Diagnosis

Main Points

Description:

Small bowel biopsy is  considered ‘gold standard’ for positive diagnosis, and is therefore desirable in all but the most clear-cut cases, because treatment involves a life-long diet that is both expensive and socially limiting. However with the increasing accuracy of serological tests, it is no longer necessary to take duodenal biopsies for suspected celiac disease in patients without antibodies. For example in patients being endoscoped for iron deficiency anaemia with negative celiac serology, the pretest value of small bowel histology is <0.03%.

If biopsies are to be taken, because the disease is sometimes patchy and it can be difficult to orientate endoscopic biopsies for histological section, four to six forceps biopsies should be taken from the second part of the duodenum. Endoscopic signs including absence of mucosal folds, mosaic pattern of the surface and scalloping of mucosal folds are often present; however, their absence is not conclusive because they are markers of relatively severe disease.

Histology: Histological changes are of variable severity and, though characteristic, are not specific. Villous atrophy can be caused by many other conditions, but celiac disease is the commonest cause of subtotal villous atrophy.

Histological examination shows crypt hyperplasia with chronic inflammatory cells in the lamina propria, and villous atrophy. The enterocytes become cuboidal with an increase in the number of intraepithelial lymphocytes. In the lamina propria there is an increase in lymphocytes and plasma cells. The most severe histological change with mucosal atrophy and hypoplasia is seen in patients who do not respond to a gluten-free diet.

In mild cases, the villous architecture is almost normal but there are increased numbers of intraepithelial lymphocytes.

Serology. Persistent diarrhoea, folate or iron deficiency, a family history of celiac disease and associated autoimmune disease are indications for serological testing.

The most sensitive tests are for endomysial and anti-tissue transglutaminase antibodies. The sensitivity of these tests is >90% though both are not always positive in the same subject. Titres of either correlate with the severity of mucosal damage so they can be used for dietary monitoring. Standard tests use IgA class antibodies. Selective IgA deficiency occurs in 2.5% of celiac disease patients but only 0.25% of normals and renders these tests falsely negative. All patients should have concomitant IgA levels tested and if deficient, IgG-based tests should then be used.

HLA typing. HLA-DQ2 is present in 90–95% of CD patients and HLA-DQ8 in about 8%, i.e. most of the rest. The absence of both alleles has a high negative predictive value for celiac disease. HLA typing may occasionally be useful for risk assessment, e.g. in patients already on a gluten free diet.

Other investigations

• Haematology. Mild or moderate anaemia is present in 50% of cases. Folate deficiency is common, often causing macrocytosis. B₁₂ deficiency is rare. Iron deficiency due to malabsorption of iron and increased loss of desquamated cells is common. A blood film may therefore show microcytes and macrocytes as well as hypersegmented polymorphonuclear leucocytes and Howell–Jolly bodies due to splenic atrophy.
• Biochemistry, liver biochemistry and function. In severe cases, biochemical evidence of osteomalacia may be seen (low calcium and high phosphate) and hypoalbuminaemia.
• Radiology. A small bowel follow-through may show dilatation of the small bowel with slow transit. Folds become thicker and in severe disease total effacement is seen. Radiology is mainly used when a complication, e.g. lymphoma, is suspected.
• Bone densitometry (DXA) should be performed on all patients because of the risk of osteoporosis.
• Capsule endoscopy is used to look for gut abnormalities when a complication is suspected.