Celiac Disease

Celiac disease, also known as gluten-sensitive enteropathy or non-tropical sprue, is an immune-mediated disorder of the small intestine in which individuals are sensitive to gluten, a protein contained in wheat, barley, and rye. Gluten acts as an antigen, causing an immune response that damages the lining of the small intestine, resulting in malabsorption of fat, calcium, vitamin B12, folate, iron, and other nutrients.

Signs and symptoms sometimes appear upon the introduction of wheat into a child’s diet (usually at age 6-12 months). In children, the presentation may include failure to thrive, delayed growth, irritability, vomiting, constipation, large stools, peripheral edema, clubbing, and frequent respiratory infections. However, the disease may not present until later in life, typically between the ages of 10 and 40. In adults, many cases are asymptomatic, but some patients may have diarrhea, weight loss, abdominal swelling, and bloating.

Affected individuals may also have non-intestinal symptoms. Malabsorption of vitamin D and calcium can result in rickets, osteoporosis, and bone fractures. Iron malabsorption can result in anemia. Amenorrhea, infertility, dermatitis herpetiformis, and neurologic symptoms (e.g., peripheral neuropathy, ataxia, seizures) may occur.

Risk Factors

Celiac disease occurs in people of all ages and ethnicities but appears to be most common in Caucasians of Northern European descent. Other risk factors include:

Genetics. More than 95% of affected patients have HLA-DQ2 and/or HLA-DQ8 mutations.[1] Celiac disease is found in approximately 1:22 of individuals with affected first-degree family members.[2]

Delayed introduction of gluten into the diet does not appear to alter risk for development of celiac disease in at-risk individuals.[3]

Associated Conditions

Immune disorders. Patients with a history of immune disorders (e.g., IgA deficiency, autoimmune thyroid disease, type 1 diabetes mellitus, inflammatory bowel diseases) are at increased risk. A significant portion of individuals with type 1 diabetes may have silent celiac disease in which they do not express any overt signs or clinical symptoms of the disease.[4]

Dermatitis herpetiformis is commonly seen in patients with celiac disease.

Down syndrome. The prevalence of celiac disease in patients with Down syndrome is significantly increased in comparison to the general population.[5]


Diagnosis in infants is suggested by a constellation of diarrhea, failure to thrive, and irritability. In adults, common symptoms include chronic diarrhea, malabsorption, weight loss, and bloating. The diagnosis should be suspected in individuals with unexplainable iron deficiency anemia, vitamin B12 or folate deficiency, chronically elevated liver function enzymes, or chronic migraines.

Serologic testing with IgA anti-tissue transglutaminase (TTGA) is the single preferred test for screening for celiac disease. Screening for IgA deficiency with total IgA levels will help rule out a false negative IgA TTGA. When there is a known IgA deficiency, TTGA IgG and deamidated gliadin peptide IgG are helpful.[6],[7] Patients should be on a gluten-rich diet, if possible, prior to any testing for celiac disease.

Small intestine biopsy establishes the diagnosis and should be done to follow up any positive serology test.[5],[8] Typical histological findings include intraepithelial leukocyte infiltration, villous atrophy, and crypt hyperplasia.[9] Biopsy is also performed when there is strong clinical suspicion of celiac disease despite negative serological testing.[9] In equivocal cases or when a patient cannot tolerate a gluten-rich diet for at least 2 weeks, HLA haplotype testing may be useful. HLA testing may also be done to determine susceptibility in offspring. Rarely, a follow-up biopsy may be performed for comparison after the patient has followed a gluten-free diet for 3-6 months.

It may also be advisable to evaluate for vitamin and mineral deficiencies once the diagnosis is made. Helpful tests include a complete blood count, serum iron, ferritin, copper, zinc, folate, vitamin B12, and the fat-soluble vitamins A, D, E, and K.


The cornerstone of treatment is dietary adjustment to avoid gluten (see Nutritional Considerations below). In addition to easing symptoms, dietary adjustment may decrease the risk of gastrointestinal malignancies and B-cell lymphoma, which occur in greater frequency in these individuals. In addition, immunosuppressant therapy with corticosteroids may be necessary for patients who do not respond to gluten avoidance. Dapsone has been used to treat associated dermatitis herpetiformis.

Nutritional Considerations

Nutritional adjustments are essential in the management of celiac disease. The key aspects of treatment are as follows:

Gluten-free diet. A gluten-free diet eliminates wheat, barley, rye, and derivatives of these grains (e.g., farro, semolina, durum, spelt, triticale, and malt). Brewer’s yeast often contains gluten traces from barley. Patients should consult with an experienced dietitian to identify gluten-containing foods and ensure adequate nutrient balance.

The oat grain does not contain gluten. However, some grain producers inadvertently contaminate oats with gluten-containing grains, prompting some producers to intentionally avoid cross-contamination and to label their products appropriately as gluten free.[10] In addition, some individuals with celiac disease do not tolerate even gluten-free oats, due to an immune reaction that is distinct from gluten sensitivity.

Typically, however, oats can be consumed by people with celiac disease. Once the disease has become quiescent, many gastroenterologists will introduce oats to the diet (less than 2 g/day), and patients may eventually be able to tolerate 40-60 g per day (1/2 cup raw oats = 40 g). For patients sensitive to oats, as confirmed by the presence of oat-specific intestinal T cells, avoidance of oats is recommended.

Patients should be aware that 100% gluten avoidance is impossible. Even naturally gluten-free products may contain 20-200 mg gluten/kg. Evidence supports setting the threshold for gluten contamination at 100 mg/kg; the intake of gluten-free flour up to 300 g/day provides 30 mg of gluten, which is within the range found to allow for mucosal recovery in clinical and challenge studies.[11]

Addressing nutrient deficiencies. Celiac disease patients’ diets and gluten-free products are often low in B vitamins, calcium, vitamin D, iron, zinc, magnesium, and fiber.[12] Consequently, newly diagnosed or inadequately treated patients often have low bone-mineral density, low fiber intake, and micronutrient deficiencies, despite increased obesity in this population.[12] Patients who have been managed on gluten-free diets sometimes reveal signs of poor nutrient status and impaired calcium absorption.[13],[14],[15] Patient counseling regarding healthful sources of micronutrients is recommended. These may include, but are not limited to, fortified soy milk for calcium and vitamin D and legumes for magnesium and iron.

The prevalence of vitamin B-complex deficiency is between 5-7% of persons with undiagnosed celiac disease, compared with 1-2% in a control population.[16] About 5% of patients diagnosed with iron and/or folate deficiency were found to have histologically confirmed celiac disease after endoscopy and biopsy.[17] In patients following a gluten-free diet for 10 years, 37% had low blood levels of folate and 20% had low blood levels of vitamin B6.[18] Between 20-40% of untreated celiac patients appear to have poor vitamin B12 status.[14],[18]

Deficiencies of fat-soluble vitamins, occurring as a result of malabsorption, are not uncommon. Cases of myopathy and vitamin D deficiency in celiac disease have been reported, and low levels of vitamin E have been implicated in neurologic complications of celiac disease. Vitamin E supplementation and a gluten-free diet reverse the resulting myopathy.[19] Malabsorption of vitamin K in untreated celiac disease may also prolong the prothrombin time, requiring parenteral administration of this vitamin.[20]


Gluten-free diet.

Nutrition consultation to assist patient with diet changes, with outpatient follow-up as needed.

Once the diagnosis and response to dietary treatment have been established, follow-up may be offered at a dietitian-led clinic.[21]

What to Tell the Family

Family members can help the identified patient avoid gluten-containing foods, recognizing that it is essential to avoid them completely. It is important to read food labels carefully.

The following organizations provide recipes, lists of gluten-free commercial products, and information on the gluten content of medications:

A diagnosis of celiac disease has implications for family members, as approximately 10% of first-degree relatives may also be affected. It may be appropriate for relatives to be screened for celiac disease and to be educated about the condition.[22],[23],[24]


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Last updated: November 30, 2022