PC2142: Clinical Overlap Between covid-19 Associated Multisystem Inflammatory Syndrome and Hemophagocytic Lymphohistiocytosis: Are They One Clinical Spectrum?

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is an autoinflammatory illness that follows COVID-19 infection. What makes this syndrome difficult to diagnose is that it can have significant overlap with other inflammatory disorders, such as Kawasaki disease, Toxic Shock Syndrome, Hemophagocytic Lymphohistiocytosis (HLH) and Murine Typhus.

Case Description: Here we present a 3-year-old male with no significant past medical history who, following a recent infection with Covid-19, came to our institution with ongoing fever, anorexia, abdominal pain and lethargy. Laboratory workup was significant for transaminitis (ALT 279 u/L, AST 513 u/L, alkaline phosphatase 509 u/L), pancreatitis (lipase 1,521 U/L), LDH of 2,260 U/L, ferritin greater than 16,500 ng/mL, hyperbilirubinemia (total bilirubin 5.8 mg/dL), and positive EBV PCR (3,110,500 copies/ml). Echocardiogram was significant for right coronary artery aneurysm (z-score +4.5). The patient was diagnosed with MIS-C and improved after being treated with aspirin, methylprednisolone, IVIG, anakinra, and ursodiol. Repeat echo prior to discharge showed complete resolution of his right coronary artery aneurysm. He was discharged home on ursodiol, aspirin and instructions on an oral steroid wean. Nine days after discharge, prior to the steroid wean, he again presented with recurrent fevers, t-max of 104.3F, abdominal distension, right leg pain and jaundice. On this occurrence, although the patient did not meet criteria for MIS-C as his CRP and ESR were below threshold, his other lab results including hyponatremia, thrombocytopenia, leukopenia, hepatitis, hypofibrinogenemia, pancreatitis, hyperferritinemia and recurrent right coronary artery dilation were consistent with his previous admission and MIS-C. At this point, due to failure to improve with typical treatment for MIS-C, other conditions were considered, especially HLH. Hematology/Oncology service was consulted and bone marrow aspirate showed frank and frequent hemophagocytosis. He met criteria for HLH (fever, cytopenia, hypofibrinogenemia, hyperferritinemia, and hemophagocytosis on bone marrow aspirate), although his pancreatitis and abnormal echocardiogram were atypical findings for HLH. Soluble IL-2 was elevated (4,416 U/mL) and CXCL9 was elevated (6,357 pg/mL). Genetic panel for Primary HLH was negative. He was treated with Emapalumab.

Discussion: Given the abnormal echocardiogram and pancreatitis, which is atypical for HLH, led us to wonder whether the patient had clinical overlap of HLH and MIS-C. At the patient’s most recent follow-up, he had completed 8 weeks of induction therapy with complete response and is currently undergoing continuation therapy based on the modified HLH 2004 protocol.

Conclusion: This case demonstrates that HLH and COVID-19 associated MIS-C may have overlapping features. In our patient, HLH and MIS-C occurred chronologically with HLH evolving from the initial MIS-C episode. This raises the question as to whether HLH and MIS-C may be part of one spectrum, both being hyperinflammatory disorders in children.