Refractory celiac disease is due to celiac disease

Abstract

Background: Refractory celiac disease (CD) is characterized by persistent symptoms (diarrhea or failure to regain weight) despite a gluten free diet (GFD). Causes for persistent symptoms include continued gluten ingestion, complications of CD (collagenous sprue, lymphoma) or other diseases (lymphocytic colitis, pancreatic insufficiency, lactose malabsorption or irritable bowel syndrome.) Recent studies Suggest these non CD etiologies are the most frequent causes of continued diarrhea in CD. We attempted to characterize the reasons for persistent diarrhea and/or failure to gain weight in a series of patients with biopsy proven CD who claim to adhere to a GFD. Methods: From a series of 116 patients followed for celiac disease 18 patients (16%) were identified as refractory despite adherence to a GFD. Clinical, laboratory and pathological data was analyzed. Of the 18 patients with refractory symptoms 16 (89%) had follow up biopsies while on a GFD and all had follow up antigliadin (AGA) and endomysial (EMA) antibodies. Patients had been following a GFD for an average of 4 years. Results: Patients were considered refractory if they demonstrated a failure to gain weight (n=9), had persistent diarrhea (n=13) or both (n=4). Patients with a positive EMA (n=5) had obvious gluten ingestion on questioning (communion wafers in 4). Positive AGA was found in 14 patients ([gG in 14, IgG and IgA in 8). The 9 patients who were only AGA positive (and EMA negative) were assumed to have inadvertant gluten ingestion though the source was not obvious from carefully interviewing patients. At endoscopy all patients had decreased duodenal folds +/scalloping and two patients had duodenal/jejunal ulcers. All patients had abnormal small intestinal biopsies: villous atrophy and crypt hyperplasia (n=15 total villous atrophy in 13, partial villous atrophy in 2), hypoplastic appearance (n=l) and subepithelial collagenous deposition (n=l). Colonoscopy was performed in 10 patients; only 1 patient had evidence of lymphocytic colitis (but was also AGA positive). Three patients with diarrhea had trials of pancreatic enzymes without benefit. Six patients were on immunosuppressants (four of these being AGA and EMA negative) including steroids, cyclosporine, or imuran; three had good responses, one had no response, and one is early in treatment. Conduslons: All of our celiac patients with refractory symptoms (either persistent diarrhea or failure to gain weight) continue to have evidence of significant villous atrophy on small intestinal biopsy at follow up of four years on GFD. Serological testing was valuable in managing patients. Those with postive EMA had obvious gluten ingestion, while AGA was useful in detecting inadvertant gluten ingestion. Continued gluten ingestion was the most common cause of persistent diarrhea and/or failure to gain weight in our series. In no patient was lymphocytic colitis or pancreatic insufficiency an obvious cause of refractory celiac disease. We conclude that refractory celiac disease is most commonly due to gluten ingestion, whether inadvertant or obvious.