Authors' objectives:

The objectives of this review were to conduct a comprehensive systematic review on five areas of celiac disease (CD): (1) sensitivity and specificity of serological tests; (2) prevalence and incidence of CD; (3) CD associated lymphoma; (4) consequences of testing for CD; and, (5) interventions for the promotion and monitoring of adherence to a gluten-free diet (GFD).

Authors' recommendations: This report has provided a systematic review of five broad areas (and corresponding sub-areas) of CD. Perhaps one of the most important findings of this report is the significance of how one chooses to define CD in the era of serological testing, and how this apparently clear-cut task has profound implications on all the results presented in this report. Specifically, can CD be diagnosed solely on the basis of serology? Is some degree of villous atrophy necessary for a diagnosis of CD. These questions have important implications downstream of the diagnosis as well. For example, do CD patients without symptoms or villous atrophy have the same risk of complications as those with villous atrophy. Is serological improvement on a GFD sufficient to reduce CD complications, or must there be documented histological improvement, and what degree of histological improvement is necessary? The results of the Celiac 1 objective suggest that in the era of EMA and tTG antibody testing, AGA antibody testing in both children and adults has a limited role. The sensitivity and specificity of EMA and tTG are quite high (over 95% for sensitivity, and close to 100% for specificity), as are their positive and negative predictive values; however, one has to be aware that the reported diagnostic parameters are taken from studies in which the prevalence of CD was, for the most part, much higher than that seen in usual clinical practice The positive predictive values reported for these tests will certainly not be as high as that reported when these tests are used to screen the general population. The bulk of the evidence on the diagnostic characteristics of these tests was derived from studies that defined CD as having at least some degree of VA. HLA DQ2/DQ8 testing appears to be a useful adjunct in the diagnosis of CD. The test has high sensitivity (in excess of 90%-95%), however, since approximately 30% of the general population, and an even higher proportion of high-risk subjects (e.g., diabetics and family members) also carry these markers, the specificity of this test is not ideal. The greatest diagnostic utility of this test appears to be its negative predictive value. Biopsy itself, when used with a strict cut-off requiring villous atrophy, appears to have high specificity, but poor sensitivity. Using a lower grade cut-off clearly improves sensitivity, but because of the wide differential of causes of histological lesions similar to Marsh I to IIIa, the specificity suffers. The use of histomorphometric measures such as quantification of gamma delta positive intraepithelial lymphocytes (+ IELs) are likely to allow for the use of lower grade cut-offs, while maintaining reasonable specificity. Ultimately, a trial utilizing multiple diagnostic tests in an attempt to capture as many CD patients in a clinically-relevant population as possible, along with a time dimension such as a response to a GFD or glute challenge, is required to fully assess the diagnostic characteristics of biopsy alone. This type of study would be able to characterize the false-positive and false-negative rates, provided that all studied patients are followed forward in time. The included prevalence studies demonstrated important differences between the studies including, execution, tests for prevalence assessment, and patient sampling. Thus, results have to be interpreted in the light of some of the limitations that have been identified regarding the diagnostic performance of the tests for CD. Nonetheless, the results of this report suggest that CD is a very common disorder with a prevalence in the general population that is likely close to 1:100 (1%). Several high-risk groups with a prevalence of CD greater than than of the general population have been identified and include: those suspected of having CD; family members of CD patients; type I diabetics; and, those with iron-defiency anemia (IDA) or low bone mineral density (BMD). Additionally, the review identified many other high-risk groups, including those with Down Syndrome, short stature, and infertility, to name a few. Their inclusion was however, beyond the scope of this report. The results of this report confirm that, apart from a few limitations, there is a strong association between CD and GI lymphoma. The report identified standard incidence ratios (SIR) for lymphoma that ranged from 4 to 40, and standard mortality ratios (SMR) that ranged from 11 to 70. A diagnostic delayin particular a diagnosis of CD in adulthood as apposed to in childhoodis associated with poorer outcomes. Fortunately, several studies suggest that adherence to a GFD reduces the risk of lymphoma in CD patients. The consequences of testing for CD in at-risk and symptomatic patients appear to be more straightforward, since these patients appear to be more compliant with a GFD and would be expected to benefit from this intervention. The data is less clear for asymptomatic screenidentified patients, particularly those who have truly silent CD and/or dont have fully-developed villous atrophy. On the one hand the outcome of such patients has not been extensively studied, and on the other hand compliance with a GFD appears problematic, particularly for those diagnosed in adulthood. Finally, no specific interventions have been identified that promote adherenc to a GFD, but education of patients and family members about CD and about the intricacies o a GFD, and participation in local celiac societies, has been shown to improve compliance Although somewhat controversial, biopsy monitoring of adherence to a GFD appears to be important, since improvement in histological grade has been associated with improved BMD, IDA, and nutritional status. The serological markers appear to be adequate for detecting gross dietary indiscretion, and respond to a gluten challenge, but appear to have poor sensitivity for detecting lesser degrees of dietary indiscretion, and inadequately correlating with histological improvement at least in the short-term. It should, however, be noted, that we could not identify a controlled study that objectively determined the level of histological improvement that would be associated with improved outcomes, and this is an area for future study. Nonetheless, based on this report it would appear that follow-up biopsy, at least 1 year after a GF in adults to document improvement of the histological grade, would be valuable.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.ahrq.gov/clinic/tp/celiactp.htm

Year Published: 2004

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: Agency for Healthcare Research and Quality

Contact Address: Center for Outcomes and Evidence Technology Assessment Program, 540 Gaither Road, Rockville, MD 20850, USA. Tel: +1 301 427 1610; Fax: +1 301 427 1639;

Contact Name: martin.erlichman@ahrq.hhs.gov

Contact Email: martin.erlichman@ahrq.hhs.gov

Copyright: Agency for Healthcare Research and Quality (AHRQ)