Celiac’s disease has life-long and serious consequences, necessitating a careful and thorough diagnostic evaluation. It is estimated a substantial proportion of celiac’s disease may remain undiagnosed. The following steps are currently recommended by experts. Besides symptomatic individuals, other high risk populations should be screened as well. These include symptomatic relatives of individuals with known celiac’s disease, individuals with iron deficiency anemia, premature or severe osteoporosis, type 1 diabetes mellitus, certain types of skin, liver, nervous system or thyroid disease, as well as specific genetic disorders (e.g. Down’s and Turner’s syndromes). A careful history, including food reactions and family history, is always required.
The tests discussed below should initially be performed before exclusion of gluten from the diet.
Blood tests
Screening for celiac’s disease is best performed in blood samples using IgA antitransglutaminase antibodies. This test is accurate in about 90% of cases, but there are differences between the different test assays available. The tests are much less exact in milder than in more severe forms of the disease. IgA antiendomysial antibody testing is an alternative, but considerably more costly and difficult to perform. Total IgA levels should be measured, if they are suspected to be low. Antigliadin antibody tests should no longer be used, except the newest generation of deamidated gliadin peptide (α-DGP) antibody tests. Finger tip prick blood tests are being marketed, but their usefulness remains to be ascertained.
In case of a positive blood antibody test, a conclusive diagnosis should be made from duodenal biopsies. The antibodies can also be used to monitor long term dietary compliance, as they correlate with the degree of intestinal inflammation due to the disease process.
In case of negative antibody tests and normal total IgA levels, small intestinal biopsy is the next diagnostic step for exclusion of celiac’s disease.
Genetic
The genetic markers HLA-DQ2 and HLA-DQ8 are very strongly associated with celiac’s disease, as about 95% of patients have DQ2 and about 5% have DQ8. However, close to 40% of western populations without celiac’s disease also have these markers. Therefore, as virtually all celiac’s disease patients have these markers, absence of the markers virtually excludes the diagnosis, but a positive test is not conclusive for celiac’s disease. Consequently, a positive test is must be confirmed by small intestinal biopsies.
Biopsy
Conclusive proof or exclusion of celiac’s disease is always by duodenal biopsy. Pathologists look for characteristic changes in the tissue samples, such as a decrease in the height of the hair-like folds (villi) and the troughs (crypts) of the duodenal lining and an increase in specific inflammatory cells in a part of this lining. These changes may be very subtle and difficult to recognize as well as unevenly distributed in the small intestine, which is why multiple (at least four, better six) biopsies deep down in the duodenum are recommended. If these first biopsies are inconclusive, a second set of biopsies taken after exposure to high concentrations of gluten for several weeks may be required. Occasional follow-up endoscopies with biopsies are recommended, especially in the case of inadequate symptom relief despite dietary adaptation. The large majority of non-response is due to dietary mistakes, although a small percentage of patients do not respond despite meticulous exclusion of gluten. In the latter case, further diagnostic evaluation by a specialist is warranted.
Further diagnostic considerations
A significant reduction of symptoms on a strict gluten-free diet is an important aspect of the diagnostic evaluation. If there is inadequate symptomatic relief, the diagnostic work-up needs to continue. This will include further biopsies, stool tests for parasites, blood tests for infectious diseases and allergies, including HIV, breath tests for food intolerances and possibly colonoscopy.Capsule endoscopy, where a miniature capsule-sized video camera is swallowed, can reveal celiac’s disease and exclude other disease. A conclusive diagnosis of celiac’s disease is, however, not possible due to the inability to take tissue samples.
Patients with celiac’s disease often have accompanying diseases or deficiencies, (e.g. vitamins and minerals). Specialist follow-up is absolutely necessary (see Celiac’s disease).
The microscopic changes seen in celiac’s disease may occasionally resemble those seen in other diseases, such as infections. If there is any uncertainty, such diseases should be excluded using further tests.