S5098 Whipple’s Disease Presenting With Peritoneal Nodularity and Pleural Effusion Mimicking Carcinomatosis

Introduction: Outside typical gastrointestinal or arthritic syndromes associated with Whipple’s disease (WD), there are rare instances where diffuse, chronic disease has presented as peritoneal abnormalities mimicking carcinomatosis. The nonspecific symptoms of weight loss, abdominal pain, and radiological findings can resemble malignancy. In these atypical cases, diagnosis of WD requires strong clinical suspicion and awareness of its capacity to involve serosal surfaces (pleura and peritoneum), as in our case of WD with peritoneal nodularity and right pleural effusion that mimicked disseminated disease. Case Description/Methods: A 61-year-old man with history of atrial flutter presented with worsening nausea, abdominal pain, and weight loss. Computed tomography (CT) abdomen showed extensive mesenteric lymphadenopathy, raising concerns for infection vs malignancy. Exploratory laparoscopy for suspected appendicitis revealed peritoneal nodules; biopsies showed xanthogranulomatous inflammation (XGI) and mesothelial hyperplasia, with no malignancy detected. On return visit for worsening symptoms and new rash, labs revealed elevated C-reactive protein and ESR. CT chest showed a large right pleural effusion, prompting thoracentesis that found exudative fluid with no malignant cells or organisms. Given no clear etiology for weight loss and symptoms, he underwent esophagogastroduodenoscopy, which revealed PAS-positive foamy macrophages on duodenal biopsy, confirming WD. He received appropriate antibiotics and showed marked improvement at 6-month follow-up. Discussion: Serosal involvement in WD is unique, with few documented cases in the literature. Diffuse peritoneal studding, pleural effusion, and rash are patterns that rarely dominate the clinical picture of WD. One case observed an exudative, sterile pleural effusion and nodularities of the peritoneum and uterine tissue in WD. The peritoneal implants' infiltrative appearance resembles carcinomatosis, leading to confusion with malignancy. XGI and mesothelial hyperplasia may serve as histological clues to chronic WD, as reports have documented these findings on serosal surface biopsies. Although uncommon, skin manifestations of WD have been seen to include widespread macular rashes on trunk and limbs, consistent with our patient's exam, and may reflect immune dysregulation in response to systemic infection. This case highlights WD’s ability to mimic malignancy and systemic inflammation, underscoring the need for early inclusion in the differential for unexplained wasting and serosal involvement.