By the time Alyson and Joshua Weinberg found out what was wrong with their daughter Josie, the toddler was too weak to walk across the room. She had sunken cheeks and a swollen belly, and she was vomiting frequently. She was clingy and scared, and her parents were petrified. No one in an office full of pediatricians in Montgomery County recognized what was wrong with her.
"There was something that was telling me this kid is literally dying and we need to do something about it, and nobody is listening," Alyson Weinberg recalled.
It wasn't until they took their daughter to a pediatric gastroenterologist in Washington that they learned what was making her so sick: the very food that was supposed to nourish her. Josie had celiac disease, a chronic ailment caused by an immune reaction to gluten, a protein found in wheat and several other grains.
That disease, it is becoming clear, is far more common than doctors have been taught. New research is revealing that celiac disease may be one of the most common genetic diseases, affecting perhaps as many as 2 million Americans. A national survey published today, for example, estimates that 1 in 133 Americans has it.
In Josie Weinberg's case, she stopped throwing up within three days of being taken off food containing gluten. Within three weeks, she was running around and singing. Over the next six months, she grew four inches.
"It was like someone had given us our child back," Alyson Weinberg said last week.
The Weinbergs' experience is an extreme example of an indisputable fact of American medicine -- most doctors miss the diagnosis of celiac disease. It's now clear that the textbook description of this once-obscure ailment is woefully incomplete and describes only a minority of cases. Below the tip of the so-called celiac iceberg is a diverse world of illness that may include thousands of people suffering from various, seemingly unrelated conditions, such as anemia, osteoporosis, infertility, irritable bowel syndrome and chronic fatigue.
"We were taught in another way. We were looking in the wrong direction. We were not putting our face under the water to see the iceberg," said Alessio Fasano, a gastroenterologist at the University of Maryland School of Medicine in Baltimore.
It is Fasano and his colleagues who are publishing the survey that estimates 1 in 133 Americans has celiac disease. About 40 percent of the afflicted report no symptoms, although the disease may be having inapparent effects, such as the loss of bone mass, subtle changes in mood and infertility. In close relatives of people with celiac disease, the ailment was especially common, with a prevalence of 1 in 22, according to the paper, which is appearing in the Archives of Internal Medicine.
The rapid expansion of a disease's prevalence is not a new phenomenon, but the rise in celiac disease is virtually without precedent.
A generation ago, physicians were taught the disease was so rare that a practitioner might go a lifetime without seeing a case. In 1993, researchers at Children's Hospital in Buffalo published a study estimating celiac disease's prevalence to be 1.3 cases per 10,000 children. Mayo Clinic researchers the next year measured a rate of 1.1 cases per 5,000 people in the Minnesota population the clinic serves. Fasano's work suggests, however, that celiac disease is 50 times more common than that.
The new estimate doesn't come from a rigorous epidemiological study, but from a survey of several heterogeneous groups -- blood donors, relatives of people with celiac disease, West Virginia schoolchildren and routine medical clinic patients. In all, 13,000 people from 32 states were tested. Despite these limitations, many experts believe the new estimate is probably close.
"I think Fasano is correct, although 1 in 133 may turn out to be a slight overestimate," said Richard Farrell, a celiac disease expert at Harvard Medical School. "It is certainly more frequent than in 1 in 10,000 or 1 in 5,000."
Epidemiological studies in Europe over the past two decades have found a prevalence of about 1 in 300 in Western Europe, with some populations having a rate of 1 in 150 (notably the Irish, which has helped fuel recent speculation that President John F. Kennedy, an Irish American, may have had celiac disease). The new estimate "is basically in the same ballpark as Europe," said Stephen P. James, head of digestive diseases research at the National Institutes of Health.
Celiac disease is characterized by a chronic inflammation of the upper portion of the small intestine. This occurs in response to gluten and similar proteins found in wheat, rye and barley. In classical cases, this leads to vomiting and diarrhea in young children soon after cereals are introduced in the diet. What's now clear is that people can develop celiac disease throughout life and that they often have few, if any, intestinal symptoms.
The symptoms they do have often arise from deficiencies of nutrients absorbed in the affected part of the intestine, such as iron, calcium and fat-soluble vitamins. Iron-deficiency anemia is the most common "clinical presentation" of adults with celiac disease. In Fasano's survey, 30 percent of people in which the disease was newly diagnosed had joint pain. One quarter had fatigue. Six percent had osteoporosis.
Celiac disease is diagnosed by testing for three antibodies -- anti-gliadin, anti-endomysial and anti-tissue transglutaminase -- that are present when an affected person is exposed to gluten but disappear when the offending grains are no longer consumed. Most physicians strongly recommend that the intestine be viewed and biopsied through a fiber-optic endoscope to confirm the diagnosis before a person embarks on a gluten-free diet, which is very hard to follow for a lifetime.
Despite its apparent commonness, there's little support for population-wide screening for celiac disease. Because the ailment can arise throughout life, it's not obvious at what age testing would be appropriate or cost-effective. In Italy, mandatory testing for 6-year-olds was abandoned after several years because a cost-benefit analysis didn't justify it and it was difficult to persuade Italian parents to put asymptomatic children on a diet that would ban pasta for life.
It is also unknown whether people without symptoms actually benefit from the strict diet. A small study from Finland published last year, however, hints they may.
Researchers there compared two groups of people with celiac disease. Diagnoses were made in members of one group because they had symptoms. Members of the other were found only when they were screened for the disease after it was diagnosed in a symptomatic relative. After a year on a gluten-free diet, however, both groups reported significant improvements in psychological well-being and fewer gastrointestinal complaints.
What no one doubts is that doctors should think of celiac disease more often than they do. A survey of 1,600 people in celiac support groups in the United States found that a person's symptoms were present for 11 years before the disease was identified.
"It usually takes years to change the practice of medicine unless it's a real breakthrough," said James of the NIH. "And part of that occurs by educating the public. More and more diagnoses today are being made because the patient says, 'Don't you think I might have this or that?' "
That is how Marjean Irwin, 68, of Catonsville, Md., was diagnosed with celiac disease. For more than five years, she had a low-grade anemia whose cause was never found; episodic diarrhea that she attributed to lactose intolerance, and autoimmune hypothyroidism (sometimes seen with celiac disease, which is also an autoimmune condition). By last spring, her weight had dropped to 108 pounds from her usual 130.
A gastroenterologist observed that she seemed to have some sort of "malabsorption" -- the category of problem celiac disease causes. She went home, borrowed a neighbor's Merck Manual and looked up malabsorption. The first disease listed was celiac, followed by a long list of familiar symptoms.
"I said, 'This is what I have. I know this is what I have,' " she recalled last week. She was right.