key: cord-259033-op94wuy4 authors: Wendling, Daniel; Verhoeven, Frank; Chouk, Mickael; Prati, Clément title: Can SARS-CoV-2 trigger reactive arthritis? date: 2020-10-27 journal: Joint Bone Spine DOI: 10.1016/j.jbspin.2020.105086 sha: doc_id: 259033 cord_uid: op94wuy4 nan The SARS-CoV-2 virus-induced COVID-19 (corona virus disease) pandemic has had a global societal impact and repercussions on rheumatological populations at different levels. The fear of infection of patients with rheumatological disease, due to rheumatological disease itself but also and above all due to the possible use of immunomodulating treatments, was at the center of the discussions and raised the question of the appropriateness of maintaining this treatment in the absence of signs of infection [1] . National and international recommendations have clearly positioned themselves in favor of maintaining rheumatological treatment in the absence of symptoms or evidence of infection with SARS-CoV-2 [1] [2] [3] . Slow-acting, biologic or targeted synthetic (JAK inhibitors) disease modifying anti rheumatic drugs (DMARDs) could be beneficial and have even been evaluated in the context of some forms of COVID-19 involving a "cytokine storm" [4, 5] . On the other hand, the pandemic and confinement have had an impact on patient monitoring and adherence to treatment, and potentially indirectly on overall disease activity. For example, in the context of spondyloarthritis, an analysis of a questionnaire sent to patients who are members of a patient association in France showed that out of more than 600 responses, more than 60% of patients reported a worsening of their disease during the confinement period, significantly associated with a change in treatment [6] . This modification mainly concerned NSAIDs, and to a lesser extent the suspension of biological treatments for fear of the risk of infection. Another possible determinant of loss of disease control is a reduction in physical activity due to confinement. Psychological factors also need to be considered. A survey of a cohort of axial spondyloarthritis patients in the United States showed that, after adjustment, patients with high levels of stress and anxiety had significantly higher disease activity scores [7] . Available data on the incidence and severity of COVID in rheumatologic populations on targeted biological or synthetic DMARDs do not show an increased risk of infection in these patients compared to the general population [6, 8] . The other rheumatologic side of COVID-19 is the induction of rheumatologic manifestations by or at a distance from SARS-CoV-2 infection. The rheumatological symptoms described during COVID are rare and hidden by other manifestations of the infection. Most often they are arthralgia in the early phase of the disease [9] . In a Spanish series of more than 300 patients with proven COVID-19, arthralgias and myalgias were found in more than a quarter of the cases in the clinical presentation [10] . A few cases of acute arthritis or dactylitis have been reported, some of which may be suggestive of reactive arthritis. To date, six compatible cases are found in the literature, but an increase in reported cases is expected in the coming months. These 6 cases are summarized in Table 1 [11] [12] [13] [14] [15] [16] . Indeed, some elements are in line with the classic or evocative aspects of reactive arthritis, defined as aseptic arthritis occurring after and distant from a site of infectious [17] . These include the predominance of males (5 cases out of 6), a delay of one to three weeks between the infection and the beginning of the rheumatological picture, a mono or oligoarticular inflammatory disease, predominant in the lower limbs, and the possibility of dactylitis or enthesitis. The joint fluid is sterile, without microcrystals. The evolution is reported to be favorable with NSAID treatment and intraarticular corticosteroid injections. The potential mechanisms at the origin of arthritis in a context of viral infection by SARS-CoV-2 remain at the hypothesis stage. The possibility of viral arthritis cannot be ruled out in the rare cases of early arthritis, but viremia is documented in only 15% of cases of COVID-19 [16] and has not been objectified in any published case with joint involvement. The presence of virus could not be detected by RT-PCR in synovial fluid in the 3 cases where this search was performed [12, 15, 16] . Histological and immunological analysis of a synovial biopsy in an early arthritis patient revealed an inflammatory synovial edema with perivascular and diffuse infiltrates expressing positivity for CD68 (histiocytic cells), CD3 (T cells) and CD138 (plasma cells) [18] . The mechanism of reactive arthritis is plausible, due to the clinical presentation, the delay between the onset (or diagnosis) of COVID and the onset of rheumatological manifestations, the usual negativation of nasopharyngeal RT-PCR at the time of onset of rheumatological involvement. Viral infections are known to potentially induce reactive arthritis patterns [17] . In this context, interleukin 17 could represent a link between the two conditions. Indeed, IL-17A is involved in the pathogenesis of both reactive arthritis and spondyloarthritis in general [17] , but also in the hyperinflammatory state of COVID-19 [19] . However, cases of symptomatic SARS-CoV-2 infection have been reported in patients treated with an anti IL-17 monoclonal antibody for spondyloarthritis [19] . Finally, non-specific mechanisms deserve to be discussed. Arthritis may be reactive to a masked pulmonary or digestive infection as a consequence of COVID [13] , or it may be a non-specific consequence of the "cytokine storm" that accompanies the symptomatic forms of the disease [20] . This new infectious disease may induce rheumatological manifestations, with the possibility of reactive arthritis. Although rare, they require special attention and the expertise of the rheumatologist for diagnosis. It also raises physiopathological issues that remain unresolved to date. The authors declare no conflict of interest concerning this manuscript 7 Managing patients with rheumatic diseases during the COVID-19 pandemic: The French Society of Rheumatology answers to most frequently asked questions up to EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2 American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID-19 Pandemic: Version 2. Arthritis Rheumatol Arnaud L How and why are rheumatologists relevant to COVID-19? Old and new antirheumatic drugs for the treatment of COVID-19 Impact of home confinement during the COVID-19 pandemic on medication use and disease activity in spondyloarthritis patients. Arthritis Rheumatol Patient-reported Disease Activity in an Axial Spondyloarthritis Cohort during the COVID-19 Pandemic. 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