Doxycycline-Responsive Hemophagocytic Lymphohistiocytosis Triggered by Scrub Typhus: A Diagnostic and Therapeutic Challenge in Tropical Medicine

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome often secondary to infections, malignancy, or autoimmune disease. Scrub typhus, endemic in Southeast Asia and the Indian subcontinent, rarely precipitates HLH; even less frequently does it mimic bacterial pneumonia on respiratory multiplex PCR. Case report: A middle-aged adult from an endemic region presented with high-grade fever, acute kidney injury (AKI), bicytopenia, and respiratory distress. Initial respiratory multiplex PCR (BioFire) identified Klebsiella pneumoniae, prompting empirical atypical bacterial infection management. However, laboratory findings—reticulocytopenia (0.2%), hyperferritinemia (1650 ng/mL), hypertriglyceridemia (598 mg/dL), elevated procalcitonin (4.5 ng/mL), and normal liver transaminases—suggested secondary HLH rather than bacterial sepsis. Serology subsequently confirmed scrub typhus (IgM positive). HScore calculation (≈220) indicated >95% probability of HLH. Doxycycline monotherapy (100 mg IV BD) initiated empirically for scrub typhus resulted in rapid defervescence within 48 hours, normalization of hematologic parameters, and resolution of AKI without HLH-directed immunosuppressive chemotherapy. Clinical Significance: This case illustrates the overlap between atypical bacterial infections and scrub typhus in triggering secondary HLH in tropical endemic areas, the diagnostic limitations of respiratory multiplex panels (BioFire), and the efficacy of directed antimicrobial therapy when primary etiology is correctly identified. It emphasizes HScore utility in adult HLH diagnosis and the potential for single-agent antibiotic therapy in infection-driven HLH without concurrent immunosuppression. Keywords: Hemophagocytic lymphohistiocytosis, scrub typhus, HLH-2004 diagnostic criteria, HScore, doxycycline, acute kidney injury, bicytopenia, tropical infectious diseases, Orientia tsutsugamushi