In more and more cases, celiac disease doesn't look the way you might expect.

Celiac disease is more common, particularly among adults, and more easily overlooked than many clinicians appreciate, according to the American Gastroenterological Association (AGA) Institute's Medical Position Statement on the condition.

The overall prevalence of celiac disease is estimated to be 1%—comparable to that of rheumatoid arthritis. What's more, “most cases remain undiagnosed until later in life,” the Position Statement says. “Clinicians should have a heightened suspicion that celiac disease may be present at any age in both sexes and in a wide variety of clinical circumstances.”

This last phrase perhaps encapsulates the most essential lesson of the AGA's statement and its accompanying Technical Review on the Diagnosis and Management of Celiac Disease. More often than not, celiac disease doesn't look the way one might expect.

“The most crucial role for primary-care physicians (PCPs) is detection,” says Joseph A. Murray, MD, professor of medicine atMayo Clinic College of Medicine in Rochester, Minn., director of its celiac clinic, and an author of the AGA's Technical Review. “While celiac disease in its classic form, severe malabsorption, [is seen by] gasteroenterologists, most patients won't present with this but with a wide diversity of less well defined conditions.”

Testing for celiac disease

Serologic testing has improved markedly in recent years. Immunoglobulin (Ig) A tissue transglutaminase antibody (tTGA) and anti-endomysial antibody (EMA) tests are considerably more sensitive and specific than the older antigliadin antibody test. These assays are “largely responsible for the recognition that celiac disease is not a rare disease” and that it has a “broad spectrum of clinical presentations,” according to the Technical Review.

Patients who have unexplained chronic GI symptoms are the most obvious candidates for testing, and those with ostensible irritable bowel syndrome—particularly if symptoms are prominent after eating—should be considered for further evaluation as well, Dr. Murray advises. Lactose intolerance may be secondary to celiac disease: Suspect the latter in individuals belonging to ethnic groups that are rarely affected by lactose intolerance.

The prevalence of celiac disease among first-degree relatives of those with the disorder is estimated at 10%; the threshold for testing should be lower for these individuals, although “there is little evidence to support screening” when they are asymptomatic, the Technical Review says. A similar approach is indicated for second-degree relatives, in whom prevalence is 2.6%-5.5%.

The possibility that diverse clinical presentations reflect “atypical” celiac disease should also be taken into account.

The authors note that:

• Endoscopic studies of patients with iron deficiency anemia (IDA) and without GI symptoms find celiac disease in 3%-9%. Screening should be considered in all patients with unexplained IDA.

• Prevalence is increased in patients with osteoporosis and bone demineralization, particularly when these occur prematurely.

• Testing also should be considered for individuals who have Down syndrome, unexplained elevations of aminotransferases, autoimmune hepatitis, and primary biliary cirrhosis.

• The prevalence of celiac disease in patients with type 1 diabetes mellitus is 3%-8%: Celiac disease may play a role in persistent hypoglycemia and peripheral neuropathy in these patients.

• An estimated 5% of unexplained infertility is related to celiac disease.

The need for biopsy

Intestinal biopsy is the next step in patients with positive serologic findings: Characteristic histologic changes in the distal duodenum are “the gold standard for establishing the diagnosis of celiac disease,” according to the authors of the Position Statement, and other findings (such as increased numbers of intraepithelial lymphocytes) may be an indication of latent disease. It is important to perform both serology and biopsy before initiating gluten restriction, lest the picture be obscured.

Additional investigation, including IgA determination, HLA genotyping, and even biopsy, might be considered despite negative serology results in situations where the clinical picture and/or family history warrant strong suspicion of celiac disease.

“Minimizing delay in diagnosis appears to have a variety of health benefits for patients with celiac disease,” the authors say. Besides the risk of osteoporosis, IDA, and other direct consequences of malabsorption, celiac disease is associated with excess mortality due to malignancy, particularly non-Hodgkin's lymphoma (NHL). Mortality increases when diagnosis is delayed more than 10 years.

Management—the gluten-free diet

Once you diagnose celiac disease, assess the patient's nutritional intake, test his bone mineral density (BMD), and address deficiencies. Iron, folate, vitamin B12, zinc, copper, calcium, and vitamin D status are particularly important, observes Dr. Murray.

The primary—and usually the only—long-term treatment for celiac disease is strict adherence to a gluten-free diet (GFD), a regimen in which wheat, rye, and barley products are rigorously excluded. “Celiac disease has become common enough that family physicians need to be comfortable monitoring the GFD,” he says.

The Technical Review cites data indicating that adherence to a GFD reduces the risk of NHL, in some studies bringing it down to that of the general population. Physical parameters, including BMD, body weight, and fat and lean mass, have also been shown to improve. The GFD appears to have a positive effect on nutritional and biochemical status, including resolution of IDA.

Patient education is a key strategy in fostering compliance with this challenging diet. “It is reasonable to suggest that interventions designed to improve knowledge about celiac disease as well as about the GFD” and the “outcomes of untreated celiac disease” are likely to improve compliance, the Position Statement notes.

The assistance of a registered dietitian is invaluable, both in designing a diet and monitoring patient adherence to it. “I recommend physicians identify one or two dietitians in their community with expertise in celiac disease,” Dr. Murray says. Local celiac disease groups can be important resources for practical information and emotional support. (Check the Web sites of such organizations as the Celiac Disease Foundation [www.celiac.org] and the Celiac Sprue Association [www.csaceliacs.org].)

“When speaking with patients, the important thing is for the doctor to be positive,” Dr. Murray says. “If he [even in some subtle way] transmits the attitude, ‘I could never follow this diet,' it sets up the patient for failure.” Expressions of interest and empathy are important for promoting the therapeutic alliance and adherence.

Follow-up

The Position Statement recommends regular evaluations to assess compliance with the GFD and to detect and manage lapses and difficulties. Beyond symptomatic improvement, repeated serologic testing after six months can help assess histologic resolution and adherence to treatment (although, as the authors point out, these tests are not sensitive to minor transient dietary transgressions).

Continuing or relapsing symptoms are usually the result of deliberate nonadherence or inadvertent gluten consumption on the part of the patient. If these have been ruled out, the possibility of separate or associated illness, such as irritable bowel syndrome, pancreatic insufficiency, or microscopic colitis, needs to be explored.

True refractory celiac disease, in which intestinal atrophy fails to respond in a patient who has been compliant with the GFD, requires referral to a gastroenterologist.

The AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease was published in Gastroenterology (2006;131:1977-1980). It is available online here. The American Gastroenterological Association (AGA) Institute Technical Review on the Diagnosis and Management of Celiac Disease was published in the same issue of Gastroenterology (2006:131:1981-2002). It is available online. Both documents were accessed November 17, 2008.

Mr. Sherman is a medical writer in New York City.