Hemophagocytic Lymphohistiocytosis Mimicking Multisystem Inflammatory Syndrome in Children: A Diagnostic Challenge

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can present with clinical and laboratory findings overlapping with multisystem inflammatory syndrome in children (MIS-C). We report a pediatric patient presenting with fever, shock, and elevated inflammatory markers, initially concerning for MIS-C in the setting of prior coronavirus disease exposure. Despite initial management directed toward MIS-C, the patient demonstrated persistent cytopenias and markedly elevated ferritin levels, prompting further evaluation for HLH. Additional workup suggested a potential infectious trigger, including Ehrlichia exposure. The patient met diagnostic criteria for secondary HLH and improved following initiation of dexamethasone and doxycycline therapy. This case highlights the diagnostic overlap between hyperinflammatory syndromes in children and emphasizes that persistent cytopenias and extreme hyperferritinemia should prompt early evaluation for HLH, even when MIS-C is initially suspected.