Multisystem Inflammatory Syndrome in a Child with Scrub Typhus and Macrophage Activation Syndrome

Abstract

Abstract Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C) and macrophage activation syndrome (MAS) have been speculated as three distinct phenotypes of hyperinflammation seen in children during coronavirus disease (COVID-19) pandemic. KD has been reported in association with dengue, scrub typhus and leptospirosis. COVID-19 and dengue coinfection has also been described. However, MIS-C with concomitant infection has rarely been reported. We report an adolescent girl with clinical and laboratory parameters of MIS-C resembling KD with positive serology for scrub typhus at presentation. Clinical manifestations resolved and laboratory parameters improved with IVIG, azithromycin and corticosteroids. However, she developed fever recurrence with thrombocytopenia, elevated inflammatory markers, hypofibrinogenemia and hypertriglyceridemia which were consistent with MAS. With the emergence of MIS-C and increase in the number of such cases being reported throughout world, physicians should be aware of different phenotypes of hyperinflammation associated with COVID-19 and the possibility of coexistence of MIS-C with other infections. LAY SUMMARY Clinical and laboratory parameters of multisystem inflammatory syndrome in children (MIS-C) mimic Kawasaki disease (KD). KD has been described in association with dengue, scrub typhus and leptospirosis. However, MIS-C with concomitant infection has rarely been reported in literature. A 14-year-old-girl presented with fever and rash with history of redness of eyes, lips and tongue. Investigations showed anemia, lymphopenia, thrombocytosis with elevated erythrocyte sedimentation rate, C-reactive protein, pro-brain natriuretic peptide, Interleukin-6, ferritin and d-dimer. Scrub typhus immunoglobulin M was positive. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) level was also elevated. A diagnosis of MIS-C with concomitant scrub typhus was proffered. Child received azithromycin, intravenous immunoglobulin and methylprednisolone. After an afebrile period of 2.5 days, child developed unremitting fever and rash. Repeat investigations showed anemia, worsening lymphopenia, thrombocytopenia, transaminitis, hypertriglyceridemia, hyperferritinemia and hypofibrinogenemia which were consistent with a diagnosis of macrophage activation syndrome (MAS). KD, MIS-C and MAS represent three distinct phenotypes of hyperinflammation seen in children during coronavirus disease pandemic. Several tropical infections may mimic or coexist with MIS-C which can be a diagnostic challenge for the treating physician. Identification of coexistence or differentiation between the two conditions is important in countries with high incidence of tropical infections to guide appropriate investigations and treatment.