. Methods: we proposed to paediatricians of free choice in west-Sicily a questionnaire about difficulties met in the follow-up of children with autoinflammatory syndromes; needs of scientific or bibliographic support, number of patients with these diseases and treated with biological drugs. Results: 55 questionnaires were collected: the most frequent recorded conditions were PFAPA and Familial Mediterranean Fever (FMF); a lower percentage followed CAPS; MVK, TRAPS. The most frequent treatment in PFAPA was steroids on demand; in FMF was colchicine. A low percentage (10%) was treated with anti-IL-1 drugs, needing the access to the hospital to receive the therapy.

All the paediatricians needed specialistic support to adequately control flares, especially in FMF, CAPS, TRAPS and MVK. PFAPA patients were almost individually controlled by paediatricians. Conclusion: Patients and paediatricians needed a specialistic help to organize the follow-up of these patients and to guarantee a good compliance to treatment. This period characterized by smart working, telemedicine, strategies to monitor remotely the patients, can find the winning strategy in the approach of the "Co-working", a new cooperation between hospital and paediatricians of free choice, in the global follow-up of autoinflammatory diseases. Introduction: Systemic autoinflammatory diseases (SAIDs) are characterized by the presence of chronic or recurrent inflammation secondary to an abnormal activation of innate immunity, generally due to mutation of genes encoding proteins with a key role in regulating inflammatory response.

Objectives: To report a familial case of an autoinflammatory disorder in order to improve our knowledge of genetic patterns associated to SAIDs. Methods: Case reports. Results: P1 was an 8-month-old male child. Since five months of life, he presented recurrent episodes of fever, perianal abscess and bloody diarrhea associated to raised inflammatory markers, elevated calprotectin level and anemia. Family history revealed death of older brother at the age of 2 years, suffering from an undefined syndrome characterized by persistent fever, diarrhea, perianal abscesses, anemia, arthritis and severe growth retardation. An older sister (9 years old) (P2) presented recurrent episodes of fever associated to exudative pharyngotonsillitis, enlarged neck lymph nodes and elevation of inflammation indexes, with good response to steroids, since the 6 months of life. Skin rash, diarrhea, arthritis and abdominal pain were not reported during the first years of illness. Suspecting PFAPA, she underwent tonsillectomy, without benefit. Over time, abdominal pain appeared during fever episodes. At laboratory investigation, P1 presented C-reactive protein (167.2 mg/L) and serum amyloid A (215 mg/L) elevation, calprotectin increase (405 mg/kg), neutrophilic leukocytosis, non-hemolytic anemia (Hb 7.8 g/dl). No signs of infection were detected. Immunological and autoimmune profiles were normal. Bone marrow aspiration was normal. Suspecting very early-onset inflammatory bowel disease (VEO-IBD), ileocolonoscopy was performed. Macroscopic findings resulted normal but a chronic inflammatory infiltrate of the lamina propria was found. Next Generation Sequencing for VEO-IBD, including Mevalonate kinase gene (MVK), was performed. The presence of two heterozygous variants, c.803T> C and c.1129G> A in the MVK gene in exon 9 and 11, causing the variants p.Ile268Thr and p.Val377Ile, was detected. Both these mutations are described as rare and pathogenetic. Due to the family and personal history, clinical and laboratory findings, a SAID was suspected, and genetic investigation was also performed in P2, revealing the same two heterozygous MVK mutations. The variant of uncertain significance c.586G> A in the MEFV gene in heterozygosity was also detected in P1. Although MVK mutations were present in heterozygosity, given the highly suggestive clinical picture and the death of a brother with similar clinical characteristics, Canakinumab was started, with clinical resolution and laboratory normalization in both patients. Parents genetic analysis is ongoing.

Conclusion: Even though MKV deficiency is inherited in an autosomal recessive pattern, both these siblings presented an autoinflammatory phenotype, responsive to anti-IL1 therapy. Allegedly, also the other brother died from an unidentified SAID. These SAID familial cases show how clinical features of autoinflammatory disorders can vary even among relatives who share common mutations: while milder clinical features resembling PFAPA were described in P2, P1 presented a phenotype compatible with a VEO-IBD. Indeed, since chronic intestinal inflammatory disease has been described in association of SAIDs, it is important to consider SAIDs in the differential diagnosis of VEO-IBD. Noteworthy, the application of NGS revealed that 4 genotypes among 8 pts remained unchanged and 17/25 pts were carriers of other mutations. Two siblings with a former negative PCR genotype but a classical phenotype turned out to have a complex genotype (M694V/R761H/R202Q). Among the 17 pts who were characterized as heterozygous by PCR, 7 were found to have a complex genotype, 9 a compound one and the remaining 1 without any mutation. The latter had a mild earlyonset phenotype and had been on medication for 15 years, but discontinued colchicine after the NGS analysis. This FMF-like pts is in clinical remission 7 years off medication ( Methods: A kick-off meeting was held on 9 th June 2020 with the main persons in charge of the 3 databases collaborating in this project (EUROFEVER, AIDnet and JIRcohort). Common research questions will be defined by the project managers and analyzed separately in every registry. Results of the research questions will then be shared between the different project partners and comparative analyses will be carried out centrally. Results including the patients of all 3 databases will be presented jointly. Results: The EUROFEVER database, the AIDnet registry and the JIRcohort represent a unique collection of information on patients with HPFs with only a minimal overlap of individual patients. Conducting joint epidemiological or clinical studies on patients from different databases remains a real challenge, mainly for reasons of IT interoperability and regulatory issues. Yet success in conducting such studies will also be a real advance in our knowledge of these diseases. Several initiatives to harmonize the different databases and develop common strategies for such studies have been launched. An example of this type of initiative is the MERITA project led by the European Rare Disease Network RITA which main objectives are to promote the interoperability of the different ERN registers and to develop a new registry for sharing essential clinical data provided by different European registries. In parallel of this initiative, we propose here an additional research strategy that will be complementary to the MERITA initiative and that could also be applied to registries that are not harmonized a priori.

Conclusion: If the experience shows to be feasible in these 3 different registries managed by 3 different teams, the methodology could be extended to other existing cohorts or registries and open the way for collaborative registry studies regardless of IT operability. Furthermore some common data elements identified during this study protocol could be shared prospectively in the MERITA project and thus participate to a wider European initiative. All patients were genetically tested by Sanger sequencing for the 9 most common MEFV mutations.

Results: There were three girls and one boy aged 6 months to 12 years. All had Mediterranean ancestry. PFMS was the first manifestation of FMF in all patients. One patient had familial history of FMF and two patients had clinical background supporting the diagnosis. Two of the patients had more than one episode of PFMS. All patients had extreme asymmetric myalgia, 3 of them had highgrade fever, and all had elevated inflammatory markers. A long comprehensive work-up was performed during hospitalization, including multiple CT and CT-angiography scans, bone marrow aspirations, and skin and muscle biopsies. MRI of the extremities as part of the workup yielded findings suggesting myositis with normal CPK levels.

After diagnosis, all patients were referred for Sanger sequencing for the 9 most common MEFV mutations (M694V, M694I, M680I, K695R, R761H, A744S, P369S, V726A, E148Q). One was homozygous for M694V mutation, two were heterozygous for M694V mutation, and one was hemizygous for the M694V and V726A mutations. Conclusion: MRI is a noninvasive no radiation method that may serve as an auxiliary diagnostic tool in the challenging diagnosis of PFMS. Objectives: To present a case of early-onset Behçet-like disease associated with trisomy 8 in order to further expand the spectrum of genetic mimics of early-onset BD. Methods: Retrospective chart review from initial presentation to last follow-up. Informed parental consent was obtained for genetic analysis and for publication. Results: The patient, a 15-year-old Caucasian adolescent, developed recurrent fevers at age 6 months. Subsequently, oral and genital ulcers, cutaneous manifestations (severe acneiform lesions, folliculitis) and asymptomatic anterior uveitis occurred. At age 7, progressive peripheral neuropathy of the right foot was noted, evolution was eventually favorable after two surgical interventions and intensive physiotherapy. She had important biologic inflammation during disease flares, but normal inflammatory markers in between flares. Trisomy 8 mosaicism was suspected on next-generation sequencing and confirmed by FISH. Treatment with colchicine, prednisone, methotrexate and golimumab was partially efficient, symptoms finally improved on azathioprine and adalimumab. Discussion. Behçet-like disease has previously been reported in adults with myelodysplastic syndromes and acquired somatic trisomy 8. More recently, a BD-like disease has been described in a few patients with constitutional trisomy 8 with and without mosaicism (1). Characteristic symptoms included early-onset recurrent fever episodes, mucocutaneous ulcers and bleeding diatheses. These patients were found to have increased monocyte activation and upregulated IL-1, TLR-and NFkB-related genes; they responded to TNFα or IL-1 blockade. We reported lately a 17-year-old Caucasian woman with developmental delay and multiple malformations resulting from a de novo complex partial 8p23.1 trisomy associated with a monosomy 7p

(2). She had recurrent episodes of fever since infancy, and subsequently developed bipolar aphthosis, abdominal pain, polyarthritis and non-thrombocytopenic purpura. Topical and systemic corticosteroids as well as colchicine were partially efficient; eventually anakinra was started with excellent response and complete resolution of inflammatory symptoms.

Conclusion: Trisomy 8 with or without mosaicism may mimic earlyonset BD. Recognition of genetic mimics of BD may help to understand the underlying pathology and guide treatment. is a special form of CSS [1] . Cytokine targeting therapies particularly started early in disease course may achieve cytokine neutralization. Increased IL-1β release has been reported in COVID-19 patients [2] . Several ongoing clinical trials investigate the role of anti-IL-1, anti-IL-6 and anti-INFƔ therapies in COVID-19. Risk factors for poor outcome in COVID-19 are old age, male sex and comorbidities, whereas pediatric patients with immunosuppressive therapy seem not to be at increased risk for severe disease course [3] . So far, there is scarce data on COVID-19 in patients with autoinflammatory diseases (AID). Objectives: To assess disease course of COVID-19 in AID patients treated with immunosuppressive therapy. Methods: Case series. Patient 1 is a 34 year-old women with rheumatoid arthritis and unclassified AID treated with methotrexate (MTX) 20 mg/weekly. She developed rhinitis, fever, headache, fatigue, cough and was tested positive for SARS-COV-2 eleven days after symptom onset. On day 10 she reported loss of taste and an episode of gastrointestinal symptoms. On day 14 she developed respiratory insufficiency with need for oxygen. On day 21 computed tomography showed typical signs of COVID-19 pneumonia. On day 40 she still suffered from dyspnea, fatigue, loss of taste and muscle pain. Patient 2 is a 14 year-old girl with Cyropyrin-Associated Periodic Syndrome (CAPS; variant Q703K) on anti-IL-1 maintenance therapy since 5 years (Canakinumab 150 mg/month). Last administration was 25 days before diseases onset. Patient 3 is a 13 year-old boy with CAPS (variant Q703K) treated like patient 2. Patients 2 and 3 developed fever, cough, fatigue and rhinitis 10 days after patient 1. Loss of taste was reported from day 4 to 13. On day 6 both had gastrointestinal complaints. After 14 days they recovered and anti-IL-1 maintenance therapy was administered. On day 28 a painful rash appeared on both arms of patient 3. As all patients live in the same household, patients 2 and 3 were not tested but clinically diagnosed for COVID-19.

Results: Patient 2 and 3 displayed typical COVID-19 disease symptoms but had a mild disease course without complications while on anti-IL-1 maintenance therapy, which was held back in the acute episode, and restarted after recovery. Patient 1 experienced a disease course more severe and ≥ 2 times longer than patients 2 and 3. Maintenance MTX treatment was paused since onset of COVID-19 symptoms.

Conclusion: As excessive IL-1 seems to be involved in COVID-19 immunopathology, IL-1 inhibition may prevent a severe disease course in COVID-19 infected AID patients. Both juvenile CAPS patients on anti-IL-1 maintenance therapy showed a milder disease course compared to the adult patient on MTX. This might be due to their younger age but also due to type of immunosuppressive therapy. This is one of the first reports about patients with AID on anti-IL-1 maintenance therapy with COVID-19. Data collection and merge of reports about these rare cases is needed to compile reliable insights on the effects of immunosuppression for AID on COVID-19 disease course.

Introduction: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoinflammatory bone condition causing bone pain, swelling and disruption to musculoskeletal function in children (1) . Although CRMO is uncommon, significant disease burden has been described from patient and family perspectives, one such example being delay to diagnosis (2) . Objectives: To describe the clinical pathways leading to CRMO diagnosis within three tertiary paediatric rheumatology centres, thereby identifying and addressing delays to diagnosis. Methods: A retrospective review of medical records was undertaken for patients presenting over a 5 year period who ultimately received a diagnosis of CRMO. A standardised spreadsheet was used to capture demographics, clinical presentation, investigations and management, and referral pathway details.

Results: A total of 45 patients were included for whom details of symptom course, referral and diagnosis were known (68.9% female, 95.3% Caucasian ethnicity, median age at symptom onset 10 years 3 months). The median time from symptom onset to diagnosis was 7 months; most (median 5 months) was within secondary care between first appointment and diagnosis. Patients saw a median of 2 specialties (range [1] [2] [3] [4] [5] . 14 children (32.5%, n=43) waited > 12 months to receive a diagnosis; median time 17 months (IQR 15-22). In patients presenting with pain exclusively in the lower limbs (n=15) the median time from symptom onset to diagnosis was 11 months compared with 5 months for patients presenting with clavicle pain (n=9). Median time from symptom onset to first rheumatology consultation in the whole group was 6 months (IQR 2-14, n=42). Table 1 shows the times from symptom onset to diagnosis according to specialties patients were first referred to and ultimately diagnosed by. Conclusion: Pattern of bone involvement which is more specific to CRMO (i.e. clavicular) appeared to be associated with quicker diagnosis. Identifying and addressing potential delays to diagnosis could help to reduce investigations and worry for patients and begin treatments sooner. * General paediatrics (9), Oncology (2) Maxillofacial surgery (1) † Oncology (2), Infectious diseases (2), Infectious diseases/rheumatology joint service (1) serum, strokes, intestinal ulcers with perforations. Glucocorticoids, mycophenolate mofetil, cyclophosphamide, intravenous immunoglobulin, rituximab, tocilizumab were used in both cases with partial effect. In terminal stages infliximab was used in one case, adalimumabin other case. There were homozygosis mutations in CECR1: c.1309G>A, p.Val437Met and c.139G>C, Gly47Arg, respectively. In two siblings one girl had onset of disease at 6 months old by macrophage activation syndrome, isolated. She received tocilizumab with good effect during 1.5 years. Then she developed livedo racemose and ischemic stroke with hemorrhagic impregnation. The glucocorticoids, mycophenolate mofetil and etanercept were admitted. After that the sister of girl had onset of disease at 4,4 years old (y.o.) by livedo racemose and high C-reactive protein (CRP) in blood serum. She started treatment with glucocorticoids and etanercept. Girls have the same heterozygosis mutations in CECR1: c.1078A>G, p.Thr360Ala. After initiation etanercept girls had not clinical features of DADA2 10 months and 1 year, respectively. In other two siblings one boy had onset of disease at 6.1 y.o. by recurrent febrile fever, livedo, colitis, ulnar nerve mononeuropathy, elevation of acute phase reactants. We followed the patient until 18 y.o., during this time he received glucocorticoids, mycophenolate mofetil, cyclophosphamide, plasmapheresis, rituximab, azathioprine with good effects. The brother of boy developed DADA2 in 7,2 y.o.. He had livedo, fever and high level of CRP. He started therapy with glucocorticoids and azathioprine with good effects, after genetic confirmation DADA2 the etanercept was initiated to prevent stroke. Boys have the same homozygosis mutations in CECR1: c.1358A>G, p.(Tyr453Cys). 7.3 years old girl developed disease by livedo, fever, arthralgia and elevation of CRP and erythrocyte sedimentation rate. She started glucocorticoids and mycophenolate mofetil with partial effect. There were detected two heterozygosis mutations in CECR1: c.1358A>G, p.(Tyr453Cys) and c.140G>C, Gly47Ala and she started etanercept. She haven`t had disease features during 4 months. Conclusion: All patients with suspicion for PAN require the identification of CECR1 mutations to prevent serious outcomes. It is unpredictable what course of DADA2 will be developed in patients with the same mutations, like in siblings. Further identification of mutations in different populations with PAN will help in understanding disease management. Introduction: Monitoring disease activity in FMF is essential to define disease effects on the general health and quality of life (QoL) of patients, to determine treatment response, optimize disease follow-up and prevent complications. The importance of monitoring disease activity and doing regularly are highlighted in the international recommendations for the management of autoinflammatory diseases. It is necessary to assess disease activity easily in research and clinical practice.

Objectives: The aim of this study is to compare Pediatric Quality Life Inventory (PedsQL), Childhood Health Assessment Questionnaire (CHAQ), the four-item Morisky Medication Adherence Scale (MMAS-4), Wong-Baker FACES pain rating scale (FACES), Children's Depression Inventory (CDI) among the patients with FMF grouped according to the number of episodes in a year to define if it is the key element to detect the disease activity in FMF. Methods: In this cross-sectional study, patients were recruited from the pediatric rheumatology outpatient clinics of tertiary hospitals in Turkey. Patients with FMF were evaluated face to face interviews to complete outcome measures such a PedsQL, CHAQ, MMAS-4, FACES, and CDI. We also recorded demographic data, main clinical symptoms of the episodes, treatment modalities, genetic mutations, possible triggers of episodes. Results: A total of 239 patients (male 44.4%, female 55.6%) were grouped according to the number of episodes in a year: first group consist of 74 patients (31%) without any attacks in a year (Group 1), 99 patients (41.4%) have 1-4 episodes in a year (Group 2), 66 patients (27.6%) have more than 4 episodes in a year (Group 3). Age at diagnosis, gender, consanguinity, family history and history of amyloidosis were not different among the groups (p>0.05). The main clinical symptoms were similar among the groups (p>0.05). The comparison of fatigue, stress, sadness among the groups were significantly different, respectively p=0.008, p=0.002, p=0.002. All of these symptoms were more common in the last group than others. Most of the patients (232 of 239 patients, 97.1%) were treated with colchicine. Groups were similar in terms of M694V, and V726A allele frequency (p=0.843, p=0.46). For parent and child PedsQL scale scores, patients in no episode group (Group 1) had higher scores that means better HRQoL than Group 2, and Group 2 had higher scores (better HRQoL) than Group 3. CHAQ scores of patients in Group 1 were significantly lower than Group 2 (p=0.006). Patients in Group 2 had lower CHAQ scores than patients in Group 3 (p=0.004). Both parent and child MMAS scores were not different among the groups. In Group 3, patients have higher parent CDI scores than no episode (Group 1) group (p<0.001). Child CDI scores were significantly lower in Group 1 than Group 2 (p=0.01), and in Group 2 than Group 3 (p=0.03). Both parent and child FACES scores were significantly lower in no episode group than Group 2, and patients in Group 2 lower than Group 3. Conclusion: In a homogeneous patient population in terms of demographic features, mutation types, clinical symptoms, and treatment, PedsQL, CHAQ, CDI, and FACES have significantly different among the groups according to number of episodes in a year. We speculate that number of episodes is the key element of disease activity in patients with FMF and can be used to assess disease activity by alone Objectives: The aim of this study is to evaluate the occurence of an autoinflammatory disease among KD patients. Methods: This is a monocentric retrospective study that include all chidren under 15 years old diagnosed as KD in the Montpellier University Hospital Center between may 2012 and may 2019. Clinical and biological data were collected (sex, age, type of Kawasaki disease, inflammatory biomarkers, hepatic cytolysis) as well as the results of echocardiographies and treatments received. Follow up consultations have been analyzed to assess the onset of relapsing fever. Results: 80 patients were included between 2012 et 2019. There was 57 boys and 23 girls.The average age was 30.2 months. Fifty percent of the patients had an anormal echocardiography. Height patients presented relapsing fever. Among these 8 patients, 3 patients met the criteria of PFAPA syndrome (Periodic Fever Adenitis, Pharyngitis Aphtous), which is more than expected in the general population (p<0.05). Conclusion: This study shows a significant increase of PFAPA syndrome frequency in children that have presented KD. A genetic popensity to auto inflammatory syndroms and altered immune response can be discussed. This association suggests an auto inflammatory origin to the KD. Introduction: Systemic Autoinflammatory Diseases (SAIDs) are a diverse group of genetic diseases caused by dysregulation in the innate immunity and often presenting with overlapping phenotypes. Advances in genetic testing over the past 20 years have led to the discovery of more than 50 monogenic AIDs but they remain largely under-recognised, undiagnosed and consequently underreported in India largely due to poor awareness in doctors and reliance on foreign collaboration for costly genetic testing. Objectives: 1. To make available a genetic testing facility for SAID in India and to test a shortlisted high-risk population of patients with the above panel. 2. To study the yield of this panel and to identify novel mutations, if any, in our population. Methods: We suspected 38 children from our clinic to have SAID based on multisystem inflammatory disease (fever, rashes, arthritis, mucocutaneous manifestations, serositis and organ specific symptoms) occurring recurrently or with prototypic features, onset early in life, consanguinity or a positive family history and elevated acute phase reactants during episodes. A 53 gene panel was curated and a local laboratory performed next generation sequencing (NGS) under our instruction. In addition to multilingual consent for genetic testing and research / publication, ethics clearance for data collection and publication was obtained. Patient contributions were supplemented by funds from donors for testing. Results: 11 of 38 patients (28.9%) received a closure in their diagnosis. Thus, in addition to the 27 patients who were previously diagnosed (largely by personal request to international centres), the total count of patients molecularly confirmed to have monogenic SAID in our centre rose to 38 ( Table 1) . Conclusion: Our centre reports the first experience in India, to use a gene panel and test locally in a shortlisted group to arrive at a diagnosis in SAID. This study will hopefully provide impetus to other Indian studies, thereby identifying the commoner SAIDs in India, resulting in the use of abbreviated and cheaper panels. With consanguinity and endogamy prevalent in our country (reaching as high as 38% in some states), and a population of 1.2 billion, in a backdrop of colonisation by various European nations where these diseases are regularly recognised, this study opens our eyes to the tip of this looming iceberg. Introduction: Mevalonate kinase deficiency (MKD) is a very rare, autosomal recessive autoinflammatory disease with multiple organ involvement. MKD is caused by mutations in the gene encoding mevalonate kinase (MVK) that lead to its reduced or deficient activity. However, not all patients have typical symptoms at the time of onset. MKD treatment remains an unsolved problem, since none of the modalities previously used for MKD treatment are fully effective in the disease control. Objectives: To analyze clinical features, laboratory, molecular genetic data and response to therapy of a group of patients with MKD. Methods: We characterize 26 patients (15 males, 11 females, median age 4.9 years (range 0.2-17 years), including four familial cases, with MKD diagnosis confirmed by detection of the MVK gene biallelic mutations via Sanger sequencing or targeted NGS panels. Mevalonic acid in urine was determined by gas chromatography-mass spectrometry in 14 patients. Results: Median age at disease onset was 1.5 months (range birth-30 months). Clinical characteristics were very diverse: all patients had periodic fever, 25/26 -peripheral lymphadenopathy, 23/26 - abdominal pain, 20/26nausea/vomiting, 19/26diarrhea, 9/26hepatomegaly, 11/26splenomegaly, 6/26hepatosplenomegaly, 10/26 -respiratory failure. Rash was seen in 12/26 patients and one patient had periorbital edema and hyperemia during attacks. Myalgia, arthralgia were observed in 14/26. Oral ulcers were noted in 15/26 children. 8/26 patients had neurological involvement including two patients who suffered from epilepsy, one -from ataxia and cerebellar cortical atrophy and one from paraparesis with myopathic syndrome. All patients had increased laboratory inflammatory markers (C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Also most patients had a variety of hematologic abnormalities: neutropenia was present in 2/26 patients, thrombocytopeniain 4/26, macrophage activation syndrome -in 1/ 26. In 3/14 patients tested increased level of mevalonic acid, and in 5/14 -of mevalonate lactone in urine were noted. In our cohort the p.Val377Ile mutation was the most common MVK gene mutation. However, we have identified 10 novel MVK mutations and four of them occurred twice in our cohort. 23/26 patients are currentlyy receiving anti-IL-1 therapy, with complete remission in 17/23 and partial in 3/23. Conclusion: MKD symptoms can be variable and sometimes atypical, which requires physician's awareness. In our cohort of MKD patients anti IL-1 therapy was highly effective.

None declared

A rare rheumatological cause of death secondary to aortic calcification: a case report of singleton-merten syndrome Objectives: We describe a case of SMS leading to death at 13 years secondary to rapidly progressive aortic calcification. Methods: Case report Results: A white-British girl of non-consanguineous parentage presented at 5 years of age with calcaneovalgus and hallux valgus deformities, proximal muscle weakness and stiffness of the joints without synovitis or swelling. A heliotrope rash was present with prominent nail fold capillaries and ichthyoses vulgaris but no Gottron's. Dentition was abnormal with dentine hypoplasia, unformed roots of permanent teeth and crowns of abnormal morphology. Routine echocardiogram showed asymptomatic pericarditis and screening of her eyes revealed severe glaucoma causing unilateral amblyopia. Autoantibodies were abnormal with positive anti-nuclear (hep2, Elisa 4.4), anti-double stranded DNA (88iu/ML), rheumatoid factor (97 IU/l) and anti-cardiolipin IgG (73 U/ml) antibodies. A tentative diagnosis of a connective tissue disease overlap with juvenile Systemic Lupus Erythematosus was given with glaucoma likely secondary to previous untreated uveitis. Treatment was commenced with prednisolone, methotrexate, hydroxychloroquine and low-dose aspirin. She responded well and surgery for glaucoma was also successful. Two years on, she developed anterior uveitis and worsening skin rashes with livedo reticularis, chilblains and vasculitic lesions. She was commenced on infliximab and remained clinically well for the following three years with CRP, ESR, autoantibodies and complement factors repeatedly within normal limits. Aged 11 years, a diagnosis of SMS was confirmed via Deciphering Developmental Disorders with trio whole exome sequencing identifying a de novo mutation of the IFIH1 gene (c.2465 G>A). Around this time, she was noted to have an ejection systolic murmur. Echocardiogram and cardiac magnetic resonance imaging confirmed aortic stenosis with mild-moderate left ventricular outflow tract narrowing. Over the following two years, she continued on infliximab with no evidence of an ongoing inflammatory process. Regular echocardiograms were stable and she remained asymptomatic. However, during a six-month interval, the aortic stenosis worsened significantly. Imaging showed unexpected and severe calcification of the aortic annulus, aortic cusps and the aortic wall up to the level of the descending aorta. Our case was discussed at length but the extent and severity of calcification was not amenable to cardiac intervention and the decision was made for palliative care. It was agreed to continue her disease-modifying medications to avoid a flare of inflammation and for symptomatic control. Sadly, three months after the aortic calcification was first noted, our patient collapsed suddenly and died later that day. Conclusion: SMS is a rare condition with fewer than twenty affected families reported. Twelve cases are reported to have succumbed to aortic calcification at variable ages from 6 to 60 years. Early treatment with aortic valve replacement has been reported. There is little known about the mechanism of arterial calcification in the context of SMS, and control of inflammation does not appear to influence progression. We report this case to highlight consideration of SMS in a child with features of an inflammatory disorder, glaucoma, abnormal dentition, lower limb deformities and cardiac disease. Our case highlights that aortic calcification in SMS can progress unexpectedly rapidly and lead to early death, despite regular cardiac monitoring and good inflammatory control of disease. Objectives: Based on the recently developed ChRonic nonbacterial Osteomyelitis MRI scoring tool (CROMRIS), in order to quantify the bone involvement at multiple sites in CNO patients, we developed a Radiological Activity Index (RAI-CROMRIS). Methods: WB-MRI images were assessed using the CROMRIS. Parameters included in our RAI-CROMRIS were: bone marrow hyperintensity, signal extension, soft tissue/periosteal hyperintensity, bony expansion, vertebral collapse. These parameters were evaluated for each bone unit yielding a score from 0 to 7. A total score was obtained adding up the scores of all bone units. We analyzed 76 treatment-naïve patients with CNO collecting clinical and radiological findings at baseline. Clinical disease activity was evaluated using a physician's global assessment (PGA). Fourty-six of 76 patients were evaluated at 6 and 12 months after baseline. Results: A significant correlation of the RAI-CROMRIS with the PGA (r s =0.32; p=0.0055), in particular with presence of functional impairment and increased inflammatory markers was found at baseline. During the follow-up, the RAI-CROMRIS decreased significantly (p= 0.0039) from a median of 17 (IQR 12-26) at baseline to a median of 12 (IQR 6-20) at 6 months and remained stable at a median of 11 (IQR 4-20; T12 vs baseline p=0.0030 and T12 vs T6 p=0.52) at 12 months. A significant correlation between the RAI-CROMRIS and the PGA was observed at baseline and during follow up with a moderate correlation at T0 (p=0.0044; r s =0.41) and a weak correlation at T6 (p= 0.025; r s =0.33) and T12 (p=0.010; r s =0.38). Patients who subsequently received bisphosphonates had higher baseline RAI-CROMRIS (median 20, IQR 13-42) compared to that of patients who received other treatments (median 12, IQR 8-18; p=0.0078). In patients who received bisphosphonates, a decrease of the RAI-CROMRIS was observed from a median of 20 at baseline (IQR 13-42) to a median of 15 at T6 (IQR 4-25) (p=0.0032). Conclusion: The RAI-CROMRIS provides a measure of the overall radiological burden of disease in individual CNO patients. It is well correlated with clinical and laboratory measures of disease activity and it shows significant short-term changes following treatment with bisphosphonates. This tool can be used in clinical practice and clinical trials after validation. Introduction: COVID -19 infection in children is commonly evaluated as mild or asymptotic. However, from the start of May 2020, there was published some reports from Europe and North America describing children and teenagers, with multisystemic inflammatory syndrome characterized as Kawasaki-like syndrome. These patients required ICU hospitalization. Hypothesis about connection this syndrome with COVID-19 was based on mostly positive serology tests. Objectives: Boys to girl's ratio was 2:1, median age = 5 (± 4,5). All patients met Kawasaki-like symptoms (fever more than 5 days, rash, scleritis, cheilitis, lymphadenopathy, edema of palms and feet), also 6/9 children had meningeal symptoms, 2/9 had acute renal injure. All patients had myocarditis. Methods: We observed 9 children with: multisystem inflammatory syndrome diagnosis, which were stated in may 2020. Our evaluation covers clinical symptoms, general blood test, CRB, PCT, ferritin, Il-6, CT, ultrasound. Results: According to laboratory tests most symptoms was similar to systemic inflammatory diseases. All patients had increase of CRP in 9 times or more than normal, PCT was positive in 7/9 cases, increased ferritin from 62,7 to 1175 μg/l. Hypoalbuminemia was common symptom in all cases (18-24.8 g/l). Leukocytosis in 5/9 children (55,5%), thrombocytopenia in 4/9 cases (64-108*10 9 /l), anemia in 4/9 cases (44.4%). In 8/9 (88.8%) children detected increased troponin (36 pg/ml -899 pg/ml). 5/9 patients were undergoing through lumbar puncture, 3 out of this 5 had aseptic meningitis. COVID IgMpositive -1/9; COVID IgGpositive 9/9 children. Results of diagnostic interventions: pericarditis -5/9, 1/9coronary alterations (ectasia LCA and RCA), pleuritis -7/9, ascites -4/9. Treatmentall patients received antibacterial therapy, IVIG, steroids -4/ 9, 1 patient was on hemodialysis. 1/9 patient required pleural puncture. Conclusion: Multisystemic inflammatory syndrome patients require complex treat with help of various specialists (rheumatologists, cardiologists, surgeon, neurologists, resuscitationist). No described strategy of management of such patients is available. Our experience declares that it's rational to administrate antimicrobial treatment (ceftriaxone, vancomycin, linezolid, sulperazone, cefepime, amikacin, meropenem), IVIG with steroids.

None declared

Novel mutation in psme4 involved in proteasome-associatedautoinflammatory-syndrome C. C. Goetzke 1 , F. Ebstein 2 , A. Brehm 3 Proteasome-associated-autoinflammatory-syndrome (PRAAS) is an extremely rare congenital interferonopathy with high morbidity and mortality. In this disease, autoinflammation is caused by dysfunction of the ubiquitin-proteasome-system. So far, PRAAScausing mutations have been restricted to genes encoding components of the proteasomal core complex and assembly helpers. These mutations may be both monogenetic (homozygous or compound heterozygous) as well as digenic.

Objectives: The aim of this study is to identify further components of the ubiquitin-proteasome-system involved in autoinflammation. Methods: Experiments were conducted using whole blood and primary fibroblasts from a clinical index patient, the patient's mother and unrelated disease and healthy controls. Results: In this work, we could detect a significantly increased expression of interferon-stimulated-genes in a clinically confirmed PRAAS patient who was devoid of genomic alterations in any of the previously published PRAAS-associated genes. Remarkably, patient's fibroblasts recapitulate diseases hallmarks including perturbed protein homeostasis, as evidenced by reduced proteasome activity and concomitant accumulation of ubiquitin-protein conjugates. Trio exome sequencing allowed us to identify in this subject a paternally inherited variant affecting the proteasome activator PSME4-as well as two maternally inherited variants within the ubiquitin-E3-Ligase HECW2 and the amino acid sensor kinase EIF2AK4 (also referred to as GCN2). In silico predictions classify these variants as disease-causing. Interestingly, cells carrying these heterozygous variants failed to express the corresponding unaffected alleles at protein level, suggesting a dominant negative mode of action. Finally, and similarly to other PRAAS patients, proteasome impairment in our subject was associated with an exhausted unfolded protein response in the IRE1α-, ATF6-and PERK-pathways. Conclusion: Thus, we propose that mutations in genes encoding proteasome activators and/ protein ubiquitination can also cause multigenic PRAAS.

Objectives: To review the current landscape of FMF diagnosis, quality measures for follow-up, decision making for management and settling a protocol for prolongation of biologic treatment intervals and take advantage of an expert panel consensus Methods: A total of 14 pediatric rheumatologists (PR) across Turkey expertised in the management of FMF participated to the study. A detailed literature search was performed by a fellow and systematic review of the literature was executed. A shortlist of 15 key points were selected by 3 PRs. Key-points were converted to 78 statements with a 9-point Likert scale and a 3-round modified Delphi panel was assessed. A sum of 75% or above agreement was accepted as consensus.

Results: Consensus was reached on 46 statements. Panelists agreed that the screening periods of patients with FMF should not be longer than 6 months of duration, SAA test at each visit was accepted as mandatory in patients resistant to colchicine, had subclinical inflammation and had family history of amyloidosis. There was no consensus regarding to routine SAA, protein/creatinine in spot urine, sedimentation testing at each visit. 64 % of the panellists found scoring systems as applicable at each visit. There was unity among panellists regarding commencing colchicine at the time of diagnosis and starting the drug to the patients with subclinical inflammation, ordering genetic analysis when clinical findings support FMF, starting colchicine when pathogenic mutations plus nonspecific findings and family history of amyloidosis are present. Response to colchicine treatment was defined as decrease in duration and number of attacks and was accepted in consensus. Defining colchicine resistance as presence of 6 or more attacks/year or ≥3 attacks in 4-6 month period or elevation of 2 of the acute phase reactants in incomplete attacks were confirmed with consensus of the panellists. All participants confessed starting biological agents to resistant FMF patients and patients with amyloidosis. Presence of adverse reactions to colchicine was not accepted as a reason for initiating biologics in consensus. Except cost of the biologic agents; efficiency, ease of use, treatment adherence, accessibility and presence of adverse events were accepted in consensus as factors choosing biologic agents. Decrease in duration and number of attacks and ceasing of subclinical inflammation was accepted as response to biologics, but scoring systems applicable at each visit for evaluating response were not accepted in harmony. In patients whose attacks went in to remission with biologics, prolongation of the duration of application of biologics were considered and asked to the panellists, they collectively welcomed this statement. All participants voted in favour of curtailing the frequency of injections in patients who are in remission both clinically and in laboratory means during last six months of biologic treatment. Conclusion: Even though recommendations are present for diagnosis, screening and treatment of patients with FMF, use of these issues in real life is not so clear. Herein, data concerning applicability and relevance of these points and prolongation of biologic intervals were evaluated with PRs who are dealing with large number of FMF patients Objectives: Our objective is to describe the bone involvement observed in our patient population of JIA in its Enthesitisrelated arthritis form (ERA) and to determine the relative effects of the activity of the disease, corticosteroids and physical activity on the development of osteoporosis in JIA. Methods: This is a retrospective monocentric study that collected patients with ERA according to ILAR criteria, in whom a bone densitometry was performed by dual-energy x-ray absorptiometry (DEXA, in order to determine their bone status. An assessment of the factors linked to the disease and to the environment which could influence the modification of the bone architecture was also carried out. Results: We enrolled 22 patients (sex ratio M / F 10); average age of onset of the disease 13.1 years. The clinical presentation was purely axial in 4 patients, peripheral in 12 patients and enthesitic in 4 patients. The average BASDAI score was 55.3 / 100, the average MASES score was 2.7. Seven patients were on general corticosteroid therapy and only 9 of our patients participated in regular sports activities. The results of the bone densitometry measured concluded that normal bone mineral status was found in 13.3%, osteopenia was objectified in 20% of patients and osteoporosis in 36.7%. An agreement was assessed between the absence of sports activity and osteoporosis (p = 0.01) as well as osteopenia (p = 0.03). A high BASDAI is strongly associated with osteoporosis (p = 0.04). No association was observed between BASDAI and osteopenia (p = 0.3). No correlation was observed between the MASES score and osteoporosis (p = 1.2). No link was observed between taking corticosteroid therapy and bone architecture abnormalities (p = 0.8). Conclusion: Osteoporosis is frequent in ERA. Like the adult onset of spondylarthritis, low bone mass is influenced by disease activity and sedentarity. Introduction: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of bone, which primarily affects children and adolescents. Dysfunction of the immune system as well as cytokine dysbalance is a key point for CNO pathogenesis. Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder of bone, which primarily affects children and adolescents. Dysfunction of the immune system as well as cytokine dysbalance is a key point for CNO pathogenesisChronic non-bacterial osteomyelitis (CNO) is an autoinflammatory disorder ofbone, which primarily affects children and adolescents. Dysfunction of the immune system aswell as cytokine dysbalance is a key point for CNO pathogenesis. Objectives: The aim of our study was to evaluate the cytokine levels in the pediatric CNO patients and compare to other immunemediated diseases and healthy controls. Methods: In the prospective study 42 children with CNO were included. For comparison plasma of non-systemic juvenile idiopathic arthritis (JIA) patients (n=28), insulin-dependent diabetes mellitus (IDDM) patients (n=17) and healthy controls (HC, n=30) with similar age were collected. In each CNO patients and comparison groups the levels of 14-3-3-η protein, S100A8/A9 protein, interleukine -4 (IL -4), interleukine -17 (IL -17), interleukine -18 (IL -18), interleukine -1β (IL -1β), tumor necrosis factor-α (TNF-α) were measured by ELISA assay. We used the chi-squared test or the Fisher's exact test, Kruskall-Wallis test, Spearman's correlation analysis and univariate and multivariate linear regression and discriminant analysis. Results: All studied cytokines in the CNO patients were higher compare to controls and IDDM, 14-3-3 protein, IL-18, IL-4, IL-17, IL-1β and TNF-α were less than in JIA patients (table 1) . In discriminant analysis ESR, 14-3-3 protein, S100A8/A9, IL-18, IL-4 and TNF-α can discriminate CNO from JIA and 14-3-3 protein, S100A8/A9, IL-18, IL-17, IL-4 and TNF-α can discriminate CNO from other diseases and HC. Table 1 . Cytokine levels in immunocompromised patients and healty controls Conclusion: our data indicate the role of cytokine imbalance in the pathogenesis of CNO. The increased level of pro-inflammatory cytokines confirms the role of monocyte-driven inflammation in CNO patients. More research is needed to validate the role of cytokines as biomarkers and potential therapeutic targets for CNO. Introduction: A principal manifestation of juvenile idiopathic arthritis (JIA) is the skeletal system alteration. One of the disease complications is a decrease in bone mineral density (BMD) with the possible osteoporosis (OP) formation. The latter can lead to a life quality deterioration and possible disability in adulthood. In rheumatic diseases, BMD impairment contributes to osteoblast function inhibition, especially in patients taking steroids. Therefore, an essential addition to dual-energy X-ray absorptiometry (DXA) in children with JIA is the assessment of biochemical markers of osteosynthesis, which include osteocalcin (OC). Objectives: We aimed to establish the specificity and sensitivity of OC levels in relation to the DXA data of JIA patients to make an intermediate assessment of BMD without the use of X-ray absorptiometry. Methods: The BMD data and serum OC levels were estimated in 134 JIA patients (88 girls, 46 boys) aged 5 to 17 years. 24 patients had the systemic form of the disease, 46 of them had oligoarticular form, and 64 had polyarticular form. The mean age was 11.5 ± 0.4 years, and the mean disease duration was 5.2 ± 0.4 years. 64 children (48%) took methotrexate, 70 (52%) took immunobiological drugs (tocilizumab (24), adalimumab (44) and etanercept (2)). Specificity and sensitivity were calculated according to generally accepted formulas.

The reference values of serum OС were 2-22 ng/ml, which were significantly lower than the levels of JIA patients with whom we were dealing. Thus, it was decided to determine the median [5 th ; 95 th procentile] for the OC levels of our JIA patients, in which DXA indices were within the normal range, and establish the sensitivity and specificity of this value. Sensitivity was measured according the formula: Sensitivity = TP / (TP + FN) × 100%, where TP is the number of true positive results in the patient group, FN is the number of false negative results. Specificity was calculated according the formula: Specificity = TN / (TN + FP) × 100%, where TN is the number of true negative results in the patient group, FP is the number of false positive results. The median OC value of JIA patients, in which BMD results were correlated to chronological age, was 26.9 [19.4; 36 .9] ng/ ml (83 children out of total 134 patients). There were 13 patients with the DXA Z-score ≤ -2 SD and 80 patients with the DXA Z-score > 2 SD among the 93 patients with OC values within the 5 th and 95 th procentile (19.4-36.9 ng/ml). Based on this, the sensitivity of these OC values was 86%. There were 36 children with negative DXA results and 5 children with positive DXA results (the OC level values exceeded the 95 th procentile in more than 3 of them) among 41 children, whose OC values were not in the 5 th -95 th procentile range (< 19.4 or > 36.9 ng/ml). The specificity of the calculated OC values was 87.8%. Conclusion: Osteocalcin levels within the 19.4-36.9 ng/ml with a sensitivity of 86% and a specificity of 87.8% correspond to the chronological age-related bone mineral density assessed by the dualenergy X-ray absorptiometry. The obtained data can be useful for the intermediate assessment of BMD without the use of DXA in JIA patients. Kikuchi syndrome, histiocytic necrotising lymphadenitis, is a rare and idiopathic disorder of the lymph node. Prompt investigation is required to rule out malignancy and to reduce complications including life-threatening secondary HLH 1 . Objectives: Case report of a 14 year old girl with Kikuchi syndrome and features of secondary HLH presenting during the 2020 SARS-COV2 pandemic Methods: A 14 year old girl presented with a 5 week history of cervical lymphadenopathy and febrile neutropenia. She had no features of systemic disease including arthritis, serositis and vasculitis. Initial blood tests revealed a pancytopenia. Bone marrow aspirate was negative for leukaemia and HLH but on-going blood monitoring showed an increasing inflammatory process. Infection screening including CMV, EBV, hepatitis, HIV and blood cultures were negative as was an auto-antibody screen. CT chest was unremarkable. MRI whole body showed significant right sided cervical lymphadenopathy. She was treated with tazocin, vancomycin and amphotericin but the inflammatory markers continued to rise. An urgent lymph node biopsy was required for diagnosis, which led to concerns about her SARS-COV2 status. She had a negative SARS-COV2 PCR at her referring centre and a normal CT making the diagnosis of SARS-COV2 unlikely. It was felt by the anaesthetic and surgical teams that repeat SARS-COV2 testing was required and that it was unsafe to take her to theatre prior to the results being available. Her excisional biopsy was postponed pending results. During this time her ferritin increased to 16000. She developed an oxygen requirement and an ECHO showed a pericardial effusion. She met HLH HScore 196 and required urgent treatment with steroids. With the underlying pathology unknown this could have led to delayed treatment of a malignancy. She received intravenous immunoglobulin on 2 consecutive days. This afforded some improvement but she continued to have pyrexia, a spreading follicular rash and a ferritin of >10000. She was eventually taken to theatre for lymph node extraction on day 7 of admission and was successfully treated.

Results: The current pandemic has caused unprecedented disruption to healthcare provision worldwide. Ethical dilemmas have included resource allocation with routine clinical care being postponed to accommodate high volumes of emergency work and the balance of providing care for patients while limiting risk to healthcare professionals. In this case emergency surgery was delayed to limit risk to medical staff which led to acute and potentially life threatening deterioration in this patient. One negative SARS-COV2 swab and a normal CT chest had to be balanced against the perceived risk of SARS-COV2 spread to multiple members of staff. This case puts the beneficence for the patient in direct conflict with the management of risk to professionals and makes us ask: how far does the ethical principle of non-maleficence apply to all those involved? Conclusion: This case illustrates one of numerous patients whose inpatient management was delayed during the SARS-COV2 pandemic; in addition to cancellations of elective surgeries, deferred preventative measures and outpatient appointments. This patient made a full recovery; she expressed understanding for the delay in management and gratitude to her medical team. The question still remains: was this a risk worth taking? Introduction: During severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) disease 2019 (COVID-19) pandemic, several drugs already with essential roles in rheumatology practice emerged as promising treatment alternatives with encouraging results. On the other hand, dysregulation of innate immunity and virus-host interactions in the etiopathogenesis serve a major concern for patients in an immunosuppressive state or under immunosuppressive treatment.

Objectives: This study set out to determine whether COVID- 19 showing a milder course in children entails a risk for patients with rheumatic diseases in terms of immunosuppressive therapy either disease-modifying anti-rheumatic drugs (DMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs). Methods: Telephone-survey was administered by conducting interviews with the parents and inviting them to participate. A message containing a link to the questionnaire was sent to their phones simultaneously. The medical records of the patients were reviewed for gathering information about demographic data and clinical followup. Results: Patients who were followed up with immunosuppressive treatment (n=439) were attempted to be contacted between 1 May 2020 and 15 May 2020. The diagnostic distribution of patients who were accessible and eligible for the study was as follows: juvenile idiopathic arthritis (JIA) (n = 243, 58.7%), autoinflammatory diseases (n = 109, 26.3%), autoimmune connective tissue diseases (n = 51, 12.3%) and vasculitis (n = 11, 2.7%). In the entire cohort, mean age (at the study) was 12 ± 4.7 years and 54.1% (n=224) of the patients were female. We identified that one patient with seronegative polyarticular JIA, receiving methotrexate and leflunomide has been diagnosed with COVID-19. Table 1 details the survey results. Conclusion: In our cohort consisting of patients who received DMAR Ds and bDMARDs for various rheumatological diseases, we identified that one patient has been diagnosed with COVID-19. None of the patients, including the patient diagnosed with COVID-19, had any severe symptoms. More than half of the household contacts have not been required to attend a hospital because they were asymptomatic. Since similar complaints were encountered in the course of rheumatic diseases, the hospital attendance rate was low among patients who had complaints such as arthralgia, myalgia, and fever during the pandemic process and no history of contact. The findings of this study support the idea that COVID-19 rarely causes serious disease in children and the use of immunosuppressive therapy does not pose an additional risk in patients with rheumatic diseases. preponderance seen in many autoimmune diseases, there appears to be a male sex bias in COVID-19 deaths and intensive treatment unit (ITU) admissions. Objectives: We present a meta-analysis of 206,128 globally reported cases, in order to determine whether males are statistically more susceptible to severe disease outcome from COVID-19 than females.

Methods: A search of government websites and published literature was performed for reports on COVID-19 cases that included sex as a variable in data describing case number, ITU admission or mortality. Covariates such as lifestyle and comorbidities could not be controlled for as data were available at the level of country summary, but not at the level of covariates for all individuals. Meta-analysis was performed to estimate an overall proportion of male infected cases with 95% confidence intervals (CI) and to estimate odds ratios (ORs) with 95% CI associated with male sex for ITU admission and death, based on pooled average effect measures that were weighted according to the size and precision of each report. Fixed and random effects models were estimated and are reported. Metaanalyses were performed using R and the "meta" package. Conclusion: We report that although differences do not exist in the rates of infection between sexes, males are more likely to require ITU admission and more likely to die from COVID-19 than females. Important differences in the immune response to infection exist between sexes, which are likely to contribute to the male bias in infectious diseases and the female bias in autoimmunity. An appreciation of how sex is influencing COVID-19 outcomes will have important implications for clinical management and mitigation strategies for this disease and highlights the importance of sex as a variable in all biological research. Methods: Retrospective analysis of patients diagnosed by KD in two main pediatric centres in Naples during the first four-month period (January-April) of the years 2019 (group 1) and 2020 (group 2). Diagnosis of KD was defined according to the 2017 criteria of the American Heart Association, including both the classic and incomplete types.

Results: The number of cases is similar in the two groups: 12 patients in group 1 (10 males, 2 females) and 13 patients in group 2 (7 males, 6 females). It is evident a different ratio of males to females, respectively 5:1 and 1,1:1. Average age at onset was 20.5 months in groups 1 (range 3-68 months) and 23 months in group 2 (range 4-65 months). Typical form is most represented in both group: 10/12 (83%) in group 1, 10/13 (77%) in group 2. Mean value of the inflammatory indexes ferritin and CRP resulted higher in group 2 (p<0. University Software System compliant with data protection. On completion of the questionnaire data were submitted electronically. Parents/carers were informed that we were sending them the questionnaire as their child/children/ young person is part of the UK wide JDM study consent was already present to approach by email for such studies. The data recorded from the questionnaire will be analysed in relation to demographics. Demographics of the whole cohort of JDCBS participants will be compared between those sent the questionnaire and those who were not. Descriptive analysis will be carried out on the data collected from the completed questionnaires. Median and inter-quartile-range (IQR) of the scores from the cohort will be used. Free text will be analysed using thematic analysis.

Conclusion: This study will provide important additional insights to the Juvenile Dermatomyositis Cohort Biomarker Study during the current time of COVID-19 lock down in the United Kingdom. The answers from the questionnaire will enable us to assess how to support the participants and their families further now and in the future. Results: 15 (75%) were male, mean age was 7 years (3 months -15 years), 6 (30%) were from Black and Asian ethnic groups. All patients were tested for SARS-COV-2 infection by polymerase chain reaction (PCR) on nasopharyngeal swab, stool and endo-tracheal secretions if intubated. Serology samples were taken for all patients and testing is in progress. 2 (10%) patients tested positive for COVID-19 on PCR. All patients except one had no pre-existent conditions. The length of stay was 6.3 days. 6 patients (30%) required short paediatric intensive care admission for inotropes administration; one required intubation. Clinical features were fever (100%), skin rash (65%) -mainly maculopapular-rash resembling Kawasaki disease and less frequently Henoch-Schönlein Purpura , gastrointestinal symptoms (55%), circulatory shock or hypotension requiring fluid resuscitation (45%), conjunctivitis (40%), lips and oromucosal changes (30%), extremities changes -mainly hyperaemia and oedema-(25%), and lymphadenitis (20%). CRP was significantly raised in all cases with the highest CRP value being 0-100mg/L in 30%, 100-150mg/L in 20%, 150-200mg/L in 20%, and >200 in 30%. Other laboratory features included liver dysfunction (84%), raised d-dimer (80%>range 466 -41758ng/ml), lymphopenia (75%, with 30% <1), hypoalbuminaemia (70%), anaemia (55%), coagulopathy (50%), thrombocytopenia (45%, range 51 -14710 9 /L) and raised ferritin (45%, range 324 -1104ug/L). Most had abnormal echocardiograms, showing impaired function and peri-cardial effusions with prominent left coronary artery a common early finding (55%). Troponin and pro-BNP were abnormal in 35% and 80% respectively. 16 (80%) received immunoglobulin therapy at 2g/kg (a single infusion in 75% and twice in 25%), 9 (45%) required IV methylprednisolone pulses (10 mg/kg, usually repeated for three consecutive days), and 6 (30%) patients received both. 19 received aspirin initially at high dose then low dose until followup. There have been no deaths and all patients have been discharged home with plan for cardiology and rheumatology follow-up. Preliminary follow-up data are reassuring. Conclusion: Our cases of PIMS-TS showed a range of hyperinflammation features overlapping with typical or atypical Kawasaki Disease and/or Toxic Shock in a large proportion of cases. Distinct clinical features included the high prevalence of early cardiologic involvement (mainly myocarditis and pericardial effusions) which responded well to immune-modulatory treatment. Distinct laboratory features included very raised CRP, d-dimer and cardiac enzymes. Treatment rapidly resolved the hyper inflammation in all cases. Short term outcomes were excellent and follow-up for a minimum of 6 weeks is planned for all patients as longer-term cardiac outcomes of the condition remain uncertain. Results: Eight children were diagnosed as KD, with an incidence rate of 2.6 per month. Only 1/8 children could be classified as an incomplete KD. Seven were Caucasian and 1 Asiatic, without any underlying disease. Six out eight recovered after one course of intravenous immunoglobulins (IVIG), no specific intensive support was required. One patient needed two IVIG courses and a young girl developed an incipient macrophage activation syndrome (MAS) responsive to a single steroid pulse. The SARS-COV-2 on nasopharyngeal swab, available in 6/8 children, was always negative. Four KD children were sampled for antibodies after recovery and resulted negative. No coronary involvement was reported. From February 1st and April 30th, 1992 nasopharyngeal swabs have been performed to the Tuscan children admitted to the hospitals: 85/1992 (4.3%) resulted positive for SARS COV-2. Fifty serological tests have been performed with 7 children positive results. Considering the previous 5 years, 165 children were diagnosed with KD (incidence 2.7 per month). Fifty-nine were incomplete forms; 3 developed MAS and 1 experienced Kawasaki disease shock syndrome (KDSS). Thirty-eight showed coronary involvement during the acute phase, 11 received steroid pulses and additional 3 biologic therapy. No statistically significant difference regarding the incidence/month was found (RR 1.09, 95% CI 0.52-2.04, p=0.76), neither limiting the analysis to the 45 KD children diagnosed during the same corresponding 3-months of the last 5 years: 3 vs 2.6 (RR 1, 95% CI 0.46-1.98, p=0.96). Chi square analysis with Fisher's exact test correction failed to detect significant differences among the principal outcomes of KD children observed during the COVID-19 time and in the last 5 years: incomplete KD 59 vs 1, c 2 =1.82; KDSS 1 vs 0, c 2 =0.04; MAS: 3 vs 1, c 2 = 3.85; coronary involvement 38 vs 0, c 2 =2.36. The same results have been detected adjusting the analysis for the 45 cases during the corresponding trimesters of the last 5 years (p=n.s, Fisher's exact test). Conclusion: In Tuscany, during the COVID-19 pandemic, almost all KD patients, showed a mild disease course and completely recovered without complications. Our data underline the important role of our pediatric network during COVID-19 pandemic. The long-lasting collaboration and the well-structured communication provided a prompt intervention in new KD cases and allowed a comparison between 2020 KD cluster and the previous ones, referring to the Tuscany KD register. A comparison between our data and the results seen worldwide will be helpful to define the multifaceted nature of the pediatric COVID-19 disease and its potential relationship with the KD.

Introduction: Kawasaki disease (KD) is an acute febrile systemic childhood vasculitis which has been known to be triggered by respiratory viral infections. Objectives: Here, we examined whether the ongoing COVID-19 epidemic is associated with an increase of Kawasaki disease. Methods: We conducted a quasi-experimental interrupted time series analysis over the last 15 years in a tertiary center in a French epicenter of COVID-19.The main outcome was the number of KD cases over time, estimated by quasi-Poisson regression. In the same center, we described the evolution (2005-2020) of hospital admissions from the emergency department and the evolution of the respiratory pathogens identified by nasopharyngeal multiplex PCR (2017-2020). These data were compared with the evolution of daily admissions due to confirmed COVID-19 in the same region, recorded by Public Health France.

We included 230 patients with KD. On April 2020, we identified a rapid emergence of KD related to SARS-COV-2 (+497% increase, 95% CI [+72; +1082], p=0.0011), starting two weeks after the peak of the COVID-19 epidemic. SARS-COV-2 was the only virus circulating at high levels during this period, and was found in 80% (8/10, SARS-COV-2 positive PCR or serology) of KD patients since April 15 th . Among these patients, five had a complete KD and 5 patients had fever with only 3 other KD criteria. The age of KD patients ranged from 18 months to 15.8 years. Six children (60%) had cardiac abnormalities, including one major coronary aneurysm (Z score: 12) and five myocarditis. Six patients (60%) required intensive care and five had inotrop treatment (50%). None required mechanical ventilation, and no fatal outcome was observed. A second peak of KD hospitalizations was detected by the model in December 2009 (+365% increase, 95% CI [+31; +719], p=0.0053), concomitant with the influenza A (H1N1) pandemic.

Conclusion: Health care providers should be prepared to manage an increased surge of patients with severe KD, particularly in countries where the peak of COVID-19 has just been reached. Results: Clinical information was obtained for 25 patients (14 males, 11 females), 18 by FIMP questionnaire and 7 evaluated in Santobono-Pausilipon Hospital. Age range from 2 to 17 years (median 11 years). No one referred contact with COVID-19 individuals, previous history of perniosis or drug intake. Lesions involved acral regions: foot (toes and heels) was mostly involved (92%) with symmetrical involvement in 80% of patients, hands in 2 patients (8%). Lesions presented as erythrocyanotic discoloration of the fingers or toe, erythemato-violaceous papules or macules of foot and hand. Associated symptoms were: erythema in 11 patients (44%), swelling in 10 patients (40%), pain in 6 patients (24%), itching in 6 patients (24%). Among hospitalized patients, all of them performed laboratory assessment: no alteration was found in blood count, inflammatory indexes, hepatic and kidney function, coagulation parameters including D-dimer, LAC, antiphospholipid antibodies, S protein, C protein, homocysteine, autoimmunity. Level of vitamin D resulted insufficient (median value 19,2 ng/ml). No infection was found. Qualitative serological test for COVID was performed resulted negative for IgM in all patients, IgG positive in one patient. 5 patients performed nasal and pharyngeal swab for SARS-COV-2 resulted negative. 2 patients underwent biopsy with similar result: lymphocytic vasculitis with edema and thickening of vessel wall associated to mural and perivascular infiltrate of lymphocytes. Concerning treatment, all patients applied topical emollient. Topic steroid was used in 12 cases outpatient, 1 case inpatient. Heparin cream was mainly used in patients with worsening of lesions after the first week. Improvement of lesions started mostly after one week, in certain cases lesions blistered and ulcerated. Resolution occurred in variable time, up to 4 four weeks from the onset, sometimes with desquamation. Conclusion: Italy was one of the most involved country by COVID-19 pandemic, extraordinary restricted measures were performed all over the national territory. Up to the May 4, at the end of the first phase, 211.938 cases were assessed, 1.9% of patients in the age 0-18 years. There has been an outbreak of chilblain-like lesions observed mainly in young patients during COVID-19 epidemic, unreported in the previous years. The direct connection with COVID-19 is not demonstrated yet, however a role has been assumed. In most patients of our cohort there was not evidenced a defined correlation with clinical or laboratory findings of COVID-19. Improvement of lesions started mostly after one week spontaneously or with topical treatment. The new life habit due to the lockdown (physical inactivity, barefoot) could play a role mimicking a similar pathway of cold exposition. Further studies are necessary to better understand mechanism underlying COVID-19 in children.

Introduction: The problem of combined organ damage (organspecific autoimmune syndromes) is relevant in systemic processes, which include juvenile idiopathic arthritis (JIA). Such lesions in rheumatoid arthritis in adults include autoimmune diseases of the thyroid gland, primarily chronic autoimmune thyroiditis. On the other hand, the basis for the development of thyroid pathology is endemic iodine deficiency. In accordance with the results of studies conducted in 2002 in 22 regions of Ukraine (with the participation of the Ministry of Health, NAMS of Ukraine, Goskomstat, specialized scientific research centers and UN Children's Fund (UNICEF), iodine deficiency detected in all studied territories. Ubiquitous iodine supplementation can lead to its excessive consumption, which is a problem in individuals who already have thyroid disorders, such as nodules, hyperthyroidism and autoimmune thyroid disease. Objectives: To evaluate the current state of iodine supply in children with JIA living in the North-Eastern region of Ukraine. Methods: Target group included 52 schoolchildren (29 girls and 23 boys) with JIA (according to ILAR classification, Edmonton, 2001) aged from 7 to 16 years (11.8±2.71). Control group included 11 children (5 girls and 6 boys), residents of the same region, of comparable gender and age (13,6±3,12). Methods: dietary iodine intake evaluation by urinary iodine concentration (Sandell-Kolthoff reaction), followed by calculation of the median. The average concentration of iodine in urine (median of urinary iodine concentration) can be used to assess iodine supply of the population. A cohort of schoolchildren is the most reflect average consumption iodine in a given territory in the general population. According to the WHO recommendation, iodine intake is considered sufficient with a median of 100-299 mcg/l in school-age children. Results: Median urinary iodine excretion in children with JIA was at the lower normal range and amounted to Me=101.7μg/l; [QR 56.5; 169.9]. Moreover, the median iodine in urine was significantly lower than in the group of healthy peers (Me=101.7 μg/l vs Me=183.7 μg/l, p=0,003 Conclusion: The risk of developing pathological changes in the thyroid gland in children with JIA is caused not only by systemic immune disorders, but also by a deficiency of iodine intake. The obtained results can serve as the base for screening testing of thyroid function in JIA and for resolving the issue of prescribing iodine-containing drugs. This should be taken into account to improve the overall prognosis of the disease and the quality of life in adulthood.

None declared

The 15-year evolution of JIA biologic therapy patterns in the Czech Republic N. Vinšová 1 , Š. Introduction: Collection of structured clinical information in the form of disease and/or pharmacovigilance registries have become a standard for many rare diseases including juvenile idiopathic arthritis (JIA). Although the total JIA paediatric population is not known in the Czech Republic participation to the Rheumatic Diseases Biologics Registry (ATTRA) has been required in order to secure drug reimbursement by insurance companies. Patient data including demography, disease activity and damage scores, comorbidities and concomitant therapies have been prospectively collected in the ATTRA registry since 2002 for the spectrum of rheumatic diseases under the auspices of the Czech Rheumatological Society. Paediatric patients have been entered since biologic therapies became available for children with JIA in late 2004. Objectives: To present country-specific policies and practice in JIA biologic therapy and analyse major trends in their use over the past 15 years. Methods: Description of the biologic therapy organisation within the Czech healthcare system. Analysis of the main demographic and disease characteristics from the JIA part of the ATTRA registry from 2005 up to January 2020. Results: JIA biologic therapy is concentrated in paediatric rheumatology units satisfying the predefined criteria agreed by the Czech Rheumatological Society. These include personnel qualifications as well as unit equipment and availability of specialised paediatric services. When used in approved indications majority of common biologics including etanercept, adalimumab, golimumab and tocilizumab are fully reimbursed via the special budget-limited contracts among approved healthcare providers and insurance companies. Reimbursement of IL-1 blockers, abatacept and rituximab requires formal application which is time consuming, but usually successful. Over the past 2 years number of units prescribing biologics has expanded from 3 towards currently 7 approved centres in the country of over 10 million population. Nevertheless, the 3 "oldest" units care for 94% (701/743) of registered patients who were further analysed. The number of registered (=ever biologic-treated) patients has been steadily increasing from the total of 50 individuals in 2005 by the 5-year annual mean of 77 patients (calculated from years 2015-20). When data from 2005 were compared with 2015-20, interval from the diagnosis to the introduction of the first biologic as well as the JADAS-71 (range 0-101) at therapy onset have been steadily decreasing from the median (5-95 th centile) of 4.8 (4-12.7) years and 21.2 (8.9-59.5) respectively to 1.1 (0.2-8.8) years and 14.3 (1.4-34.7), respectively. From the total of 1186 patients currently followed by the 3 largest units 30% (356) of patients are receiving following biologics: TNF inhibitors (85%), tocilizumab (10%), IL-1 inhibitors (5%). Data on patient demography, JIA subtype distribution and disease complications (mainly uveitis), treatment efficacy, relapse and switch to different agent rates as well as adverse events are further presented in detail. Conclusion: Biologic therapy has been well established in the Czech Republic and is currently being received by one third of JIA paediatric patients. Its accessibility is somewhat limited by reimbursement rules and by the budget, but TNF and IL-6 inhibitors are readily available without delay when used in approved indications. Decreasing interval from disease onset to the start of therapy as well as generally milder disease (as reflected by JADAS) required for treatment initiation illustrate their expanding use over the past years in line with available treatment recommendations and similar to other JIA series.

Introduction: High disease activity, the presence of prognostically unfavorable syndromes of systemic lupus erythematosus in children much more often requires the appointment of a more aggressive than in adults complex of immunosuppressive therapy (hormones, cytostatics, immunobiological drugs). The development of endothelial dysfunction, immaturity of the regulatory systems (central nervous and endocrine) further create the conditions for the formation of irreversible damage in many organs with the development of their insufficiency. The nature of these injuries in childhood and the period of their formation remain unclear. Objectives: The purpose of the study was to determine the frequency and nature of irreversible changes (damage index) in children with systemic lupus erythematosus (SLE), depending on the duration of the disease, the nature of the course, and activity of the process. Methods: 53 patients with SLE at the age of 7-18 years old and suffering from more than one year were examined in dynamics twice at intervals of 12 months. The average duration of disease was 37,92± 7,90 years at the time of the first examination. Changes in the cardiovascular system were determined (using an ECG in 12 main leads, an echo test, a 6-minute walk test), kidneys (according to glomerular filtration rate, serum creatinine concentration, proteinuria level and the range of changes in the specific gravity of urine during days), pulmonary system (according to X-ray examination and spirometry). The presence of pathology of the organ of vision, the nervous system (assessment of neurological status, conductivity, sensitivity of the cranial and peripheral nerves, EEG, MRI of the brain, the use of the Montgomery and Åsberg Depression Rating Scale), changes in the musculoskeletal system (by X-ray, ultrasound, MRI of the joints , bone Introduction: As available treatment options for juvenile idiopathic arthritis (JIA) have expanded over the last decades, there is a need for studies to characterize its long-term outcome, especially in patients treated with biological therapy. Objectives: To study clinical and patient related outcomes of adults with JIA on biological treatment after transition to adult care. Methods: In this cross-sectional study, adult JIA patients under treatment with biologicals and followed in the University Hospital of Leuven were included. Patient-administered questionnaires were used to examine social and professional participation, overall wellbeing(VAS), physical disability(HAQ), health-related quality of life(SF-36), fatigue(MFI-20), perception of illness(IPQ-R), coping(UCL) and self-efficacy(ASES). We registered disease and treatment characteristics, disease activity(DAS28-CRP), joint damage(JADI-A), systemic sequelae and side effects of biologicals from the patient's medical record. Results: Twenty-five patients with a mean age of 32.6 years were included. All JIA subgroups were represented, but the polyarticular JIA was the most common. At their last hospital visit, 7/25 patients used low-dose steroids, 12/25 were treated with cDMARDs and 24/25 were on biological therapy. After a mean follow-up time of 23.6 years, 4/ 25 participants had active disease defined as DAS28≥ 2.6. The mean JADI-A and HAQ score were 6.5 and 0.8 resp. 3/25 patients developed serious infections, 4/25 developed MAS during their disease course. None developed malignancies. Arterial hypertension was present in 8/25, pulmonary hypertension occurred in 2/25. Two patients had osteoporosis, while 6 had osteopenia. Growth failure was identified in 4/25. 5/25 developed discrepancy in leg length. 2/25 underwent surgery for excessive varus or valgus deformity of the limbs. Patients scored their health-related quality of life with a mean of 71.6/100±18.3 on the VAS. The SF-36 physical and mental component score (PCS and MCS) were calculated, resulting in a mean (± SD) of 40.9±11.7 for PCS and 52.0±12.2 for MCS. A mean (± SD) of 13.2±4.4 was found for the MFI-20 subscale "general fatigue". The mean (± SD) for the ASES subscale "pain" was 3.3±0.8, and for "other symptoms" 3.8±0.7. Almost 3/4 of participants practiced sports. 18/25 participants were employed, 15/25 were in a relationship and 6/25 had a child. Conclusion: In this cross-sectional study, we examined clinical and psychosocial outcomes of JIA patients under treatment with biological therapy after transition to adult care. Although the population was biased to a more severe subtype due to our inclusion criteria (use of biological therapy), disease activity at the last hospital visit was lower in our cohort compared to previous studies. The proportion of patients using steroids and cDMARDs remained stable during follow-up but the steroid dose declined over time. The presence of side effects of biological therapy was in line with data from previous studies. Despite lower disease activity and joint damage scores, our patients experienced more physical disability and pain compared to the general population and recent studies in adult JIA patients. Their fatigue, illness perception and coping levels were however comparable to those of patients with other rheumatic conditions. Compared to the general population, our cohort had a similar health-related quality of life, employment rate and social participation. Participation in sports was surprisingly high. Overall, we may conclude that the access to biological therapies for JIA patients seems to improve disease control, resulting in an overall good physical functioning as well as psychological well-being. Introduction: The caregiver is the most active in caring for a child with a rheumatic disease, once the patient grow, the responsibility of care need to be passed to the adolescent. Transition programs in rheumatology have shown improving quality of life and disease activity.The best transitional care model in rheumatology is still uncertain. Objectives: The aim of this study was to describe the process of design a program that provide an uninterrupted, multidisciplinary and coordinated attention to adolescents during transition from pediatric to adult services in Mexico Methods: Between January and June 2017 we created the care model protocol according to three steps: 1. Creation a Multidisciplinary team. A group of specialists were invited to participate. 2. Evaluation of transition skills of patients and caregivers.The Spanish version of the Got Transition questionnaire was applied to youth and parents/caregivers, includes: "Transition Importance and Confidence", "My Health" and "Using the Health Care System". Analyzed using SPSSv.24, concordance were compared using Spearman's test. 3. Establish a model of care.We appraise variables which includes chronological age, maturity, medical status, adherence, independence, transitional issues, adolescent readiness, and availability of an adult physician. Results: Step 1.Creation a Multidisciplinary team. The team was made up of three pediatric rheumatologists, two adult rheumatologists, two physical medicine and rehabilitation specialists, one child psychiatrist, two nutritionists, one clinical psychologist, one nurse and one social worker.

Step 2. Evaluation of transition skills of patients and caregivers. 38 questionnaires were applied to 19 patients and their caregivers. Most of the youth were female (79%), with median age of 18 years. Juvenile Idiopathic Arthritis and Systemic Lupus Erythematosus were the most frequent.We observed that parents/caregivers reported less confidence about their child´s ability to change to an adults' doctor. We also observed a low correlation (rho coefficient < 0.7) between the reported skills (in "My Health" and "Using the Health Care System" items) by youth and the parent/caregiver perception.

Step 3. Establish the model of care. We established a three steps model: pre-transition, transition clinic and pos-transition, divided in eight phases. Each phase includes different administrative activities and abilities which must be met in order to continue with the next phase. (Figure 1 ) Conclusion: The transition clinic that we presented represents the first step to establish a program to get selfcare capabilities in patients from a low-resource setting. Approaching in a multiassessment manner, allowing personalized interventions.The transition model proposed is a possible intervention in developing countries.

Introduction: It is known that in adult patients with rheumatoid arthritis (RA) the risk of cardiovascular disease associated with atherosclerosis increases by almost 50% compared to the general population. Atherosclerotic process usually begins long before its clinical manifestation. Similar studies are also conducted in the pediatric population of patients with JIA. However, how persistent these changes are in childhood is not fully understood. Objectives: The aim of the study was to determine the state of the blood lipid spectrum in dynamics under the conditions of treatment of the disease. Methods: 65 children (8-18 years) with JIA (oligoarthritis 61.5% and polyarthritis 38.5%) were examined twice in the dynamics with an interval of 1 year. Among patients females predominated (66.2% (43 girls) vs males 33.8% (22 boys)). The average duration of the disease was (74.1 ± 6.3) months. All patients received methotrexate (MTX), including in combination with TNF-α blocker -adalimumab 8 people (12.3%).The physical development of children was within the age population norms. Children with signs of chronic rheumatoid cachexia or overweight and obesity were not included in the development. Control group included 19 children, residents of the same region, of comparable gender and age. General clinical assessment, disease activity and drugs were rated. Total cholesterol (TCh), triglycerides (TG), high density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL),very lowdensity lipoprotein cholesterol (VLDL)apolipoprotein B, ApoA-I and lipoprotein-α, atherogenic coefficient were evaluated. Results were analyzed using IBM SPSS Statistics for Windows with p<0.05 considered spastically significant. Introduction: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease affecting children and adolescents, but many refractory forms continue into adulthood. In the era of biologic therapy we experienced an increasing willing for childbearing in many patients due to outcome improvement. Currently data regarding pregnancies in JIA patients are scarce. Objectives: The aim of this study was to describe a monocentric case series of pregnant women affected by JIA and therefore to evaluate pregnancy outcome, the presence of major complication in newborns and the impact of gestation on disease activity. Methods: All pregnant women affected by JIA referring to the Transition Clinic, Division of Rheumatology, G. Pini Institute of Milan, in a period of twenty years were enrolled in this study. Data regarding pregnancy outcome, drug exposure and disease activity were recorded. Gestational age, birth weight, APGAR score and newborn conditions were also collected. Results: We collected data from 28 women affected by JIA and 35 pregnancies. All patients presented long standing refractory JIA. All patients were treated with DMARDs close to conception, of whom 85,7 % with bDMARDs.Exposure to biologic treatments included mostly anti-TNF agents (17 etanercept, 3 adalimumab, 5 golimumab and 2 certolizumab), but also other agents (3 rituximab,1 sarilumab). bMARD were used in monotherapy (28/30) or in association with csDMARDs (1 leflunomide, 1 methotrexate), hydroxycloroquine (3), or both (1 cyclosporine and hydroxycloroquine). All patients discontinued therapy at gravindex positive test or during first trimester. Pregnancies outcomes and data regarding drugs exposure are reported in table 1. One case of cleft palate was observed. We did not observe any major early or late complications in infants. Eight patients underwent intra-articular glucocorticoid injections during pregnancy, while 23 patients resumed therapy shortly after childbirth. One patient needed to start a biologic treatment after delivery. Conclusion: Despite a large amount of studies demonstrating the safety of anti-TNF during pregnancy, data in young women affected by JIA who become pregnant are still limited. In our monocentric experience, no greater number of unexpected complications were observed during pregnancy and also in children, compared to other autoimmune disease. Discontinuation of therapy increased the risk of flares confirming that EULAR recommendations for the use of biologics during pregnancy may be applied also in JIA patients. 1 Introduction: Musculoskeletal (MSK) problems in children and young people (CYP) are common. The majority will present to healthcare professionals in the community but it can be challenging to identify those with serious disease requiring onward referral. pGALS (paediatric Gait, Arms, Legs and Spine) was developed as a simple, quick MSK clinical assessment to discern abnormal joints. Anecdotally, pGALS can detect joint and functional problems in CYP with other serious conditions but alone is unlikely to be specific enough. Objectives: Our aim was to scope the literature about MSK assessments applicable to CYP used in clinical practice, focusing on evidence of validity in the context of diagnosis and assessment of Juvenile Idiopathic Arthritis (JIA), Mucopolysaccharidoses (MPS), 

There is very limited information and awareness about pediatric rheumatic and immunodeficiency diseases amongst primary physicians in Gujarat and to make this matter even worse, we are not having a single exclusive pediatric rheumatology and immunology center for a population of around 60 million. [1] [2] [3] Objectives:

To measure an effectiveness of Subspecialty Pediatrics e-Case Series (SPeCS) in spreading awareness and alertness amongst pediatricians about rheumatic and immunodeficiency diseases in children.

On 28th may 2020, I and my endocrinologist colleague decided to deliver weekly one e-class consisting of three real life case discussions from a single or two pediatric subspecialties .Duration of eclass was kept limited to 45 minutes. We propagated this idea for the next two days through various social media platforms to reach to a maximum numbers of pediatricians. Pre e-class evaluation forms were sent to the registered participants. First preliminary e-class was completed on 31st may 2020 which was a fusion of one endocrinology and three rheumatology cases. Post e-class feedback forms were sent to the registered participants. Second e-class was completed on 5th June 2020 which was again a fusion of endocrinology and rheumatology cases.

Though the numbers of participants were less during first e-class but the feedbacks from the attendees were outstanding. Subsequently in a second e-class there was a wonderful response and social media feedbacks from all the participants. On 7th June 2020, SPeCS was officially launched with some innovative modifications under the aegis of Rajkot academy of pediatricians (AOP) in view of outstanding feedbacks given by the attendees. The next e-class would be planned under a new name SPeCS-AOP Rajkot in a couple of weeks with more fascinating talks and cases from practicing pediatricians under a guidance of senior expert pediatricians and subspecialists from our region.

SPeCS is proven to be successful in terms of spreading awareness and alertness amongst pediatricians about untouched diseases which are used to be missed easily in day to day practice. A new model would be definitely more beneficial for presenters, attendees, residents and ultimately our little patients. Conclusion: The experience in our paediatric rheumatology clinic suggests that WBMRI is a helpful tool in situations characterized by non specific constitutional and musculoskeletal manifestations, in which the conventional work-up findings are negative or uninformative. WBMRI has proven to be useful both in the definition of some specific diagnosis, and in their differential diagnosis. In our experience, CRMO resulted the disease that mostly benefits from its use, allowing the early detection of lesions and defining their exact number and distribution. All of the respondents used MSK-USS performed by radiologists. MSK-USS and MRI scans were requested equally frequent, median 4-7/month. 80% (n=32) consultants and all paediatric rheumatology trainees felt that MSK-USS performed by a clinician in clinic would benefit their patients. Majority stated that for urgent cases, it could take up to 2 weeks in their centre for a departmental USS to be done and reported. Only 32.5% (n=13) could arrange MSK-USS on the same day for urgent scans. 70% (n=28) of the clinicians and trainees have access to an ultrasound scanner. Majority of clinicians expressed their enthusiasm (median of 80%) for an interactive paediatric rheumatology musculoskeletal ultrasound online module combined with a platform in which images and clips can be uploaded and discussed. 100% (n=7) of trainees were keen to learn MSK-USS as part of their training and majority felt that they could dedicate regular time for it alongside their other clinical duties. Conclusion: In summary, MSK-USS is a tool commonly used in paediatric rheumatology. MSK-USS performed by the clinician is seen as beneficial for the patient by the majority, but a small group reports reservations which need to be addressed. There seems to be a demand in the UK for a training module in MSK-USS in paediatric rheumatology. Results: Average age of children (6 boys and 2 girls ) in our group was 5.3 years. Table 1 showed characteristics of eight paediatric patients with suspected PIDs in rheumatic conditions in children Conclusion: All above cases reemphasize the need for an extremely detailed history, family history, pattern recognition and high index of suspicion in paediatric rheumatology.. In our cohort, the features like arthritis pattern different than JIA, early age of onset for autoimmune features, endocrine manifestations, significant family history, recurrent inflammatory episodes and recurrent and/or severe and/or unusual infections at unusual site were some of the important clues which inspired me to suspect PIDs in these patients.

Introduction: ALPS is a rare disorder due to a defective apoptotic mechanism leading to abnormal lymphoproliferation and autoimmunity. It is characterized by lymphoadenopathy and hepatosplenomegaly with autoimmune haemolytic anemia, neutropenia or thrombocytopenia. The disease is difficult to identify in the early phase when it may be misdiagnosed. Elevated TCR alpha-beta CD4-CD8-lymphocytes (double negative T lymphocytes DNT) together with hypergammaglobulinemia, high levels of IL10, Il18, vitamin B12 and soluble Fas ligand have been suggested as the main ALPS hallmarks (1). Therefore, a specific flow cytometry panel (number of DNT cells, the ratio of CD25+CD3+ to HLA−DR+CD3+ cells, increased B220+ T-cells, and decreased CD27+ memory B cells) has been proposed to serve as a diagnostic screen for ALPS (2). Conclusion: The use of specific LS in patients with undefined autoinflammatory or autoimmune disorders may identify a subgroup of patients with ALPS. Oliveira's criteria where useful in the identification of patients, but the cut-off identified for DNT is not probably strong enough to identify real ALPS patients when used in a pediatric population affected with different immune-mediated conditions.

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. With the exception of the systemic JIA it is considered an autoimmune disease. Objectives: To evaluate whether there are differences in the prevalence of coexisting autoimmune diseases in children according to the different subtypes of juvenile idiopathic arthritis. Methods: A retrospective, single small center study was performed. All patients diagnosed with JIA who were examined at our pediatric clinic in the last 10 years were enrolled. JIA was classified according to the International League Against Rheumatism (ILAR) criteria. Data was collected from patients' medical records. Results: A total of 111 patients were included. The results are presented in Table 1 . The mean age was 8.1 years. 71 patients (64%) were female. 3 patients (2.7%) were diagnosed with undifferentiated arthritis. In our cohort none of the patients had rheumatoid factor positive polyarthritis. 1 patient with systemic JIA developed macrophage activation syndrome (MAS). 28 patients (26.1%) presented with a family history of autoimmune disease. The most common coexistent autoimmune disease was uveitis, which was most commonly present in patients with oligoarthritis and enthesitis related arthritis. Associated autoimmune diseases were most frequent in patients with oligoarthritis whereas patients with systemic and undifferentiated arthritis had none of them. This confirms the hypothesis that systemic JIA is an autoinflammatory and not an autoimmune disease. Conclusion: Our study demonstrated that autoimmune diseases are frequently coexistent in children with JIA, especially in patients with oligoarthritis. Therefore, all patients with JIA and especially those with oligoarthritis should be regularly screened for associated autoimmune diseases.

Coverage and facilitators of influenza vaccine uptake among JIA patients in Greece Square was used to explore factors associated with vaccine uptake& the significance level was set at p≤ 0.05. Results: A total of 65 caregivers(72% females) with a mean age of 42.1years(SD=7.6) participated.Country of origin was Greece(75%),followed by Albania(19%). The majority of the participants were employed(67.7%),married(87.7%) and held a secondary education degree(42%).Principal diagnosis was polyarticular JIA(29%),followed by oligoarticular JIA(26%),while 14% of caregivers were unaware of the child's diagnosis.JIA patients' mean age was 9.8 years(SD=3.8) with a mean disease duration of 4.7years(SD=3.3). Most of them were on systemic treatment(88%). Of note,74% were fully vaccinated according to national vaccination schedule and 80% had received influenza vaccine in the past (median:4 times),while only a patient had previously experienced vaccine-related adverse event. A total of 46 children(71%) were vaccinated against influenza during the current season(2019-20) and in 96% the disease status was stable.Most participants were informed by their pediatric rheumatologist(65%) and/or their pediatrician(51%).The highest vaccine uptake was recorded among Greek participants(83%),while only 33% of Albanian caregivers vaccinated their children(p< 0.05).Caregivers of secondary or tertiary education were more likely to vaccinate their children(81.5% & 80.8% respectively) compared to those with elementary education(25%)(p<0.05).All children with psoriatic JIA were vaccinated,while children whose caregivers did not know the diagnosis reported the lowest vaccine uptake(11.1%)(p< 0.05).Disease duration was not related to vaccination rate.Among vaccinators,93.5% were under systemic treatment,81% were fully vaccinated according to national vaccination schedule and 96% of them had been vaccinated during the previous years(p<0.05). Caregivers who were informed of influenza vaccine recommendation by medical staff were more likely to vaccinate their children against influenza in the current season(78.5%,p<0.05). Among non-vaccinators,78.9% did not have the chance to discuss their concerns with a specialist.Being uninformed of the need to immunize against influenza(52.6%) was the major reason for nonvaccination,while few caregivers reported fear of disease flare and not being aware of requiring flu immunization on an annual basis(10.5% respectively).Caregivers suggested that informing in advance(71%) and organizing national campaigns(63%) may improve vaccine uptake in the future,while most of them(71%) disapproved reminder calls/sms. Conclusion: Influenza vaccine uptake in JIA patients in Greece is moderately high.Those previously vaccinated and those fully vaccinated according to national vaccination schedule were more likely to be vaccinated during the current season.Higher education, thorough informative discussion and notifying families in advance may address fears and lead to universal vaccine coverage in children with JIA and other rheumatic diseases. Vancouver and I/E criteria and received etanercept SC (0.8 mg/kg QW, max 50 mg per week) in combination with methotrexate (10-15 mg/m 2 QW). Effectiveness evaluation was performed at months 6, 12, and 18 after treatment initiation with results reported on an intention-to-treat group. To assess articular manifestations of JPsA, we applied ACRpedi criteria, and BSA and PASI scores to estimate the surface area of involved skin and severity of psoriasis. To assess the impact of disease activity on patient's growth, we used a total activity index (TAI) -сJADAS-27 (4 components of the Juvenile Arthritis Disease Activity Score for 27 joints) for the last 12 months. We evaluated the growth velocity (GV) expressed in % for the previous year regarding the appropriate ageand gender values and body mass index (BMI). Some patients underwent hand X-ray to assess bone age. Insulin-like growth factor-1 (IGF-1) in blood serum were measured in children with growth delay. Quantitative indicators distribution is given as a median [5th;

95th procentile], the calculations were carried out using the Mann-Whitney U test, and the correlation was studied by multiple regression analysis. ; 62] respectively. The relative growth velocity for the previous year was significantly higher in patients with both oligoarticular (U = 225.5, p = 0.009) and polyarticular (U = 222.5, p = 0.0001) forms of disease when used bDMARDs. In a group of patients on bDMARDs, the relative growth velocity is 2% higher in patients with oligoarticular form and 30% higher in patients with polyarticular form, compared with the use of MTX alone. 19 patients (13.4%) had an underweight, 8 patients (5.6%) were overweight, and 7 patients (4.9%) had obesity. Most overweight or obese children did not have a history of long-term use of corticosteroids (CS). 4 patients with height delay < 2-3 SD and 1 patient with height delay > 3 SD were ahead of the bone age by 4 years. In 17 children (10 of whom had height delay), IGF-1 in blood serum was age-appropriate. The TAI has a significant inverse correlation between the growth index expressed in SD (β = -0.4, p = 0.005) and GV (β = -0.62, p = 0.000009). Thus, the higher is the total disease activity index, the greater is the growth velocity delay. There was no detected correlation between these indicators and the disease duration, the age of onset, the total dose of CS and cJADAS-27 at the moment of the study.

The disease activity affects growth pattern. The relative growth velocity for the previous year was significantly higher in patients when used bDMARDs. The results were analyzed depending on patient's age (up to 6 years, from 6 to 10 years, from 10 to 14 years and older than 14 years), variant of the disease (oligoarthritis, polyarthritis, undifferentiated arthritis) and basic therapy (the presence of methotrexate or his absence). The study was conducted twice: the first -in the absence of additional intake of vitamin D, the second -after 6 months of supplementation of 2000 IU of vitamin D. The control group consisted of 20 peers who did not take vitamin D. Serum 25hydroxyvitamin D [25 (OH) D] levels were measured using chemiluminescent method (Cobas 6000, Roche Diagnostics, Switzerland). Results: The average serum vitamin D level was 22.26±2.53 ng/ml, that was significantly lower than in children in the control group (28.67±2.38 ng/ml; p<0.05). No gender dependence was found. A correlation was established between the age of patients and the level of vitamin D. Children under 6 years of age had a significantly higher vitamin D status compared than older children (p<0.05). The dependence of the concentration of vitamin D in serum on the variant of the disease in children during the initial study was not found. An analysis of the vitamin D content in a re-examination showed that male patients had a positive trend compared with female patients; in young children compared with older patients than 14 years; an oligoarthritis compared with other variants; in the presence of basic therapy with methotrexate compared to therapy without it (table) . Conclusion: In patients with JIA there was an insufficient level of vitamin D which increased after an additional intake of 2000 preparations of vitamin D for 6 months. Girls, children over 14 years old, patients with non-deferred arthritis and polyarthritis as well as patients who did not receive basic methotrexate therapy, had insufficient level recovery of vitamin D, that requires a review of the regimen of additional vitamin D intake and basic therapy in these categories of patients.

Introduction: S100A8/A9 (calprotectin) has been widely studied as candidate biomarker for predicting disease activity and treatment response in rheumatic diseases. Its high levels may also predict disease flares in systemic juvenile idiopathic arthritis (JIA). In clinical practice, ultrasound (US) could be a useful tool to define the disease activity status. To our knowledge there are no published articles to examine simultaneously the correlation between S100A8/A9 levels, clinical and US assessment in JIA.

Objectives: To explore the association between S100A8/A9, clinical and US assessment in JIA patients. Methods: Patients with JIA were blinded assessed by clinical examination and ultrasound and serum levels of S100A8/A9 were measured by chemiluminescence solid phase assay. Ultrasonographic B-mode and Power Doppler assessment of 44 joints for each patients were performed. Clinical disease activity was evaluated using Wallace criteria.

Results: Thirty (18 F) consecutive patients with diagnosed nonsystemic JIA were prospectively included in our study (Table 1) . S100A8/A9 levels were also measured in age matched healthy controls. Median age at disease onset was 10.6 yrs (mean 10.8, range 2-16) and mean disease duration was 5.4 yrs (range 0. . S100A8/A9 levels correlated moderately with CRP (Spearman r=0.4380; p=0.01) but no correlations were found with ESR (Spearman r 0.193; p=0.325). Only 6 pts (4 out of 6 with polyarticular course) showed calprotectin levels higher than normal. Conclusion: S100A8/A9 levels were moderately correlated with CRP while no correlation were found with JIA categories. High serum calprotectin levels could be related with a polyarticular disease either in clinical activity or in subclinical remission. Our preliminary study need to be extended with large number of patients and designed prospectively. Objectives: The aim of this study was to analyze monocyte (MON) response to methotrexate (MTX) and other treatment methods for the juvenile idiopathic arthritis (JIA) patients. Methods: We performed a retrospective single-center study. All children diagnosed with JIA were included into the study, excluding systemic JIA. Complete blood count (CBC) before (at the time of diagnosis) and during the treatment (in disease exacerbation and remission) was analyzed. All patients were divided into MTX monotherapy group (T1), MTX and biological disease modifying antirheumatic drug (bDMARD) group (T2), and other (bDMARDs only, low doses prednisolone, NSAIDS, sulfasalazine) (T3). Data were analyzed using SPSS 20. P value <0.05 was considered significant. Results: 30 patients were included into the study, 60% of whom were female. Mean age of first diagnosis was 9.06±4.08 years. We found 77 documented exacerbations for all these patients from the first diagnosis till the retrospective analysis start. A meadian of 2.57 exacerbations per patient (min 0, max 15). 23 of them were during Introduction: In recent years more attention has been paid for the complex parameters seen in the complete blood count (CBC) that could help to evaluate the course of chronic diseases (1). Defining the exact stage (remission or exacerbation) of the juvenile idiopathic arthritis (JIA) could influence the long term immunosuppressive treatment strategy in these patients. Objectives: The aim of this study was to analyze changes of complete blood count (CBC) parameters during different stages of the disease in the juvenile idiopathic arthritis (JIA) patients. Methods: We performed a retrospective single-center study. All children diagnosed with JIA in the last 7 years were included into the study, excluding systemic JIA. CBC before (at the time of diagnosis) and during the treatment (in disease exacerbation and remission) was analyzed. We compared a CBC results in different stages of the disease and evaluated the predictive ability of different parameters, such as leucocyte (LEU), lymphocyte (LYM), neutrophil (NEU) and platelet (PLT) counts, mean platelet volume (MPV), platelet distribution width (PDW), platelet larger cell ratio (P-LCR), platelet neutrophil lymphocyte ratio (PNLR) and neutrophil lymphocyte ratio (NLR). Data were analyzed using SPSS 20. P value <0.05 was considered significant. Results: 30 patients were included into the study, 60% of whom were female. Mean age at first diagnosis was 9.06±4.08 years (min-13 months, max-17 years). We found 77 documented exacerbations for all these patients from the first diagnosis till the retrospective analysis start. An average of 2.57 exacerbations per patient (min-0, max-15) and 6.4 per year for all patients were found. Higher count of PLT in JIA exacerbation compared to remission was observed (348.12± 92.6 vs 310.5±68.9), but it was not significant (p=0.0976). Also, there were no differences in LEU, LYM, NEU, MPV, PDW or P-LCR levels between remission and exacerbation. However, we found significantly higher PNLR (604±412.8 vs 482±339.8, p=0.027) and NLR (1.74±1.99 vs 1.6±1.2, p=0.049) during exacerbation. Besides this, we looked at possible prediction of disease exacerbation or remission. PNLR below 143.9 predicted JIA remission with likelihood ratio (LR) of 5.55 (AUC 0.63, p=0.027) and NLR below 0.46 predicted remission with LR 5.55 (AUC 0.61, p=0.049). Also, we found that P-LCR more than 27.2 predicted JIA exacerbation with LR 2.42 (AUC 0.66, p= 0.039). When comparing first CBC (treatment naïve, on time of JIA diagnosis) with clinical remission CBC, we found that NEU below 3.15 predicted JIA remission with LR of 5.85 (AUC 0.67, p=0.016). Conclusion: Findings of the study could be useful to predict the course of the disease according to the changes seen in the complete blood count parameters such as NEU, PNLR, NLR and P-LCR. Further prospective studies are required to estimate changes of the blood cells and their ratios in different stages of JIA and possible influence of different treatment strategies. This would help to define full remission in the patients of this chronic disease in cellular level.

Introduction: Juvenile Psoriatic Arthritis (JPsA) is an inflammatory arthritis associated with irreversible joint damage among pediatric population and is associated with psoriasis in most cases. There are few validated screening tools for diagnosis of arthritis for adults patients with psoriasis those screening tools were never evaluated in children.

Objectives: The aim of this study was to evaluate two screening tools among pediatric patients with psoriasis. Methods: Thirty nine patients with the diagnosis of psoriasis were administered two screening questionnaire: the new Early ARthritis for Psoriatic patients (EARP) questionnaire and the Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire. All patients were evaluated by rheumatologist for the diagnosis of JPsA and the diagnostic accuracy of the two questionnaires for the diagnosis of JPsA was compared. Results: four patients were diagnosed with JPsA (10.2%). Four patients of 39 patients had a PEST questionnaire score of ≥ 3 all were with the diagnosis of JPsA. Thus, the sensitivity and specificity of the PEST in diagnosing JPsA were 100% and 100%,respectively, the median PEST score of the patients without the diagnosis of JPsA was 0 (0-2).

For the EARP questionnaire, 7 patients of 39 had a screening questionnaire score of ≥ 3 suggestive of JPsA, 4 were true positive and 3 were false positive. Thus, the sensitivity and specificity of EARP in diagnosing JPsA were 100% and 92%, respectively. Conclusion: Both PEST and EARP questionnaire were easy to use and with high sensitivity for pediatric population with psoriasis, PEST questionnaire had higher specificity than EARP. Introduction: Deletions of the long arm of the chromosome 18 (18q-) occur in 1/40.000 live-born infants. Common clinical features are facial dysmorphism, short stature, foot deformities, congenital aural atresia, variable intellectual disability, microcephaly, cerebral white matter abnormalities. Kidney malformations, bone dysplasia, growth hormone deficiency, congenital heart disease, IgA deficiency are less commonly reported. Autoimmune diseases such as juvenile idiopathic arthritis (JIA), thyroiditis, type 1 diabetes mellitus (DM1)have been described. Objectives: We report a case of a 10-years-girl suffering from JIA associated to dysmorphic features who was diagnosed to carry a distal 18q deletion. Methods: A 10 years old girl came to our department because of pain in her left knee and ankles for the past 5 weeks. Her parents were consanguineous, her 2 sisters were healthy. She was born at term with normal weight and length. After birth inter-ventricular septum defect and pulmonic stenosis were diagnosed, and the latter was corrected through cardiac catheterisation at 12 months. At 2 years ataxic gait was noted.The musculoskeletal examination showed arthritis of the both ankles, left knee .At neurological examination horizontal nistagmus, dysmetria of finger nose test, hyporeflexia, unstable gait were present. Romberg test was negative. Her height and her weight were normal.The genetic evaluation revealed facial dysmorphism, hypertelorism, thickened ears with prominent antitragus, squared tip of the nose, smooth and long nasolabial filter, prominent chin, thin lips, dental crowding and narrow palate. Proximal implant of the first finger of both hands with hypoplastic last phalanx, and both fifth fingers clinodactyly were noted; at the feet medially deviated large first toes with short I metatarsus and short Vth finger with nail hypoplasia were detected. The geneticist requested an Array CGH and a brain MRI. Results: Blood test revealed increase in CRP (5,52 mg/dL)and ERS (68 mm/h). ANA was positive with a titer of 1:640. Patient presented IgA deficiency (< 5mg/dL) and increase in thyroglobulin antibody (305UI/ mL), with normal levels of thyroid hormones. The left knee and ankles ultrasound showed moderate joint effusion. Thyroid gland ultrasound showed a dishomogeneous echoic pattern in line with a thyroiditis. An eye examination was normal.Brain MRI showed dysmelination of white matter, segmental stenosis of the third distal part of the aqueduct of Sylvius with enlarged lateral ventricles. The Array CGH revealed a de novo heterozygous 18q22->qter deletion, a syndrome which explain all features of our child. The patient underwent to steroids intraarticular injection in the left knee, then methotrexate and folic acid were prescribed. After a clinical response, one year later she presented arthritis of both ankles, so etanercept was started. A control brain MRI showed progression of ventriculomegaly and subependimal trasudation, thus she underwent endoscopic ventriculocisternotomy. At last rheumatologic evaluation the patient was in good general condition, and did not present signs of active arthritis, biologic treatment was confirmed. Conclusion: Our report provides an example of how autoimmune diseases can associated to genetic diseases. The association of 18q deletion to several autoimmune diseases offers chances to identify one or more genes implicated in regulation of immunity and predisposition to autoimmunity. This is the first report of acqueductsl stenosis linked to the distal 18q deletion syndrome.

None declared related arthritis (ERA), 9 (7.8%); psoriatic and undifferentiated, 3 (2.6%) each; systemic, 1 (<1%). The proportions of pts achieving JIA-ACR70 response and cJADAS10 ID are shown in Table 1 (pt with systemic JIA excluded). Conclusion: Abatacept treatment resulted in rapid, clinically important and sustained JIA-ACR70 response in all JIA categories with polyarticular or oligoarticular disease course and few achieved cJADAS10 ID. Limitations of the study include a low number of pts with ERA, psoriatic, undifferentiated and systemic JIA. treatment of the disease on the eve of the transition. At the same time, 25(51.0%) respondents believe that the decision to reduce/cancel biologics is advisable after the patient with JIA has been in a state of stable remission for 2 years, 2(4.1%) prefer to continue biologics until 5 years of remission. 12(24.5%) responders consider it possible to stop biologics >5 years before reaching the age of 18; 27(55.1%) think that it possible to stop them 1 year before the transfer, at the same time 10(20.4%) specialists prefer to follow therapeutic strategy without any changes. In case of combined DMADRs therapy, 37(75.5%) pediatric rheumatologists initially taper methotrexate or other synthetic DMARDS, which also differs from approaches at the adult service. Regarding the patient's readiness for transition, 26(53.1%) of responders chose the need for a comprehensive procedure taking into account the opinions of specialists from both services, parents, a psychologist and the results of a patient survey; 18(36.7%) specialists believed that a pediatric rheumatologist can independently determine the patient's readiness for transition, while 4(8.1%) believed that the results of one survey are enough. The main problem of the transfer to the adult service of 19(38.8%) pediatric rheumatologists noted the lack of a collaboration between pediatric and adult rheumatological services and 19(38.8%) noted the complication of access to the rheumatologist in the adult service. Conclusion: In Ukraine, there is no unified approach to the procedure for transition of patients with from pediatric to adult rheumatology service. Among the main difficulties pediatric rheumatologists determined: the lack of a standardized approach for diagnosis formulation, assessing the disease activity, therapeutic tactics of a patient, including biological therapy. The issue of creating structures to coordinate the patient's transition for maintaining their access to treatment, rehabilitation programs and psychological support in Ukraine is extremely relevant. Introduction: Infectious complications are one of the leading causes of adverse outcomes in rheumatic diseases. The early administration of immunosuppressive and biotechnological drugs has significantly changed the course and outcome of diseases, but at the same time, it causes the risk of activation of latently ongoing comorbid infections. In this regard, it is urgent to prevent both the onset and exacerbation of chronic infections, primarily bronchopulmonary and urinary systems, which complicate the course of the underlying disease and require additional treatment costs. Objectives: The goal of the study is to determine the frequency and role of comorbid infections in children with juvenile idiopathic arthritis (JIA). Methods: Material and methods. A total of 147 children with JIA were examined in the rheumatology department of the 4th City Children's Clinical Hospital in Minsk. Enthesitis-associated arthritis was diagnosed in 8 children (5.4%). Systemic onset JIA was detected in 20 children (13.6%). Polyarticular JIA was detected in 48 children (32.7%). Oligoarticular JIA was observed in 71 children (48.3%). The determination of antigen in the biological environments of the body (blood, saliva, urine) was carried out by PCR. A bacteriological study of nasal and pharynx was carried out for the presence of pathogenic flora. The presence of a nasopharyngeal infection (sinusitis, pharyngitis or tonsillitis) was noted in 18 (25.3%) children with oligoarticular JIA, in 10 (20.8%) children with polyarticular JIA, in 6 (30%) children with systemic onset JIA. About 1/3 of the patients answered positively to the question about the relationship of the exacerbation of the disease with an acute respiratory viral infection (35.2% of children with oligoarthricular JIA, 37.5% of children with polyarticular JIA, 35% of children with systemic onset JIA and 25% of children with enthesitisrelated arthritis). Due to the persistence of a high degree of disease activity, 18 patients with JIA were prescribed adalimumab in combination with methotrexate, and 22 patients received tocilizumab. Among children with JIA treated with methotrexate and adalimumab, a respiratory tract infection developed in 22.2%, including severe infection in 5.5% of patients. Among children treated with tocilizumab, a respiratory tract infection developed in 27.3% of patients. Herpetic rashes on the lips, wings of the nose and other parts of the face in most children appeared 2-3 times a year, in some cases up to 7-8 times a year. The most prone to relapse of this viral infection were patients with systemic onset JIA. Urinary tract infection was observed in 13 (18.3%) children with oligoarticular JIA, in 10 (20.8%) children with polyarticular JIA, and in 5 (25%) children with systemic JIA. The incidence of urinary tract infections in children with JIA treated with methotrexate and adalimumab was 5.5% when using methotrexate, 11.1% when using adalimumab. Among children receiving tocilizumab, urinary tract infection was noted in 13.6%. Conclusion: Conclusion The data obtained indicate first of all the importance of infection in the initiation of a number of JIAs and the need for a thorough history taking in children with JIA, which will allow them to identify comorbid infectious diseases that complicate the course of the underlying disease and choose the optimal treatment regimen. Introduction: Juvenile Idiopathic Arthritis (JIA) is a heterogeneous, idiopathic, chronic inflammatory disease of unknown cause which begin before 16 years of age. Vaccination is the most effective way to prevent infectious diseases. In the literature, there is limited data regarding hepatitis B vaccine response in patients with the recent diagnosis of JIA. Objectives: With this study; we aimed to evaluate and compare the presence of antibodies against hepatitis B vaccine at the time of diagosis of JIA with the healthy peers. Methods: Between January 2015 and January 2020, patients referred to three pediatric rheumatology outpatient clinic with the recent diagnosis of JIA were evaluated for the presence of antibody titers against hepatitis B vaccine. A response to the HBV vaccine was accepted as the production of an anti-HBs antibody level ≥ 10 IU/L. The results were compared with the age and sex matched control group consisting of patients without any chronic disease but prepared for surgery, their blood tests anti-HBs ab levels were obtained before surgical operations. Results: The study included 262 patients with JIA and 275 healthy controls. The most common JIA subtypes were 98 (37.4%) oligoarticular followed by 49 (18.7%) enthesitis related arthritis, 33

Introduction: Steroids and disease-modifying anti-rheumatic drugs (DMARDs) are widely used in the treatment of juvenile idiopathic arthritis (JIA). Dermatologic adverse events including psoriasis have been reported in treatment of various inflammatory diseases (1) (2) (3) . However, data regarding the occurrence of dermatologic adverse events in JIA patients are scarce (4) (5) (6) . Objectives: To determine the prevalence of dermatologic adverse events in JIA patients treated with systemic steroids and DMARDs. To investigate an association between drugs and dermatologic adverse events and the association between anti-TNF treatment and psoriasiform lesions.

Methods: Data from the international, observational registry Pharmachild were used. It includes patients with JIA who were treated with NSAIDs, steroids and/or synthetic and biological DMAR Ds. Pharmachild started in 2011 and data on adverse events were collected. Treatment of patients with and without a dermatologic adverse event was compared. The start date of the drug had to be at least one day before the adverse event date and the end date needed to be similar or later than the adverse event date. Results: Among 8841 patients, 439 (5.0%) patients had at least one dermatologic adverse event and in total 492 dermatologic adverse events were reported. Median follow-up time was 3.9 years. Erythema, rash and pruritus occurred in 65 of 492 (13.2%) dermatologic adverse events, other dermatologic adverse events in 46 (9.3%), eczema in 34 (6.9%), hair disorders in 33 (6.7%), and psoriasisform lesions in 30 (6.1%). Several drugs were used more often in patients with such an event than patients without. In five of eight patients with psoriasiform lesions during anti-TNF treatment the lesions disappeared with the discontinuation, reduction or interruption of the dose. Conclusion: A wide range of dermatologic adverse events was reported in this cohort underlining the importance to be aware of such adverse events. Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood with an estimated incidence of 10-20 per 100,000 children. The conventional treatment of JIA includes non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and disease modifying anti-rheumatic drugs (DMARDs) . However, some patients do not experience complete response to conventional first-line options and require second-line therapy with biologic agents(BA). Though the BA provide JIA patients a better disease control, knowledge concerning switching patterns of BA in JIA is scarce. Objectives: To evaluate the clinical responses and safety profiles of patients who required switching from one biological therapy to another for any reason Methods: Children with JIA who received at least one biologic drug were included to the study. Disease activity was evaluated by juvenile arthritis disease activity score 71 (JADAS71). Demographic, clinical and laboratory findings, switching patterns and etiology of switching were recorded. Results: A total of 191 (91 girls, 100 boys) JIA patients receiving BA were included into study. The mean ± SD age of diagnosis was 9.1± 4.9. Biologic drugs were prescribed with a median of 14 (2-66) months after diagnosis. Among 191 patients, 37 (19.3%) patients required to switch BA with a median of 10.5 (1-38) months after first biologic initiation. Tocilizumab (n=19) was the most commonly switched drug. The main reason of switching was inadequate response (n=32). The frequency of biologic switch was higher in patients with extended oJIA and pJIA and also in patients with uveitis. Biologic drugs were switched twice in nine and three times in three patients. When compared the 1 st switchers to 2 nd and 3 rd switchers, there were not any differences in terms of JIA subgroups whereas, 2 nd and 3 rd switchers had higher active joint number and JADAS71 scores at the 6 th month of first biologic drug initiation. Conclusion: Some JIA patients could not achieve remission despite to the first prescribed biologic. Therefore, the biological drug has to be replaced by a second BA in these patients. We demonstrated both patterns and etiologies for switching that may facilitate the management approach of those dealing with JIA.

None declared

Early registration of myocardial disorders in children with Juvenile Idiopathic Arthritis using the 4th generation electrocardiography A. Artsymovych, O. Oshlianska Pediatrics #1, Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine Correspondence: N. Aktay Ayaz Pediatric Rheumatology 2020, 18(Suppl 2):P117 Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and often leads to disabilities due to joint and non-joint lesions, especially cardiovascular (CV) ones. New diagnostic methods may be useful to find these lesions before clinical manifestations or even predict them. Objectives: To evaluate the results of electrocardiography (ECG) of the 4 th generation (signal-averaged ECG obtained by processing several electrocardiographic complexes except atypical) in children with JIA in early diagnosis.

Methods: 46 patients with JIA (60.9% f, 9.69±0.93 y.o., duration of the disease 1.45±0.51 y.) were examined using 4 th generation hardware-software complex ECG "Cardio plus P". Disease course and activity (JADAS27) were rated. In addition to standard laboratory&instrumental markers the level of immunoglobulins (IG), IL6, TNFα in the serum of patients was determined by ELISA, a correlation analysis of clinical and laboratory parameters was made. Results: There were no instrumental (by standard ECG and cardiac ultrasound (US)) and laboratory signs of CVS injury among observed group, 50% JIA patients had unfavorable course of the disease (UCD), 10.5% had hepatosplenomegalia, JADAS27 9.7±2.04. Serum level of IL6 was 5.19±2.21 pg/ml, ALT, AST, LDG, cholesterol were normal. Using the 4 th generation ECG showed the presence of significant changes in the myocardium in the majority of patients. Following indicators of heart rhythm variability and myocardium state evaluation in patients with JIA were deviated most often: stress index was 245.96±44.33s -2 (69.56% cases), condition of regulation reserves 61.65±2.77 (86.96%), overall heart rate variability 2279.74±406.36 (65.21%), immediate control of condition of myocardium 51.56±3.91 (95.65%), its reserve 61.04±1.82 (95.65%), Twave/R-wave ratio lead I was 0.67±0.11 (80%), amplitude-areas index lead I-III from 48.65±2.64 to 61,17±4,33 (up to 95.65%), Macruz index 1.39±0.76 (94%), complex indicator of condition of myocardium 56.30±2.57 (95.65%) complex indicator of functional state 66.13±2.41 (65.2%). Previously, the best combination of ECG indicators to evaluate activity was found using CART algorithm: integral indicator of form ST-T lead II (55.41±5.09), T wave symmetry based on derivatives ratio and on areas of triangles (1.78±0.71, deviation in 100%) & T amplitude lead II (112.23±71.96 uV, in 86.36%), heart ratio, alpha QRS angle in the frontal plane. Some correlations between these parameters and other data were found: immediate control of the regulation with serum IL6 (r=-0.73, p<0.05), and with UCD (r=-0.53, p<0.05); heart ratio with ESR (r=0.53, p<0.05), hepatosplenomegalia (r=0.57, p<0.05), cholesterol serum level (r=0.58, p<0.05); integral indicator of form ST-T with serum IgG (r=-0.55), IgA (r=-0.55); T wave symmetry based on derivatives ratio had correlations with metabolic myocardial changes (r=-0.68, p>0.1), IgA (r=0.85, p>0.1), DMARD replacement (r=0.51, p>0.1); T wave symmetry based on areas of triangles with hepatosplenomegalia (r=0.67, p<0.05), US reactive changes of parenchymal organs (r=-0.96, p>0.1), IgM, IgA (r=0.74 and 0.98), serum TNFα (r=-0.59, p>0.1); T amplitude, lead II with IgG total (r=-0.72, p>0.1), TNFα (r=0.99, p>0.1); alphaQRS angle with ALT (r=-0.72, p<0.05), cholesterol (r=0.49, p<0.05), NSAIDs (r=0.82, p<0.05); complex indicator of condition of myocardium with cholesterol (r=-0.62, p<0.05). Conclusion: With the help of "Cardio-Plus P" the changes in CVS and latent heart rhythm disorders in children with JIA can be found more frequently by evaluating complex indicators than using standard 12channel ECG. Most of registered changes had no other clinical, laboratory or instrumental signs, in accordance with the obtained correlations they may be due to immune inflammation.

None declared P118 A family history of autoimmunity is a risk factor for celiac disease and Juvenile Idiopathic Arthritis co-occurrence R. Naddei, S. Di Gennaro, R. Troncone, V. Discepolo, M. Alessio Mother and Child Department, University of Naples Federico II, Naples, Italy Correspondence: R. Naddei Pediatric Rheumatology 2020, 18(Suppl 2):P118 Introduction: Autoimmune disorders share common predisposing factors and immune pathogenic mechanisms. The prevalence of celiac disease (CD) has been reported to be consistently higher in patients with juvenile idiopathic arthritis (JIA) in comparison to the general population, however not negligible variations in the prevalence have been observed in distinct geographic locations. functioning (p <.001), social functioning (p=.005), and school functioning (p=.001).Regarding PedsQL arthritis module, patients with EAM had also significantly lower scores than did patients without EAM on the domains of pain and hurt (p<.001), daily activities (p=.008) and worry (p= .001). Conclusion: Conclusion EAM are prevalent among JIA patients and have a negative impact on their HRQoL. So, early identification and treatment are highly recommended.

Association of the TRAF1-C5 locus on chromosome 9 with juvenile idiopathic arthritis

TRAF1-C5 as a Risk Locus for Rheumatoid Arthritis -A Genomewide Study

The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease

Highthroughput identification of noncoding functional SNPs via type IIS enzyme restriction

Novartis O047 Patient-reported adverse events and treatment adherence in JIA: analysis of two large international cohorts A

Aghia Sophia Children's Hospital

Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

Speaker Bureau of: Novartis and Sobi, I. Penades: None declared, B. Flato: None declared, A. Boteanu: None declared, H.-I. Huppertz: None declared, J. Jaller: None declared, D. Graham Shareholder of: Pfizer, Employee of: Pfizer, C. Borlenghi Shareholder of: Pfizer, Employee of: Pfizer, B. Vlahos Shareholder of: Pfizer, Employee of: Pfizer, C. Zang Shareholder of: Pfizer, Employee of: Pfizer

This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties. The registry is funded by Bristol-Myers Squibb Company

None declared, A. Zeft Shareholder of: Merck, Opko Health, Teva, G. Horneff Consultant for: AbbVie, Novartis, Pfizer

Juvenile idiopathic arthritis. The Lancet

Chief Scientist Office, Health and Care Research Wales, Public Health Agency. National Standards for Public Involvement in Research

Genetics Home Reference website

Efficacy of anti-IL-1 treatment in Majeed syndrome

Dramatic response of familial majeed syndrome to interleukin-1 antagonist therapy: Case report

Chronic recurrent multifocal osteomyelitis: a new clinical-radiological syndrome

Chronic Recurrent Multifocal Osteomyelitis (CRMO): Presentation, Pathogenesis, and Treatment

The multifaceted presentation of chronic recurrent multifocal References Haytoglu Z, Gundeslioglu OO. Mediterranean fever gene variants and colchicine therapy in periodic fever, aphthous stomatitis pharyngitis, adenitis syndrome in a Mediterranean region

MEFV Variants in Patients with PFAPA Syndrome in Japan

Clinical evaluation of R202Q alteration of MEFV genes in Turkish children

Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p

Familial chilblain lupus-a monogenic form of cutaneous lupus erythematosus due to a heterozygous mutation in TREX1

Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production

On the alert for cytokine storm: Immunopathology in COVID-19

Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-COV-2): antiinflammatory strategies

Coronaviruses and immunosuppressed patients. The facts during the third epidemic

Chronic non bacterial osteitis-a multicentre study

Disease burden and social impact of pediatric chronic nonbacterial osteomyelitis from the patient and family perspective

Akikusa Royal Children's Hospital

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review

Immunologic, and Molecular Spectrum of Patients with LPS-Responsive Beige-Like Anchor Protein Deficiency: A Systematic Review

Gain-of-Function Mutations in STAT1: A Recently Defined Cause for Chronic Mucocutaneous Candidiasis Disease Mimicking Combined Immunodeficiencies Sanem Eren Akarcan, 1 Ezgi Ulusoy Severcan, 1 Neslihan Edeer Karaca, 1 Esra Isik

The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis

ALPS-like syndrome in patients with undefined autoinflammatory or autoimmune disorders: a multivariate analysis approach in a pediatric rheumatology tertiary center

Istituto Giannina Gaslini; 2 DINOGMI, University of Genova; 3 Center for Autoinflammatory diseases and Immunodeficiencies

Laboratory of Genetics and Genomics of Rare Diseases

Berce Pediatric clinic

The autoimmune burden in juvenile idiopathic arthritis

Coexistence of endocrinopathies in children with rheumatic diseases

Autoimmune endocrine disorders and coeliac disease in children and adolescents with juvenile idiopathic arthritis and rheumatic fever

The new Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry: design, rationale, and characteristics of patients enrolled in the first 12 months [Electronic resource Pediatric Rheumatology

Update on malignancies in children with juvenile idiopathic arthritis in the German BIKER Registry

Clinical management of psoriatic arthritis. The Lancet

None declared P096 Correlation between serum calprotectin (S100A8/A9) levels and disease activity status in patients with Juvenile Idiopathic Arthritis M

Pini-CTO; 2 Casa di cura

Pediatric Rheumatology, Meyer Children University Hospital, Florence; 5 Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano; 6 Department of Clinical Sciences and Community Health

ESR mm/h, median, (range)

Macrophages -silent enemies in juvenile idiopathic arthritis

Academy of medicine

Correlation of mean platelet volume, neutrophil-to-lymphocyte ratio, and disease activity in children with juvenile ıdiopathic arthritis

Department of Pediatrics and Pediatric Rheumatology service, Ruth Children's Hospital, Rambam Health Care Campus; 2 Department of pediatric B, Ruth Children's Hospital Rambam health care campus

Tel-Hashomer; 6 Department of Pediatrics A, Edmond and Lily Safra Children's Hospital, Sackler Faculty of Medicine

a selective T-cell co-stimulation modulator, has been demonstrated to be safe and effective in two Phase III studies. 1,2 The ongoing Phase IV Pediatric Rheumatology Collaborative Study Group and Paediatric Rheumatology International Trial Organization (PRINTO-PRCSG) registry aims to provide monitoring data from a real-world setting regarding longitudinal effectiveness of ABA in JIA. Objectives: To assess effectiveness of ABA in JIA categories in patients (pts) who enrolled ≤1 month after starting treatment

3%); polyarticular RF+

Introduction: Approximately 5-10% of children with juvenile idiopathic arthritis have rheumatoid factor-positive (RF+) arthritis (RF+ JIA), which requires earlier administration of more aggressive therapy due to rapid progression. Objectives: To analyze epidemiological, clinical characteristics and treatment of patients (pts) with RF+ JIA in the single center

6% -lymphadenopathy, 4.3% -rheumatoid lung disease, 2.9% -rheumatoid nodules, 1.4% -pericarditis. Secondary Sjögren's syndrome was diagnosed in 15

DMARDs (methotrexate (MTX) alone -78.3%, 2 DMARDs -14.5%, 3 DMARDs consecutive -7.2%), biologics (B) -94.2% of pts. B was started during the 1 st year of disease in 78

The reasons for substitution therapy were serious adverse effects, subsequent loss of effect. The frequency of ACCP+ was not statistically different in groups with the effective use of only 1 B and, if necessary, replacement. In the presence of systemic manifestations, preference was given to TCZ or RTM, with secondary Sjogren's syndrome -RTM or ABA. Conclusion: RF+ JIA is rare subtype of JIA, which characterized by high activity at onset. Most pts required the early appointment of aggressive therapy in connection with the rapid progression of the erosive process. The presence of systemic manifestations/secondary Sjogren's syndrome influence on choice of therapy. An analysis of the prescribed therapy did not reveal the effect of ACCP+ on preferred choice B or frequency of replacement B. Disclosure of Interest None declared (12.5%) polyarticular, 11 (4.1%) systemic, 6 (2.2%) psoriatic arthritis and 4 (1.5%)unclassified. Of the cohort, 262 patients diagnosed with JIA 135 were boys and 127 were girls

Methods: retrospective analysis of demographic, clinical and laboratory features and body mass index (BMI) collected at the start of TNFi treatment in patients with oligoarticular and rheumatoid factor (RF)-negative polyarticular JIA. Patients were divided into obese and non-obese; demographic, clinical and disease features were compared in the two groups. The distribution of obese, overweight, healthy-weight and underweight patients according to the achievement of CID at 6 months was investigated. Results: 234 patients with JIA (39% RF-negative polyarthritis, 25% extended oligoarthritis, 36% persistent oligoarthritis) were enrolled in the study. Obesity (BMI ≥95 th percentile for age and gender) was present in 31 patients (13.2%). Obese patients compared to non-obese patients, had an older age at disease onset (p=0.020), lower frequency of antinuclear-antibody positivity (p=0.043), a higher number of active joints at baseline (p=0.0048) and higher C-reactive protein at baseline (p=0.043). Obese JIA patients achieved clinical inactive disease (CID) at 6 months with a lower frequency compared to non-obese patients (p= 0.005)

Conclusion: obesity negatively affects response to TNFi in oligo-and RF-negative polyarticular JIA, independently from other diseaseassociated variables. Disclosure of Interest None declared P108 Use of telemedicine in pediatric rheumatology in one

Introduction: Arthritis is one of the commonest presentations of rheumatological illnesses in children.It is often accompanied by fever,rash,uveitis,hepatosplenomegaly,lymphadenopathy and serositis.Growing up with arthritis is often challenging. With optimal care and treatment,most children with arthritis live life to full potential. Objectives: To present clinical,laboratory characterstics and treatment in patients with Childhood -Arthritis followed up in Pediatric -Rheumatology-Clinic(PRC) at DR .Rajendra Prasad Government Medical College

Cyclophosphamide was started in 1 patient with SLE arthritis and 1 patient with systemic-JIA is on Tocilizumab.16(36.36%) patients are on regular follow-up with mean duration of 93.92 person-months. Conclusion: We highlighted various clinical and labortary characterstics in children with arthritis.Oligoarthritis-JIA is the commonest subtype in our study.Unusual causes like CACP and SLE arthritis were seen among study population.Childhood musculoskeltal pain is still a dilemma among pediatricians

Paediatric Rheumatology INternational Trials Organisation, CC at IRCCS Istituto Giannina Gaslini

Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: An analytical and comprehensive overview

Characteristics of skin lesions associated with anti-tumor necrosis factor therapy in patients with inflammatory bowel disease: A cohort study

Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study

Tumor necrosis factor-α inhibitor-induced psoriasis in juvenile idiopathic arthritis patients

Adalimumab-induced cutaneous lupus erythematosus in a 16-year-old girl with juvenile idiopathic arthritis

Biological therapies for the treatment of juvenile idiopathic arthritis: Lessons from the adult and pediatric experiences

We figured out that half of the patients were detected with vitamin D deficiency (40 cases (48,19 ± 5,17) %), that exceeded frequency of vitamin D insufficiency (31 cases (37,35 ± 4,68) %, p> 0,05) and observed more often than number of them with normal amount (12 cases (14,45 ± 4,21) %, p< 0,01)

Mannouba, Tunisia Correspondence: H. Ferjani Pediatric Rheumatology

Juvenile idiopathic arthritis-associated uveitis

i094 Juvenile idiopathic arthritis and extra articular manifestations: current diagnostic criteria and management

Mean age was 6,2 ± 4,2 years. Most of the patients had oligoarthritis by the time of the diagnosis (n = 299, 53%), 17% (n = 107) had poliarthritis (9% with positive rheumatoid factor) and 9% (n = 51) had systemic arthritis. A total of 404 (72%) patients had only one joint affected at the presentation of JIA. Lower limbs joints were more frequently involved (n = 334, 83%), followed by upper limbs joints (n = 42, 10%) and axial joints (n = 28, 7%)

Conclusion: This study emphasizes the frequency of the first joint involvement in different JIA subtypes with only one joint affected at presentation. Lower limb's joints are the most affected ones, specially knee and ankle. However any joint can be the first one involved in JIA. Hip's involvement is common in pediatric rheumatology, although among rheumatological disorders, JIA is a less probable diagnosis if hip is the first joint affected. Cervical spine's prolonged involvement should raise the diagnosis of JIA ab initio. Disclosure of Interest None declared Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. About this supplement These abstracts have been published as part of Pediatric Rheumatology

We thank our patient and his family Trial registration identifying number: According to the legal status in our country, ethics committee approval is not required for case reports. It is adequate to obtain informed patient consent. Introduction: Children with rheumatic diseases are considered as a population at risk of severe influenza disease and are therefore targeted for vaccination.Nonetheless, influenza vaccine coverage among JIA patients is still unclear. Objectives: We investigated knowledge,attitudes& practices about influenza vaccine uptake among caregivers of children with JIA in Greece,aiming to depict the current situation and identify barriers and determinants to improve influenza vaccination rate. Methods: This was a dual-centre cross-sectional study that took place across Pediatric Rheumatology Units in Athens,Greece.A detailed questionnaire about knowledge,practices and attitudes regarding influenza vaccination was disseminated among JIA caregivers.Chi-Results: We observed 18 patients with JPsA aged from 2 to 13 years, who were initiated by etanercept. The clinical and demographic characteristics are presented in Table  1 .

In patients with JPsA who received a combination of etanercept with methotrexate, at month 6 ACRpedi NoResp/30/50/70 was 5.56/94.4/ 55.56/5.56%. ACRpedi 90 and ACRpedi 100 at month 6 were not achieved. At month 12 -ACRpedi 30/50/70 was 94.4/88.9/61.1%. ACRpedi 90 and ACRpedi 100 were 11.1% and 5.56%, respectively. Drug-induced remission at month 18 was 11.1%. At month 18 -ACRpedi 30/50/70 was 77.8/77.8/72.2%. ACRpedi 90 and ACRpedi 100 were 33.3% and 11.1%, respectively. Drug-induced remission at month 18 was 33,3%. The BSA at months 6, 12, and 18 was 4.9 (1.0-7.0)%, 1.5 (0.75-3.15)%, 0.7 (0.5-1.0)%, respectively.The PASI 75, PASI 90 and PASI 100 at months 6 were 38.5/13.4/7.7%, at month 12 -76.9/53.8/15.4%, and at month 18 -69.2/61.5/23.1%, respectively. Drug-induced remission of psoriasis at month 18 was 23.1%. No serious adverse events occurred during the study. Conclusion: our clinical study showed the effectiveness and safety of etanercept in JPsA patients with active articular manifestations and psoriatic lesions.

The impact of covid 19 on a spanish pediatric rheumatology unit: patient-reported outcomes (pro) utility J. Arroyo Palomo, P. Morán Álvarez, Á. Andreu, L. Villalobos Sánchez, A. Boteanu Hospital Ramón y Cajal, Madrid, Spain Correspondence: J. Arroyo Palomo Pediatric Rheumatology 2020, 18(Suppl 2):P060 Introduction: COVID-19 outcomes remain poorly understood in children with rheumatic diseases. Objectives: To describe the impact of COVID-19 in a cohort of pediatric patients with rheumatic diseases attended in a Spanish tertiary hospital; assessing the possible effects on the clinical course, functional ability using Juvenile Arthritis Functionality Scale (JAFS) and health-related quality of life (HRQoL), through patientreported outcomes (PRO). Methods: A cross-sectional study was conducted. We performed an e-health record review and an e-survey. We collected:Juvenil Arthritis Multidimensional Assessment Report (JAMAR)1, questions related to activity from other autoimmune or autoinflammatory diseases (AIDs), JAFS, HRQoL tests and COVID-19 aspects. We also included questions about medical visits and the ease of contacting with the rheumatologist during the lockdown. Results: 146 patients received the survey, of which 94 answered, 50 of them did not answer back in time, and 2 refused to participate. Mean age was 14 years. Of the 94 patients who answered the survey, the diagnoses were: 45 (47.9%) non-systemic JIA; 10 (10.6%) childhood-onset Systemic Eritematous Lupus (cSLE); 10 (10.6%) AIDs, including HIDS and OCMR; 8 (8.5%) systemic JIA (sJIA); 4 (4.3%) Behçet disease; 4 (4.3%) vasculitis; 2 (2.5%) Juvenile Dermatomyositis; and 1 (1%) Juvenile Scleroderma. 45.7% of them received biological disease modifying anti-rheumatic drugs (bDMARDs): Adalimumab (ADA) 16%, Tocilizumab (TCZ) 9.6%, Etanercept 7.4% and Belimumab 3.2%, among others. 36.26% of patients were treated with methotrexate and 10,5% with hidroxychloroquine. Related to SARS-COV2 infection, 12 patients (12.8%) reported being under COVID-19 suspicion. 5 patients underwent PCR, of which 2 of them were positive. Both patients also suffered from pneumonia. One of the children, treated with Canakinumab due to sJIA, was admitted to the Intensive Care Unit and the other one, diagnosed with cSLE, did not required hospitalization. No deaths were registered.Introduction: In cohort studies and transition research there has been little focus on the rate of non-referral of patients with Juvenile Idiopathic Arthritis (JIA) for ongoing adult care and the reasons why this occurs. Objectives: To determine the characteristics of JIA patients at a tertiary paediatric rheumatology centre not referred for adult care and the frequency of and reasons for non-referral. Methods: JIA patients in the Royal Children's Hospital (RCH) rheumatology database who turned 18 y.o. between 2012-18 were identified. The medical record of each patient was examined and those who had not been referred for adult care were entered into the study. Data regarding diagnosis, treating clinician and date of first and last RCH visit was collected. Note was made of any documented plan where the last RCH visit was intentionally the final visit for formal rheumatologic care and of subsequent events where it was unintentional. Results: 177 patients were identified. 63 (~35%) were not referred for adult care. Of these, 24 (38.1%) had been in long term remission and were discharged back to the GP. The commonest JIA subtypes in this group were persistent oligoarticular (45.8%) and systemic JIA (25%). The remaining 39 (61.9%) patients were not referred as they had been lost to clinic follow-up at a mean age of 15.1yr. Of this group, 21 (53.8%) had been in long-term remission. 16 (41%) were lost to follow-up despite having recently active disease or being on clinic-prescribed medication, most frequently in the context of multiple missed and cancelled clinic appointments. Conclusion: At our centre a significant minority of patients with JIA are not referred for adult care. In many cases this is due to patients being in long-term remission and occurs as either a deliberate decision by the treating rheumatologist or their failure to attend clinic appointments and eventual loss to follow-up. A substantial number of patients are lost to follow-up despite having active disease and/or being on clinic-prescribed medications. The outcome of these patients is unknown. Results: 178 patients were identified. 64% were referred for adult care. Mean follow-up prior to transition was 7.4 years. The commonest subtypes referred were seronegative polyarticular (30.7%) and oligoarticular JIA (19.3%). 65.8% were referred to public hospital rheumatology services with the remainder referred to private rheumatologists. Confirmation of transition occurred in 62.3% with correspondence received from adult services in 49.1%. There was no difference in rate of return correspondence from public versus private providers (47.9 vs. 53.8%, p=0.69). 37.7% had an unknown outcome after referral to adult care as a result of no correspondence from the adult service and no follow-up at the RCH. The use of 'backstop' appointmentsfinal review at RCH several months after the estimated date of adult reviewwas more likely in those with confirmed transition (66% vs. 30%, p=0.0002). Conclusion: Lack of confirmation of transition for JIA patients moving to adult care is common and has the potential for suboptimal outcomes in substantial numbers of patients during this critical period. Strategies to improve communication with the referring centre following initial assessments with adult services and vigilance regarding potential loss to follow-up during this time by paediatric centres would minimise this risk. densitometry) were studied. The blood lipid spectrum of patients (total cholesterol, triglycerides, HDL, LDL, VLDL-cholesterol, atherogenic coefficient) was investigated. Results: In half of children and adolescents with SLE (52.83%), potentially irreversible organ injuries were revealed. During the initial examination lesions of the nervous system dominate (20.75%), lung injuries were next (13.21% of patients), which were represented mainly by pleural fibrosis. Visual organ damage (11.32%) in the form of cataracts was registered with a slightly lower frequency. On repeated examination the frequency of irreversible changes has increased (68,92%), wherein eyes lesions (18,87%), stunted growth (18,87 %), lungs changes (16,98 %) are added, that is a feature characteristic of juvenile debut SLE. Growth retardation (9,43%)was characteristic of the age of SLE onset up to 8 years. Menstrual disorders were observed in 13.04%, mainly at the onset of SLE at 8-12 years. Presence of atherogenic dyslipoproteinemia (22.64%), insulin resistance (13.21%), osteopenia (22.64%) can be considered as precursors of damage (atherosclerosis, diabetes mellitus, osteoporosis) in the further course of the disease. The accumulation of irreversible organ damage occurs with an increase in the duration of the disease (r = 0,355; р < 0,001) and is associated with persistent activity of the lupus process (r = 0,515; р < 0,001) and long-term cytostatic therapy (r = 0,3; р < 0,01).

The results of study indicate the need for prospective monitoring of the state of organs and systems for the formation of persistent damage in order to timely correction of therapy. Introduction: Adolescence and puberty are associated with significant changes which are initiated and mediated by sex hormones. There is evidence that sex hormones also influence the development and regulation of the immune system, and with it auto-immune rheumatic diseases (ARDs). A clear sex bias exists in the incidence of ARDs, with females being at significantly higher risk. However, there is a limited understanding of the physiological mechanisms for sex-specific immune modulation. Previous research has observed a relationship between puberty and ARD onset, suggesting that sex hormone changes at puberty play an immunomodulatory role in triggering ARD onset and development. In addition to triggering autoimmunity, sex hormones can influence various outcomes of ARDs, and testosterone is thought to exert a protective effect. No previous systematic reviews have addressed the impact of puberty on disease outcome measures in ARDs, or the impact of ARDs on puberty-related outcomes. Understanding the interplay between the neuroendocrine and immune systems can provide valuable insights into the immune-pathogenesis of the peri-pubertal onset of ARDs, and help to improve the clinical approach to treatment of these patients in the long term. Objectives: To elucidate the bidirectional relationship between puberty and autoimmune rheumatic diseases (ARDs). Methods: Studies published in English until October 2019 were identified using a systematic search on bibliographic databases and manual checking of reference lists. Information was extracted on study design, sample size, demographics, puberty outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS) for non-randomised trials. Results: 14 non-randomised studies reporting on the impact of puberty on ARD outcomes (n=7), ARD impact on puberty-related outcomes (n=6), or both (n=1) have been identified. One study focused on patients with juvenile idiopathic arthritis (JIA)-associated uveitis, all others investigated patients with juvenile systemic lupus erythematosus (JSLE) or healthy controls who developed adult-onset SLE. Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4-9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment. Conclusion: It is clear that a bidirectional relationship exists between puberty and ARDs. More and better research is required to elucidate this relationship. Therefore, we propose a comprehensive set of clinical assessments of patients with ARDs, to be recorded at hospital visits. Increased awareness of the relationship between puberty and ARDs, and subsequent monitoring of the impact of disease and treatment on the normal development of young people with ARDs, can benefit clinicians, patients and their families. Moreover, it will facilitate future research into new strategies of minimising the negative impact of ARD on pubertal development as well as managing ARD flares from a broader perspective, which should take into account pubertyrelated outcome measures, ultimately shedding light on this complex but important relationship. 

Methods: Scoping review using the Newcastle University Library search tool and Google Scholar, and consulting NICE guidance and pathways. Search terms included dyspraxia, paediatric MSK assessment, screening tools, balance, rheumatology, assessment tools for MD, MPS, JIA. Studies cited within relevant articles uncovered through searches were also checked. The search was conducted between 1 st October and 1 st December 2018, publication date limited to post 1998, and all languages included unless translation was unavailable. Results: 32 journal articles were deemed appropriate, describing specific assessment or screening tools in the context of diagnosis of our target conditions. Within DCD, motor co-ordination test batteries are part of specialist assessment, but are regarded as too lengthy for the purpose of screening; a questionnaire may be useful as a firststep diagnostic tool, along with an assessment of static balance (found to be significantly worse in children with DCD). In paediatric rheumatology, pGALS is the only validated screening tool to discern normal from abnormal joints. Other tools to assess health and wellbeing, disability and function are validated in the context of established disease only. For neuromuscular conditions the North Star Ambulatory Assessment is valid, reliable and practical as a functional assessment, and includes activities that are necessary to remain functionally ambulant. With regards to MPS, searches did not reveal specific MSK tests, but evidence suggests that skeletal malformations and joint problems were the most frequently presenting signs. pGALS performs well to identify abnormal joints with restriction within an MPS group. Conclusion: This review supports the development of 'pGALSplus' to facilitate identification and assessment of CYP with potentially serious MSK disease. pGALSplus will be targeted at community-based clinicians and likely include physical examination, questionnaire(s) and appropriate adjuncts. Our group is currently developing pGALSplus, aimed at multi-professionals to describe feasibility and acceptability with educational and training resources.

None declared

Explaining Juvenile Idiopathic Arthritis (JIA) and its treatment to paediatric patients using pictorial education materials and easy-toread texts C. Reiser 1 , N. A. Zeltner 2,3,4 , B. Rettenbacher 5 , P. Introduction: In order to reach adherence to therapy, understanding of the disease and the treatment options are of utmost importance. Standardised validated pictorial education materials and texts in an easy-to-read language are an important tool to improve patients' knowledge of JIA. Objectives: To develop specially designed graphic depictions complemented by standardised, easy-to-read textual information materials supporting a comprehensible informative medical dialogue with paediatric patients starting from school-age. The information material was tested in order to validate its comprehensibility. Methods: The graphic depictions were designed by a graphic artist after detailed introduction to the topic by pediatric rheumatologists. Informative texts were written by pediatric rheumatologists and consecutively transformed to easy-to-read language to improve comprehensibility.The materials are designed as a modular system allowing physicians to select individually the information needed for each specific patient. The materials were tested for comprehensibility in healthy children and adolescents (controls) and in children and adolescents affected by JIA (patients). A standardised presentation to the probands was given by a student of psychology. Gain of knowledge about the illustrated items was quantified using a short questionnaire before and after the training session. Results: 38 patients and 45 unaffected healthy individuals were tested in a standardised setting. In both groups gain of knowledge was significant (patients: M = 2.58, SD = 2.13, t(37) = 7.48, p<0.001, controls: M = 3.53, SD = 2.14, t(44) = 11.08, p <0.001). Conclusion: Explanation of rheumatic diseases and therapeutic strategies is a time-consuming part of our daily practise. To avoid incomprehensible explanations in medical jargon, graphics with accompanied easy-to-read texts were created. Standardised presentation of the newly created materials resulted in a highly significant improvement of disease knowledge in patients and controls. Our created graphics allow a fast instruction to the disease and its management that can also be performed by trained medical staff. Introduction: About half of the children with rheumatic diseases need ongoing medical care during adolescence and adulthood. A good transition into adult rheumatology is essential. A structured transition process has therefore been recommended by the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology European Society (PReS). However, these recommendations are not yet widely implemented. Objectives: To assess the current practice of transitional care (TC) in Switzerland in relation to EULAR/PRES standards and to describe gaps and challenges in following the recommendations. Methods: All ten pediatric Swiss rheumatology clinics offering transition service to adult care agreed to participate. In each clinic the responsible pediatric (n= 10) and adult (n= 10) rheumatologist were separately interviewed using a structured manual addressing EULAR/PRES transitional care standards. Results: The median number of patients in follow-up in pediatric centers ranged from 50 to 363 (median 140). Fifteen of twenty rheumatologists reported to have a written procedure for TC. Three pediatric and two adult rheumatologists used a checklist. The start of TC varied between the ages of eleven and twenty. Adherence to medication and appointments followed by disease activity and age were rated as important for initiating TC. Topics discussed most often by rheumatologists during consultations were vocational issues (n= 17), effects of alcohol, smoking on disease/treatment (n= 16) medication (n= 16) and the impact of disease/treatment on daily life, sexuality, fertility and pregnancy (n= 15). All pediatric teams performed consultations with the patients alone whereas only two performed consultations with the parents alone. Median clinical experience of female two concurrent genetic events are required: a mutation at the specific disease gene and an inactivation of the corresponding normal allele. Finally, since there appeared to be a small link between twins and x-linked diseases then it could potentially be said that (as with many other reported cases of x-linked diseases), that the process responsible for monozygotic twinning may play a part to the emergence of LNS in females (potentially by triggering skewed X-inactivation). Depending on the duration of the JIA, there was no significant difference in the mean JADI-A score. Mean JADI-E score showed a clear tendency to its gaining with increasing of the disease duration (p < 0.05). It was found that the mean score JADI-E was independent on the type of baseline therapy and was not significantly different in patients receiving only methotrexate compared to those, who treated with methotrexate in combination with IBT. Mean JADI-A score was significantly higher in patients treated with methotrexate alone than in children treated with combination therapy (p < 0.05).

Conclusion: The accumulation of irreversible persistent changes in patients with JIA does not depend on sex, disease activity, positivity in RF and ANA. With the increase in the duration of the disease, progressive accumulation of joint lesions does not occur. Therapy with methotrexate in combination with IBT significantly improves the average JADI-A score. Extra-articular changes accumulation has a clear dependence on the duration of the disease, regardless of the type of baseline therapy. Standard radiographs showed minimal to moderate pinching in 9 cases and destructive hip disease in 5 cases. All patients were initially treated with a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and rehabilitation. Disease modifying anti-rheumatic drugs were initiated in 11 patients (salazopyrine in 2 cases and methotrexate in 9 cases). Hip joint injection of steroid has been indicated in 11 cases with improvement in clinical symptoms in 9 cases. Total hip replacement (THR) was necessary in 2 cases. The average duration of progression of JIA at the time of THR was 9 years and 6 months. No patient had any post-surgical complications. Conclusion: Hip involvement is common and estimated to occur in approximately 35-63% of children with JIA. It is a predictor of disease severity because of the disability it can cause. Hence the need for early diagnosis and management to delay the progression of the disease and the use of THR. Introduction: Depression is a known comorbidity in juvenile idiopathic arthritis (JIA) and has an impact on quality of life and therapy outcome. In clinical routine, depression is probably underdetected.

Objectives: Prevalence of depressive symptoms, manifest depression and suicidal ideation was evaluated and associations with patient characteristics, disease activity and treatment were analysed in a cross sectional study.Methods: Patients aged 10-18 years from a pediatric rheumatology centre were screened with the BDI-FS. An abnormal score of ≥4 points (out of 21 ) led to psychologically evaluation. Results: 148 JIA patients (72% female) were evaluated. 19 (13%) had an abnormal BDI-FS score.. Frequent statements were sadness (n=31, 21%), lack of joy (n=43, 29%), hopelessness (n=23, 16%) and self-blame (n= 26, 18%). Suicidal ideation was present in 9 (6%). 4 (3%) patients had a previously diagnosed depression, 10 (7%) were newly diagnosed with depression. Patients with an increased BDI FS score more frequently presented with a diagnosis in JIA subcategories RF-negative and -positive polyarthritis and psoriatic arthritis but rarely with extended oligoarthritis or enthesitis related arthritis. There was an association between an increased BDI FS score and pain experienced by patients in both the patient reported pain visual analogue scale (VAS) (p= 0.002) and in the number of painful joints (p=0.017). Patients with a BDI-FS ≥4 also had significantly higher scores concerning disease activity as measured by physician and patient global assessment of disease activity and by the JADAS 10. A significantly higher percentage of patients with a normal BDI FS were in remission and had minimal disease activity. Patients with an abnormal BDI-FS score also had a significantly higher disability index as measured by the CHAQ (p=0). More patients with a BDI-FS ≥4 were taking NSAR, steroids, biologicals or a combination of biologicals and DMARDs as well as an overall higher number of different drugs. Two were diagnosed solely based on positive serology that normalized after the beginning of the glutenfree diet (GFD). One patient received a diagnosis of Potential CD (positive serology in the absence of villous atrophy). All of them started a GFD. Only in one patient CD onset preceded JIA, that occurred despite the GFD. The remaining seven developed JIA first. Most of those (5/7, 71,4%) were asymptomatic and diagnosis followed the screening for CD that all JIA patients undergo in our clinic. In our cohort the prevalence of CD was higher than that reported in the general population (2.4% vs 1%, p<0.05). No differences were observed in regard to JIA subtype and ongoing treatment for JIA (p=0.59) between patients with or without CD. Notably, 87.5% patients with JIA and CD had at least one family relative with an autoimmune disorder compared to 45.8% of those without CD (p<0.05). In none of those patients GFD promoted clinical improvement, nor prevented JIA relapse. Indeed, five patients required a new disease modifying antirheumatic drug (DMARD). Finally, 87.5% patients with JIA and CD required both a conventional DMARD and a biological DMARD (bDMARD) over time compared to 36.8% (118/ 321) of those without CD (p=0.006).Conclusion: A higher prevalence of CD in patients with JIA was found in our wide southern Italian cohort in comparison to the general population. Notably, a positive family history of autoimmunity was found to be associated with a higher co-occurrence of JIA and CD, suggesting that common predisposing factors shared across autoimmune disorders may contribute to both diseases. Furthermore, our patients with JIA and CD more frequently required a bDMARD than patients without CD, suggesting that JIA course can be more aggressive in children with CD. Our findings support the need for an active screening for CD in patients with JIA, especially in those with a positive family history of autoimmunity. This is clinically relevant since the clinical course seems to be more aggressive in these patients and require a step-up therapy.