Etiologies and Predictors of Diagnosis in Nonresponsive Celiac Disease

Background & Aims: Nonresponsive celiac disease (NRCD) is a common problem affecting from 7% to 30% of celiac patients. Because NRCD comprises varied and potentially morbid entities, efficient and cost-effective patient care requires knowledge of the specific causes of this disorder. The aim of this study was to determine the common etiologies of NRCD in a tertiary referral center. Methods: All cases of biopsy examination–proven celiac disease (CD) seen at our institution over the preceding 5 years were included in this study. NRCD was defined as a failure to respond to at least 6 months of treatment with a gluten-free diet or the re-emergence of symptoms or laboratory abnormalities typical of CD while still on treatment with a gluten-free diet. Results: A total of 113 patients with NRCD meeting the earlier-described criteria were seen from a total of 603 patients with CD (19%), however, among patients for whom we provided primary specialist care the incidence of NRCD was 10% (P < .001). Gluten exposure was the most common cause of NRCD (36%), followed by irritable bowel syndrome (22%), refractory CD (10%), lactose intolerance (8%), and microscopic colitis (6%). The mean immunoglobulin A tissue transglutaminase level in the gluten-exposed group was 67 vs 17 U/mL (normal, <20) for other diagnoses (P < .05). Weight loss and male sex were highly predictive of refractory CD (P < .05 and < .001, respectively). Conclusions: NRCD is a common phenomenon affecting 10%–19% of celiac patients. A limited number of etiologies account for the majority of cases. Clinical factors may be used to guide evaluation.