key: cord-0703171-hzo6ts3r
authors: Docampo‐Simón, Alexandre; Sánchez‐Pujol, María José; Gimeno‐Gascon, Adelina; Palazón‐Cabanes, Juan Carlos; Juan‐Carpena, Gloria; Vergara‐De Caso, Eduardo; González‐Villanueva, Iris; Blanes‐Martínez, Mar; Betlloch‐Mas, Isabel
title: No SARS‐CoV‐2 antibody response in 25 patients with pseudo‐chilblains
date: 2020-10-05
journal: Dermatol Ther
DOI: 10.1111/dth.14332
sha: 6efd37cf9ffd2033316065be2adf774fb68a637b
doc_id: 703171
cord_uid: hzo6ts3r

Chilblain‐like acral lesions have been identified in some coronavirus disease 2019 (COVID‐19) patients. It has been suggested that these pseudo‐chilblains could be a specific marker of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Most patients with these lesions have had negative polymerase chain reactions (PCRs), but some authors believe serology tests are likely to give positive results. We designed a prospective study including all patients with pseudo‐chilblains treated in outpatient department in April and May 2020 and then performed SARS‐CoV‐2 PCR and serology tests on all available patients. We evaluated 59 patients, of whom 17 had undergone PCR before the study period, all with negative results. For the present study, we performed 20 additional PCRs, serology tests in 25 patients, and a parvovirus B19 antibody test in 15 patients. All results were negative. Our findings counter the hypothesis that serology is likely to reveal SARS‐CoV‐2 infection in patients with pseudo‐chilblains. One hypothesis for our negative results is that the time period between symptom onset and antibody production is longer in these patients; another is that the lesions are caused by behavioral changes during lockdown rather than SARS‐CoV‐2 infection. We nevertheless maintain that COVID‐19 should be ruled out in people presenting with chilblain‐like lesions.

infection. Most patients with these lesions have had negative polymerase chain reactions (PCRs), but some authors believe serology tests are likely to give positive results. We designed a prospective study including all patients with pseudo-chilblains treated in outpatient department in April and May 2020 and then performed SARS-CoV-2 PCR and serology tests on all available patients. We evaluated 59 patients, of whom 17 had undergone PCR before the study period, all with negative results. For the present study, we performed 20 additional PCRs, serology tests in 25 patients, and a parvovirus B19 antibody test in 15 patients. All results were negative. Our findings counter the hypothesis that serology is likely to reveal SARS-CoV-2 infection in patients with pseudo-chilblains. One hypothesis for our negative results is that the time period between symptom onset and antibody production is longer in these patients; another is that the lesions are caused by behavioral changes during lockdown rather than SARS-CoV-2 infection. We nevertheless maintain that COVID-19 should be ruled out in people presenting with chilblain-like lesions. however, most SARS-CoV-2 polymerase chain reaction (PCR) tests have resulted negative in these patients. [6] [7] [8] [9] One explanation put forward for the negative results is that the lesions are a late manifestation of COVID-19, and PCR may have been positive if performed earlier. 1, 6 Some authors suggest that serology testing could detect the infection where PCR fails, but in the few published cases where serology testing has been employed, the results have mostly been negative. 8 This study was reviewed and approved by the Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL).

We evaluated 59 patients with pseudo-chilblain lesions. Their epidemiological and clinical features are summarized in Table 1 . Clinical pictures of two patients are shown in Figure 1 . We had previously performed PCR on 17 patients, and all results had tested negative.

These findings have already been published. 11 

Our findings counter the suggestion that patients with pseudochilblains will have negative PCRs but positive serology tests because their lesions are a late manifestation of SARS-CoV-2. It is very unlikely that in a sample of 25 patients all results were false negatives, and so other explanations must be considered. 12 One alternative hypothesis is that these negative results were due to lymphocyte exhaustion and viral-associated immunosuppression resulting in a lack of antibody production. 10 In our case series, the average time between the onset of lesions and performing the test was 26.5 days; it may take longer to generate detectable antibodies. Some studies have demonstrated that the vast majority of patients with COVID-19 generate antibodies within 2 weeks of developing symptoms, 12 

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases

Cutaneous clinico-pathological findings in three COVID-19-positive patients observed in the metropolitan area of

Cutaneous manifestations of COVID-19: report of three cases and a review of literature

Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia

COVID-19) infection-induced chilblains: a case report with histopathological findings

Chilblains in children in the setting of COVID-19 pandemic

Clustered cases of acral perniosis: clinical features, histopathology and relationship to COVID-19

Chilblain and acral purpuric lesions in Spain during Covid confinement: retrospective analysis of 12 cases

Assessment of acute acral lesions in a case series of children and adolescents during the COVID-19 pandemic

No antibody response in acral cutaneous manifestations associated with COVID-19?

Are chilblain-like acral skin lesions really indicative of COVID-19? A prospective study and literature review

Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

Concurrent chilblains and retinal vasculitis in a child with COVID-19

No SARS-CoV-2 antibody response in 25 patients with pseudo-chilblains

The authors declare no conflicts of interest.

The data that support the findings of this study are available from the corresponding author upon reasonable request. Isabel Betlloch-Mas https://orcid.org/0000-0003-0050-6178