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Thursday, August 5, 2010
Celiac Disease Diagnosis Up 4-Fold Worldwide
From Medscape Medical News
by Megan Brooks

July 30, 2010 — Studies from the United States, Europe, and elsewhere indicate that the prevalence of celiac disease (CD) has increased significantly in the last 3 decades — possibly by as much as a factor of 4.

"More and more studies indicate a prevalence of CD of more than 1% in both adults and children. This should be compared with lower prevalence figures [from] 20 to 30 years ago," Jonas Ludvigsson, MD, from the Department of Medicine, Epidemiology Unit, at the Karolinska Institute and Orebro University Hospital, Sweden, and an expert in CD, noted in an email to Medscape Medical News.

"The reason for this increase is mutlifactorial, but there is probably a true underlying increase. This has been shown when old sera have been analyzed with modern techniques, (eg, in Finland)," Dr. Ludvigsson pointed out.

Mayo Clinic Research Confirms Rise in CD

Researchers at the Mayo Clinic also report an increase in CD, according to an article in the summer issue of the Mayo Clinic's research magazine Discovery's Edge. Joseph Murray, MD, and colleagues analyzed stored blood samples, taken from Air Force recruits in the early 1950s, for gluten antibodies. They assumed that 1% would be positive, mirroring today's rate. That assumption was wrong — the number of positive results was far smaller, indicating that CD was "rare," Dr. Murray noted in the article.

This led him and his colleagues to compare those results with 2 more recently collected sets from Olmsted County, Minnesota. Their findings suggest that CD is roughly 4 times more common now than in the 1950s.

"This tells us that whatever has happened with CD has happened since 1950," Dr. Murray said. "This increase has affected young and old people. It suggests something has happened in a pervasive fashion from the environmental perspective," he added.

Excess Mortality Seen With CD and Latent CD

Recent research by Dr. Ludvigsson's team (JAMA. 2009;302:1171-1178) and others supports the concept of "latent CD" or "gluten sensitivity." Latent CD, defined in the Journal of the American Medical Association study by Dr. Ludvigsson's team as having normal small intestinal mucosa but positive CD serology, is something that is estimated to occur in at least 1 in 1000 individuals.

Dr. Ludvigsson's team has also reported evidence that in 1 year, 10 of 1000 individuals with CD will die compared with an expected 7 in 1000 without the disease.

"Not only is the mortality raised in patients with [CD] but also in those individuals with latent [CD]," Dr. Ludvigsson noted in a statement from the United European Gastroenterology Federation.

However, in comments to Medscape Medical News, he emphasized that "although patients with CD are at increased risk of a number of disorders, and at increased risk of death, the absolute risk increase is very small."

A Tricky Disease

CD remains a "tricky disease," Dr. Ludvigsson said. "It can be asymptomatic; have so-called traditional symptoms such as diarrhea, weight loss, failure to grow (in children), fatigue, and malnutrition; and have nontraditional symptoms such as osteoporosis, depression, adverse pregnancy outcome; and increased risks of both malignancy and death."

The onset of certain autoimmune disorders including autoimmune liver disease, thyroid disease, type 1 diabetes, and Addison's disease can actually signal CD, he noted. "This means that clinicians should consider CD in a number of symptoms and disorders."

CD Often Undetected; Cause Unknown

CD often goes undetected, although the percentage of undetected cases varies between countries, Dr. Ludvigsson noted. "In most countries, at least two thirds of individuals with CD have not received a diagnosis by a doctor." The reason for the high percentage of undetected disease is that the disease can be difficult to diagnose, and "it is sometimes almost asymptomatic," he added.

Detection Methods Are Improving

Over the years, Dr. Ludvigsson told Medscape Medical News, "we have improved existing means to diagnose CD. Antibody tests are becoming better and better, although a positive antibody test should be confirmed with a small intestinal biopsy before the diagnosis is certain. Transient increases in CD antibody levels occur. In the future, I expect microscopy in the very small intestine to become a tool for diagnosis."

Alternatives to the Gluten-Free Diet?

At this time, Dr. Ludvigsson said, the gluten-free diet remains the cornerstone of treatment for CD. However, "in the future, alternative treatment strategies may be available. The recent discovery of the structure of transglutaminase 2 may help in designing inhibitors of transglutaminase 2 to treat CD," he said. "Another potential treatment strategy is to ingest enzymes that digest gluten, thereby increasing the safe threshold for gluten intake.

"There is also ongoing research on the topic of decreasing the bowel's permeability to gluten, Dr. Ludvigsson told Medscape Medical News. He added, however, that the safety of this approach is unclear, as "a decreased permeability here might mean that the body cannot absorb other needed substances.

"Finally, agricultural research may mean that we can modify the gluten structure in wheat produce a kind of wheat that will not illicit an immune response in patients with CD," the researcher noted.

Counseling CD Patients Is Important

Although evidence is scarce, said Dr. Ludvigsson, "most researchers believe that a gluten-free diet will reduce the risk of complications/comorbidity in CD, and it is important for the doctor to underline this for the patients. In patients with CD who do not become better on a gluten-free diet, the most common reason is probably that the patients do not eat a strictly gluten-free diet," he said.

Dr. Murray advocates greater vigilance in CD patients. "It's not enough to say, 'You've got CD, be gluten-free, goodbye,' " he said. "CD requires medical follow-up."

This October, at the United European Gastroenterology Week in Barcelona, Spain, Dr. Ludvigsson will be 1 of 8 researchers to receive the Association of National European and Mediterranean Societies of Gastroenterology and United European Gastroenterology Federation Rising Stars award.

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