S4884 Ulcerative Colitis in a Patient With Type II Von Willebrand Disease: A Rare Coexistence of Monogenic and Polygenic Disorders

Introduction: Ulcerative colitis (UC) typically presents with diarrhea and hematochezia due to mucosal inflammation. Pathogenesis involves immune dysregulation, genetics, environmental triggers, and gut microbiota. Von Willebrand disease (VWD) is a rare inherited bleeding disorder caused by quantitative or qualitative defects in von Willebrand factor (VWF), essential for hemostasis. The co-occurrence of inherited VWD and newly diagnosed UC is exceptionally rare and presents unique diagnostic and management challenges. To our knowledge, this is the first documented case. Case Description/Methods: We present a 28-year-old man with Type II VWD and ulcerative pancolitis, currently in deep clinical and endoscopic remission on infliximab and methotrexate. Diagnosed with VWD at age 3, he had easy bruising, hematomas, and abnormal labs (FVIII 41%, VWF: RCo <12.5%, VWF: Ag 32%, normal multimers). He did not respond to DDAVP and required Humate-P infusions perioperatively. At age 23, he developed hematochezia and abdominal pain. Colonoscopy showed pancolitis; initial treatment with mesalamine and adalimumab provided brief relief. At 24, he experienced a flare with severe rectal bleeding requiring steroids and infliximab induction. Humate-P was administered to manage bleeding. Methotrexate was added to optimize immunogenicity. He has remained in remission for 5 years, with a colonoscopy 2 years ago confirming mucosal healing. Notably, his brother also had UC requiring colectomy. Discussion: VWD is a monogenic disorder, while UC is a complex polygenic disease. Though acquired VWD has been reported in inflammatory bowel disease, this is the first known case of inherited VWD preceding a UC diagnosis. Coexistence of these conditions complicates both diagnosis and treatment. VWD may obscure UC symptoms by causing mucocutaneous or gastrointestinal bleeding, potentially delaying UC diagnosis or exacerbating bleeding during flares. This case underscores the need for clinical vigilance in recognizing overlapping pathologies, especially when bleeding is more severe than typical UC flares. Prompt endoscopic evaluation and coordinated hemostatic and anti-inflammatory therapy are essential. This case highlights the complexity of managing concurrent monogenic and polygenic disorders, and the need for coordinated, multidisciplinary care in such patients.