key: cord-0754997-okrlbem9
authors: Tammaro, A.; Karim, D.; Adebanjo, G.A.R.; Parisella, F.R.; Chello, C.; Salih, A.F.; Rello, J.
title: COVID‐19 cutaneous manifestations in pediatric patients: 24 multisystem inflammatory syndrome in children and six Kawasaki disease cases
date: 2021-12-01
journal: J Eur Acad Dermatol Venereol
DOI: 10.1111/jdv.17828
sha: 50432a07f3aeb6b79fdb88b61449c8f84d9d9447
doc_id: 754997
cord_uid: okrlbem9

The scientific understanding of the dermatological implications of COVID-19 is rapidly evolving. A variety of cutaneous manifestations associated to COVID-19 have been described in recent reports published in the literature1 . Emerging evidence shows that children with COVID-19 can develop a condition called "multisystem inflammatory syndrome in children" (MIS-C), which is also known as "pediatric inflammatory multisystem syndrome temporally associated with COVID-19, that is clinically close to Kawasaki disease (KD)1 .

To the Editor, The scientific understanding of the dermatological implications of COVID-19 is rapidly evolving. A variety of cutaneous manifestations associated to COVID-19 have been described in recent reports published in the literature. 1 Emerging evidence shows that children with COVID-19 can develop a condition called "multisystem inflammatory syndrome in children" (MIS-C), which is also known as "pediatric inflammatory multisystem syndrome," temporally associated with COVID-19, that is clinically close to Kawasaki disease (KD). 1 Kawasaki disease is a medium-sized vessel vasculitis and its clinical spectrum, and that of MIS-C, includes numerous cutaneous signs. 1 There are no univocal diagnostic criteria to identify MIS-C yet, but the Centers of Disease Control and Prevention and the World Health Organization have listed preliminary case definition criteria to recognize this new entity. 2 In this study we collected and summarized the clinical data of a cohort of hospitalized pediatric COVID-19 patients who presented skin manifestations from the Pediatric Cardiology Department of the University Hospital of Sulaimani (Iraq).

Thirty-two hospitalized pediatric patients with COVID-19 and cutaneous manifestations were identified (Fig. 1) . The cutaneous lesions were protean and they included vesicular lesions, erythematous rashes, macular rashes, and papular lesions.

Three groups of patients were identified (Table 1) : the first one included COVID-19 patients with cutaneous manifestations (two children), the second group COVID-19 patients with Kawasaki disease (six children), and the third group patients with MIS-C on top of COVID-19 (24 children).

Over the last months, the cutaneous manifestation of COVID-19 in children has received increasing interest from the scientific community worldwide.

Researchers have hypothesized that the cutaneous involvement of children with COVID-19 may be attributed to a T, B, and NK cell-predominant immune response in synergy with a weaker pro-inflammatory response and less ACE2 receptors compared to adults. 3 A systematic review identified a total of 600 patients who developed MIS-C: these patients were older than the ones with Kawasaki disease and presented a higher incidence of respiratory, gastrointestinal, and cardiac signs and symptoms. 4 This applies to our cohort for certain manifestations (Table 1) , but this finding is likely to have been influenced by the fact that way more cases of MIS-C were identified compared to the KD ones. The data collected from published cases highlights a higher incidence of conjunctivitis, lymphadenopathy, and mucosal involvement in children with KD, 4,5 which is evident in our patients ( Table 1) .

The mechanism that leads to MIS-C is still under investigation, however many conjectures have been made: immune dysregulations and the ability of the novel coronavirus to halt interferon responses have been proposed as possible explanations for the appearance of this condition. 5 Another matter that is still unsolved is the explanation behind the higher number of MIS-C cases seen in COVID-19 patient in Western countries compared to the ones reported in the East, given that KD is more prevalent in Asia.

The cutaneous manifestations of KD are well-known (polymorphous rash which is never vesicular that spreads from the trunk to the extremities and that disappears with fever resolution 6 ), but the ones of COVID-19 and MIS-C are still being studied. Interestingly, MIS-C has been associated with nonspecific rashes, urticarial, petechial, purpuric, polymorphic, morbilliform, and maculopapular lesions, to name a few. 5 The localization of these manifestations is variable as well. 5 Unfortunately, histopathological information regarding these lesions is not available yet because biopsies are generally not performed on children. 5 We hope that our findings may provide further insight into the clinical and cutaneous characteristics of COVID-19 and MIS-C in children. However, we believe that further studies are needed to define the dermatological implications of COVID-19 and MIS-C as both are still being in the process of being unraveled.

The novel coronavirus (SARS-CoV-2) has crippled the world by its fatality and protean manifestations, of which multisystem inflammatory syndrome seems to be a relatively new trick under its sleeve. A myriad of dermatological manifestations with incompletely understood pathophysiology such as maculopapular rash, erythema multiforme-like lesions, vesicular and urticarial lesions, chilblains, livedo reticularis-like lesions have been reported in COVID-19. 1 A 24-year-old male presented with a high-grade fever for 8 days accompanied by a subacute onset progressive holocranial headache, vomiting, malaise a day later followed by a generalized maculopapular rash, which appeared on the 5th day of fever, initially on his right arm and then gradually involved all the limbs 

Cutaneous manifestations of COVID-19 in children (and adults): a virus that does not discriminate

Cutaneous manifestations related to COVID-19 immune dysregulation in the pediatric age group

Cutaneous and histopathological features of coronavirus disease 2019 in pediatrics: a review article

COVID-19 associated multisystem inflammatory syndrome: a systematic review and meta-analysis

Dermatologic manifestations of COVID-19-associated multisystem inflammatory syndrome in children

Kawasaki disease for dermatologists

Multisystem inflammatory syndrome in adults (MIS-A): a new addition to COVID-19 puzzle

The guardians of the patients in this manuscript have given informed consent to publication of their case details Rome, Italy, 2 Department of Medicine, The University of Queensland, Brisbane, QLD, Australia, 3 

Nothing to declare.

None.

The data that support the findings of this study are available from the corresponding author upon reasonable request.A. Tammaro, 1,* D. Karim, 1 G.A.R. Adebanjo, 1 F.R. Parisella, 2 C. Chello, 1 A.F. Salih, 3 J. Rello 4,5,6