INTRODUCTION: Histoplasma capsulatum is an environmental mold that typically causes mild, self-limited respiratory symptoms; in immunosuppressed patients more severe disseminated infection may occur. Symptoms of gastrointestinal (GI) histoplasmosis are nonspecific and can manifest in many ways. CASE DESCRIPTION/METHODS: Case 1 is an 80-year-old male with multiple myeloma status post auto-stem cell transplant 12 years prior, currently on lenalidomide. The patient presented with 4-year history of worsening diarrhea, vomiting, weight loss and fevers that led to an ICU admission for hypovolemic shock. He was diagnosed with disseminated pulmonary histoplasmosis based on positive blood cultures and innumerable small pulmonary nodules on CT scan. A colonoscopy revealed erosions of the right colon; biopsies were positive for histoplasma. Diarrhea persisted despite treatment with amphotericin B and itraconazole. Twelve weeks later, the patient was re-admitted for continued symptoms. Findings from a repeat colonoscopy are shown in Figure 1. He developed a partial small bowel obstruction requiring a 23-cm ileocecal resection. Pathology confirmed fibrostenotic histoplasmosis of the ileocecum (Figure 2). The patient recovered from surgery; colonoscopy with biopsies 11 months after initiation of treatment was negative for infection. Case 2 is a 54 year-old male with refractory Hodgkin’s lymphoma that was admitted to the ICU with hypovolemic shock due to 3 months of diarrhea, headaches, weight loss, and fevers. MRI of the brain showed leptomeningeal enhancement consistent with disseminated histoplasmosis. Upper endoscopy findings are shown in Figure 3, colonoscopy had similar results. The patient improved with itraconazole. DISCUSSION: GI manifestations of histoplasmosis can be severe, as demonstrated by these 2 cases. Case 1 is unique as only a few cases of fibrostenotic histoplasmosis of the GI tract have been reported in the literature. Case 2 is distinctive given that histoplasmosis has rarely been reported to involve the small bowel. Histoplasmosis of the GI tract may also present with colitis, perforation, or GI bleed. GI symptoms can manifest with or independent of other systemic symptoms. It is critical to consider histoplasmosis in immunocompromised patients. Prompt diagnosis by endoscopy with biopsies in patients with suspected GI histoplasmosis is imperative in order to direct appropriate treatment.Figure 1.: (A) Endoscopic image of a deformed, strictured ileocecal valve, precluding intubation of the terminal ileum. (B) Polypoid lesions in the right colon. (C) H&E stain of the colonic mucosa at 400x shows lymphohistiocytic expansion of the lamina propria and active neutrophilic cryptitis. (D) Grocott’s Methenamine Silver (GMS) stain of the colonic mucosa at 400x shows the characteristic 2–5 um yeast forms of Histoplasma capsulatum within the lamina propria between the ileocecal crypts.Figure 2.: (A) Surgical specimen showing the dilated ileum, ileocecal stricture which was unable to be transected with surgical scissors. (B) H&E stain of the specimen shows transmural necrotizing granulomatous inflammation with mucosal ulceration. (C) H&E stain at 400x shows peripheral palisading macrophages (left) at the edge of the central necrosis (right). (D) GMS stain at 600x shows characteristic uniform, round 2–5 um yeast forms, consistent with Histoplasma capsulatum.Figure 3.: (A) Duodenal erythema, superficial erosion. (B) H&E Stain of the duodenal mucosa at 40x shows lymphohistiocytic expansion of the lamina propria associated with partial blunting of the villous architecture. (C) GMS stain at 400x shows the characteristic 2–5 um yeast forms of Histoplasma capsulatum within the lamina propria clustering with macrophages.
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