Celiac disease: the great masquerader.

I recently saw a woman in her 50s who consulted me because she had osteopenia despite eating a good diet and engaging in regular vigorous physical exercise. She had also been found on routine screening to have a monoclonal gammopathy that suggested multiple myeloma; however, a bone marrow biopsy and full body scan were negative for multiple myeloma. Laboratory work had also demonstrated iron deficiency, which could not be explained by typical factors such as menstruation, use of nonsteroidal anti-inflammatory drugs, or vegetarianism. She had been experiencing low-level depression and had tried a selective serotonin reuptake inhibitor, but had discontinued it when it caused side effects and did not relieve the depression.

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I hypothesized that she might have celiac disease, which can present as either unexplained osteoporosis or unexplained iron deficiency. In addition, it was conceivable that the immunoglobulin spike found on her blood test was simply a high titer of tissue transglutaminase antibody (TTG), the antibody that is elevated in people with celiac disease and that is used as a diagnostic test for the disease. Although the patient denied having any gastrointestinal symptoms, it is not uncommon to encounter "silent" celiac disease (i.e., celiac disease in the absence of gastrointestinal symptoms). She was therefore advised to have a blood test for TTG and for antiendomysium antibodies (another serologic test for celiac disease). Both tests were positive, and the TTG titer was above the maximum level that could be quantified by the laboratory. Although she did not undergo a small-bowel biopsy to confirm the diagnosis, the probability that a person has celiac disease if he/she is positive for both antiendomysium antibodies and TTG is virtually 100%.

Based on the results of the blood tests, the patient went on a gluten-free diet. Within a week or two, her depression had resolved. Her fairly constant intestinal bloating, which had been present nearly her entire life, also disappeared rapidly after she started the diet (she had originally denied having intestinal symptoms, because she thought intestinal bloating was normal). In addition, her mental concentration improved considerably. It is still too soon to retest her bone mineral density. However, consumption of a gluten-free diet typically has a positive influence on bone mineral density in patients with celiac disease. The patient's monoclonal gammopathy will be reevaluated in about a year, since it takes 9 to 24 months for the TTG test to become negative after patients go on a gluten-free diet.

Celiac disease, also called gluten-sensitive enteropathy, is a chronic gastrointestinal disease caused by intolerance to gluten. Ingestion of gluten by a person with celiac disease causes gastrointestinal damage, which results in malabsorption and multiple nutritional deficiencies. Manifestations of celiac disease may include diarrhea and other gastrointestinal symptoms, failure to thrive, weight loss, fatigue, anemia, osteopenia or osteoporosis, epilepsy or other neurological disorders, defective gallbladder emptying, liver disease (including hepatic steatosis and progressive hepatitis), and infertility. Conditions less commonly associated with celiac disease include arthritis, asthma, schizophrenia, psoriasis, alopecia, premature graying of the hair, chronic urticaria, oral lichen planus, erythema nodosum, dental anomalies, recurrent pericarditis, reversible insensitivity to androgens, and immune-system abnormalities (a decreased proportion and a decreased absolute number of circulating T lymphocytes). Many of the manifestations of celiac disease may be due in whole or in part to nutritional deficiencies, whereas other celiac-disease-associated conditions may result from autoimmune damage to various tissues induced by gluten consumption.

While most patients with celiac disease have gastrointestinal symptoms, some do not, and the disease is not detected until the patient presents with anemia, osteoporosis, infertility, or other extraintestinal manifestations. Therefore, celiac disease should be considered in the differential diagnosis of a wide range of medical conditions, whether or not the patient presents with classical intestinal symptoms.

The most reliable diagnostic test for celiac disease is the demonstration of villous atrophy on small-intestinal biopsy. However, two different blood tests (antiendomysium antibodies and TTG) are also used to diagnose or screen for the disease. Both of these blood tests have a fairly high degree of sensitivity and specificity, but the TTG test costs less. Genetic testing can be used to confirm the antibody tests, since celiac disease is strongly associated with human lymphocyte antigen (HLA) types DR3 and DQw2. The availability of these noninvasive tests in recent years has made it possible to diagnose more cases of celiac disease.

Celiac disease affects about 1 in 130 people living in the US and about 1 in 50 people who have symptoms consistent with the disease. While these numbers might seem small, it is important to maintain a high index of suspicion that a person has the disease, because diagnosing and properly treating celiac disease can be a life-changing event for many people.

Alan R. Gaby, MD