Celiac disease (CD), also known as gluten-sensitive enteropathy or nontropical sprue, is an immune-mediated disorder of the small intestine in which individuals are sensitive to gluten, a protein 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 micronutrients.

Signs and symptoms may appear in children and present as failure to thrive, delayed growth, irritability, vomiting, constipation, large stools, peripheral edema, clubbing, and/or frequent respiratory infections. However, CD may not present until later in life, typically between the ages of 10 and 40. Common GI-related symptoms in adults with CD include bloating, abdominal pain, diarrhea, and/or constipation.

Affected individuals may also have extraintestinal manifestations due to malabsorption. Calcium malabsorption may lead to osteoporosis and fractures. Iron malabsorption can result in anemia. Amenorrhea, infertility, dermatitis herpetiformis, and neurologic symptoms (e.g., peripheral neuropathy, ataxia, seizures) may also occur.

Risk Factors

Celiac disease (CD) 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] CD 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 the risk for the development of CD in high-risk individuals.[3]

Associated Conditions

Immune disorders. Patients with a history of autoimmune disorders (e.g., IgA deficiency, autoimmune thyroid disease, type 1 diabetes mellitus, inflammatory bowel diseases) are at increased risk for developing CD.[4]

Dermatitis herpetiformis is commonly seen in patients with CD.

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

Diagnosis

Infants commonly present with a constellation of symptoms including 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 unexplained 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 preferred test for CD screening. 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 the recommended lab studies to obtain.[6][7] Patients should not be on a gluten-free diet when these screening tests are performed as they can provide a false negative test result.

Duodenal biopsies establish the diagnosis and should be performed after any positive CD serology.[5][8] Typical histological findings include intraepithelial leukocyte infiltration, villous atrophy, and crypt hyperplasia. Biopsies are also performed when there is strong clinical suspicion of CD despite negative serological testing.[9] In equivocal cases or when a patient cannot tolerate a gluten challenge (i.e., gluten-reintroduction for at least 4-8 weeks), HLA haplotype testing may be useful in that it has a strong negative predictive value when these genotypes are absent. HLA testing may also be done to determine susceptibility in offspring.

Once the diagnosis is made, it is advisable to evaluate for vitamin and mineral deficiencies. Evaluating levels of iron, vitamin D, B12, folate, and zinc, as well as obtaining a baseline bone density scan (DEXA) within the first 1-2 years after diagnosis, is recommended.[10]

Treatment

The cornerstone of treatment is complete avoidance of dietary gluten and gluten-containing products, including hygiene products, medications, and supplements. Adhering to a gluten-free diet (GFD) improves GI-related symptoms, allows for mucosal healing and nutrient absorption, and reduces risk of associated GI malignancies, including small intestinal B-cell lymphoma. Poor adherence to a GFD over time can also increase the risk of refractory CD despite a GFD and the need for pharmacologic interventions.

Nutritional Considerations

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

Gluten-free diet. A GFD is one that does not contain wheat, rye, barley, or derivatives of these grains (e.g., farro, semolina, durum, spelt, triticale, and malt). If available, patients with CD should be referred to a registered dietitian with experience on CD to provide guidance on dietary options that provide the necessary nutrients for optimal health.

Avoiding cross contamination is also essential. Although oat grain is inherently gluten-free, some grain producers inadvertently contaminate oats with gluten-containing grains. Products should be labeled “Certified Gluten-Free” to reduce the risk of cross contamination. This can occur quite commonly when dining out or when preparing food at home if utensils and plates are being used for gluten-containing products. In addition, some individuals with CD do not tolerate even gluten-free oats, due to an immune reaction that is distinct from gluten sensitivity.

Addressing nutritional deficiencies. CD patients’ diets and gluten-free products are often low in B vitamins, calcium, vitamin D, iron, zinc, magnesium, and fiber.[11] 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. Patients who have been managed on GFDs sometimes reveal signs of poor nutrient status and impaired calcium absorption.[12][13][14] Patient counseling regarding healthful sources of micronutrients is recommended. These may include but are not limited to fortified nondairy milk or orange juice 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 CD, compared with 1-2% in a control population.[15] About 5% of patients diagnosed with iron and/or folate deficiency were found to have histologically confirmed CD after endoscopy and biopsy.[16] In patients following a GFD for 10 years, 37% had low blood levels of folate, and 20% had low blood levels of vitamin B6.[17] Between 20-40% of untreated patients with CD appear to have poor vitamin B12 status.[13][17]

Deficiencies of fat-soluble vitamins, occurring as a result of malabsorption, are not uncommon. Cases of myopathy and vitamin D deficiency in CD have been reported, and low levels of vitamin E have been implicated in neurologic complications of CD. Vitamin E supplementation and a GFD reverse the resulting myopathy.[18] Malabsorption of vitamin K in untreated CD may also prolong the prothrombin time, requiring parenteral administration.[19]

Orders

Gluten-free diet.

Referral to a registered dietitian with experience in CD. Once the diagnosis and response to dietary treatment have been established, follow-up may be offered on an as-needed basis.[20]

Annual serologic testing may be considered to monitor adherence to a GFD or help patients identify inadvertent, ongoing gluten exposure.

Because CD is associated with hyposplenism, prophylactic administration of pneumococcal vaccine is recommended.

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:

• National Celiac Association (nationalceliac.org)
• Gluten Intolerance Group (gluten.org)
• Celiac Disease Foundation (celiac.org)
• Coeliac UK (coeliac.co.uk)
• Canadian Celiac Association (celiac.ca)
• Beyond Celiac (BeyondCeliac.org)

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.[21][22][23]

References