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At a glance

  • Celiac disease (CD) is an autoimmune disorder that affects absorption of nutrients through destruction of intestinal villi.
  • Since CD is a multisystem disorder, individuals will exhibit diverse symptoms, with most cases going undiagnosed.
  • If CD is suspected, refer t he patient to a gastroenterologist for a small-intestine biopsy.
  • Patients diagnosed with CD must avoid products that are clearly derived from wheat, barley and rye.

What do infertility, osteoporosis, and anemia have in common? How about skin rash, abdominal pain, diarrhea, constipation, and weight loss? These are all conditions or symptoms that may be associated with celiac disease (CD), a complex autoimmune disorder. Celiac disease has become more widely diagnosed during the past few years, with an increased need for clinicians to stay current regarding diagnosis and management. Clinicians need to be especially knowledgeable about the dietary requirements of CD in order to counsel patients on how to begin and maintain a gluten-free diet (GFD).

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CD is an autoimmune disorder that affects absorption of nutrients through destruction of intestinal villi. Although the exact cause has not been identified, CD is known to have genetic, environmental, and immunologic components. Specific genetic markers known as human leukocyte antigen (HLA)-DQ2 and HLA-DQ8 are associated with CD susceptibility, with nearly 100% of affected individuals having one or both of these markers.1 It is estimated that one out of 133 people in the United States has CD, and it occurs in first-degree relatives at a prevalence rate of 1:22 (1:39 in second-degree relatives).2 CD is associated with other medical conditions, occurring in 3%-8% of individuals with type 1 diabetes mellitus.3

The intestinal villi damage seen in CD is triggered when a genetically susceptible individual ingests gluten found in wheat, rye, and barley. Although the event that triggers the immune response to gluten is not readily identified, it could be infection, injury, surgery, pregnancy, puberty, or any number of other possibilities. Intestinal permeability increases with disruption of the tight junctions, allowing gliadin (the protein fractions of gluten that are antigenic) and other macromolecules to pass into the intestinal submucosa.4 Both B-cells and T-cells are involved in the immunologic response to gliadin, recognized as foreign by T-cell receptors. Cytokines, synthesized by the T-cell receptors, damage the intestinal mucosa, and lymphocytes migrate to the site of damage. Although the exact mechanism is unknown, intraepithelial lymphocytes (IELs) are thought to be responsible for the damage seen in CD.5 The proliferation and infiltration of IELs into the lamina propria lead to crypt hyperplasia, villous shortening, and villous flattening. Malabsorption is a consequence of this flattening, resulting in a variety of malnutrition-related conditions seen in CD.

B-cell differentiation in relation to exposure to gluten results in the production of immunoglobulin (Ig)A and IgG antibodies against gliadin, endomysium, and tissue transglutaminase (tTG). Tissue transglutaminase, which is an enzyme released in response to cell injury or inflammation, has been identified as an autoantigen in the immune response in CD.6 Although several antibodies have been used in serologic testing for CD, tTG-IgA is the test of choice in most settings, as long as the individual is not IgA-deficient.6

Clinical presentation

CD was long thought to be a relatively uncommon disease of childhood, persisting into adulthood. In recent years, however, it has been recognized that CD can develop at any age, even in the elderly.7

Because CD is a multisystem disorder, individuals will exhibit diverse symptoms (including no symptoms), with most cases going undiagnosed. The term “celiac iceberg” has been used to describe CD, with the “tip” of the iceberg representing those cases that are symptomatic at diagnosis.8 Classic symptoms of CD are those related to malabsorption (e.g., diarrhea, steatorrhea, flatulence, weight loss, vomiting, abdominal pain); other GI complaints include constipation, bloating, abdominal distension, and anorexia. Symptomatic individuals may also present atypically with extraintestinal symptoms (e.g., iron-deficiency anemia; unexplained folic-acid deficiency; dental enamel defects; aphthous stomatitis; infertility; and a pruritic, vesicular rash).8 This presentation with extraintestinal symptoms may lead to misdiagnosis or delayed diagnosis in a large number of cases. At times, the diagnosis is made only after treatment for several other disorders has failed. Table 1 lists a broad overview of symptoms that may be present in untreated CD.

“Silent” CD refers to cases in which individuals report no symptoms; such patients are most likely to be diagnosed through serologic screening of high-risk groups and confirmed through small-intestine biopsy. These high-risk groups include asymptomatic first- and second-degree relatives and persons with type 1 diabetes mellitus. Individuals with abnormal serologic tests but with a negative biopsy may potentially develop CD, which may not manifest with severe villi damage for years.9 Undiagnosed CD and potential CD represent the large “submerged” part of the celiac iceberg.

History and physical examination

A person may present to the primary-care setting with any number of complaints or just a vague complaint of not feeling well or having low energy. The patient could possibly be an asymptomatic family member of someone with CD and interested in knowing if he or she has the disease as well. As with any health concern, the clinician should begin with obtaining a thorough history. The history should be inclusive of GI complaints as well as seemingly unrelated symptoms. Ask about characteristics of the stool (i.e., odor, consistency [often greasy, clay-colored, foul-smelling]) and presence of bloating and flatus. Symptoms related to lactose intolerance (e.g., gassiness, bloating, diarrhea after ingesting dairy products) may also be reported. A thorough diet history may help identify other causes of discomfort. Patients may report they suspect a food allergy but are unable to track down the cause. Also ask about the patient’s energy level and emotional status, as well as bowel changes, skin changes, stability of weight, and—for children—the effects on growth and development.