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Letters to the Editor

Second Episode of Multisystem Inflammatory Syndrome in Children

Relapse, Rebound, or Recurrence?

Pawar, Ravindra Shamrao MBBS, DCH, DNB, FNB; Tarkasband, Vyankatesh Arun MBBS, MD; Patil, Rupali Kapil MBBS, DNB; Naik, Amar Vilas MBBS, MD

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The Pediatric Infectious Disease Journal: November 2021 - Volume 40 - Issue 11 - p e452
doi: 10.1097/INF.0000000000003249
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To the Editors:

Multisystem Inflammatory Syndrome in children (MIS-C), occurring few weeks after severe acute respiratory syndrome - coronavirus 2 infection (symptomatic or asymptomatic), is theorized as being a postinfectious autoantibody mediated phenomenon, and shares some clinical and immunopathophysiologic features with Kawasaki disease.1 Kawasaki disease is known to have recurrences,2 but such recurrences have not been reported with MIS-C. We describe a teenager who had second episode of MIS-C after 4 weeks of first episode.

A 17-year-old boy, known case of Down Syndrome (DS), was admitted with a history of high-grade fever, rash, loose stools and pedal edema for 3 days before admission. Significant past history was operation for Tetralogy of Fallot, at 9 years of age. He had history of coronavirus disease 19 (COVID-19) exposure 2 months back but was never symptomatic. On admission, vitals were normal, was febrile, had a generalized macular rash, a midline sternotomy scar and bilateral mild pedal edema. The history of fever, loose stools and rash made us suspect post COVID-19 MIS-C, and he was investigated accordingly. His Anti SARS-Cov2 IgG antibody was positive, IgM antibody negative; had normal leucocyte counts with relative neutrophilia and lymphocytopenia, normal platelet counts, and raised inflammatory markers (Table 1). Chest radiograph showed mild cardiomegaly and normal lungs. Echocardiography on admission showed intact VSD closure patch, mild ventricular dysfunction, normal coronaries, no pericardial effusion, mild pleural effusion, and no signs of infective endocarditis. He was started on high-dose methylprednisolone and low molecular weight heparin for 5 days. He improved symptomatically, the rash disappeared over 3–4 days, and echocardiography done on day 6 showed normal ventricular function. Oral steroids were started and continued for 1 more week. He was discharged after 11 days, with investigations normalized, and steroids were tapered over next 2 weeks.

TABLE 1. - Laboratory Results on First and Second Admission and Discharge
Test First Admission First Discharge Second Admission Second Discharge
Hemoglobin, g/dL 11.3 13 11 10
Leucocyte count, cells per mm3 5300 8,600 11300 7700
% neutrophils/% lymphocytes 75/20 60/36 82/15 64/33
Platelets, per mm3 150,000 130,000 136,000 166,000
CRP, <6 mg/L 39.6 5.28 78.7 24.14
ESR, mm/h 22 14 26 -
LDH (225–450 U/L) 897 - 705 -
D-dimer (<0.5 μg/mL) 3.16 2.8 4.18 0.614
Troponin-I (<0.02 ng/mL) 0.04 - - -
Anti-SARS-CoV-2 Antibodies
 IgG 118.3 - 5.42 -
 IgM 0.19 0.0
Sodium (136–155 mEq/L) 125 138 126 132
Blood urea (16.6–48.5 mg/dL) 54 45 56 53
Serum Creatinine (0.82–1.2 ng/mL) 1.35 1.1 1.4 1.09
NT-proBNP (<250 pg/mL) 21,699 13,159 5569 -
Blood culture No growth No growth
CRP indicates C-reactive protein; ESR, erythrocyte sedimentation rate; LDH, lactate dehydrogenase; NT Pro-BNP, N-terminal pro–B-type natriuretic peptide.

He was asymptomatic at 1-week follow-up after discharge. After 8 days of stopping steroids, he started getting a macular rash over the body, mild fever and fatigue. He was readmitted (4 weeks after first discharge), with features of shock and was started on inotropes. His blood investigations this time again showed hyperinflammatory state (Table 1). Echocardiography showed normal biventricular function, no signs of infective endocarditis, and no pleural or pericardial effusions. He was started on injectable steroids and intravenous immunoglobulin. Clinical improvement was seen in 48 hours. The rash waned off over 3–4 days. He was discharged after 1 week. At 1-month follow-up, he was asymptomatic.

A recurrence may be defined as a repeat episode of the disease after complete resolution of the previous episode.1,3 Rebound is manifestations of disease occurring within 4–6 weeks of stopping treatment or while tapering drugs, and a Relapse is worsening of disease while under treatment.3 Since there was no re-infection (Anti severe acute respiratory syndrome - coronavirus 2 antibodies were not rising again), it was not recurrence. It may be called as a rebound because he got symptomatic within few days of completion of treatment. Immune dysregulation is known in DS, and they are more prone to complications of COVID-19.4 Whether this increases the propensity for rebound or recurrences of MIS-C in DS is open to discussion. Our case makes us aware of such a possibility, and what is otherwise thought of as a one-time episode, may require longer follow-up and high index of suspicion for a repeat episode.


1. Consiglio CR, Cotugno N, Sardh F, et al.; CACTUS Study Team. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell. 2020;183:968–981.e7.
2. McCrindle BW, Rowley AH, Newburger JW, et al.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for Health Professionals From the American Heart Association. Circulation. 2017;135:e927–e999.
3. Saxena A, Kumar RK, Gera RP, et al.; Working Group on Pediatric Acute Rheumatic Fever, Cardiology Chapter of Indian Academy of Pediatrics. Consensus guidelines on pediatric acute rheumatic fever and rheumatic heart disease. Indian Pediatr. 2008;45:565–73.
4. Espinosa JM. Down syndrome and COVID-19: a perfect storm? Cell Rep Med. 2020;1:100019.
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