Celiac Disease: On the Rise
Celiac disease, an immune reaction to eating the protein gluten, is far more than an occasional tummy upset. Mayo Clinic research suggests the disease is becoming a major public health issue. Although the cause is unknown, celiac disease is four times more common now than 60 years ago, and affects about one in 100 people. According to Mayo studies, undiagnosed celiac disease can quadruple the risk of death. Mayo researchers are working to discover the causes and improve diagnosis. Their efforts have been aided by a 1950s streptococcus outbreak and a pizza delivery truck.
Sarah Berg suffered from severe gastrointestinal symptoms for six years. “I had gone to the doctor over and over again. I just didn’t feel good most of the time.” She had never heard of celiac disease until a colleague urged her to be tested at Mayo Clinic. Her diagnosis “was such a relief,” she says.
The latest research at Mayo shows that Berg is far from alone. The prevalence of celiac disease appears to be rising dramatically. Joseph Murray, M.D., a Mayo gastroenterologist, says celiac disease is becoming a public health issue. Studies show four times the incidence compared to 1950, with fatal complications if it goes untreated.
“Celiac disease was rare, but it’s now more common in all age groups,” Dr. Murray says. Although the cause is unknown, celiac disease affects about one in 100 people. What’s more, Mayo has found a fourfold higher death risk for people with undiagnosed gluten intolerance.
As one of the largest celiac disease treatment centers in the United States, Mayo seeks to raise awareness and improve screening. Celiac patients may suffer severe stomach pain and diarrhea if they eat even traces of the protein gluten, which is found in wheat, rye, barley and in many supermarket foods. Once gluten is eliminated from the diet, celiac disease is usually manageable.
Mayo investigators also are trying to discover why celiac disease is on the rise. With its team research approach, Mayo is ideally suited for an effort that encompasses not only treatment of patients but also genetics lab work and maybe, someday, wheat farming.
Celiac disease is an immune response to this common protein. The immune system attacks the villi, hairlike projections that line the small intestine. Because villi increase the intestine’s surface area, they help the body absorb nutrients. Think of the inside of a healthy intestine as looking like a deep-pile carpet. In a patient with untreated celiac disease, Dr. Murray says, the intestine “looks like a tile floor.” Patients may experience severe abdominal pain, diarrhea and weight loss. Not all individuals experience the same symptoms. Untreated gluten intolerance is associated with certain cancers, osteoporosis, infertility, skin rashes and joint pain. Diagnosing celiac disease is fairly simple: The patient’s blood is tested for gluten antibodies.
Dr. Murray’s first encounters with celiac disease came in the 1970s, as a medical student in his native Ireland. “There’d be children admitted every week to the hospital with severe celiac disease,” he says. “It was just considered part of the wallpaper.”
When Dr. Murray moved to Iowa in 1988, he saw about one celiac patient per year. Initially, he assumed the disease — then frequently attributed to infant feeding practices — was uncommon in the U.S. Over time, however, he and other physicians suspected it was underdiagnosed. Dr. Murray started screening patients with digestive problems. By 1997, the hospital he worked at was diagnosing 100 celiac cases each year. “My hypothesis was, ‘We’re now really looking, so we’re finding what was always there,’” he says.
After joining Mayo, Dr. Murray decided to research the long-term effects of this “hidden” celiac disease. To do so, he needed to identify people who lived for decades with undiagnosed gluten intolerance. As it turns out, just up the road in Minneapolis lay a gold mine of information: A collection of blood samples taken from Air Force recruits in the early 1950s amid concern about streptococcus outbreaks in barracks.
Well-preserved blood samples dating back that far are extremely rare. These had been stored for decades in a researcher’s walk-in freezer in Cleveland. The freezer’s condenser leaked, and the rubber-corked glass test tubes “Were hermetically sealed in an iceberg,” Dr. Murray says. Eventually, the samples were donated to the University of Minnesota and shipped there in a frozen-pizza delivery truck.
Dr. Murray’s team tested the 50-year-old blood for gluten antibodies, assuming that 1 percent would be positive — the same as today’s rate of celiac disease. But the number of positive results was far smaller, indicating that celiac disease was extremely rare among those young airmen. Surprised, the researchers compared those results with two recently collected sets from Olmsted County, Minn. One blood-sample set matched the birth years of the airmen. Those elderly men were four times likelier to have celiac disease than their contemporaries tested 50 years earlier. The second set matched the ages of the airmen at the time their blood was drawn. Today’s young men were 4.5 times likelier to have celiac disease than the 1950s recruits.
“This tells us that whatever has happened with celiac disease has happened since 1950,” Dr. Murray says. “This increase has affected young and old people. It suggests something has happened in a pervasive fashion from the environmental perspective.”
Intrigued, Dr. Murray still wondered about the long-term effects. From the airmen’s public health records, Mayo researchers learned that those whose gluten intolerance had not been diagnosed in the 1950s were four times likelier to have died. “Having undiagnosed celiac disease is not good for you,” Dr. Murray says. “It may take 20 to 30 years for that risk to become apparent. But there’s a good chance it’s a problem.”
In a subsequent study, Dr. Murray found that nearly half of celiac patients diagnosed during adulthood don’t experience complete intestinal healing. A small proportion — not more than 1 in 50 — has “refractory celiac disease”; the intestine doesn’t improve at all after gluten is eliminated. “As many as half of those patients may be dead within three years,” Dr. Murray says. “That’s a rare condition, but one which we’ve been very invested in because that’s the sharp end of celiac disease.”
Because of these findings, Mayo advocates greater vigilance in celiac cases. “It’s not enough to say, ‘You’ve got celiac disease, be gluten-free, goodbye,’” Dr. Murray says. “Celiac disease requires medical follow-up.”
He also urges people who suspect they have the disease to be tested before eliminating gluten from their diet, as that can cause a false-negative test result. At Mayo, patients considered at risk for gluten intolerance are routinely screened. At-risk patients include celiac patients’ family members and patients with type 1 diabetes, chronic diarrhea, irritable bowel syndrome, premature bone disease and infertility. Eventually, Dr. Murray says, celiac testing may become routine. “We’re amassing more evidence to suggest that we have to screen people rather than just waiting for the disease to become apparent.”
Berg is doing well and is happy she has found an answer to her illness. “Finally, there was a reason for the symptoms and something I could do to fix it,” she says.
Giving up gluten was difficult, especially at Christmas. “I come from a very Norwegian family, so the thought of not being able to have those treats was pretty hard,” Berg says with a laugh. But learning about complications such as intestinal cancer was a powerful motivator, she says, and she now feels “outstanding.”
Discovering what triggers celiac disease in people like Berg is a complex process. About one-third of the population carries the genetic background for gluten intolerance — but only 1 percent of people have it. Before causes can be tested in the lab, researchers must develop an animal model with celiac disease.
Chella David, Ph.D., a geneticist and immunologist at Mayo, specializes in breeding mice with the genes for human autoimmune disorders. When Dr. Murray asked for help developing a mouse model for celiac disease, the task seemed straightforward. Gluten intolerance has the same gene as diabetes, and Dr. David already had a mouse model for that. His lab team began feeding gluten to those mice. However, the model is taking time to perfect.
“The mice get serious digestive problems, but not classic celiac disease like humans,” Dr. David says. “The simple fact could be that mice eat a lot of garbage. Because of that, their digestive systems have learned to cope with a lot of bad stuff, whereas humans have not. We keep refining the technology. We’re hoping that eventually we’ll have a mouse which is identical to the human disease.”
Dr. Murray lists several possible environmental causes of celiac disease. The “hygiene hypothesis” suggests the modern environment is so clean that the immune system has little to attack and turns on itself. Another potential culprit is the 21st century diet. Although overall wheat consumption hasn’t increased, the ways wheat is processed and eaten have changed dramatically. “Many of the processed foods we eat were not in existence 50 years ago,” Dr. Murray says. Modern wheat also differs from older strains because of hybridization. Dr. Murray’s team hopes someday to collaborate with researchers on growing archival or legacy wheat, so it can be compared to modern strains.
Dr. Murray says this wouldn’t be possible elsewhere. “Very few centers are like ours, going all the way from basic research in the lab to clinical practice and epidemiological work,” he says. “Here, there’s an atmosphere of openness, collaboration and teamwork.” As a research scientist, Dr. David agrees such collaboration is crucial. “I don’t know anything about human diseases,” he says. “I couldn’t do my work without the clinicians. And they couldn’t do their work without the kind of expertise we have in our labs. It’s a very mutual and productive experience.”
— Barbara Toman, July 2010