D155 - Disseminated Histoplasmosis Presenting as Crescentic Glomerulonephritis and Secondary Hemophagocytic Lymphohistiocytosis in a Renal Transplant Recipient

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Author Block: A. Ullah¹, R. Sodhi², D. Jain², S. Akkina², N. Clark³, M. Picken³, V. Peev², ¹Nephrology, Loyola University Medical Center, Maywood, IL, ²Transplant Nephrology, Loyola University Medical Center, Maywood, IL, ³Loyola University Medical Center, Maywood, IL
*Purpose: Histoplasmosis is an uncommon but severe opportunistic infection in solid organ transplant recipients. Disseminated disease can mimic graft rejection or post-transplant lymphoproliferative disorder and may trigger secondary hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory state associated with significant morbidity.
*Methods: We report a 48-year-old African American male with end-stage renal disease secondary to hypertension who underwent a cadaveric renal transplant. The donor and recipient were CMV and EBV seropositive. Induction immunosuppression included thymoglobulin and methylprednisolone followed by maintenance with belatacept, mycophenolate, and prednisone.Eight months post-transplant, the patient presented with fever, malaise, night sweats and diarrhea. Laboratory workup revealed elevated creatinine (4.8 mg/dL; baseline 2-2.4 mg/dL), pancytopenia, and markedly elevated inflammatory markers (CRP 90.5 mg/dL, procalcitonin 6.4 ng/mL, soluble IL-2 receptor 51,614 pg/mL and serum ferritin of 11,764 ng/ml). Infectious and autoimmune serologies were largely negative, except for urinary Histoplasma (6.83 ng/mL) and Blastomyces (3.39 ng/mL) antigens. Additionally, comprehensive serologic work up for crescentic glomerulonephritis was unremarkable (ANCA negative).CT imaging showed pulmonary ground-glass opacities, mediastinal, cervical lymphadenopathy and splenomegaly. Bronchoalveolar lavage with lymph node biopsy demonstrated growth of Histoplasma capsulatum. Bone marrow biopsy revealed macrophage proliferation consistent with HLH. Renal graft biopsy showed focally crescentic glomerulonephritis with mild T cell-mediated rejection and strong CD68+ macrophage activation staining, and occasional yeast-like structures on PAS stain. The patient was treated with liposomal amphotericin B and pulse corticosteroids, resulting in clinical improvement and stabilization of renal function.
*Results: This case underscores the diagnostic complexity of disseminated histoplasmosis in transplant recipients. The coexistence of HLH further highlights the need for early recognition and prompt antifungal therapy. Cross-reactivity of fungal antigens and overlapping inflammatory findings can obscure diagnosis without tissue confirmation.
*Conclusions: Disseminated histoplasmosis can be associated with HLH and crescentic glomerulonephritis in renal transplant recipients presenting with systemic inflammation, cytopenia, and renal dysfunction. Combined antifungal and immunomodulatory therapy can be lifesaving.