LAUSR

Bone marrow biopsy showed presence of intracellular yeast forms along with rare histiocytes showing hemophagocytosis. Histoplasma serum Ag was positive and fungal blood and bone marrow cultures grew H. capsulatum. MRI of the brain with contrast did not show any evidence of fungal infection. Full body PET-CT was performed and showed multiple enlarged lymph nodes throughout the chest and abdomen, as well as splenomegaly. Diagnostic lumbar puncture was performed and cultures were sent, including fungal culture. Cerebrospinal fluid Histoplasma serum Ag was 0.96 (positive). Additional studies for evaluating HLH were sent: SolIL2R was elevated at 3331 units/ml (normal 45–1105 unit/ml), CD163 was elevated at 10,138 ng/ml (normal 387– 1785 ng/ml), and natural killer (NK) cell function was low, supporting the diagnosis of HLH. Genetic testing with a targeted HLH gene panel was sent to determine if the patient had primary (familial) HLH. The patient did not have evidence of familial (primary) HLH because she had no homozygous familial HLH abnormalities. While she did have a heterozygous mutation in Munc13-4, no mutations were found in any other HLH genes (perforin and syntaxin), supporting a diagnosis of secondary HLH related to disseminated histoplasmosis and CMV infection. The patient was started on daily IV liposomal amphotericin B at a dose of 5 mg/kg/day for treatment of disseminated histoplasmosis. In addition, IV ganciclovir was also started due to elevated bone marrow CMV PCR (2000 IU/ml) in conjunction with increasing blood CMV PCR (1900 IU/ml). Within 2weeks of starting this antimicrobial regimen, her fever and hematologic abnormalities slowly resolved. After 28 days of daily IV liposomal amphotericin B, therapy was changed to three times per week (after the HD sessions) for 12 months, while monitoring Histoplasma serum Ag levels. The Histoplasma serum Ag level gradually decreased and became negative after 12 months of liposomal amphotericin B, treatment which then was changed to oral itraconazole (Graph 1, Table 1). In addition, after 3 weeks of IV ganciclovir, CMV-directed therapy was changed to oral therapy with valganciclovir and continued for an additional 6 weeks. At the completion of antiviral therapy, the CMV viral load was undetectable. Two years after the initial diagnosis, she remains disease free.