To investigate the diagnostic and therapeutic strategies for disseminated histoplasmosis (DH) complicated with secondary hemophagocytic lymphohistiocytosis (HLH).

The diagnosis and treatment process of a 67-year-old male patient with DH complicated with secondary HLH admitted to the First Affiliated Hospital of Chongqing Medical University on February 26th, 2023 were analyzed, and the relevant literatures were reviewed.

The case exhibited symptoms of fever and anorexia for 3 days after returning Chongqing municipality from a trip to Guangxi Zhuang Autonomous Region, accompanied by fatigue and weight loss. Throughout his illness, he experienced recurrent episodes of high fever and presented with evidence of HLH, including reduced blood cells, elevated ferritin levels, decreased natural killer (NK) cell activity and hepatosplenomegaly. Diagnostic confirmation of DH was achieved through bone marrow aspirate smear microscopy, peripheral blood metagenomic next-generation sequencing (mNGS), and enhanced computed tomography (CT) of chest images. A therapeutic regimen was initiated, comprising low-dose dexamethasone induction therapy (5 mg daily intravenously for 14 days, followed by 2.5 mg daily for 7 days), in conjunction with amphotericin B liposomal (17 mg at the first day, the dose gradually increased from 17 mg daily to 100 mg daily over three days, and maintained for a subsequent 21 days), followed by a maintenance therapy with itraconazole (200 mg every 12 hours). A follow-up enhanced chest CT scan after three months of post-diagnosis and treatment indicated a near-complete resolution of the lesions.

For patients with DH combined with secondary HLH, the primary treatment strategy should focus on addressing the primary disease, supplemented by hormone induction therapy. The avoidance of immunosuppressive drugs to mitigate infection can significantly improve the prognosis.