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Patients with mild intestinal inflammation and gluten sensitivity have a higher risk of death, even if their symptoms are not severe enough to warrant a diagnosis of full-blown celiac disease, a new Swedish study found.

Though still modest in absolute terms, risk of mortality increased by 75% for patients with mild inflammation of the small intestine at a median follow-up of 7.2 years (95% CI 1.64 to 1.79), and by 35% for patients with latent celiac disease (defined as gluten sensitivity) at median follow-up of 6.7 years (95% CI 1.14 to 1.58), according to a report in the Sept. 16 Journal of the American Medical Association.

The study also found that patients diagnosed with celiac disease had a 30% greater risk of death at a median follow-up of 8.8 years (95% CI 1.33 to 1.45). This supports previous research that found higher mortality rates in celiac patients.

The main causes of death for celiac patients were cardiovascular disease and cancer.

In all cases, the absolute mortality risk associated with celiac disease and the milder intestinal problems was modest, with an excess mortality of 2.9 deaths per 1,000 person-years in celiac disease and 10.8 and 1.7 deaths per 1,000 person-years in inflammation and latent celiac disease, respectively.

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

Celiac disease is an immune-mediated disorder triggered by ingesting glutens, the storage proteins of wheat, rye and barley. The disease, which affects about 1% percent of people living in Western countries, impairs digestion of nutrients through the small intestine, resulting in frequent diarrhea and weight loss.

Most previous studies have found an increased risk of death associated with the disease, but several of those were not population-based, lacked children and outpatients, or were limited by small numbers of participants.

Furthermore, little is known about the long-term consequences of milder forms of small-intestinal inflammation. In these cases, patients show no signs of villous atrophy, an abnormality in celiac patients that results in the flattening of the innermost membrane of the intestinal wall.

Ludvigsson and colleagues studied 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 had inflammation of the small intestine and 3,719 had latent celiac disease, in which patients tested positive for blood antibodies used as markers for celiac disease but had no signs of intestinal inflammation or damage.

The researchers compared the patient data to records of the Swedish Total Population Register to estimate 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.

"Risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased," they concluded.

The researchers theorized 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 preexisting diseases might have caused the increase in mortality. They also cautioned that some patients with inflammation could have been misclassified as having latent celiac disease or partial villous atrophy, resulting in an overestimate of mortality rates for the latent celiac disease group.

The researchers did not adjust for smoking, weight, and height, and data on patients symptoms were not available.

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

"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," he wrote.

"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."

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