A 9-year old girl presented at the emergency department of a peripheral hospital with fever, abdominal pain, vomiting, diarrhea, and a skin rash since 1 day. One month before she developed fever and headache, and tested positive for SARS-CoV-2 infection. She was hospitalized and was given IV fluids, Augmentin and Clarithromycin. Laboratory findings showed leucocytosis with neutrophilia, thrombocytopenia, elevated C-reactive protein, elevated liver function tests and ferritin. Serology testing showed no active hepatitis A or B infection, EBV and CMV infection in the past, and was negative for adenovirus, influenza virus, Borrelia and Herpes simplex virus. Mycoplasma serology (IgM) was borderline positive. SARS-CoV-2 IgG test results were strongly positive.
Due to further deterioration of her general condition, she was transferred to UZ Brussels Paediatric Intensive Care Unit (PICU) for further analysis of the inflammatory laboratory findings, liver test abnormalities together with the clinical findings of fever, headache, diarrhea, rash, and ataxia. Clinical dermatological examination of the child showed facial oedema, bilateral conjunctival injection, cracking of the lips, erythematous urticarial eruption on the trunk and extremities including hands and feet. The skin was not painful or itching. She showed intermittent episodes of staring and absence. An EEG examination showed normal functions, no focal or epileptic abnormalities. Abdominal sonography showed steatotic hepatosplenomegaly. Cardiac sonography showed coronary wall thickening but no aneurysmata. Anatomopathological examination of the skin revealed necrotic keratinocytes and a sparse lymphocytic inflammatory infiltrate, findings which could be seen in Kawasaki disease. Direct immunofluorescence was negative. Given the constellation of signs, she was diagnosed with Kawasaki-like MIS-C, associated with COVID-19.
She was treated with intravenous Immunoglobulins and high dose intravenous Solu-Medrol, together with acetylsalicylic acid and supportive therapy with high flow oxygen and morphine. Within a few days the skin rash reduced with a more livid-blueish colour. Clinical and biochemical findings normalized. A control cardiac sonography showed normal images, and she was transferred back to the paediatric hospitalization unit in the peripheral hospital.
The WHO declared COVID-19 a pandemic on March 11, 2020. Paediatricians noticed a growing number of hospitalizations of children who developed fever and multisystem inflammation. Some of them had characteristics that were similar to Kawasaki disease (KD). The American Heart Association criteria for KD describe: persistent fever and 4 or 5 mucocutaneous features (erythema and cracking of the lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa, bilateral bulbar conjunctival injection without exudate, rash (maculopapular diffuse erythroderma), erythema and oedema of hands and feet in the acute phase and/or periungual desquamation in the subacute phase, and cervical lymphadenopathy (>1.5 cm diameter).
This case represents a report of a KD-like illness with serologic evidence of a previous COVID-19 infection. This condition has been termed multisystem inflammatory syndrome in children (MIS-C), also referred to as paediatric multisystem inflammatory syndrome (PMIS), paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), paediatric hyperinflammatory syndrome, or paediatric hyperinflammatory shock. Emerging reports depict the phenotype of MIS-C as a combination of KD, toxic shock syndrome, and macrophage activation syndrome, all syndromes with dysregulated immune responses. We emphasize the importance of recognition of the possibility of this syndrome across specialties, as care for these patients necessitates prompt treatment. Given the evolving understanding of MIS-C, standardised treatment guidelines have yet to be established.
Sources
- Whittaker E., et al.; Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020 Jul 21; 324(3):259-269.
- Licciardi, F. et al; “SARS-CoV-2–Induced Kawasaki-Like Hyperinflammatory Syndrome: A Novel COVID Phenotype in Children.” Pediatrics 146.2 (2020): e20201711. Web. 01 Oct. 2020.
- Son M.B.S., Kevin Friedman K., Coronavirus disease 2019 (COVID-19): Multisystem inflammatory syndrome in children (MIS-C): clinical features, evaluation, and diagnosis. Uptodate, Sep 2020.
- Lee P.Y., et.al. Distinct clinical and immunological features of SARS-CoV-2-induced multisystem inflammatory syndrome in children. J Clin Invest. 2020 Jul 23:141113.
A. Van Averbeke1, M. Grosber1, D. Bulckaert2, G. van Berlaer2, K. Vergaelen3, L. De Raeve1
1Department of Dermatology UZ Brussel, Vrije Universiteit Brussel
2Emergency Department UZ Brussel, Vrije Universiteit Brussel
3Department of Intensive Care UZ Brussel, Vrije Universiteit Brussel