Disseminated Talaromyces marneffei infection mimicking tuberculosis in an HIV-negative adult with anti–IFN-γ autoantibodies: a case report

Talaromyces marneffei (TM) is an opportunistic fungus causing life-threatening disseminated infections in immunocompromised individuals. While classically associated with HIV, TM is increasingly reported in HIV-negative patients, often misdiagnosed due to nonspecific manifestations. A 38-year-old HIV-negative Chinese woman with a history of thyroid cancer presented with a three-month history of fever, cough, weight loss, and subcutaneous masses. Imaging revealed diffuse pulmonary nodules and osteolytic bone destruction. She was initially misdiagnosed with tuberculosis and received anti-TB therapy without improvement. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid identified TM, which was later confirmed by fungal culture. Anti–interferon-gamma autoantibodies (anti–IFN-γ auto-Abs) were markedly elevated (111.72 ng/mL). She was treated with liposomal amphotericin B(L-AmB) followed by itraconazole, achieving temporary remission. One month post-discharge, TM recurred with new Sweet syndrome–like skin lesions. Immunomodulatory therapy combined with antifungals led to disease control. This case highlights three key clinical insights: (1) TM can closely mimic tuberculosis, especially in HIV-negative individuals; (2) mNGS is a valuable diagnostic tool when conventional tests fail; and (3) Anti–IFN-γ auto-Abs may underlie recurrent or refractory TM infections. Clinicians in endemic regions should consider TM and evaluate immune status early in atypical or treatment-resistant cases. Talaromyces marneffei (TM) infection may mimic tuberculosis or malignancy in HIV-negative patients, leading to delayed diagnosis and inappropriate therapy. Anti–interferon-gamma autoantibodies (anti-IFN-γ auto-Abs) are a key risk factor for disseminated TM infection and may explain recurrent or refractory cases in apparently immunocompetent hosts. Metagenomic next-generation sequencing (mNGS) enables rapid and accurate identification of TM, especially when routine microbiological tests are inconclusive. Sweet syndrome-like skin lesions may be a clinical clue in TM cases associated with anti-IFN-γ auto-Abs, especially in relapsing disease. Early consideration of immune status and geographic risk factors is essential for diagnosing TM in non-HIV patients with atypical presentations or poor response to empirical therapy.