A 52-year-old female executive, mother of two teenagers, went to her internist with what she assumed were perimenopausal symptoms—irregular bowels and tiredness. Laboratory testing showed that she had vitamin B12, vitamin D, and iron deficiencies. The patient also noticed a burning in her tongue.
Rebecca J. Kurth, FACP, said just a few years ago she would have assumed this patient was anemic due to menstrual bleeding and poor diet. She would have missed the real diagnosis, celiac disease. But as she's become more aware of the possibility and its symptoms, she listens carefully to patients to connect the dots.
“Listen to the symptoms, get to the basis, and make accurate attributions,” said Dr. Kurth, a solo practitioner and associate professor of clinical medicine at Columbia University's College of Physicians and Surgeons in New York. “See the constellation of things and think, ‘That's a lot of things, maybe there's something underneath it all.’”
There are more cases of celiac disease now than even a few years ago. In fact, 1% of the U.S. population may have it, according to Joseph A. Murray, MD, professor of medicine at the Mayo Clinic and author of ACP's Physician's Information and Education Resource (PIER) module on celiac disease. “It actually has become more common,” he said. One study, he said, indicated a fivefold increase in occurrence between 1950 and 2000.
The reason for the increase is unknown. Possibilities include changes in quantity, quality, or processing of cereal; changes in wheat genetics and bread processing; and even changes in patterns of early childhood infection, among other reasons suggested in “Increased Prevalence and Mortality in Undiagnosed Celiac Disease,” published in Gastroenterology in 2009. That article also found undiagnosed cases associated with a nearly fourfold increased risk of death compared with subjects without serologic evidence of the disease.
It's no surprise that physicians who barely learned about celiac disease in medical school may not be prepared for the increased incidence.
“Physician awareness is the main problem with the primary care physician, the most likely candidate to recognize the patient who possibly has celiac disease, test for it, and refer for endoscopy,” wrote Peter H.R. Green, MD, in a July 2007 American Journal of Gastroenterology editorial, “Where Are All Those Patients with Celiac Disease?”
But it's also likely that internists are missing the signs of celiac disease, because those have changed too. “You may not be diagnosing much CD, but you may be seeing a lot of patients who have it,” Dr. Murray said.
Looking for signs
When Dr. Kurth was in medical school in the 1980s, celiac disease was taught as a failure to thrive in children and wasn't even on the radar as a disease of adults. The average age of diagnosis is now in the 50s, though some patients are being diagnosed in their 70s and 80s, said Sheila Crowe, FACP, professor in the division of gastroenterology and hepatology in the department of medicine at the University of Virginia, who will be presenting on celiac disease at Internal Medicine 2010 this month in Toronto.
Furthermore, the disease's clinical presentation has actually changed. Today few patients present with malabsorption: lost weight, diarrhea, iron deficiency, and low calcium, according to Dr. Murray. “That whole picture is now pretty rare as a presentation of CD, which is what most of us learned in medical school,” he said.
Dr. Green published a study in the April 2005 Gastroenterology finding that of 227 patients with biopsy-proven celiac disease, most had non-diarrhea-predominant presentations or silent celiac disease.
Because its presentation is now more varied, internists need to consider a wide range of symptoms. Physicians should consider celiac disease for patients who present not only with chronic diarrhea, but also with any of the following:
- bloating or gastrointestinal symptoms,
- severe constipation that isn't triggered by anything else,
- irritable bowel syndrome (IBS),
- anemia that doesn't correct when taking a supplement, especially in young women,
- osteopenia without other risk factors,
- type 1 diabetes (5% to 6% of these patients have celiac disease),
- another autoimmune disease such as thyroid disease,
- dermatitis herpetiformis,
- peripheral neuropathy or
- a family member with celiac disease.
“The face of celiac disease has changed,” said Dr. Green, professor of clinical medicine at Columbia University Medical Center and director of its Celiac Disease Center. “It's more of a multisystem disorder.”
In addition, some patient populations are more at risk; there are high rates of celiac disease in patients from South Asia and Mexico, he noted.
Because physicians often have a preconceived idea of what to expect, they may see anemia and attribute it to menstrual blood loss. “It's not clicking,” Dr. Green said. “It's an awareness phenomenon. Lots of my colleagues thought I was nuts seeing [celiac disease] here and there.”
His advice to internists: “Have no preconceived idea that people can't have CD.”
Making the diagnosis
Once physicians suspect celiac disease, they can use new sensitive and specific blood tests as well as a genetic test to help make the diagnosis.
“Serologic tests are largely responsible for the recognition that celiac disease is not a rare disease,” said the American Gastroenterological Association (AGA) in its 2006 “Technical Review on the Diagnosis and Management of Celiac Disease.”
Dr. Green recommended starting with the tissue transglutaminase (TTG) IgA test, which is also recommended in the AGA's position statement on celiac disease. The AGA said the test will correctly predict celiac disease 90% to 95% of the time. It's also a relatively easier and cheaper option than the gold standard for diagnosis, a biopsy of the small intestine.
However, the TTG IgA test can yield false-negative results because 3% of celiac disease patients are IgA deficient, Dr. Murray noted, so a patient in whom celiac disease is strongly suspected should be referred for biopsy even if the blood test is negative. Because false-positive results are possible, the diagnosis should be confirmed by intestinal biopsy, Dr. Murray said.
Before ordering a test, Dr. Green advised making sure patients are not already on a gluten-free diet, which could skew the results. To ensure an accurate result, a patient who has been on a gluten-free diet should go back to a regular diet for at least two to six months before the test, Dr. Green said. However, he cautioned that there is inadequate evidence that all those with celiac disease will develop an antibody response within that time period during a gluten challenge.
In addition, genetic testing can determine if a patient has the potential to get celiac disease. Patients have to have human leukocyte antigen (HLA) DQ2 or HLA DQ8 to get celiac disease, but having either doesn't mean the disease is inevitable. Only 2% to 3% of all people with those genes will ever develop celiac disease, according to the AGA.
Complicating the diagnosis is what Dr. Murray calls the “no man's land” of gluten sensitivity, a condition somewhere between celiac disease and IBS. “This is a confounding area, not well studied,” he said.
Gluten sensitivity is defined by immunological, morphological or symptomatic signs that may also occur with celiac disease and IBS. Although it shares its origins with celiac disease, gluten sensitivity does not fulfill the other's diagnostic criteria, according to an article Dr. Murray co-wrote in the May 19, 2009, American Journal of Gastroenterology.
Dr. Crowe explained that gluten sensitivity occurs when patients have many of the symptoms of celiac disease but a normal intestinal biopsy. They may have the gene for celiac disease and feel better on a gluten-free diet.
“You can't convince them they don't have CD,” Dr. Crowe said. But they could be feeling better because they're cutting out junk food and eating healthier. “It may not be the gluten but something else.”
A treatment plan
Following a gluten-free diet—the only treatment plan for celiac disease patients—is not easy or inexpensive. “It's a lifelong diet, and socially inconvenient,” Dr. Green said.
Although increased awareness of celiac disease and gluten-free products is making the diet somewhat easier to follow, Dr. Green recommended referring patients to a dietician experienced with such diets, preferably one at a local celiac disease center if available.
A gluten-free diet requires avoiding processed foods and ingredients that may contain wheat, rye and barley, including beer, bouillon cubes, candy, cold cuts, French fries, malt, sauces, soups, soy sauce, matzo, communion wafers and certain medications, according to the American Dietetic Association. (A complete list of foods are here; the ADA's lists of foods to avoid are here and here) .
Follow-up plans for patients with celiac disease should be prepared to address why they may not be responding to a gluten-free diet. Internists should also consider serologic tests to help monitor patients on a gluten-restricted diet and should schedule a follow-up appointment one month after diagnosis, according to the College's PIER module on celiac disease.
Dr. Green recommended following up with checks of bone density and levels of vitamins B12 and D. Patients also should take calcium supplements and a gluten-free vitamin, he said. He recommended repeating the TTG IgA test annually; it should be normal after 12 months of following a gluten-free diet. Dr. Kurth said she checks antibodies six months after the patient eliminates gluten and checks in periodically to see if symptoms recur.
Dr. Crowe said she repeats the TTG IgA test until it's normal since some patients aren't 100% compliant with the diet. “Nobody knows how gluten-free you have to be to be healthy because this is new history on this,” she said. She also rechecks iron three months after the patient starts a gluten-free diet and repeats the antibody test.
The timing and necessity of performing a follow-up biopsy to ensure the disease is under control are somewhat controversial, Dr. Crowe said. Dr. Green advocates two or three years after the first biopsy unless a TTG IgA test is positive, indicating that the patient is not on a gluten-free diet. Dr. Murray also routinely orders repeat biopsies for patients diagnosed as adults after one to two years of a gluten-free diet, since many adult patients do not heal.
As awareness of celiac disease continues to increase, so too will the number of gluten-free products. In addition, researchers are looking into new treatments such as drugs to degrade gluten in the intestine, Dr. Crowe said.
A spit test is now available that can tell patients whether they have a celiac disease gene, according to Dr. Green, but he cautioned that 40% of the population may have a positive result. In addition, a fingerstick TTG IgA test is available in Canada.
For now, Dr. Green emphasized that the most important step is for internists to become better educated in celiac disease diagnosis. “There's no money in CD, so the only way to increase the rate of diagnosis is the primary care physician,” he said.
Dr. Kurth emphasized that diagnosis improves as internists better understand how to connect those dots. “So stay updated. Do your CME or talk to specialist colleagues. Be curious,” she said. The key, she added, is looking at the whole patient and having a high index of suspicion for celiac disease. “That's why general internists are the perfect people to pick this up.”