When You Hear Hoof Beats, Sometimes You Have to Think of Zebras
Abstract & commentary
By Allan J. Wilke, MD, Associate Professor of Family Medicine, University of Alabama at Birmingham School of MedicineHuntsville Regional Medical Campus, Huntsville; Dr. Wilke reports no financial relationship to this field of study.
Synopsis: A significant portion of patients with irritable bowel syndrome will test positive for celiac disease.
Source: Ford AC, et al. Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: Systematic review and meta-analysis. Arch Intern Med 2009;169:651-658.
Irritable bowel syndrome (IBS) and celiac disease (CD) share many of the same symptoms, including abdominal pain, diarrhea, and bloating. IBS is more common with a prevalence of 7-10%;1 CD is an order of magnitude less.2 Since CD has a specific therapy, namely elimination of gluten from the diet, it would be tragic to misdiagnose a patient with IBS, if the true disease were CD, or miss coexisting CD.
This group of researchers performed a systematic review and meta-analysis of studies that report CD in patients who carry the diagnosis of IBS to estimate its prevalence in this setting. They searched MEDLINE and EMBASE. Inclusion criteria were case series or case-control studies with at least 90 unselected adult subjects with an IBS diagnosis who had serologic testing for CD. The diagnoses were made by physician opinion, questionnaire data, or symptom-based criteria, such as the Rome III criteria.3 The serologic tests included IgA-class antigliadin antibodies (AGAs), endomysial antibodies (EMAs), and tissue transglutaminase antibodies (tTGAs). In some studies, distal duodenal biopsies were performed when subjects had positive serology. They winnowed 7522 studies to 14 with 4204 subjects. IBS was diagnosed in 2278. The studies were evenly divided between case series and case-control studies.
When looking at the studies where IgA-class AGAs were measured, the prevalence of CD in IBS subjects ranged from 0% to 18%; the pooled prevalence was 4.0% (confidence interval, 1.7%-7.2%). In the studies that offered duodenal biopsy when screening was positive, 30% had histologic findings consistent with CD. Among subjects who met criteria for IBS, 3.6% had positive IgA-class AGAs, whereas only 1.0% of subjects who did not meet criteria tested positive (odds ratio [OR], 3.40). When EMAs or tTGAs were used for screening, the positive tests ranged from 0% to 11.4%, with a pooled prevalence of 1.63%. Ninety-two percent of those subjects testing positive had duodenal biopsies consistent with CD. Comparing individuals who met criteria for IBS to those who did not, the percentages testing positive for EMAs or tTGAs were 3.0% vs 0.7%, respectively (OR, 4.34). Having constipation-predominant or diarrhea-predominant IBS did not affect the results, nor did location of the study or whether the population tested was based in primary care or specialty care.
Commentary
The medical terminology here is a little confusing. Gluten-sensitive enteropathy (GSE) is the correct term for the diseases formerly called celiac disease (in children) and nontropical sprue (in adults). Treatment is lifelong and not easy because it involves the elimination of wheat, rye, and barley from the diet. Gluten is the major protein in these grains. Its alcohol-soluble component is gliadin; hence, the testing of antigliadin antibodies. Gluten can "hide" in processed foods, so maintaining a gluten-free diet is difficult. Failure to do so results not only in symptomatic disease, but places the patient at risk for intestinal lymphoma4 and other complications.5
There are two important pieces of information from this meta-analysis. The first is that the percentage of individuals who meet criteria for irritable bowel syndrome and who have a serology positive for GSE is not insignificant. The second is that tests for EMAs or tTGAs performed better than tests for IgA-class AGAs. The question of whether it is cost-effective to screen patients with IBS for GSE depends on its prevalence. The percentages presented here make that case.
It is estimated that only 5% of North Americans with GSE are diagnosed.6 Not everyone will present with weight loss or diarrhea. Looking for it among patients with IBS, unexplained anemia, chronic unexplained diarrhea, chronic fatigue, autoimmune disorders (especially thyroiditis), type 1 diabetes mellitus,7 and Down or Turner syndrome will increase our rate of detection and initiation of treatment. A clinical decision tool that was 100% sensitive in identifying patients with GSE was published in 2007.8
References
1. American College of Gastroenterology Task Force on IBS. An evidence-based systematic review on the management of irritable bowel syndrome. Am J Gastroenterol 2009; 104:S1-S35.
2. Fasano A, et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: A large multicenter study. Arch Intern Med 2003;163:286-292.
3. Longstreth GF, et al. Functional bowel disorders. Gastroenterology 2006;130:1480-1491.
4. Silano M, et al. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci 2008;53:972-976.
5. Haines ML, et al. Systematic review: The evidence base for long-term management of coeliac disease. Aliment Pharmacol Ther 2008;28:1042-1066.
6. Catassi C, et al. Detection of Celiac disease in primary care: A multicenter case-finding study in North America. Am J Gastroenterol 2007;102:1454-1460.
7. Smyth DJ, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 2008;359:2767-2777.
8. Hopper AD, et al. Pre-endoscopy serological testing for coeliac disease: Evaluation of a clinical decision tool. BMJ 2007;334:729.
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