key: cord-0790209-nnyor5bz
authors: Schnapp, A.; Abulhija, H.; Maly, A.; Armoni‐Weiss, G.; Levin, Y.; Faitatziadou, S.M.; Molho‐Pessach, V.
title: Introductory histopathological findings may shed light on COVID‐19 paediatric hyperinflammatory shock syndrome
date: 2020-06-29
journal: J Eur Acad Dermatol Venereol
DOI: 10.1111/jdv.16749
sha: 671fcb6d581bb21c2585886a9aa72bacfb59628e
doc_id: 790209
cord_uid: nnyor5bz

Numerous pediatric cases of hyperinflammatory shock syndrome (demonstrating features reminiscent of Kawasaki vasculitis) were recently associated with infection by COVID-19. Clinical presentation includes unrelenting fever, variable rash, conjunctivitis and abdominal pain, progressing to hemodynamic shock with severe myocardial involvement. Recent report from Italy reported a 30 time increase in the rate of Kawasaki-like presentation during the COVID-19 pandemic among children, In many cases the nasopharyngeal swabs taken from these children were negative for COVID-19, and the association with COVID-19 infection is unclear.

Introductory histopathological findings may shed light on COVID-19 paediatric hyperinflammatory shock syndrome Editor The full clinical spectrum of SARS-CoV-2 disease (COVID-19) is not fully known.

Numerous paediatric cases of hyperinflammatory shock syndrome (demonstrating features reminiscent of Kawasaki vasculitis) were recently associated with infection by COVID-19. Clinical presentation includes unrelenting fever, variable rash, conjunctivitis and abdominal pain, progressing to haemodynamic shock with severe myocardial involvement. 1 Recent report from Italy reported a 30-time increase in the rate of Kawasakilike presentation during the COVID-19 pandemic among children. In many cases, the nasopharyngeal swabs taken from these children were negative for COVID-19, and the association with COVID-19 infection is unclear. 2 We hereby present an adolescent who developed distinctive scalp cutaneous lesions as part of COVID-19 hyperinflammatory shock syndrome.

A 16-year-old boy with unremarkable medical history was admitted due to 3-day history of severe abdominal pain and fever. A migratory rash composed of mildly oedematous and erythematous plaques was noted on the trunk and extremities. Echocardiography demonstrated impaired left ventricular function with dilatation. Laboratory workup revealed significant lymphopenia (up to 200 cells/µL) with mild neutrophilia, elevated creatinine levels (up to 2.65 mg/dL), elevated levels of C-reactive protein (up to 33.5 mg/dL) and D-dimer (1.61 mg/dL). Ferritin, fibrinogen and triglycerides' levels were mildly elevated. Empiric antibiotic treatment was initiated with no improvement. Expeditiously, the patient developed multiorgan dysfunction including cardiac failure requiring mechanical ventilation and inotropic support. High-dose intravenous methylprednisolone therapy was initiated, and the patient regained normal cardiopulmonary and renal functions. Extensive investigations failed to disclose an inflammatory or infectious aetiology, including repeated RT-PCRs for SARS-CoV-2 of nasopharyngeal, stool and bronchoalveolar lavage specimens. However, two serologic tests were positive for SARS-CoV-2 IgG.

Soon after cardiopulmonary stabilization was attained, two painful dusky erythematous plaques were noted over the posterior scalp (Fig. 1) . A 3-millimetre punch skin biopsy revealed findings consistent with leukocytoclastic vasculitis including necrosis of the epidermis and most of the dermis with extravasation of erythrocytes and fibrin thrombi in the capillaries, as well as infiltration of neutrophils with nuclear debris in vessels' walls (Fig. 2) . Direct immunofluorescence demonstrated deposition of C3 and IgA in a vascular pattern. RT-PCR from affected tissue was negative for SARS-CoV-2, indicating an immune reaction rather than direct pathogen involvement.

The clinical course, as well as positive serology tests in our patient, is consistent with COVID-19-associated Kawasaki-like shock syndrome. To the best of our knowledge, this is the first report of histopathological findings in this novel paediatric disorder.

Multiple skin phenomena related to COVID-19 have been described, including maculopapular and vesicular eruptions, urticaria and chilblains. 3 Livedo reticularis or skin necrosis limited to the extremities has been correlated with more severe cases. 4 Non-specific rashes have also been described in COVID-19 Kawasaki-like shock syndrome 1 , but none has been studied meticulously and histologic data have not been given so far, although advocated repeatedly. 5, 6 Cutaneous leukocytoclastic lesions are typically seen in a symmetric distribution on the extremities and trunk, a manifestation previously reported in a COVID-19 patient. 7 Location only to the scalp is very unusual and has been rarely reported, such as in limited granulomatosis with polyangiitis. 8 The pathological findings reported here may shed light on the yet unknown pathogenesis of the hyperinflammatory shock syndrome associated with COVID-19. The presence of IgA-and complement-mediated vasculitis with extensive necrosis may represent similar pathological abnormalities in affected internal organs and may be a key factor of understanding this novel disease. 

Hyperinflammatory shock in children during COVID-19 pandemic

An outbreak of severe Kawasakilike disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases

Vascular skin symptoms in COVID-19: a French observational study

Dermatology staff participate in fight against Covid-19 in China

Cutaneous manifestations in COVID-19: a first perspective

Symmetric cutaneous vasculitis in COVID-19 pneumonia. J Eur Acad Dermatol Venereol 2020

A case report of limited Wegener's granulomatosis presenting with a chronic scalp ulcer

The patient in this manuscript and guardians have given written informed consent to the publication of this case's details.

The authors have no conflicts of interest to disclose.A. Schnapp, 1