Coeliac disease was described with great accuracy by Samuel Gee more than a century ago. 1 However, the harmful effect of ingested wheat gluten was not recognised until the late 1940s by Dicke. 2 Soon after this discovery peroral small-bowel biopsy, the cornerstone for making an accurate diagnosis, was introduced. Life-long glutensensitive disorder, characterised by malabsorption in its classical form, and the typical small-bowel histological lesion are well understood. However, during the 1980s and 1990s, it has become apparent that coeliac disease is underdiagnosed and that the clinical features of the disease have changed in both children and adults. Genetic and immunobiological reseach has taken a leap forward. This seminar focuses on the established facts of coeliac disease and introduces advances in clinical and basic research.

Diagnostic criteria The diagnostic criteria, as stated by the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) in 1970, are: small-bowel mucosal atrophy with improvement or normalisation on a gluten-free diet and a deterioration of the villous morphology during intake of a gluten-containing diet. In 1990, these criteria were modified. 3 The findings of characteristic small-bowel mucosal atrophy and clinical remission on a gluten-free diet are essential. In symptom-free patients, a second biopsy sample is needed to show mucosal recovery on treatment with a gluten-free diet. The presence of circulating antibodies and their disappearance on a glutenfree diet support the diagnosis. The old ESPGAN criteria, including gluten challenge, may be used when needed—eg, in children younger than 2 years who live in countries where intolerance to protein in cow’s milk is common, or in patients for whom the findings from their first biopsy sample was equivocal. Gluten challenge after mucosal healing in children who are initially negative for serum reticulin or endomysial antibodies is also advisable (the challenge should not be done in children younger than 6 years). 3 In developed countries, coeliac disease is generally indicated by a manifest mucosal lesion with typical villous atrophy and crypt hyperplasia in adults and in children older than 2 years with or without symptoms or signs of malabsorption (figure 1). Small-bowel biopsy sampling is essential, and the diagnosis should not be based on symptoms or serological tests alone. By definition, coeliac disease is excluded in patients who have a normal small-bowel mucosal morphology when they are on a normal gluten-containing diet. However, gluten sensitivity is no longer restricted to villous atrophy. Smallbowel mucosal damage develops gradually from normal mucosal morphology to overt atrophy with hyperplasia of