Celiac Disease: Ten Things That Every Gastroenterologist Should Know

Amy S. Oxentenko; Joseph A. Murray


Clin Gastroenterol Hepatol. 2015;13(8):1396-1404. 

In This Article

9. What Is the Approach to the Nonresponsive Celiac Patient?

Nonresponsive celiac disease (NRCD) is defined as a lack of response to 6 months on a GFD or recurrence of celiac-related features despite compliance.[30,67] NRCD is common and has been reported in 10%–19% with CD.[68,69] Applying a stepwise approach to NRCD is imperative.[3]

The first step in those with NRCD is to verify the diagnosis of CD, reviewing baseline serologic titer(s) and intestinal biopsies. In the patient with enteropathy but negative serology on a gluten-containing diet, other causes of villous atrophy need to be considered, including, but not limited to, small intestinal bacterial overgrowth, autoimmune enteropathy, tropical sprue, drug-associated enteropathy (eg, olmesartan), Crohn's disease, combined variable immunodeficiency, collagenous sprue, and eosinophilic gastroenteritis.[70,71] CD can be excluded by the absence of HLA DQ2 and DQ8.[70]

If the initial diagnosis of CD is robust, the next step is to evaluate whether gluten exposure (blatant, surreptitious, or inadvertent) is ongoing.[61] A persistent or recurrent elevation of serologic titer suggests gluten ingestion, although a normal value does not ensure compliance.[72] There may be gluten exposure in non-food items such as medications, supplements, cosmetics, and glues.[49,73]

If gluten ingestion is unlikely, then duodenal biopsies should be performed. Biopsy the duodenum for RCD and the colon for microscopic colitis, which is 50-fold to 72-fold more common in CD.[74,75]

If duodenal and colonic biopsies are normal, then other causes of diarrhea need to be considered, such as disaccharidase deficiency, small intestinal bacterial overgrowth, pancreatic insufficiency, or irritable bowel syndrome; the latter is most common among these associated conditions and reported in 22% of NRCD.[68]

Practical Suggestion

In NRCD, verify the original CD diagnosis, and seek gluten ingestion. If gluten exposure is not present, then duodenal and colonic biopsies can be helpful. If these tests are negative, then systematic evaluation is needed.