Overview and Risk Factors
Celiac sprue, also known as celiac disease, gluten-sensitive enteropathy, and nontropical sprue, is an immune-mediated disorder of the small intestine in which patients are sensitive to gluten, a protein contained in wheat, barley, and rye. Gluten acts as a foreign antigen, causing an immune response that damages the lining of the small intestine, resulting in malabsorption of fat, calcium, iron, folate, and other nutrients.
Classically, signs and symptoms initially appear upon the introduction of wheat into a child's diet (usually at age 6 to 12 months). However, the disease may not present until later in life, typically between the ages of 10 and 40. In children, the presentation may include failure to thrive, delayed growth, irritability, vomiting, constipation, large stools, peripheral edema, clubbing, and frequent respiratory infections. In adults, most cases are asymptomatic, but some patients may have diarrhea, weight loss, abdominal swelling, and bloating.
Patients may also have nonintestinal symptoms. Malabsorption of vitamin D and calcium may result in rickets, osteoporosis, and bone fractures. Iron malabsorption can result in anemia. Amenorrhea, infertility, dermatitis herpetiformis, and neurologic symptoms (peripheral neuropathy, ataxia, seizures) may occur.
Celiac sprue 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. Celiac sprue occurs in 10% of first-degree relatives of affected patients.
Immune disorders. Patients with a history of immune disorders (eg, IgA deficiency, autoimmune thyroid disease) are at increased risk.
Environment. Infectious agents, including respiratory and gastrointestinal viruses, may play a role in susceptible patients.
Type 1 diabetes mellitus. About 5% of patients with type 1 diabetes mellitus also have celiac disease.
Down syndrome. Patients with Down syndrome have double the risk of celiac disease, compared with the general population.
Diagnosis and Treatment
Diagnosis in infants is suggested by a constellation of diarrhea, failure to thrive, and irritability.
Serologic testing with IgA antitissue transglutaminase or antiendomysial antibody is used to screen for celiac disease. Antigliadin antibody testing is no longer routinely used.
In equivocal cases, a small-intestine biopsy or 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 to 6 months.
It may also be advisable to assess hematologic indices to check for iron deficiency anemia.
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 esophageal carcinoma, small bowl carcinoma, and B-cell lymphoma, which occur in greater frequency in these patients. 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 adjustments are essential to the management of this disorder. The key aspects of treatment are as follows:
A gluten-free diet eliminates wheat, barley, rye, and other gluten-containing foods. Patients should consult with an experienced dietitian to identify these foods and ensure adequate nutrient balance.
Although gluten is also found in oats, some studies suggest that pure oat flour can be tolerated without disease recurrence. Thus, 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 to 60 grams per day. However, some patients are sensitive to oats, a sensitivity confirmed by the presence of oat-specific intestinal T cells. Further caution regarding oats is justified by the fact that commercial oat products may be contaminated with other gluten-containing grains.1
Patients should be aware that 100% gluten avoidance is impossible. Even naturally gluten-free products may contain 20 to 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.2
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. 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.3
The prevalence of vitamin B-complex deficiency is between 5% and 7% of persons with undiagnosed celiac disease, compared with 1% to 2% in a control population.4 About 5% of patients diagnosed with iron and/or folate deficiency were found to have histologically confirmed celiac disease after endoscopy and biopsy.5 In patients following a gluten-free diet for 10 years, blood levels of folate were low in 37%, and blood levels of vitamin B6 were low in 20%.6 Between 20% and 40% of untreated celiac patients appear to have poor vitamin B12 status.7,8
Nutritional 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.9 Malabsorption of vitamin K in untreated celiac disease may also prolong the prothrombin time, requiring parenteral administration of this vitamin.10
Nutrition consultation to assist patient with diet changes, with outpatient follow-up as needed.
What to Tell the Family
The importance of complete abstinence from gluten-containing foods should be stressed to all family members. Careful reading of labels on food products is imperative. A diet based on unprocessed or minimally processed foods is required.
2. Collin P, Thorell L, Kaukinen K, Maki M. The safe threshold for gluten contamination in gluten-free products. Can trace amounts be accepted in the treatment of coeliac disease? Aliment Pharmacol Ther. 2004;19:1277-1283.
3. Kupper C. Dietary guidelines and implementation for celiac disease. Gastroenterology. 2005;128(suppl 1):S121-S127.
5. Howard MR, Turnbull AJ, Morley P, Hollier P, Webb R, Clarke A. A prospective study of the prevalence of undiagnosed coeliac disease in laboratory defined iron and folate deficiency. J Clin Pathol. 2002;55:754-757.
7. Dickey W. Low serum vitamin B12 is common in coeliac disease and is not due to autoimmune gastritis. Eur J Gastroenterol Hepatol. 2002;14:425-427.