Original article
Etiologies and Predictors of Diagnosis in Nonresponsive Celiac Disease

https://doi.org/10.1016/j.cgh.2006.12.006Get rights and content

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.

Section snippets

Methods

A database of all patients seen at our institution from January 1, 2000, to April 1, 2006, coded for CD under the International Classification of Diseases 9th edition code 579.0 was compiled and predetermined clinical data were recorded. From this list, 603 patients were found to have biopsy examination–proven CD. Individuals without definitive evidence of CD in the form of duodenal biopsy examination, or skin biopsy examination in cases of dermatitis herpetiformis, were not included in this

Results

A total of 113 of 603 (18.7%) individuals with CD were found to have NRCD. Of the 113 patients, 74 (65%) were referred by clinicians from outside our institution and the remaining 39 (35%) patients were cared for at our institution from the initial diagnosis of CD onward. NRCD accounted for 35% of the 211 new referrals to our celiac center. The majority of the remaining referrals were for either confirmation of diagnosis or general management of previously diagnosed CD. Thirty-nine of the 392

Discussion

In this study we report the incidence, etiology, and clinical characteristics of 113 consecutive NRCD patients seen at our center over the preceding 5 years. Our findings are consistent with those of other reports; however, the larger size of our patient population allows for increased statistical power and for us to make diagnostic predictions based on presenting symptoms. As in past studies,8 gluten exposure remains the most common cause of NRCD and is the only diagnostic category

References (40)

  • G.F. Longstreth et al.

    Functional bowel disorders

    Gastroenterology

    (2006)
  • G. Luzi et al.

    Duodenal pathology and clinical-immunological implications in common variable immunodeficiency patients

    Am J Gastroenterol

    (2003)
  • S. Case

    The gluten-free diet: how to provide effective education and resources

    Gastroenterology

    (2005)
  • J. Askling et al.

    Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis

    Gastroenterology

    (2002)
  • J.A. Murray et al.

    Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease

    Am J Clin Nutr

    (2004)
  • J. Wei et al.

    Gene, gut and schizophrenia: the meeting point for the gene-environment interaction in developing schizophrenia

    Med Hypotheses

    (2005)
  • P.A. Pynnonen et al.

    Mental disorders in adolescents with celiac disease

    Psychosomatics

    (2004)
  • R.J. Farrell et al.

    Celiac sprue

    N Engl J Med

    (2002)
  • W. Dieterich et al.

    Identification of tissue transglutaminase as the auto-antigen of celiac disease

    Nat Med

    (1997)
  • W. Dieterich et al.

    Pathomechanisms in celiac disease

    Int Arch Allergy Immunol

    (2003)
  • Cited by (0)

    Supported by a National Institutes of Health T32 research grant.

    View full text