key: cord-0945065-23biemnl
authors: Neri, I.; Conti, F.; Virdi, A.; Guglielmo, A.; Leonardi, L.; Corsini, I.; Ghizzi, C.; Gabrielli, L.; Lazzarotto, T.; Lanari, M.; Patrizi, A.; Misciali, C.
title: Chilblains in a child with confirmed SARS‐CoV‐2 infection: a red flag for late‐onset skin manifestation in previously infected individuals
date: 2021-03-14
journal: J Eur Acad Dermatol Venereol
DOI: 10.1111/jdv.17194
sha: d61f9c06420c255ef01e47163e003d903aa6122c
doc_id: 945065
cord_uid: 23biemnl

During the COVID-19 pandemic an outbreak of chilblain lesions has been described worldwide. The relationship with SARS-CoV-2 infection is still debated. Emerging literature regarding this possible correlation focuses on two hypotheses: an endothelial infection or the result of an IFN type I-mediated immune response.

Dear Editor, During the COVID-19 pandemic, an outbreak of chilblain lesions has been described worldwide. The relationship with SARS-CoV-2 infection is still debated. [1] [2] [3] Emerging literature regarding this possible correlation focuses on two hypotheses: an endothelial infection or the result of an IFN type I-mediated immune response. 4, 5 We present the case of a 6-year-old girl with confirmed mild COVID-19 and late-onset chilblains.

Asymptomatic SARS-CoV-2 infection occurred 2 months before our first examination. Nasopharyngeal swab RT-PCRbased SARS-CoV-2 detection was performed because both parents resulted COVID-19 positive. Three weeks after molecular testing, the patient was hospitalized for 5 days due to the onset of diffuse papulopustular rash on the trunk and upper thighs, chilblains associated with severe pain, low-grade fever and marked asthenia. At that time, nasopharyngeal swab for SARS-CoV-2 was negative, routine blood tests were within normal range including C-reactive protein (CRP) and coagulation profile, while IL-6 serum levels were slightly increased. The skin lesions disappeared within 2 weeks.

Three weeks later, on August 2020, the girl was referred to our dermatology unit because of a relapse of the painful lesions on the feet, associated with gait impairment, low-grade fever (37.2°C) and marked asthenia. Clinical examination revealed painful red-purple nodular lesions on the toes and lateral sides of the feet, associated with palmar and fingertips erythema with slight desquamation (Fig. 1) . The clinical picture was suggestive of chilblain. Furthermore, the mother reported that her daughter often presented cold and sweating extremities.

RT-PCR nasopharyngeal swab for SARS-CoV-2 was repeated, being negative, while serology test confirmed the positivity of the specific SARS-CoV-2 IgG.

A 4 mm punch biopsy of a right foot lesion showed superficial and deep perivascular dermatitis. Oedema, slight perivascular lymphocytic infiltrate, some thick-walled vessels and proliferation of thin-walled vessels with swollen endothelial cells (endothelialitis) were detected in the dermis (Fig. 2) . RT-PCR performed on tissue was negative for SARS-CoV-2. Laboratory assessment was normal, including routine blood test, CRP, coagulation profile (PT, aPTT, INR, fibrinogen, D-dimer), ferritin and inflammatory cytokines profile (including IL6, IL8).

The skin manifestations cleared spontaneously in 3 weeks. A chilblain relapse was observed after 3 months and negative nasopharyngeal swab RT-PCR ruled out virus re-infection.

This case highlights the relationship between the chilblain manifestation and SARS-CoV-2 infection, confirmed by nasopharyngeal swab RT-PCR and serology test. Moreover, to the best of our knowledge this is the first report of recurrent chilblains in a confirmed COVID-19-infected case. Skin lesions onset was accompanied by low-grade fever and asthenia, thus representing mild features of COVID-19, as similarly reported by other authors. 6 Histopathology showed endothelialitis of the dermis vessels, which has been reported during the COVID-19 pandemic. The proliferation of thin-walled vessels with swollen endothelial cells represents a peculiar histological feature of toe chilblain. No fibrin, nuclear debris or neutrophils were detected in the vessels. No histological findings of leucocytoclastic vasculitis were observed. 7 The negative result of RT-PCR assay on the skin lesion, combined with the positivity of serology tests (IgG) performed during the chilblain relapse, supports the hypothesis that the acral skin injury might not be the result of endothelial infection, but of immune-mediated response triggered by SARS-CoV-2. A robust IFN-I response therefore explains the contemporary low viraemia (often with negative PCR testing) and the localized endothelial damage in the acral site with mild or no associated symptoms. 5 Genetic, hormonal and environmental factors may also contribute to the development of SARS-CoV-2 chilblains. 9,10 Further studies are needed to demonstrate this hypothesis in order to better clarify the biological processes underlying SARS-CoV-2-related chilblains.

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