A sensitivity to gluten is the precipitating factor leading to the changes found in the intestinal mucosa in patients with CD. These proteins are found in all forms of wheat (including durum, semolina, spelt, kamut, einkorn, and faro) and related grains such as rye and barley. The disease is closely associated with genes that code for human leukocyte antigens (HLA) DQ2 and DQ8. Transglutaminase 2 appears to be an important component of the disease, both as a deamidating enzyme that can enhance the immunostimulatory effect of gluten and as a target autoantigen in the immune response. The prevalence of CD in children between 2.5 and 15 years of age in the general population is 3 to 13 per 1,000 children, or approximately 1:300 to 1:80 children. The female to male ratio is of 2:1.

The age at which cereal is introduced into the diet and the amount and type of cereal ingested may affect the presentation of the disease. Breast-feeding also may provide temporary protection. Precocious presentation may occur in children between 10 and 18 months of age and includes frothy, liquid, foul-smelling stools. Affected children acquire the celiac aspect, characterized by wasting and severe abdominal distention, at approximately 1 year of age. The other form of presentation occurs in children between ages 2 to 3 years old and includes poor feeding, lack of weight gain for several months or actual weight loss, irritability, and diarrhea consisting of foul-smelling, bulky stools (Box 361.1). Monosymptomatic forms may present with constipation or severe, recurrent abdominal pain. The disease has been diagnosed in adolescents who had no major gastrointestinal complaints but consulted a physician because of short stature. Less common forms of presentation include anemia and, in adults, CD may be associated with a wide spectrum of neurologic manifestations including cerebellar ataxia, epileptic seizures, dementia, neuropathy, myopathy, and multifocal leukoencephalopathy (Box 361.2).

Laboratory analyses are nonspecific. Serum abnormalities such as low hemoglobin, iron, albumin, cholesterol, calcium, phosphate, vitamin A, or carotene levels are related to the malabsorption but are nonspecific for the disease. Fat globules may be identified in a stool smear, and the malabsorption of fat can be quantified by means of a 72-hour stool collection (i.e., normal absorption, 95% of ingested fat), but this test rarely is needed. The test to measure absorption of D-xylose no longer is used. Antigliadin antibodies no longer should be ordered as a screening test because they have low sensitivity and poor specificity. Although elevated serum levels of tissue transglutaminase are highly indicative of the disease, the diagnosis requires a peroral small bowel biopsy. In cases of immunoglobulin A deficiency,
which sometimes is associated with CD, the test could provide a false-negative answer. Therefore, in individual cases, the assessment of serum Ig A may be helpful. A small-bowel biopsy can demonstrate moderate to severe villous atrophy and a chronic inflammatory infiltrate of the lamina propria. If the biopsy results support the clinical and laboratory findings, affected patients are placed on a gluten-free diet for 6 to 12 months. Small-bowel biopsy repeated at the end of this period should demonstrate a normalization of the villous architecture. The third, confirmatory biopsy, after the patient has been reexposed to gluten, is needed only in certain situations, one of which is if the diagnosis was done prior to the patient reaching 2 years of age. Determination of HLA-DQ2 may have a role in excluding the diagnosis in equivocal cases, but its utility is limited because of its high frequency of occurrence in the normal population.