Etiologies and predictors of diagnosis in nonresponsive celiac disease

Clin Gastroenterol Hepatol. 2007 Apr;5(4):445-50. doi: 10.1016/j.cgh.2006.12.006. Epub 2007 Mar 26.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Biopsy, Needle
  • Celiac Disease / diagnosis*
  • Celiac Disease / diet therapy
  • Celiac Disease / etiology*
  • Colitis, Microscopic / complications*
  • Endoscopy, Gastrointestinal
  • Feeding and Eating Disorders / complications*
  • Female
  • Glutens / adverse effects
  • Humans
  • Incidence
  • Intestinal Mucosa / pathology
  • Irritable Bowel Syndrome / complications
  • Male
  • Predictive Value of Tests
  • Probability
  • Prognosis
  • Recurrence
  • Registries
  • Retrospective Studies
  • Risk Assessment
  • Sex Factors
  • Treatment Failure


  • Glutens