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A 25-year-old female graduate student presented to her primary care physician after she was rejected as a blood donor because she was anemic. She was told her hemoglobin was 9 g/dL. She had donated blood 6 years before this attempt without difficulty. The patient was otherwise healthy and had no major symptoms. She noted some generalized fatigue but had been attributing this to her “stressful life.” She had been prescribed the oral contraceptive ethinyl estradiol/levonorgestrel (Seasonale) 9 months earlier and had her menses once every 3 months. She denied any abdominal pain, nausea, vomiting, melena, hematochezia, or changes in weight or appetite. She was a nonsmoker, drank occasional alcohol on the weekends, and denied any illicit drug use. There was no family history of anemia or other hematologic problems. Physical examination revealed a healthy-appearing young woman in no acute distress. Conjunctivae were not pale. Findings on cardiac examination were normal (no evidence of murmurs, rubs, or gallops), as were findings on lung examination. Abdominal examination revealed normal active bowel sounds. The abdomen was soft, nontender, nondistended, with no obvious masses. Gynecologic examination was also unremarkable. Laboratory testing yielded the following results: hemoglobin, 10.2 g/dL; hematocrit, 29.7%; mean corpuscular volume, 77.8 fL; red cell distribution width, 19.6%; white blood cell count, 5.3 × 109/L; and platelets, 439 × 109/L.
Celiac disease is an autoimmune gluten-sensitive enteropathy that occurs as a result of a combination of genetic and environmental factors when gluten is ingested.8 Gluten, the protein component of wheat that is also found in barley and rye, is not well absorbed in the upper gastrointestinal tract. Gliadin, the alcohol-soluble portion of gluten, contains the toxic components and remains in the intestinal lumen after ingestion of gluten because it is not degraded by intestinal enzymes. Patients with celiac disease produce an immune response to gliadin, causing inflammation in the small intestine with an increase in proinflammatory cytokines. This inflammatory reaction leads to villous injury, atrophy, and subsequent malabsorption.8
A familial predisposition exists for the development of celiac disease and has been associated with the major histocompatibility alleles HLA-DQ2 and HLA-DQ8. Environmental factors, such as early introduction of gluten in children younger than 4 months, have been associated with an increased risk of celiac disease.1 The prevalence of celiac disease approaches 1%.6,9
Adults presenting with iron deficiency anemia have occult celiac disease up to 9% of the time.1,2,10 In addition, iron deficiency anemia can be found in up to 46% of patients with subclinical celiac disease.11 Patients are considered to be at higher risk if they have first- or second-degree relatives with celiac disease, unexplained iron deficiency anemia, underlying osteoporosis, type 1 diabetes mellitus, liver disease, thyroid disease, Down syndrome, or other autoimmune diseases. These high-risk patients should be considered for celiac disease testing.1 Dermatitis herpetiformis is a frequently associated finding and presents as a pruritic, blistering rash, most commonly on the extensor surfaces. Granular IgA depositions are present along the basement membrane. The diagnosis is supported by serologic findings, including positive findings on IgA endomysial antibody or IgA tTG antibody assays. Although both tests have sensitivities greater than 90%, recent studies have suggested that the IgA tTG assay may have a higher sensitivity than the IgA endomysial antibody assay.4,6 In addition, the IgA tTG assay has excellent specificity (95%) and is less time-consuming than the antiendomysial antibody assay. In patients in whom IgA deficiency is suspected, it may be appropriate to also obtain an IgG tTG level.1 Even with the high predictive value of serologic tests, the mainstay for diagnosis remains findings on small bowel biopsy of villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia.4 Improvements in these findings can be seen in response to a strict gluten-free diet.
In patients in whom serologic testing and small bowel biopsy are not suggestive of celiac disease but in whom the diagnosis is still suspected because of clinical findings, HLA testing may play a role in excluding celiac disease. Because approximately 95% of patients with celiac disease test positive for either the HLA-DQ2 or HLA-DQ8 allele, the absence of these alleles would make the diagnosis of celiac disease very unlikely.1
Treatment is directed at avoiding the offending agent, gluten. Gluten is mainly found in such foods as wheat, pastas, cereals, and breads. However, it can also be found in many other foods, including seasonings and sauces, and thus close attention to food labels is essential. Diagnostic studies should be performed before initiating a gluten-free diet. Patients must commit to a lifelong gluten-free diet. Clinical improvement usually occurs within days to weeks of initiation; however, histologic recovery may require more than 24 months.4,9 Adherence to a gluten-free diet is also essential for maintaining adequate nutrition because micronutrient malabsorption can occur with nonadherence. In addition, patients with celiac disease are at higher risk of developing malignancies, such as enteropathy-associated T-cell lymphoma, and adherence to a gluten-free diet has been shown to partially protect against this complication.12 Follow-up serologic testing after initiation of a strictly gluten-free diet has not been shown to correlate appropriately with histologic recovery, and therefore its value is controversial.3,4 However, if nonadherence to a gluten-free diet is suspected or if monitoring for inadvertent ingestion of gluten is desired, a follow-up anti-tTG antibody assay would be reasonable. Also recommended is an annual clinical evaluation, including weight, complete blood cell count, and folate, calcium, and alkaline phosphatase levels.1
Correct answers: 1. a, 2. e, 3. c, 4. b, 5. d