Rationale: Murine typhus, caused by Rickettsia typhi , is a globally distributed flea-borne rickettsiosis. Although rarely recognized, it can trigger hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome. Nonspecific febrile illness and atypical petechial eruptions frequently lead to delayed or missed diagnoses. This report aims to illustrate the diagnostic process and clinical implications of murine typhus-associated HLH in a pediatric patient, and to evaluate the utility of metagenomic next-generation sequencing (mNGS) as an unbiased detection tool for occult pathogens. Patient concerns: A 10-year-old child was admitted with unexplained recurrent fever and generalized petechiae, refractory to treatment at outside hospitals. Diagnoses: The patient was ultimately diagnosed with murine typhus-associated HLH caused by R typhi , based on a comprehensive diagnostic work-up. Interventions: Empirical dexamethasone was initiated promptly to control hyperinflammation. After mNGS confirmation, oral doxycycline was added for targeted anti-rickettsial therapy. Outcomes: The patient’s clinical status continued to improve, culminating in discharge. Lessons: Murine typhus-associated HLH should be considered in febrile children with unexplained cytopenias and petechiae. Early empiric HLH-directed immunosuppression followed by pathogen-specific therapy improves prognosis. mNGS provides a rapid, unbiased method to detect rare, overlooked pathogens and guide definitive treatment when conventional tests are negative.
Duan et al. (2026) studied this question.