Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic

Abstract

IMPORTANCE Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. OBJECTIVE To examine the association of chilblain-like lesions with SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. MAIN OUTCOMES AND MEASURES Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. RESULTS Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. CONCLUSIONS AND RELEVANCEThis study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis.These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection.Ongoing studies will help clarify the etiopathogenic mechanisms.

Lack of association between pandemic chilblains and SARS-CoV-2 infection

“…In this detailed study of a cohort of patients with chilblain eruptions presumed to be caused by SARS-CoV-2, we do not find evidence supporting an association with prior infection. Many observational reports have offered circumstantial evidence pointing toward an association with SARS-CoV-2 infection, although the immunological and PCR data have been more limited, with only the minority of cases having evidence of infection ( 1 , 4 – 8 ) and some studies having none whatsoever ( 2 , 3 , 12 ). Importantly, PC cases are being diagnosed and managed differently than idiopathic chilblains due to this presumed relationship with SARS-CoV-2 ( 19 ).…”

“…Despite this purported association between PC and SARS-CoV-2 infection, the majority of these patients lack evidence of prior infection ( 1 , 4 – 8 ). Although testing was not widely available in early studies, this relationship has nonetheless held in later studies with more comprehensive testing ( 2 , 3 , 12 ). Arguments for this persistent inability to detect prior infection include 1) a missed window, with PCR testing too late and antibody testing too early; 2) loss of antibody positivity over time; and 3) that PC patients may feature a robust SARS-CoV-2 innate immune response that impedes the development of a detectable antibody signal ( 13 ).…”

Evolution of incidence of chilblain‐like lesions in children during the first year of COVID‐19 pandemic

“…While investigations to understand the pathophysiology of pandemic‐associated pernio continue, 16 , 17 , 18 , 19 evidence has shown that SARS‐CoV‐2 spike protein and robust IFN‐1 response are seen in the skin of patients with chilblains, suggesting an excessive innate immune skin response to SARS‐CoV‐2. These findings suggest IFN‐1 signaling may affect host outcomes to COVID‐19.…”

Nails and COVID ‐19 – A comprehensive review of clinical findings and treatment

“…In these patients, a SARS‐CoV‐2 infection was excluded by in situ hybridization and serologic testing. 11 …”

“…In these patients, a SARS-CoV-2 infection was excluded by in situ hybridization and serologic testing. 11 Thirty-three patients (mean age 23.4 years) with chilblains during the COVD-19 pandemic presented with erythematous and purpuric papules on the toes or fingers with edema and pruritus or burning sensation. Histology (n = 5) revealed superficial dermal lymphocytic infiltrates around vessels and eccrine sweat glands.…”