Abstract
BACKGROUND: Talaromycosis is increasingly recognized in immunocompromised individuals beyond those with HIV, including patients with primary immunodeficiencies such as Hyper-IgE syndrome (HIES). However, diagnosing disseminated infection remains challenging due to nonspecific clinical manifestations and limitations of conventional diagnostic methods. CASE PRESENTATION: We report a rare case of recurrent disseminated Talaromyces marneffei (T. marneffei) infection in a 25-year-old male with STAT3-mutated HIES. Initially presenting with abnormal liver function tests, the patient had a history of T. marneffei pulmonary infection successfully treated with itraconazole. During the current admission, he developed intermittent fever, jaundice, and splenomegaly. Initial evaluations led to a misdiagnosis of chronic drug-induced liver injury (DILI). Subsequent fever recurrence and worsening liver function prompted further investigation. Metagenomic next-generation sequencing (mNGS) and histopathology of liver revealed T. marneffei, confirming disseminated infection involving the liver. Histopathological examination of the liver showed granulomatous inflammation with IgG4-positive plasma cell infiltration, further complicating the differential diagnosis. The patient responded well to intravenous voriconazole, with significant improvement in liver function and radiological findings. CONCLUSION: Disseminated talaromycosis should be considered in immunocompromised patients presenting with unexplained fever, hepatosplenomegaly, or organ dysfunction, even in the absence of classic symptoms. Integration of mNGS into diagnostic workflows enhances pathogen detection, and long-term antifungal prophylaxis may be necessary in patients with persistent immune deficiencies.