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New Clues to Risks From Celiac Disease

New Clues to Risks From Celiac Disease Study Shows Patients With Less Severe Form of Celiac Disease May Be at Higher Risk of Death WebMD Medical News By Kathleen Doheny...

Sept. 15, 2009 -- Patients with celiac disease -- a genetic, inherited disorder marked by intestinal damage -- are at a modestly increased risk of death, as suspected, according to a new study.

But in a surprise finding, the researchers discovered that those with less severe degrees of celiac disease are at higher risk of death than the others.

"There is an increased risk of death from celiac disease," says Jonas Ludvigsson, MD, PhD, the study's lead author and an associate professor of pediatrics at Orebro University Hospital, Sweden. Depending on the severity of the disease, he found the increased risk to range from 35% to 72%.

"But the risk of dying is still very uncommon," he tells WebMD. "Most researchers would have expected the increase [in risk to be higher]," he says. The study is published in this week's issue of TheJournal of the American Medical Association.

About one of every 133 people has celiac disease, according to the Celiac Sprue Association, but only about 3% have been diagnosed. In people with the disease, eating certain types of protein known as gluten -- found in many breads and crackers -- triggers an autoimmune response that results in small intestine damage. That damage, in turn, decreases the ability of the small intestine to absorb nutrients. Malnutrition and other complications follow. Treatment focuses on eating a gluten-free diet.

Celiac Disease and Death Risk

Although the risk of death for celiac disease patients has been known, less is known about those with a less severe form of the disease. "We studied the early stage of celiac disease as well, inflammation and latent celiac disease," Ludvigsson says.

Ludvigsson and his colleagues looked at data reports on intestinal tissue studied at the microscopic level, collected from biopsies that had been taken from Swedish patients from the years 1969 to 2008.

They divided the biopsy data from more than 46,000 patients into three groups: those with celiac disease, defined by the presence of villous atrophy (intestinal damage); those with a less severe form, in which there is inflammation without villous atrophy of the intestinal lining; and those with latent disease. Patients with latent disease have positive blood tests but no physical findings of intestinal damage or inflammation, and doctors typically take a wait-and-see approach with them before treating.

The researchers compared all patients with a comparison group from the general population and followed them for a median of about seven to nine years (half were followed longer, half less). Among those with celiac disease, there were 3,049 deaths; among those with inflammation, 2,967 died and among the latent group, 183 died.

The increased risk of death, the researchers found, differed by group:

  • Those with inflammation had a 72% increased risk of death.
  • Those with celiac disease had a 39% increased risk of death.
  • Those with latent disease had a 35% increased risk of death.

But Ludvigsson puts the finding in perspective. The most important finding, he says, is the relatively low overall risk of death, even though it is increased. It translates, he says, "into very few actual deaths."

The researchers also found that those diagnosed before age 20 had nearly twice the risk of death, overall, but Ludvigsson says that, too, needs to be put into perspective. "Kids are at increased risk of mortality," he says. Even though the risk is increased, he says, it is still very low.

The higher risk in those with less severe disease, Ludvigsson says, may be because of the untreated inflammation, as those patients may not be told to follow a gluten-free diet.

The risk of death was found to be highest in the first year of follow-up, then decreased.

Deaths were often from malignancy or cardiovascular disease, the researchers found. Exactly why isn't known, but Ludvigsson says that the longtime inflammation associated with celiac disease may boost the risk of other disorders, such as heart disease and cancer.

Second Opinions

The findings that those in the less severe group have risk of death, and sometimes higher than others, are concerning, says Daniel Leffler, MD, director of clinical research at The Celiac Center, Beth Israel Deaconess Medical Center, Boston, and an assistant professor of medicine at Harvard Medical School, who reviewed the study for WebMD.

The other surprise to him was that the risk of death, although it declined after the first year of diagnosis, did not normalize. "Other studies have shown that once you treat, the risk of death goes back to that of the normal population. This study didn't show that. It went down but didn't go down to normal."

In an accompanying editorial, Peter Green, MD, a doctor at the Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, concludes that: "more attention should be given to the lesser degrees of intestinal inflammation and gluten sensitivity."

Even though the study didn't go into the effects of treatment, Ludvigsson says he thinks the advice is clear. "I believe the take-home message is: adhere to a gluten-free diet. Although this study did not show that gluten-free diet protects against death, there are strong indications that a gluten-free diet diminishes the risk of complications in celiac disease.'' 

Leffler agrees, noting that there is no way to know from the data whether or not the patients studied were adhering to a gluten-free diet. Treatment, he says, would be expected to have an important effect on death risk.

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