Dataset Information

Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic.

ABSTRACT:

Importance

Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.

Objective

To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic.

Design, setting, and participants

In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included.

Main outcomes and measures

Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis.

Results

Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19.

Conclusions and relevance

Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.

Trial registration

ClinicalTrials.gov Identifier: NCT04344119.

SUBMITTER: Hubiche T

PROVIDER: S-EPMC7689569 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceChilblain-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.ObjectiveTo examine the association of chilblain-like lesions with SARS-CoV-2 infection.Design, setting, and participantsThis 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 measuresMacroscopic (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.ResultsOf 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.