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. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages 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 two cases. Blood examinations 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.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.16682

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.

OBJECTIVE\nTo propose simple capillaroscopic definitions for interpretation of capillaroscopic morphologies and to assess inter-rater reliability.\n\n\nMETHODS\nThe simple definitions proposed were: normal--hairpin, tortuous or crossing; abnormal--not hairpin, not tortuous and not crossing; not evaluable--whenever rater undecided between normal and abnormal. Based upon an aimed kappa of 0.80 and default prevalences of normal (0.4), abnormal (0.4) and not evaluable (0.2) capillaries, 90 single capillaries were presented to three groups of raters: experienced independent raters, n = 5; attendees of the sixth EULAR capillaroscopy course, n = 34; novices after a 1-h course, n = 11. Inter-rater agreement was assessed by calculation of proportion of agreement and by kappa coefficients.\n\n\nRESULTS\nMean kappa based on 90 capillaries was 0.47 (95% CI: 0.39, 0.54) for expert raters, 0.40 (95% CI: 0.36, 0.44) for attendees and 0.46 (95% CI: 0.41, 0.52) for novices, with overall agreements of 67% (95% CI: 63, 71), 63% (95% CI: 60, 65) and 67% (95% CI: 63, 70), respectively. Comparing only normal vs the combined groups of abnormal and not evaluable capillaries did increase the kappa: 0.51 (95% CI: 0.37 ,: 0.65), 0.53 (95% CI: 0.49, 0.58) and 0.55 (95% CI: 0.49, 0.62). On the condition that the capillaries were classifiable, the mean kappa was 0.62 (95% CI: 0.50, 0.74) for expert raters (n = 65), 0.76 (95% CI: 0.69, 0.83) for attendees (n = 20) and 0.81 (95% CI: 0.74, 0.89) for novices (n = 44).\n\n\nCONCLUSION\nThis multicentre, international study showed moderate reliability of simple capillaroscopic definitions for describing morphology of capillaries by rheumatologists with varying levels of expertise. Novices were capable of distinguishing normal from abnormal capillaries by means of a 1-h training session. In future studies, the class not evaluable may be obsolete.

An EULAR Study Group pilot study on reliability of simple capillaroscopic definitions to describe capillary morphology in rheumatic diseases

Nailfold capillaroscopy findings in patients with coronavirus disease 2019: Broadening the spectrum of COVID-19 microvascular involvement.

The burden of pandemic COVID-19 is growing worldwide, as the continuous increases of contagion Only 10-15% of the entire infected population has the necessity of intensive care unit (ICU) treatments But, this relatively low rate of patients has absorbed almost the whole availability of ICU during few days, becoming at least in Italy, an emergency for the national health system In COVID-19 ICU patients massive aggression of lung with severe pulmonary failure, as well as kidney and liver injuries, heart, brain, bowel and spleen damages with lymph nodes necrosis and even cutaneous manifestations have been observed Moreover, increased levels of cytokines so-called "cytokines storm (CS), and overt intravascular disseminated coagulation have been also reported The hypercoagulation and CS would speculate about a microvascular dysfunction Unfortunately, no specific observations have been performed on microcirculatory dysfunction in COVID-19 patients Hence the presumed pathophysiological pathways and models about a microvascular involvement can be gathered by sepsis models studies But despite this lack of evidence, the COVID-19 has emphasized the compelling need for microcirculation monitoring at the bedside in ICU patients

The compelling arguments for the need of microvascular investigation in COVID-19 critical patients.

Nailfold capillaroscopy in common non-rheumatic conditions: A systematic review and applications for clinical practice.

https://www.zora.uzh.ch/id/eprint/182086/1/1-s2.0-S156899722030001X-main.pdf

Boris Garro

Papers

Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud's phenomenon and systemic sclerosis