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Gluten Sensitivity, Celiac Disease Carry Higher Mortality Risk

Celiac.com 09/28/2009 - According to the results of a new Swedish study,  patients with mild intestinal inflammation and gluten sensitivity face an elevated risk of death, even in the absence of symptoms severe enough to merit a clinical diagnosis of celiac disease.

A number of studies have shown that people with gluten sensitivity and intestinal inflammation, but just how great is the risk? However, of those previous studies that show an increased risk of death associated with the disease, many were not population-based, lacked children and outpatients, while others were hampered by small numbers of participants.

A team of Swedish researchers led by Jonas F. Ludvigsson, MD, PhD, of Sweden's Örebro University Hospital, recently set out to conduct a large-scale, population-based study regarding mortality risk levels for people with celiac disease, and also for those with "gluten intolerance."

Ludvigsson and colleagues examined histopathology data from tissue biopsies collected from 46,121 Swedish patients nationwide between July 1969 and February 2008. Of those patients, 29,096 had celiac disease, while 13,306 showed inflammation of the small intestine and 3,719 showed latent celiac disease, elevated blood antibodies used as markers for celiac disease, but no sign of gut inflammation or damage.

The researchers compared the patient data to records of the Swedish Total Population Register to calculate mortality rates for the three groups of patients. They found that among the patients there were 3,049 deaths among those with celiac disease, 2,967 deaths for those with inflammation, and 183 deaths for patients with latent celiac disease.

The overall risk was not great, mortality risk was 75% higher for patients with mild intestinal inflammation at a median follow-up of 7.2 years (95% CI 1.64 to 1.79), and 35% higher for patients with latent celiac disease, or gluten sensitivity, at median follow-up of 6.7 years (95% CI 1.14 to 1.58).

The study also revealed that people diagnosed with celiac disease faced a 30% greater risk of death at a median follow-up of 8.8 years (95% CI 1.33 to 1.45). That means that over the 8.8 years following the study, 30% more people with celiac disease died compared to the control group.

These findings confirm previous studies that show higher mortality rates in celiac patients. Major causes of death for people with celiac disease are cardiovascular disease and cancer.

Still, overall mortality risk associated with celiac disease and intestinal inflammation for gluten intolerance was small, with just 2.9 additional deaths per 1,000 person-years for people with celiac disease, and 10.8 and 1.7 additional deaths per 1,000 person-years for people with inflammation and latent celiac disease, respectively.

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Of the population-based study, Jonas F. Ludvigsson, MD, PhD, of Örebro University Hospital in Sweden, and colleagues writes,
"we examined risk of death in celiac disease according to small-intestinal histopathology...Excess mortality was observed independent of histopathology, but absolute excess mortality risk was small, especially in children."

In an accompanying editorial, Peter H. R. Green, MD, of Columbia University Medical Center, writes that the study's findings on patients with latent celiac disease, those patients who, in the United States, would be labeled as having "gluten sensitivity," were the most intriguing.

Dr. Green writes that until recently, "gluten sensitivity has received little attention in the traditional medical literature, although there is increasing evidence for its presence in patients with various neurological disorders and psychiatric problems."

Furthermore, researchers currently know little about the long-term consequences of mild gut inflammation. In such cases, patients typically show no sign of villous atrophy,  the flattening of the innermost membrane of the intestinal wall common to people with clinical celiac disease.

Overall, the "risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased," the researchers concluded.

The researchers speculate that the increase in mortality might result from chronic inflammation that damages patients' small intestines (the duodenum, specifically) or from malnutrition that saps their vitamins and energy.

The researchers did not, however, rule out the possibility that mortality may be due to other existing conditions. They also cautioned that some patients with inflammation may have been misclassified as having latent celiac disease or partial villous atrophy, skewing mortality rates upward for the latent celiac disease group.

Green concludes that the "study by Ludvigsson and colleagues reinforces the importance of celiac disease as a diagnosis that should be sought by physicians. It also suggests that more attention should be given to the lesser degrees of intestinal inflammation and gluten sensitivity."

Source:
JAMA. 2009;302(11):1171-1178.

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