7Diagnosis of coeliac disease
Section snippets
Who should have serologic testing?
The clinical suspicion of coeliac disease may be based on the presence of gastrointestinal symptoms, i.e. those with classical, diarrhea-predominant syptoms with or without a malabsorption syndrome. The next most common group in whom the diagnosis should be considered are those with manifestations of malabsorption of nutrients or vitamins. This includes patients with iron deficiency anemia in the absence of gastrointestinal bleeding, folic acid deficiency, manifestations of calcium or vitamin D
Serology testing
The widespread availability of serologic tests has permitted the diagnosis of coeliac disease to be considered and tested for by any physician. The most sensitive tests are based on the use of IgA isotypes. The available tests include antigliadin antibodies as well as connective tissue antibodies: reticulin, endomysial and tissue transglutaminase antibodies. The lower sensitivity and specificity of the antigliadin antibodies (70–80%) have resulted in their use being called into question for the
Selective IgA deficiency
Selective IgA deficiency (SIgAD) occurs more commonly in patients with coeliac disease than the general population.45 As a result, patients with coeliac disease lack IgA-EMA, IgA-tTG and IgA-antigliadin antibodies.46, 47 In order to detect coeliac disease in those with SIgAD a total IgA level should be incorporated into the testing for coeliac disease,47 as well as an IgG antibody-based test, either IgG-antigliadin or IgG-tTG.48
Seronegative coeliac disease
Several studies have demonstrated that serologic studies may lack sensitivity when used in the practice setting.26, 30, 49, 50 Reliance on EMA as a single test has, in fact, underestimated the prevalence of coeliac disease by at least 20–25%.26, 29, 30, 51 This is mainly due to the inclusion of patients with mild mucosal changes, a situation when patients may not express an EMA.25, 28, 49, 52, 53 A similar situation occurs with tissue transglutaminase, with titers decreasing as the mucosal
Role of HLA DQ2/DQ8 assessment
The HLA DQ2 is found in up to 90–95% of patients with coeliac disease, while most of the remaining patients are HLA DQ8.62, 63 However, these HLA alleles are found in up to 40% of the general population. They appear to be a necessary, but not sufficient, factor in the pathogenesis of coeliac disease. The role of determining whether an individual carries HLA DQ2 or DQ8 in the assessment of coeliac disease lies in their high negative predictive value.64 The main roles are in determining whether
Biopsy and histology
Biopsy of the small intestine remains the gold standard in the diagnosis of coeliac disease (Figure 2). Biopsies of the descending duodenum, rather than the more distal intestine seem sufficient for the diagnosis of coeliac disease.65, 66 Due to the patchy nature of villous changes in coeliac disease67, 68, 69 multiple biopsies are necessary, though standard sized forceps are sufficient.66
The recognition of the spectrum of histological changes in coeliac disease, as classified by Marsh1, 70 or
Endoscopic Markers of coeliac disease
Multiple endoscopic signs have been described in patients with coeliac disease. They include scalloping of folds,82 reduced or absent duodenal folds,83 mucosal fissures or grooves84 and visible vascularity of duodenal mucosa.85 However, these endoscopic signs are neither particularly sensitive for the diagnosis of coeliac disease,86, 87, 88 nor specific.75
Biopsy should be performed if the diagnosis of coeliac disease is considered, irrespective of the visual appearance of the mucosa. In
Other proposed antibody tests for coeliac disease
Antigliadin antibodies, EMA and tTG antibodies are recovered in duodenal secretions and stool of patients with coeliac disease90, 91, 92 as well as normal individuals,90, 91 some of whom may have latent gluten sensitivity in the absence of symptomatic coeliac disease.90, 93 IgA-tTG antibodies are also recovered in saliva of patients with coeliac disease94 and have been advocated as a non-invasive screening test for coeliac disease by some investigators,94 but not all.95 Recently both salivary
Conclusion
The diagnosis of coeliac disease depends on the finding of characteristic small intestinal pathological abnormalities together with clinical or histologic improvement on a gluten-free diet. Lesser degrees of mucosal change must be recognised as reactions to gluten in sensitised individuals and must, therefore, not be ignored or dismissed as ‘non-specific’. EMA and tTG antibodies have high sensitivity and specificity towards celiac disease, though there are some pitfalls in their use, as
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