Cutaneous Manifestations of SARS-CoV-2 Infection

Thy Huynh; Xavier Sanchez-Flores; Judy Yau; Jennifer T. Huang


Am J Clin Dermatol. 2022;23(3):277-286. 

In This Article

Multisystem Inflammatory Syndrome in Children (MIS-C)/Pediatric Inflammatory Multisystem Syndrome (PIMS)-associated Skin Findings

Clinical Presentation

In the pediatric population, there have been a number of cases of a severe hyperinflammatory condition associated with SARS-CoV-2 that share many clinical features with Kawasaki disease (KD), an acute, systemic inflammatory vasculitis that is generally diagnosed in children under 5 years caused by an exaggerated innate immune response in genetically susceptible individuals.[32] This condition, otherwise known as MIS-C in the United States or pediatric inflammatory multisystem syndrome (PIMS) in Europe, has an incidence of 11.4 cases per 100,000 people younger than 20 years of age and was first recognized in the United Kingdom in April 2020.[33] The diagnosis criteria for KD includes a fever for > 5 days as well as a constellation of other signs and symptoms (Table 2); however, there are < 25% of children with MIS-C that met the clinical features for KD. In a case series study of 45 children with MIS-C due to SARS-CoV-2 infection, Whittaker et al. reported that these patients were older (median age of 9 vs 2.7 years), had increased inflammatory markers like C-reactive protein, and were more likely to have developed shock in comparison with patients with KD.[34] Patients with MIS-C secondary to SARS-CoV-2 are more likely to develop myocarditis, have elevated creatine kinase (CK) and increased cardiac injury markers, while KD patients are more likely to develop coronary artery aneurysms. In addition, patients with MIS-C due to SAR-CoV-2 infection are more likely to develop gastrointestinal symptoms like diarrhea, which was shown in 100% of children in a French prospective observational study.[35]

MIS-C is a multisystemic syndrome that affects various organ systems including the brain, eyes, kidneys, and hematologic system. Skin manifestations occur in 50–76% of patients with MIS-C.[33] Both KD and MIS-C present with similar cutaneous findings: polymorphous maculopapular eruptions on the trunk and flexural areas, acral erythema, extremity swelling and desquamation, mucositis, and fissured lips.[36]


MIS-C associated with SARS-CoV-2 infection is due to an overactive innate immune response that has similar pathologic abnormalities in affected internal organs and skin. IgA and complement in the vessel walls have been shown by direct immunofluorescence examination, which may play a role in vasculitis.[13]


Different microscopic findings have been reported for SARS-CoV-2-related MIS-C skin patterns ranging from leukocytoclastic vasculitis to erythema multiforme-like changes with nonspecific inflammatory infiltrate with mild intraepidermal neutrophils and necrotic keratinocytes.[13]


In a case series study, Whittaker et al. reported 58 pediatric patients that met criteria for MIS-C, where 26% tested positive for SARS-CoV-2 from PCR tests and 87% were positive for SARS-CoV-2 IgG, and 50% needed intensive care.[34] Andina-Martinez et al. assessed 21 patients exhibiting mucocutaneous symptoms with 18 (86%) patients fulfilling the criteria for MIS-C who also needed intensive care. This shows that patients exhibiting mucocutaneous symptoms secondary to SARS-CoV-2 are at a higher risk of intensive care unit admission.[37]

The treatment for MIS-C secondary to SARS-CoV-2 infections depends on the severity of the symptoms. It may include supportive care, inotropic support, intravenous immunoglobulins (IVIG), aspirin, corticosteroids, anakinra, and infliximab.[33]