key: cord-0750543-2dyy3pxx
authors: Blatz, Allison M; Oboite, Michelle; Chiotos, Kathleen; Castelo-Soccio, Leslie; Odom John, Audrey R
title: Cutaneous findings in SARS-CoV-2-associated Multisystem Inflammatory Disease in Children (MIS-C)
date: 2021-02-16
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofab074
sha: f590edd2141f60e65f7f8a83f7d5e69a29272df6
doc_id: 750543
cord_uid: 2dyy3pxx

Rash is a common feature of the multisystem inflammatory syndrome in children (MIS-C), a post-infectious hyperinflammatory disease associated with prior SARS-CoV- 2 infection. Because the differential diagnosis of fever and rash in children is broad, understanding clinical characteristics of MIS-C may assist with diagnosis. Here we describe the cutaneous findings observed in a series of children with MIS-C-associated rash.

A c c e p t e d M a n u s c r i p t

Rash is a common feature of the multisystem inflammatory syndrome in children (MIS-C), a postinfectious hyperinflammatory disease associated with prior SARS-CoV-2 infection. Because the differential diagnosis of fever and rash in children is broad, understanding clinical characteristics of MIS-C may assist with diagnosis. Here we describe the cutaneous findings observed in a series of children with MIS-C-associated rash.

A c c e p t e d M a n u s c r i p t

In April 2020, a hyperinflammatory condition apparently associated with SARS-CoV-2 was recognized in children. This syndrome, now termed multisystem inflammatory syndrome in children (MIS-C), 4 is characterized by fever, profound systemic inflammation, multi-organ involvement, and often rash. 23 Here, we describe the dermatologic manifestations of MIS-C at a single institution.

All children admitted to our tertiary care, academic, pediatric medical center with concern for MIS-C per CDC criteria are routinely evaluated by an expert multidisciplinary committee to reach diagnostic consensus. 5 Skin findings were photographed and included in the secure electronic health record.

Clinical characteristics were abstracted through chart review. As of 28 July 2020, a total of 24 children were diagnosed with MIS-C, of whom 18 (75%) exhibited mucocutaneous changes and photographs had been obtained during the course of clinical care for 10 (41.7%). Consent was obtained for 7 patients. Clinical and laboratory findings of patients 1, 2, and 4 have been previously reported. 6

The design of this work was reviewed by the Institutional Review Board of the Children's Hospital of Philadelphia, who deemed this exempt research. Verbal informed consent for photograph use was obtained from the parents or legal guardians of all children whose images are included in this study.

Patients with MIS-C exhibited a variety of cutaneous clinical findings ( Figure 1 , Table 1 cheek (not shown).

A variety of erythematous lesions were observed, classified as urticarial, morbilliform, and livedoid.

These skin changes were observed in patients with diverse skin tones and pigmentation. The most common lesions observed were small-to-medium annular plaques (taking on an urticarial appearance) in 57% (4/7) of patients, although morbilliform eruptions with coalescing papules to plaques (Fig. 1K ) and coalescing macules were also noted, each in one patient. Reticulated plaques and patches (taking on a livedoid appearance) were noted in 2 patients (29%) (Fig. 1L, M, N) . 29% (2 of 7) of children described the rash as mildly pruritic. In one patient, rash did not occur until the fourth hospital day, following recrudescent fever after IVIG and steroids; the rash resolved with an additional dose of IVIG. Purpura were seen in 4 (57%) of 7 patients. Most commonly (3 of 4), purpura were noted in the center of annular (urticarial) plaques, mimicking the appearance of erythema multiforme-like lesions. All skin findings completely resolved by the time of hospital discharge. In contrast to rashes associated with Kawasaki disease, none of the rashes desquamated.

MIS-C, thought to be a post-infectious complication of SARS-CoV-2 infection, remains largely a diagnosis of exclusion, as its clinical manifestations, including fever, gastrointestinal distress, and rash, are common to many other pediatric infections. Acute COVID-19 has presented with a myriad of cutaneous findings in children, including erythema multiforme, urticaria, vesicular exanthem, polymorphic rash, purpura, and pityriasis rosea-like eruption. 7 The pathophysiology of SARS-CoV-2associated rashes are poorly understood, and may overlap with that of MIS-C-associated mucocutaneous changes.

We find that no unique, stereotypic rash was observed in patients who were treated for MIS-C, although annular plaques in the proximal medial lower extremities were common, a finding that warrants further study in larger cohorts. We note overlap between cutaneous findings of MIS-C and those observed in rickettsial illness (palmar/plantar involvement), toxic shock syndrome (diffuse rash A c c e p t e d M a n u s c r i p t and some erythroderma), Kawasaki disease (diffuse rash, mucocutaneous changes, extremity changes), and viral exanthems, which continue to pose a significant diagnostic dilemma.

Limitations include a small sample size, due in part to the rarity of MIS-C and challenges imposed by isolation precautions, as well as the imprecision of MIS-C diagnostic criteria.

Cutaneous manifestations are common in MIS-C, although the underlying pathophysiology is not well understood. We anticipate these images and descriptions will aid clinicians in the diagnosis of future cases.

We thank the Children's Hospital of Philadelphia MIS-C Research Collaborative for its contribution to A c c e p t e d M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t A c c e p t e d M a n u s c r i p t 

Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study

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

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

Inflammatory Syndrome in Children (MIS-C) Associated with Coronavirus Disease 2019 (COVID-19). Health Alert Network

Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series

Skin manifestations of COVID-19 in children: Part 2. Clinical and Experimental Dermatology