Scrub typhus-associated hemophagocytic lymphohistiocytosis among healthy children: A case series from northern Thailand

Hemophagocytic lymphohistiocytosis (HLH) is a serious, life-threatening complication of scrub typus. We report three cases of previously healthy female children, aged 14 to 23 months, who developed HLH secondary to confirmed scrub typhus. All were referred from district or provincial hospitals to our tertiary care center due to severe scrub typhus that was unresponsive to initial anti-rickettsial therapy and supportive treatment. Each patient exhibited persistent high-grade fever lasting 7 to 21 days, lymphadenopathy, hepatosplenomegaly and worsening anemia with thrombocytopenia. An eschar was observed in one case. The diagnosis of scrub typhus was confirmed in all cases by an indirect immunofluorescent antibody assay. During hospitalization, all three exhibited five of the eight HLH-2004 diagnostic criteria, including the presence of hemophagocytic activity in bone marrow aspirations. Treatment included anti-rickettsial antibiotics (oral doxycycline, intravenous chloramphenicol, or intravenous azithromycin), intravenous immunoglobulin, and supportive treatment. One patient also received corticosteroids due to severe illness. All cases had a full recovery without residual hematologic complications and were discharged after hospital stays ranging from 9 to 23 days. HLH is a rare but potentially fatal complication of scrub typhus. High suspicion as well as prompt diagnosis and appropriate management are important for reducing mortality and improving outcomes.