Disseminated histoplasmosis in a renal transplant patient

A 73-year-old African-American female patient underwent a living-related donor kidney transplant for end-stage renal disease. She experienced an episode of acute rejection, which was successfully treated. She was thereafter continued on appropriate immunosuppression with tacrolimus and mycophenolate mofetil. She received trimethoprim– sulfamethoxazole and valganciclovir for Pneumocystis jiroveci and cytomegalovirus prophylaxis, respectively. She also continued her antifungal prophylaxis with clotrimazole. A steroid taper was attempted, but was unsuccessful. Three months after her transplant, she presented to the hospital with severe sepsis. She was not neutropenic at presentation (absolute neutrophil count of 2.4 3 10/L) with a total white blood count of 2.9 3 10/L. Her hemoglobin was 8.1 gm/dL, which was considered secondary to anemia of chronic disease. The platelet count was normal at 190 3 10/L. An initial peripheral smear showed Dohle bodies, which was consistent with septicemia. She was started on broad-spectrum antibiotics and caspofungin due to a history of candida infection in a superficial wound. However, she continued to have persistent fevers with normal white blood counts. A repeated peripheral smear revealed numerous 3–4 lm intracellular yeast organisms in her leucocytes (white arrows) (Fig. 1). A bone marrow aspirate and trephine biopsy was performed. Grocott‘s methenamine silver stain (GMS) showed diffuse histiocytic infiltrates (black arrow) with innumerable narrow-budding yeast species (yellow arrow). Bone marrow and blood cultures eventually both grew Histoplasma capsulatum. The broncho-alveolar lavage analysis, urine histoplasma antigen, and serologic assays all came back positive for histoplasma. She also had a lumbar puncture, which was negative. Interestingly, the transplanted kidney was not affected, which was proven by a renal biopsy. She was treated with amphotericin B, which was then changed to itraconazole with complete eradication of the fungus and resolution of her sepsis. The donor was a family member who lived in the same household as the patient (recipient). They both had negative pre-transplant histoplasma serologies done 2 months prior to the transplant date. Interestingly, the repeat histoplasma serology of both the donor and recipient done 3 months after the transplant date were positive. No epidemiologic risk factors for histoplasma exposure were determined in either. The donor remained completely asymptomatic during this period, while the recipient presented with severe sepsis due to disseminated histoplasmosis. It is conceivable that the donor had a sub-clinical histoplasma exposure during the period between the testing of the pre-transplant serologies and the actual transplant date (a period of 2 months), thereby validating a case of donor-derived infection. It is also possible that both the donor and recipient had simultaneous exposure after the transplant date, consistent with a case of donor–recipient common source infection. This case highlights the importance of a careful review of peripheral blood smear for intracellular organisms for an A. Swaika S. Ailawadhi Department of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Road South, Jacksonville, FL 32224, USA