The diagnosis of celiac disease involves serologic testing (generally for IgA anti–tissue transglutaminase antibodies first) followed by upper endoscopy with biopsy for confirmation in most patients. Patients with celiac disease should follow a lifelong, strict gluten-free diet. The latest article in our Clinical Practice series, Celiac Disease, comes from Drs. Alessio Fasano and Carlo Catassi at the University of Baltimore School of Medicine.
Celiac disease is a systemic immune-mediated disorder triggered by dietary gluten in genetically susceptible persons. Gluten is a protein complex found in wheat, rye, and barley. Celiac disease is characterized by a broad range of clinical presentations, a specific serum autoantibody response, and variable damage to the small-intestinal mucosa.
• What is the prevalence of celiac disease?
Celiac disease affects 0.6 to 1.0% of the population worldwide, with wide regional differences in Europe (e.g., the prevalence is 0.3% in Germany and 2.4% in Finland) for reasons that are unclear. Celiac disease is also common in developing countries, particularly in North Africa and the Middle East. In India, celiac disease is observed mainly in the northwestern part of the country, where wheat is a staple food. Cases of celiac disease also have been described in China. The frequency of celiac disease is increasing in many developing countries because of westernization of the diet, changes in wheat production and preparation, increased awareness of the disease, or a combination of these factors.
• What are the risk factors for celiac disease?
The prevalence of celiac disease is 1.5 to 2 times as high among women as among men and is increased among persons who have an affected first-degree relative (10 to 15%), type 1 diabetes (3 to 16%), Hashimoto’s thyroiditis (5%) or other autoimmune diseases (including autoimmune liver diseases, Sjogren’s syndrome, and IgA nephropathy), Down’s syndrome (5%), Turner’s syndrome (3%), and IgA deficiency (9%).
Genetic background plays a key role in the predisposition to the disease. The HLA-DQ2 haplotype (DQA1*0501/DQB1*0201) is expressed in the majority of patients with celiac disease (90%), whereas it is expressed in one third of the general population. In another 5% of patients with celiac disease, the HLA-DQ8 haplotype (DQA1*0301/DQB1*0302) is expressed, whereas almost all the remaining 5% of patients have at least one of the two genes encoding DQ2 (DQB1*0201 or DQA1*0501).
Morning Report Questions
Q: What are the symptoms and signs of celiac disease?
A: Frequent symptoms and signs include chronic diarrhea, weight loss, and abdominal distention (in 40 to 50% of patients). Other manifestations include iron deficiency with or without anemia, recurrent abdominal pain, aphthous stomatitis, short stature, high aminotransferase levels, chronic fatigue, and reduced bone mineral density. Unusual manifestations of celiac disease include dermatitis herpetiformis, a blistering rash with pathognomonic cutaneous IgA deposits; gluten ataxia, a sporadic form of ataxia with positive serologic markers for gluten sensitization (although the association with celiac disease is still debated); and celiac crisis, a rare life-threatening syndrome, mostly observed in children, that is characterized by severe diarrhea, hypoproteinemia, and metabolic and electrolyte imbalances. Clinically silent celiac disease has been increasingly detected by means of serologic screening.
Q: What is the most useful laboratory test for the diagnosis of celiac disease?
A: Measurement of serum IgA anti-tissue transglutaminase antibodies is recommended for initial testing in persons who do not have concomitant IgA deficiency because of its high sensitivity (94%), high specificity (97%), and excellent standardization; IgG anti-tissue transglutaminase antibodies can be measured in persons with IgA deficiency. Measurement of IgA anti-endomysial antibodies is nearly 100% specific for active celiac disease, but it should be used only as a confirmatory test in the case of borderline positive or possibly false positive results of tests for anti-tissue transglutaminase antibodies, as occurs in other autoimmune diseases, including type 1 diabetes. Measurement of deamidated gliadin peptide antibodies of the IgG class, which has recently been introduced as an alternative test, is reported to have better sensitivity and specificity than measurement of IgG anti-tissue transglutaminase antibodies as a screening test for celiac disease in IgA-deficient patients. The sensitivity of serologic testing is markedly reduced in patients with a gluten-restricted diet; patients should therefore not restrict their diet before testing.