Multisystem inflammatory syndrome associated with SARS-CoV-2 in a Japanese girl.

Since the start of the coronavirus disease (COVID‐19) pandemic, COVID‐19‐related multisystem inflammatory syndrome in children (MIS‐C) has been reported mainly in Europe and North America, , but there are a few reports from Asia. Here we report a case of confirmed MIS‐C with cardiac dysfunction in a Japanese girl. A case of COVID‐19‐related Kawasaki disease has been reported in a Japanese infant but, as far as we are aware, this is the first case of MIS‐C to be reported in Japan.

A previously healthy, 10‐year‐old, Japanese girl was admitted to our hospital with a 3‐day history of fever, abdominal pain, and frequent watery diarrhea in December, 2020 (Fig. 1a). She had not had any contact with anyone symptomatic for COVID‐19 within the few months preceding her admission. Her body temperature was 38.9 °C; heart rate, 127/min; respiratory rate, 24/min; blood pressure, 107/61 mmHg; and her oxygen saturation was 97% in room air. She had mild tenderness in the lower right quadrant of her abdomen. Abdominal ultrasonography revealed diffuse bowel wall thickening, predominantly in the terminal ileum and ascending colon (Fig. 1b). Abdominal contrast‐enhanced computed tomography showed enlarged mesenteric lymph nodes, thickening and increased brightness of the peritoneum, ascites, and bowel wall thickening (Fig. 1c). Laboratory examination showed a mild increase in white blood cell count (10 900/µL) and an elevated C‐reactive protein (CRP) level (21.9 mg/dL).

Fig. 1

(a) Clinical course. The X‐axis shows time. The treatment course is shown at the top, with doses. The time course of fever and symptoms are shown in the middle. The course of the laboratory results are shown in the table at the bottom. (b) Sonographic image of right iliac fossa showed marked cecal wall thickening (between white arrows) with an enlarged mesenteric lymph node (black arrow). (c) Contrast‐enhanced computed tomography scan of the lower abdomen revealed extensive thickening of the cecal wall with multiple mesenteric nodes and increased brightness of the peritoneum. (d) Chest radiograph showed cardiomegaly (cardiothoracic ratio, 61%) and blunt costophrenic angles. (e) Echocardiography showed dilatation of the left main coronary artery (4.6 mm, Z‐score, 3.88) (arrow). ASA, aspirin; BNP, brain natriuretic peptide; BT, body temperature; CMZ, cefmetazole; CRP, C‐reactive protein; IVIG, intravenous immunoglobulin; PSL, prednisolone; TAZ/PIPC, tazobactam/piperacillin; WBC, white blood cells. (), BT; (), CRP.

We initially diagnosed her with enterocolitis and peritonitis, and treated her with intravenous antibiotics. All patients admitted to our hospital undergo screening for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) using a polymerase chain reaction (PCR) test. Her PCR test was positive on the day of admission. On receiving the result, we considered the possibility of concurrent infectious enterocolitis and asymptomatic SARS‐CoV‐2 infection. However, her high fever persisted, and she developed bilateral conjunctival injection on the third day of hospitalization. She also developed inflamed cracked lips, a strawberry tongue, tender bilateral cervical adenopathy, and small annular erythema on her left shoulder on hospital day 4. Laboratory examination showed a decrease in the platelet count (74 000/µL), elevated D‐dimer levels (24.3 µg/mL), and an inflammatory reaction (CRP 19.20 mg/dL, ferritin 3,685 ng/mL). Chest radiography showed cardiomegaly (cardiothoracic ratio, 61%) and blunt costophrenic angles (Fig. 1d). Echocardiography revealed reduced left ventricular contraction (ejection fraction, 47%), pericardial effusion, and dilatation of the left main coronary artery (4.6 mm, Z‐score 3.88]) with perivascular brightness (Fig. 1e). Her brain natriuretic peptide levels were elevated (487 pg/mL). Considering her negative blood and stool cultures and positive IgG and IgM antibody titers against SARS‐CoV‐2, we diagnosed her with COVID‐19‐associated MIS‐C based on WHO and CDC diagnostic criteria of MIS‐C on hospital day 4. We immediately administered 2 g/kg of intravenous immunoglobulin (IVIG) and started administering 30 mg/kg/day of oral aspirin and 2 mg/kg/day of intravenous prednisolone. She developed moderate anasarca with a weight gain of 4 kg and hypoalbuminemia (1.7 g/dL). She was treated with continuous infusion of furosemide (1 mg/kg/day) and albumin supplementation. In addition, heparin was administered to prevent thrombosis associated with MIS‐C and steroid administration.

Her fever and Kawasaki‐like symptoms (annular erythema, enlarged, tender cervical lymph nodes, and red lips) disappeared promptly after administration of IVIG and prednisolone. Around this time, her abdominal pain resolved and the ascites and pleural effusion gradually decreased. Echocardiography also showed gradual improvement of the reduced left ventricular contraction and pericardial effusion, although mild dilatation of the left main coronary artery (3.9 mm, Z‐score 2.54) persisted. The prednisolone dose was tapered from 2 to 1 to 0.5 mg/kg/day as her symptoms and CRP levels improved. She was discharged on hospital day 16 once her chest X‐ray and ultrasonography findings became normal. After discharge, she developed non‐membranous desquamation of the fingertips.

This case serves as a reminder that MIS‐C can present with a broad range of clinical symptoms, including fever and gastrointestinal symptoms. Early recognition of MIS‐C and anti‐inflammatory treatment, including IVIG and corticosteroids, are important, as children with MIS‐C can rapidly deteriorate and require more intensive care, such as the use of extra corporeal membrane oxygenation. During the rapid expansion of the COVID‐19 pandemic in Japan, all pediatricians need to keep MIS‐C in the differential diagnosis, even in pediatric patients who do not initially fulfil the diagnostic criteria for MIS‐C and whose presentations mimic a more common diagnosis.

Disclosure

The authors declare no conflict of interest.

Author contributions

T.B., T.M., K.M., and S. Kogaki managed the patient. T.B. drafted the manuscript. T.M., S. Katsuragi, and S. Kogaki critically reviewed the manuscript. All authors have read and approved the final manuscript.

Informed consent

Informed consent for publishing this case report was obtained from the patient’s parents.