Celiac disease (CD) is a chronic inflammatory condition that results in immune-mediated damage to the mucosal lining of the small intestine. It occurs in genetically predisposed people who consume gliadin — a protein in gluten-containing foods such as wheat, rye and barley — and usually responds to a gluten-free diet.
Although the immune response genes HLA-DQ2 and DQ8 — present in about 40 percent of the population — increase susceptibility to CD, they do not cause it, even in people who regularly consume gluten. More than a dozen non-HLA genes have been identified that may contribute to CD as well as environmental factors such as pregnancy, stress and infection.
A recent study co-authored by Mayo Clinic gastroenterologist Joseph A. Murray, M.D., of Mayo Clinic in Rochester, Minn., found a strong association between celiac disease and gastroenteritis and other bacterial intestinal infections.
"The study suggests that adults who have gastroenteritis are more likely to be diagnosed with celiac disease within a couple of years," he says. "Gastroenteritis may be the match that lights the fuse of gluten intolerance."
Other studies have found that children who experience early infections are more prone to CD and that a robust gut microbiota — and possibly breast-feeding — may be protective. So far, however, the triggering mechanism of the disease remains unknown.
Also unclear is the reason for the dramatic upswing in diagnosed cases — a five-fold increase from 1999 to 2008 — and why, in spite of this, CD remains undiagnosed in most of the nearly 2 million Americans estimated to have it. Dr. Murray, who co-authored a definitive study on diagnosed and undiagnosed CD prevalence, points out, "Only 1 in every 5 people with celiac disease will be diagnosed — the remaining four will elude diagnosis, so we're not doing a very good job of detecting it."
The issue isn't a lack of diagnostic tools. Newer seriologic testing, despite its limitations, has made evaluation for CD less complicated and more reliable. Tissue transglutaminase antibody (tTG-IgA), perhaps the most accurate test for diagnosing celiac disease, has high sensitivity and reasonably high specificity. And new celiac test algorithms can rule out CD in most patients, even those who have already reduced gluten in their diets.
Dr. Murray says the real problem in diagnosing celiac disease is that it is often hiding in plain sight. Although it damages the small intestine, CD can affect any part of the body, including the nervous, reproductive, endocrine, skeletal and cardiopulmonary systems. A substantial number of patients may not present with classic gastrointestinal symptoms, such as diarrhea, weight loss, bloating and abdominal pain, but rather with anemia, osteoporosis, peripheral neuropathy, ataxia or cognitive impairment.
In effect, Dr. Murray says, CD is everywhere — "a disease of the masses" — but clinicians often fail to recognize it. "If a patient with osteoporosis or infertility isn't responding to treatment, suspect celiac disease," he says. It should also be suspected in patients with type 1 diabetes, rheumatoid arthritis, Sjogren's syndrome or other autoimmune disorders, as well as in cases of irritable bowel syndrome or chronic diarrhea.
"Even after all that, most patients will elude diagnosis because the disease hasn't produced enough of an impact to cause symptoms," Dr. Murray says. That argues for universal screening. At Mayo Clinic, asymptomatic people considered at risk of gluten intolerance are routinely screened, including family members of celiac patients. Eventually, Dr. Murray thinks, celiac testing may become routine for everyone. "We're amassing more evidence to suggest that we have to screen people rather than just waiting for the disease to become apparent," he says.
Rubio-Tapia A, et al. The prevalence of celiac disease in the United States. The American Journal of Gastroenterology. July 2012;107:1538.