A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain‐like lesions: lights and shadows on the relationship with COVID‐19 infection

El Hachem, M.; Diociaiuti, A.; Concato, C.; Carsetti, R.; Carnevale, C.; Ciofi Degli Atti, M.; Giovannelli, L.; Latella, E.; Porzio, O.; Rossi, S.; Stracuzzi, A.; Zaffina, S.; Onetti Muda, A.; Zambruno, G.; Alaggio, R.

BACKGROUND: Acral chilblain‐like lesions are being increasingly reported during COVID‐19 pandemic. However, only few patients proved positivity for SARS‐CoV‐2 infection. The relationship between this skin manifestation and COVID‐19 infection has not been clarified yet. OBJECTIVE: To thoroughly characterize a prospective group of patients with chilblain‐like lesions, and to investigate the possible relationship with SARS‐CoV‐2 infection. METHODS: Following informed consent, patients underwent: (i) clinical evaluation, (ii) RT‐PCR and serology testing for SARS‐CoV‐2, (iii) digital videocapillaroscopy of finger‐ and toe‐nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence, and, in selected cases, electron microscopy. RESULTS: Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu‐like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillarcosopy showed pericapillary oedema, dilated and abnormal capillaries, and microhemorrhages both in finger and toe in the majority of patients. Major pathological findings included: epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in 2 cases. Blood exams were normal. Nasopharyngeal swab for SARS‐CoV‐2 and IgG serology for SARS‐CoV‐2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS‐CoV‐2 spike protein was positive in 6 patients and borderline in 3. CONCLUSIONS: Chilblain‐like lesions during COVID‐19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS‐CoV‐2 infection in our patients, history data and the detection of anti‐SARS‐COV‐2 IgA strongly suggest a relationship between skin lesions and COVID‐19. Further investigations on the mechanisms of SARS‐CoV‐2 infection in children and pathogenesis of chilblain‐like lesions are warranted.