Celiac Disease

Celiac Disease: The Great Pretender

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Celiac disease is an immune-mediated disorder characterized by chronic inflammation of the small intestinal mucosa, which can result in malabsorption and a variety of clinical manifestations. While considerable scientific progress has been made in the understanding and management of celiac disease, unfamiliarity with the multidisciplinary presentation is a significant barrier to diagnosis and treatment.   

A Long History

Writing in his diaries in 250 AD, the Greek physician Aretaeus of Cappadocia included detailed descriptions of an unnamed intestinal disorder, now known as celiac disease. He referred to these patients as “koiliakos,” which meant “a suffering in the bowels or abdomen.”[1] Fast forward another 17 centuries to the early 19th century when Dr. Mathew Baillie published his observations on a chronic diarrheal disorder of adults characterized by malnutrition and a gas-distended abdomen. He went on to observe that “some patients appear to derive considerable advantage from living almost entirely upon rice.”

In 1887, an English physician named Samuel Gee described celiac disease as “a kind of chronic indigestion which is met with in persons of all ages, yet is especially apt to affect children between one and five years old.” He also surmised that “errors in diet may perhaps be a cause.”[2] Identification of wheat as a possible trigger is attributed to Willem-Karel Dicke, a Dutch pediatrician. He reported that a World War II-related shortage of bread in the Netherlands led to a significant drop in mortality among children previously affected by celiac disease—from greater than 35% to essentially zero.[3] When wheat became more abundant after the war, the mortality rate soared to previous levels. Following up on Dicke’s observation, other scientists discovering that gluten, the major protein in that grain, was the culprit.[4]


Once thought to be a disease of childhood characterized by diarrhea, celiac disease—also known as nontropical sprue or gluten-induced enteropathy—is actually a multisystemic disorder caused by an immune response to ingested gluten. There is a strong genetic predisposition to the condition, with the major risk attributed to the presence of HLA class II genes HLA-DQ2 and HLA-DQ8. Celiac disease has a female to male ratio[5] of approximately 2:1 with middle-aged women accounting for up to 70% of new cases in adults.[6]

People with the disorder are unable to eat foods that contain gluten, a protein found primarily in wheat, rye, and barley. Gluten binds to the HLA-DQ2 and HLA-DQ8 genes and triggers an abnormal immune response that causes destruction of the villi in the small intestine.[7] Villi—the tiny, fingerlike protrusions lining the small intestine—normally allow nutrients from food to be absorbed through the walls of the small intestine into the bloodstream. When the villi are damaged, malabsorption can occur.

The typical gastrointestinal symptoms of celiac disease, such as abdominal bloating and pain, chronic diarrhea, or weight loss are observed more frequently in infants and young children. Malabsorption of nutrients during times of critical growth and development can result in problems such as failure to thrive, delayed growth and short stature, delayed puberty, and dental enamel defects of the permanent teeth.

Screening studies have revealed that adults are more likely to present with atypical gastrointestinal symptoms or symptoms not necessarily related to the gastrointestinal tract.[8] Adults may have constipation rather than diarrhea. Disruption of iron and folate absorption can cause anemia.[8] Malabsorption of calcium over time may lead to osteoporosis. Patients may complain of dermatitis herpetiformis, an autoimmune, intensely itchy skin disease. The rash manifests as itchy bumps or blisters, most often on the elbows, knees, back, and buttocks and occurs almost exclusively in patients with celiac disease. Other patients may present with a neuropathic, tingling sensation in the hands and feet. In fact, neurologic complications are estimated to occur in 10% of affected patients. Ataxia and peripheral neuropathy are the most common problems and may occur with or without the GI symptoms.[8,9] Still other patients have no symptoms at all and discover they have celiac disease only when a family member is diagnosed with it.

Who’s at Risk?

Individuals with chronic gastrointestinal symptoms—including chronic diarrhea, malabsorption, weight loss, and abdominal distention—should be tested for celiac disease. Because the prevalence of celiac disease increases in patients with other autoimmune and genetic diseases,[10] patients at high risk for such conditions might also be good candidates for testing (Table 1).[11,12] Because current data do not indicate a clear outcome benefit for early detection and treatment of asymptomatic patients in these groups, routine screening cannot be recommended at this time; however, individual discussions regarding the benefits and consequences of testing are warranted. At this time, there are insufficient data to recommend screening of the general population for celiac disease.[12]



Celiac disease has been dubbed the “great pretender,” as its symptoms can easily masquerade as a number of other illnesses. In women, it’s often misdiagnosed as irritable bowel syndrome, iron-deficiency anemia caused by menstrual blood loss, inflammatory bowel disease, diverticulitis, intestinal infections, or chronic fatigue syndrome.

According to data published by the University of Maryland Center for Celiac Research, nearly 1 out of every 133 Americans suffers from celiac disease. It is twice as common as Crohn’s disease, ulcerative colitis, and cystic fibrosis combined.[10] The projected number of people in the United States with celiac disease could be as high as 3 million, yet only a small fraction of these cases has been correctly diagnosed and treated by primary care practitioners.[10,13] Consequently, the majority of individuals with celiac disease remain undiagnosed in the United States, with a calculated ratio of diagnosed to undiagnosed cases estimated at 1 to 50-100.[10]

The first step in diagnosing celiac disease is to consider it, despite its myriad clinical features. While intestinal biopsy is the gold standard for confirming a diagnosis of celiac disease, blood tests to measure antibodies such as tTG-IgG and EMA-IgA provide an effective first step in identifying biopsy candidates.[14,15] Both tests are estimated to have sensitivities greater than 90% and specificities greater than 95%.[16] If the serology results are positive, the patient should be referred to a gastroenterologist for a biopsy of the proximal small bowel. It’s important that serologic testing and biopsies both be performed while the patient is still eating gluten-containing products, as a gluten-reduced diet may impact the blood tests and interpretation of the biopsy results.[14,15]

Genetic testing (via either blood test or cheek swab) can stratify patients to high or low risk for celiac disease. Greater than 97% of patients with celiac disease have these markers, compared with approximately 40% of the general population. Therefore, someone who tests negative for DQ2 or DQ8 is unlikely to have celiac disease.[12]

There are two main reasons for using genetic testing when evaluating a patient for celiac disease. The first case is to “rule out” celiac disease. People who test negative for the gene would not be required to undergo regular antibody screening for the remainder of their lives. For example, offspring of a parent with celiac disease could have the test; the results would allow the parent to know if and which children need close monitoring. A case for genetic testing can also be made for patients who have been on a gluten-free diet for some time but who have not undergone a biopsy. A negative gene test would indicate that symptoms are not due to celiac disease.[17]

Management of Celiac Disease

While most patients with celiac disease are managed by a gastroenterologist, a study published in July, 2012 suggests that a large percentage of patients with celiac disease have less than optimal medical follow-up with a gastroenterologist. Among 113 patients followed for more than 4 years, only 35% received follow-up care consistent with guidelines produced by the American Gastroenterological Association. As the initial point of care, therefore, it behooves primary care providers to understand the etiology, screening, and management of celiac disease.[18]

Currently, the only proven treatment for celiac disease is strict lifelong adherence to a gluten-free diet that excludes wheat, rye, and barley. The strict definition of a gluten-free diet remains controversial due to the lack of an accurate method to detect gluten in food products and the lack of scientific evidence for what constitutes a safe amount of gluten intake.[19] While oats appear to be safe for use by most individuals with celiac disease, their practical inclusion in a gluten-free diet is limited by potential contamination with gluten during processing.

Complete removal of gluten from the diet will result in symptomatic, serologic, and histologic remission in the majority of patients.[20] Growth and development in children returns to normal with adherence to the gluten-free diet and, in adults, many disease complications are avoided. Some data suggest that up to 70% of patients report an improvement in symptoms within 2 weeks of initiating the gluten-free diet.[21]

Patients who are new to the gluten-free lifestyle may be confused as to which foods are allowed. Many foods are gluten-free, such as milk, butter, and cheese; fresh, frozen, or canned fruits and vegetables; fresh meats, fish, poultry, eggs, beans, seeds, nuts; corn, and rice. Gluten is found predominantly in breads, cereals, and pastas, as well as seasonings, sauces, marinades, soy sauce, soups, salad dressings, and conveniently packaged flavored rice. It is critical that a patient ensures that each product is gluten-free by carefully reading food labels or by contacting food companies.

Eating and baking gluten-free has become easier in recent years, with increases in the availability of gluten-free food products—a market estimated at $2.5 billion in 2010.[22] Consumers can purchase gluten-free breads, buns, rolls, pizza crusts, donuts, pastas, pretzels, cereals, and desserts. Gluten-free cookbooks provide recipes and helpful tips for successful gluten-free baking. Common ingredients in gluten-free breads and baking mixes are cornstarch, potato flour/starch, tapioca flour/starch, and brown/white rice flour. Patients should be aware that unlike wheat and rye flour, most gluten-free flours are not fortified with B vitamins and minerals. Gluten-free baked goods also tend to be high in fat and calories to enhance flavor, texture, appearance, and overall acceptability of the gluten-free products, which may be of concern for those patients who do not wish to gain weight.[18,21]

Although evidence supports the need to treat celiac disease with a gluten-free diet, adults may find a change in lifelong dietary patterns overwhelming. Children may find the dietary restrictions too restrictive and stigmatizing. Therefore, patient education is of paramount importance. Causes of nonadherence include insufficient education and misinformation and the restrictive nature of the diet.[23,24] Ideally, a team approach, consisting of the patient, clinician, dietitian, and local support groups, should be used when educating the newly diagnosed patient with celiac disease. The National Institutes of Health Consensus Development Panel on Celiac disease[12] identified 6 elements essential to managing patients who have celiac disease:

Consultation with a skilled dietitian

Education about the disease

Lifelong adherence to a gluten-free diet

Identification and treatment of nutritional deficiencies

Access to an advocacy group

Continuous long-term follow-up by a multidisciplinary team

Participation in an advocacy group can also promote adherence to a gluten-free diet and may provide emotional and social support. Following initial diagnosis and treatment, individuals should return for periodic visits with the primary care provider and the dietitian to assess symptoms and dietary adherence and monitor for complications. In children, this includes evaluation of growth and development. During these visits, healthcare providers can reinforce the benefits of adhering to a strict gluten-free diet for life.


Celiac Disease Awareness Campaign, sponsored by the National Institutes of Health

Offers educational materials, a newsletter, and practice guidelines and tools

Celiac Disease Foundation

Offers patient education and dietary information


Jill Shuman, MS, ELS
Published on August 21, 2012



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