Inflammatory Bowel Disease (IBD) is becoming more common in an increasingly diverse population. Exposure history is important, especially when prescribing immunosuppressive therapy. We present a case of suspected disseminated histoplasmosis in a gentleman with longstanding Ulcerative Colitis (UC) on anti-TNF with an atypical, large, non-healing duodenal ulcer. We aim to highlight risks, presentation, and management of histoplasmosis in IBD patients on immunosuppression with anti-TNFs. A 49-year-old-male with a 21-year history of left sided UC in remission on Infliximab (10 years) presented to our ED with orthostatic symptoms and melena. He reported two months of heartburn and epigastric pain refractory to acid suppression. In the ED, vitals were unremarkable. Labs showed BUN 38 mg/dL, hemoglobin 13.3 g/dL, and abnormal AST/ALT. Evaluation of mild chest discomfort revealed normal EKG and calcified nodule in the left lower lobe on chest X-ray. Tuberculosis testing was negative. EGD found a massive, 3-4cm, cratered, medial wall, hemi-circumferential ulcer from duodenal apex into the second duodenal segment (D2). Biopsies revealed acute inflammation, without CMV, dysplasia, malignancy or helicobacter pylori. CT identified a large mass 5×3.1×3.2cm in the pancreaticoduodenal groove from D2 without pancreatic duct dilation. There were prominent right axillary and sub-pectoral lymph nodes and the calcified granuloma seen on X-ray. He denied NSAID use. Symptomatic improvement occurred on aggressive acid suppression. EGD a month later showed persistent ulcer with unchanged pathology. EUS showed significant peri-duodenal thickening without malignant findings. IgG/IgG4 immunostains were negative. CEA and CA 19-9 were normal. Subsequent EGDs and imaging showed no changes. He developed duodenal stenosis requiring dilation. Hematology/Oncology evaluation was unrevealing and hyper-secretory disorder was ruled out. Lack of healing over seven months prompted referral to Infectious Disease. They identified bird dropping exposure with repeated deck pressure washing. Positive Histoplasma immunodiffusion M band indicated prior infection. Given exposure, lab, chest imaging and endoscopic findings, treatment for disseminated histoplasmosis (DH) with Itraconazole was initiated. Infliximab was held and mesalamines were restarted. Histoplasmosis is endemic to the Ohio/Mississippi River Valley and other countries. Disseminated histoplasmosis, typically found in the immunocompromised, presents in many ways with GI involvement in 70%. Diagnosis can be difficult as histoplasmosis mimics other diseases, including IBD. Prognosis is poor if left untreated. Endoscopically, ulcerations, mass-like lesions, or strictures are seen. Aside from identifying yeast, pathology is nonspecific. Severity guides treatment, classically involving Itraconazole. In IBD and diseases managed with immunosuppression (e.g. anti-TNFs), stopping therapy during infections is standard of care. Therapy may resume after treatment response. Treatment may be a year for DH. Prophylaxis for histoplasmosis, the most common fungal infection with anti-TNF use, is controversial. Literature exists where anti-TNF was continued during treatment of histoplasmosis with good outcomes. There were no recurrences with continuation or re-initiation of anti-TNF after treatment. However, many patients switched therapies. Though histoplasmosis rarely causes infection in IBD patients, outcomes can be poor. We must be aware of possible exposures, atypical or presentations mimicking IBD to identify infection early, stop immunosuppression and provide timely treatment.