Introduction: Isolated collagenous gastroduodenitis (CGD) with no colonic involvement is an extremely rare entity with only 2 cases reported in the literature. We report a case of isolated CGD presenting as nausea, vomiting, abdominal pain and profound weight loss. Case: A 63-year-old African American woman presented with two-year history of nausea, vomiting, upper abdominal pain and sixty pounds weight loss. There was no history of diarrhea, gastrointestinal (GI) bleeding or skin changes. Prior evaluation, including esophagogastroduodenoscopy, colonoscopy with biopsies and a video-capsule endoscopy only revealed gastric mucosal edema. Celiac serologies were negative and a gluten free diet failed to improve her symptoms. She was hospitalized for severe malnutrition and total parenteral nutrition (TPN) was started. Laboratory evaluation revealed Hemoglobin of 12.4g/dl, albumin 2.6g/dl, positive antinuclear antigen (1:640), and positive anti SCL-70 antibody. Push enteroscopy showed inflammatory changes in the stomach and the small bowel (SB) wall mucosa appeared edematous and nodular. Biopsies revealed inflammatory changes and thickened collagen table consistent with CGD. She was started on oral prednisone, mycophenolate mofetil (MMF), and high dose proton pump inhibitors. Prednisone was eventually tapered off and the TPN was discontinued. At 4 months, repeat push enteroscopy showed normal looking SB mucosa. Biopsies revealed no collagen table. She has regained her baseline weight and is currently maintained only on MMF. Discussion: Collagenous gastroenteritides are characterized by marked subepithelial collagen deposition with mucosal inflammatory infiltrate. Isolated collagenous gastritis presents with anemia, weight loss, dyspepsia and epigastric pain. Endoscopy shows thickened and nodular mucosa, erosions, and ulcerations. Diagnosis is made by histology, with increased subepithelial collagen band thickness to at least 10 μm and inflammatory cell response with predominant mononuclear infiltrate in the lamina propria. GI involvement in scleroderma can also present similarly, however, endoscopic findings are more consistent with gastric antral vascular ectasia (GAVE) and histology is characterized by mucosal capillary dilatation with fibromuscular hyperplasia. The histological features in our case typify CGD and were not consistent with GI scleroderma. A variety of therapies for CGD have been tried including corticosteroids, Bismuth subsalicylate, Mesalazine, and hypoallergenic diets. Steroids can lead to clinical improvement, however, endoscopic or histological improvement has not been documented. The uniqueness in our case is significant clinical, endoscopic and histologic response to steroid and MMF therapy. With increased awareness and reporting of such cases, diagnostic and management strategies may be better elucidated.