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Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults

Detlef Schuppan, MD, PhD
Walburga Dieterich, PhD
Section Editor
J Thomas Lamont, MD
Deputy Editor
Shilpa Grover, MD, MPH


Celiac disease (also called gluten-sensitive enteropathy and nontropical sprue) was first described by Samuel Gee in 1888 in a report entitled "On the Coeliac Affection," although a similar description of a chronic, malabsorptive disorder by Aretaeus from Cappadocia (now Turkey) reaches as far back as the second century AD [1].

The cause of celiac disease was unexplained until the Dutch pediatrician Willem K Dicke recognized an association between the consumption of bread and cereals and relapsing diarrhea. This observation was corroborated when, during periods of food shortage in the Second World War, the symptoms of his patients improved once bread was replaced by unconventional, non-cereal-containing foods; this finding confirmed the usefulness of earlier, empirical diets that used pure fruit, potatoes, banana, milk, or meat [1-3].

Since symptoms reoccurred when bread was reintroduced after the war, Dicke and van de Kamer initiated controlled experiments exposing children with celiac disease to defined diets and then determined fecal weight and fecal fat as a measure of malabsorption. Wheat, barley, rye, and (to a minor degree) oats triggered malabsorption, which could be reversed after exclusion of these "toxic" cereals from the diet [4]. Shortly after, the toxic agents were found to be present in gluten, the alcohol-soluble fraction of wheat protein [5].

The celiac lesion in the proximal small intestine was first described in 1954. The primary findings were mucosal inflammation, crypt hyperplasia, and villous atrophy (picture 1) [6]. With the development of peroral biopsy, it became apparent that celiac disease and adult nontropical sprue shared the same features and pathogenesis [7]. When unrecognized and untreated, celiac disease is associated with increased mortality. (See 'Risk of malignancy and mortality' below.)

The epidemiology, pathogenesis, and clinical manifestations of celiac disease will be reviewed here. Its management and the use of antibodies for diagnosis are presented separately (see "Management of celiac disease in adults" and "Diagnosis of celiac disease in adults"). This topic is also discussed in an official position statement issued by the American Gastroenterological Association [8].


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