Joint BAPEN and British Society of Gastroenterology Symposium on 'Coeliac disease: basics and controversies'. Coeliac disease in the twenty-first century.

ABSTRACT

Coeliac disease (CD), traditionally perceived as a rare childhood condition presenting with malabsorption, is instead an autoimmune multisystem disorder usually presenting in adulthood, affecting > or = 1% of the population and linked to the genetic expression of human leucocyte antigens (HLA) DQ2 and DQ8. Presentation occurs most often in the 40-60 years age-group, but potentially at any age. Symptoms attributable to the gut or to malabsorption may be mild, non-specific or absent; under one-third of patients have diarrhoea and almost half are overweight. Histological diagnosis no longer requires small intestine villous atrophy. The Marsh classification recognizes increased intraepithelial lymphocytes and crypt hyperplasia with intact villi as part of the gluten enteropathy spectrum, while some individuals have more subtle abnormalities identified only on electron microscopy. Serological testing for CD autoantibodies (to endomysium and tissue transglutaminase) has revolutionized diagnosis, shifting the process towards primary care. However, a substantial number of patients with CD are seronegative, particularly those without villous atrophy. The autoantibody to endomysium may be produced before histological change. The immune response to transglutaminase is crucial to the disease process. An exciting new development is the link between antibodies to organ-specific transglutaminases and clinical presentation; transglutaminases 2 (gut), 3 (skin) and 6 (nervous system). Negative testing for CD does not preclude its development later and HLA testing may allow 'once and for all' exclusion. In conclusion, an increasing proportion of patients with CD do not meet the 'classic' picture of malabsorption, positive serological testing and villous atrophy. Insisting on all these criteria for diagnosis will result in under diagnosis.