S6224 Beyond the Bowel: Chronic Diarrhea as the Sentinel Symptom of Idiopathic Multicentric Castleman Disease

Introduction: Idiopathic Multicentric Castleman Disease (iMCD) is a rare, non-clonal lymphoproliferative disorder characterized by cytokine excess, systemic inflammation, and multiorgan involvement. While most patients present with lymphadenopathy and constitutional symptoms, GI manifestations such as chronic diarrhea are rare and easily misattributed. We report a diagnostically challenging case where small bowel diarrhea was the dominant presentation, delaying recognition of a life-threatening systemic disease. Case Description/Methods: A 45-year-old previously healthy, HIV-negative man presented with 4 months of profuse, non-bloody diarrhea (6–8 episodes/day), along with fatigue, anorexia, early satiety, bilateral leg edema, and a 25-pound unintentional weight loss. He denied fevers, travel, antibiotic use, or exposures. On exam, he appeared thin and mildly tachycardic, with bilateral inguinal and cervical lymphadenopathy, hepatosplenomegaly, and pitting edema. Labs revealed normocytic anemia (Hb 8.9 g/dL), thrombocytosis (540 K/μL), hypoalbuminemia (2.7 g/dL), elevated CRP (29 mg/L), ESR (81 mm/hr), and polyclonal hypergammaglobulinemia. Stool studies, celiac panel, and thyroid tests were unremarkable. Colonoscopy with biopsies was normal. Computed tomography showed diffuse lymphadenopathy and mild ascites. Esophagogastroduodenoscopy with duodenal biopsies revealed nonspecific inflammation and intraepithelial lymphocytosis, raising suspicion for an immune-mediated small bowel process. Given persistent symptoms and systemic signs, lymph node excision was performed, revealing regressed germinal centers and interfollicular vascular proliferation—consistent with hyaline vascular Castleman variant. HHV-8 and HIV were negative. Bone marrow showed no malignancy. After excluding mimickers (lymphoma, autoimmune enteropathy, Whipple’s), iMCD was diagnosed. Treatment with siltuximab led to rapid symptom resolution. Discussion: Though not classic for iMCD, diarrhea may result from cytokine-driven mucosal inflammation or lymphatic obstruction. Chronic small bowel diarrhea in the absence of clear GI pathology should prompt consideration of systemic illnesses, especially with lab abnormalities and subtle systemic signs. Conclusion: GI symptoms may be the initial clue to iMCD. When conventional workups are inconclusive, clinicians should broaden the differential to include infiltrative or inflammatory systemic diseases. Early recognition and IL-6–targeted therapy are key to improved outcomes.