Janssens, Laurens P

Abstract Background There are limited data on how vedolizumab (VDZ) impacts extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). The aim of this study was to determine the clinical outcomes of EIMs after initiation of VDZ for patients with IBD. Methods A multicenter retrospective study of patients with IBD who received at least 1 dose of VDZ between January 1, 2014 and August 1, 2019 was conducted. The primary outcome was the rate of worsening EIMs after VDZ. Secondary outcomes were factors associated with worsening EIMs and peripheral arthritis (PA) specifically after VDZ. Results A total of 201 patients with IBD (72.6% with Crohn disease; median age 38.4 years (interquartile range, 29-52.4 years); 62.2% female) with EIMs before VDZ treatment were included. The most common type of EIM before VDZ was peripheral arthritis (PA) (68.2%). Worsening of EIMs after VDZ occurred in 34.8% of patients. There were no statistically significant differences between the worsened EIM (n = 70) and the stable EIM (n = 131) groups in term of age, IBD subtype, or previous and current medical therapy. We found that PA was significantly more common in the worsening EIM group (84.3% vs 59.6%; P < 0.01). Worsening of EIMs was associated with a higher rate of discontinuation of VDZ during study follow-up when compared with the stable EIM group (61.4% vs 44%; P = 0.02). Treatment using VDZ was discontinued specifically because of EIMs in 9.5% of patients. Conclusions Almost one-third of patients had worsening EIMs after VDZ, which resulted in VDZ discontinuation in approximately 10% of patients. Previous biologic use or concurrent immunosuppressant or corticosteroid therapy did not predict EIM course after VDZ.

INTRODUCTION: Gastroparesis is defined as delayed gastric emptying in the absence of mechanical obstruction. Diabetes and medication side effects are common causes. AL amyloidosis is a systemic disease due to extracellular fibril deposition that can affect multiple organs. Gastro-intestinal (GI) involvement is less common than in other organ systems but can present in many different ways, including gastroparesis. CASE DESCRIPTION/METHODS: A 77 year old non-diabetic man from Mississippi presented with a one year history of intermittent abdominal distention, nausea and bloating. In addition, he had increasing dyspnea on exertion and lower extremity edema. Outside work-up consisted of multiple imaging studies demonstrating marked gastric distention as well as delayed gastric emptying (Figures 1 and 2). Outside colonoscopy was unrevealing and EGD was negative except for a distal esophageal ulcer and focal active duodenitis. He was started on a PPI and trialed on an alternating regimen of metoclopramide and erythromycin, without symptomatic relief. He was referred to our hospital for further diagnostic work-up. Repeat colonoscopy showed congested distal ileal mucosa and friable ascending colonic mucosa. Biopsies from both sites revealed amyloid deposits by Congo red stain (Figure 3). Serum protein electrophoresis noted a monoclonal IgG lambda peak with M-spike of 1.5 g/dL and bone marrow biopsy revealed approximately 70% of marrow cellularity consisting of plasma cells. Echocardiogram confirmed severely increased concentric left ventricular wall thickening consistent with cardiac amyloidosis. Interestingly, neither fat pad biopsy nor bone marrow biopsy showed presence of amyloid. The patient was diagnosed with myeloma and AL amyloidosis with gastro-intestinal and cardiac involvement. DISCUSSION: This case highlights the broad differential for gastric distention and dysmotility. When the ‘usual suspects’ such as diabetes, medication, post-surgery and neurological disease have been ruled out, rarer causes like an infiltrative process should be considered. Common manifestations of GI tract amyloidosis include GI bleeding, malabsorption, protein-losing enteropathy and chronic dysmotility. The diagnosis of amyloidosis is based on positive tissue diagnosis. While the combination of a fat pad and a bone marrow biopsy has a high sensitivity (89%) for diagnosing AL amyloidosis, negative results do not rule out amyloid elsewhere and tissue sampling from the affected organ site is essential, as demonstrated in this case.