Management of Celiac Disease

David Elliot, M.D.
The University of Iowa
Peer Review Status: Internally Peer Reviewed
First Published: Spring 2003
Last Revised: August 2003

Celiac disease (CD) is a common and clinically important food allergy with variable manifestations; it is rare in African-Americans and Asian-Americans as compared with the rest of the U.S. population. Since CD can present without gastrointestinal symptoms, the diagnosis is easily overlooked. The estimated prevalence of CD is 1:133 to 1:400 of the U.S. population. There is increased prevalence of CD coexisting with Type 1 diabetes mellitus (~10%), Sjogren's syndrome (~10%), and Down syndrome (~10%). Most of these patients remain undiagnosed. Patients with undiagnosed or untreated CD are at risk for malabsorption, mineral or vitamin deficiency, osteoporosis, autoimmune diseases, and intestinal lymphoma.

Celiac disease is an allergy to proteins present in wheat, rye, and barley. It was first described in 1888 as a progressive wasting illness with malabsorption. William Dicke identified the etiologic role of wheat for CD in 1953. The classic intestinal pathology was described in 1954 as villous atrophy, crypt hyperplasia, and inflammation (Fig. 1). The intestinal inflammation and associated malabsorption resolve when patients avoid exposure to products made from wheat, rye, or barley. At present, this is considered to be the only effective treatment for CD.

New Facts

Celiac disease is caused by delayed-type cellular hypersensitivity to the alcohol-soluble prolamin proteins gliadin (present in wheat), secalin (in rye), and hordein (in barley). These gluten proteins share regions rich in the amino acids proline and glutamine. In wheat, there is an undigestible 33aa peptide fragment, which contains several antigenic sequences. These are taken up by macrophages, processed, and presented to the T-cells, thus triggering a CD4+ response in the intestinal lamina propria that results in inflammation.

Before they are presented to the T-cells, amide groups are removed from the glutamine residues in the 33aa antigenic peptide using the enzyme tissue transglutaminase (tTG). The 33aa peptide has high affinity for tTG and can become cross-linked to the enzyme. This 33aa-tTG complex becomes a "modified self" and is antigenic to B-cells, which make anti-tTG antibodies of the IgA class. Anti-tTG antibodies can be visualized by anti-endomysial antibody assay (labor-intensive and expensive) or by using specific ELISA. The anti-tTG ELISA is inexpensive, sensitive (80-85%), and specific (>95%) for CD, making it an excellent screening test. Upon starting a gluten-free diet, IgA anti-tTG titer should drop. After a year, the titer should be in the normal range (<20). Therefore, anti-tTG titer can be used to monitor compliance.

The gold standard for diagnosis of CD, however, is intestinal biopsy while the patient is still on a wheat-containing diet. If there is significant concern that a patient may have CD, then that patient should have endoscopy with intestinal biopsy. Endoscopy may demonstrate atrophic duodenal mucosa with a "cracked earth" appearance. But most commonly, the endoscopic picture is normal. On biopsy, low-grade inflammation is identified as an increased number of intraepithelial lymphocytes (IEL) without other damage. The norm is 20 or fewer IEL for every 100 intestinal epithelial cells (IEC). Patients with celiac disease have more than 40 IEL/100 IEC.

The classic symptoms of malabsorption and wasting are rare with modern diets. Typical patients complain of bloating, dyspepsia, loose stools, and fatigue. Asymptomatic patients may present with unexplained anemia, transaminase elevation, or osteopenia. Because the symptoms of celiac disease are vague, patients can complain for years before the diagnosis is made. Often, they are told they have irritable bowel disease or anxiety disorder. Doctor shopping is frequent.

In fact, patients with untreated CD and a delay in diagnosis greater than 10 years have a nearly four-fold increase in mortality compared to age-matched controls. Patients who do not adhere to a gluten-free diet have a six-fold increase in mortality. Mortality is highest in patients with frank malabsorption.

Figure 1.
Hematoxylin-eosin stained cross-sections of intestinal villi: normal epithelium (left) and celiac epithelium (right), characterized by infiltration of intraepithelial lymphocytes and flattened villi.

Practice

The Marsh stages scale, derived from a study of patients with known CD who were fed gluten, is used to assess the level of intestinal damage inflicted by CD on each individual patient. Damage starts as an increase in IEL (Infiltrative, Marsh 1), then an increase in crypt length (Hyperplastic, Marsh 2), followed by flattening (atrophy) of the villi (Destructive, Marsh 3). Severe, relentless injury will result in loss of crypts and villous atrophy (Hypoplastic, Marsh 4). Often a patient's symptoms do not correlate with endoscopic or histological damage. Patients with mild symptoms may have severe damage, whereas patients with severe symptoms may have mild damage.

Up to 36% of CD patients have severe osteoporosis or osteomalacia with T scores below -2.5. Therefore, newly diagnosed patients should have bone density scans. CD is approximately 10 times more common in patients with osteoporosis than in the general population. Axial bone density improves after instituting a gluten-free diet and normalizes within five years.

Long-standing CD may "set the stage" for other autoimmune diseases, such as dermatitis herpetiformis (an intensely pruritic vesicular rash that can drive patients to suicide), type 1 diabetes mellitus, autoimmune hepatitis, autoimmune thyroiditis, autoimmune gastritis, connective tissue diseases, alopecia totalis, psoriasis, and epilepsy due to cerebral calcifications. Patients diagnosed with CD at a young age (<2 years) and started on a gluten-free diet have a 5% risk of developing an autoimmune disease. This risk raises to 16% in patients diagnosed between ages four and 12. Patients diagnosed after age 20 have a 34% risk.

Untreated CD can progress to refractory sprue. As the name implies, malabsorption due to refractory sprue does not improve on a gluten-free diet. Patients with refractory sprue have a hypoplastic (Marsh 4) injury pattern on biopsy and often develop intestinal T-cell lymphoma. Actually, unrecognized or untreated CD is the major cause for intestinal T-cell lymphoma. This lymphoma is characterized by aberrant IEL that express CD3 but not CD4 or CD8. Enteropathy-associated T-cell lymphoma is usually progressive and unresponsive to current therapies. Thankfully, it is rare.

Some patients with CD may appear to have refractory sprue, but their malabsorption is actually due to another more benign cause. Patients may have unrecognized lactose intolerance, hyperthyroidism, or a motility disorder. Patients may have scarring at the Oddi sphincter and develop pancreatic insufficiency. However, most often patients have an occult exposure to wheat, rye, or barley.

The complex nature of CD makes education an important component of successful treatment. Wheat products can masquerade as a host of food additives, and suspect foods and related grains must be identified. Candies, for example, are often dusted with flour.

At UI Hospitals and Clinics, when we diagnose CD, we arrange an exhaustive teaching session with our dietitians. We place the patient on a strict gluten-free diet avoiding wheat, rye, barley, oats, and related grains. We draw a baseline anti-tTG titer and get bone density scans. A gastroenterologist specializing in CD sees the patient at three, six, and 12 months to get repeat anti-tTG and for reeducation. Thereafter, patients are seen every year or two to make sure they remain gluten free. If a patient is doing well on a gluten-free diet and has normalized the anti-tTG level, we try to reinstitute oats, which are well tolerated by many patients.

Equally important is patient involvement in local and national support groups. Local support groups help identify sources for buying gluten-free products. They also can buy special products in bulk to reduce cost. Local and national groups share recipes, call manufacturers, permit dissemination of new information, and help organize research.

See related Provider Textbooks about Internal Medicine.

See related Provider Topics Celiac Disease, Digestive System, Food Allergy, Food, Nutrition and Metabolism, Gastrointestinal, Immune System/AIDS or Internal Medicine.

See related Patient Textbooks about Internal Medicine.

See related Patient Topics Celiac Disease, Digestive System, Food, Nutrition and Metabolism, Gastrointestinal, Immune System/AIDS or Internal Medicine.

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