I know you are doing your share to alert people to this disease...
Belatedly, an Illness Of the Intestines Gets Notice in U.S.
Long Well-Known in Europe, Celiac Disease May Affect Up to 3 Million Americans
Mr. Martin's Misdiagnoses
From the December 9, 2005 THE WALL STREET JOURNAL

Growing up in the Midwest during the Depression, John Dryden was a sickly child with constant gastrointestinal complaints. Over the years, doctors ascribed Mr. Dryden's problems to appendicitis, irritable-bowel syndrome, kidney stones and bone cancer.

Mr. Dryden bore the discomfort into his mid-60s. Then his symptoms worsened, causing him to lose considerable weight amid recurrent fatigue. In 1998, the retired engineering designer visited the Mayo Clinic in Rochester, Minn. After an intestinal biopsy, a gastroenterologist named Joseph Murray identified Mr. Dryden's problem as a seemingly rare condition known as celiac disease.


Dr. Murray's origins were fortuitous: He is from Ireland. Celiac disease, a condition in which so-called gluten proteins in grains such as wheat and barley trigger an immune-system attack on the small-intestine lining, has a long history in Europe. Doctors there are trained to look routinely for the condition. In the U.S., by contrast, doctors have long assumed the disease was a rare childhood disorder.

Only in the past few years has it become evident that celiac disease may be more widespread. A report last year by experts convened by the National Institutes of Health declared that the disease affects 0.5% to 1% of the U.S. population, or roughly 1.5 million to 3 million Americans. They may have varied symptoms or none at all. The NIH estimate emerged after expatriate European and Australian researchers pushed to study the disease more aggressively in the U.S.

The story of celiac disease shows how blind spots can develop in the U.S. medical system. In Europe, a self-reinforcing cycle got under way in which patient groups spurred government-funded research, and the research led to publicity, more diagnoses and more funding. In the U.S., that process worked in reverse, as the perceived rarity of the condition depressed interest among researchers.

Lack of incentives also played a role. Treating celiac disease usually requires little more than a strict dietary regimen: Patients must avoid foods containing gluten, which rules out bread, pasta, beer and most packaged foods. As a result, it attracted little attention from drug companies. Academic researchers who saw few opportunities to develop new surgical or drug treatments for celiac disease preferred to study diseases for which innovative treatment options were needed.

"Looking back historically, the really great things done in celiac disease were all European," says Cyrus Rubin, a retired professor at the University of Washington and a U.S. pioneer in celiac disease. "Why did it take so long for gastroenterologists to treat it here? Mainly, we didn't discover it first, so it couldn't be right."

Celiac disease isn't the only medical condition to fall into an American blind spot. It took a decade or more for U.S. doctors to accept a 1982 Australian discovery that most stomach ulcers are caused by the bacterium Helicobacter pylori. The discovery made it possible to replace expensive drug and surgical treatments with a cheap course of antibiotics. It won the Nobel Prize for two scientists this year.

While celiac disease is rarely fatal, it can debilitate patients with diarrhea, fatigue, nausea and weight loss as their intestines lose the ability to absorb nutrients. Many specialists think untreated celiac disease -- even without obvious symptoms -- can also lead to osteoporosis, anemia, infertility and cancer. The condition is linked to other autoimmune disorders such as Type 1 diabetes.

Much remains unknown about celiac disease. Diagnosis can be difficult, because the disease can produce a variety of gastrointestinal symptoms, seemingly unrelated complaints, or no symptoms at all. Blood tests for celiac-related antibodies have improved, but still produce both false positives and false negatives. An intestinal biopsy is generally required for a firm diagnosis, but even that test can confuse damage from other diseases with the symptoms of celiac disease.

Many celiacs bounce from doctor to doctor for help with symptoms that stubbornly defy treatment. "I thought I had three weeks to live" at the time of diagnosis, says Mr. Dryden, now 74. After four weeks on the gluten-free diet, he says, "I felt like I was a young man again." Last year, he bought a houseboat and sailed 870 miles along rivers from Minneapolis to Kentucky. He still takes supplements for his bones, made brittle by years of celiac-related osteoporosis.

A 2001 survey by Peter Green and colleagues at Columbia University found that U.S. celiacs experience symptoms for 11 years on average before diagnosis.

Descriptions of an ailment resembling celiac disease date back to the ancient Romans. An English pediatrician formally described the condition in British children in 1888. An effective treatment emerged in 1950, when Willem Dicke, a Dutch doctoral student, noticed that celiac children had improved after World War II disrupted flour supplies. Dr. Dicke eventually fingered gluten, a generic term for certain proteins in wheat, rye and barley, as the culprit.

During a brief flowering of U.S. celiac-disease research in the 1960s, scientists such as Dr. Rubin devised new ways of testing small-intestine-tissue samples. Under the microscope, such tissue could reveal the destruction of the tiny hair-like extrusions, or villi, that line the intestines and absorb nutrients from food digested in the stomach. Such biopsies rapidly became a standard part of celiac-disease diagnosis.

Once the scientific puzzle of what was happening in the gut was solved, interest among U.S. researchers in celiac disease faded. Its seeming rarity made it an unpromising subject for ambitious scientists. Younger academics were drawn to poorly understood gastrointestinal disorders such as Crohn's disease and ulcerative colitis, where new findings might more readily translate into innovative treatments.

Dr. Murray of the Mayo Clinic recalls that when he was a medical student in Galway, Ireland, in the late 1970s and early 1980s, diagnoses of celiac disease were so common they were "part of the medical wallpaper." After he moved to a job at the University of Iowa in 1988, Dr. Murray once diagnosed a celiac alongside a senior professor. "This will be the last such case you see, since we never see this in America," Dr. Murray remembers the professor saying.

According to the Institute for Scientific Information, a unit of Thomson Corp. of Toronto, U.S. scientists contributed to only 10% of research papers on celiac disease published from 1985 to 1990. Scientists in the United Kingdom and Italy contributed to 38% of the papers.

As U.S. celiac research dwindled, so did medical awareness. The assumption that celiac disease rarely occurred in the U.S. became a self-fulfilling prophecy, as fewer doctors considered it as an explanation for illnesses.

Martin Family
Mike Martin and his wife, Debbie, in July 2004.

Mike Martin, a Navy veteran in New Jersey, began to suffer in 1977 from stomach problems and diarrhea that forced him to quit his job as a delivery worker. He lost 40 pounds and began visiting doctors, who either found nothing wrong or ascribed his problems to irritable-bowel syndrome, a catch-all diagnosis for gastrointestinal distress. Even after Mr. Martin developed dermatitis herpetiformis, a rare skin condition linked to celiac disease, no doctor considered a celiac diagnosis until two years ago, when by chance he visited a gastrointestinal specialist trained in India.

Mr. Martin, now 51, never returned to work and is supported by his wife, Debbie. He has regained some weight on a gluten-free diet but still can't properly digest many foods.

Meanwhile, European researchers advanced celiac studies. Alessio Fasano, an Italian researcher formerly at the University of Naples, says celiac patients groups "helped create a political and health-care agenda" to promote research into the disease. He also says European countries that have national health-care systems pay more attention than the U.S. to preventing diseases through early diagnosis.

In the 1970s and 1980s, new blood tests for celiac-related antibodies let researchers screen larger groups of schoolchildren and blood donors. Those tests showed that celiac disease was more common than thought in many European countries. By the 1990s, researchers concluded that celiac disease might affect as much as 1% of many countries' populations.

European scientists, with help from a U.S. group, eventually pinpointed a genetic variant common to celiacs and began to unravel the biochemical events that lead the body to mobilize against gluten and attack intestinal tissue. Health authorities stepped up efforts to make family doctors aware of the condition.

The new thinking made little headway in the U.S. at first. A 1994 Mayo Clinic study reinforced U.S. complacency by suggesting that celiac disease affected only one American in 5,000. However, the researchers hadn't done any blood testing. The figure reflected only cases in one Minnesota county diagnosed through classical gastrointestinal symptoms.

A handful of foreign scientists who moved to the U.S. to take advantage of greater academic freedom and better career opportunities began to press their contention that celiac disease was more common in the U.S. Dr. Fasano, who moved to the University of Maryland in 1993, published a 1996 paper in a Norwegian journal titled, "Where Have All the American Celiacs Gone?" In the mid-to-late 1990s, the NIH awarded a few grants to study prevalence of the disease.

Susan Goldstein, a 61-year-old graphic designer in White Plains, N.Y., was unexpectedly rejected as a blood donor in 1991 when tests showed her to be severely anemic. A visit to a Columbia University hematologist led her to Dr. Green, an Australian doctor who had schooled his fellow specialists to look for celiac disease.

Ms. Goldstein turned out to be a celiac. So did two of her three adult children, neither of whom exhibited classical gastrointestinal symptoms. All three have been on gluten-free diets since. Ms. Goldstein helped found a local celiac-support group and raised funds for a celiac research center at Columbia, which Dr. Green now directs.

In 2003, researchers led by Dr. Fasano reported that one American in 133 has celiac disease, after screening more than 13,000 people. The following year, the NIH held its "consensus conference" to lay out the state of the art in the disease and help settle controversy. It produced the estimate that as many as one in 100 Americans has the condition.

Nonetheless, celiac disease remains today "kind of an orphan, even though it's a very common disease," says Charles Elson, a gastroenterologist at the University of Alabama in Birmingham who chaired the NIH conference. "There are no pharmaceutical or biotech companies pushing a product and calling on doctors."