Refining Diagnosis and Treatment for Celiac Disease
ABSTRACT: Better understanding of celiac disease and improved diagnostic tests indicate celiac disease is far more common than previously thought.
CME OBJECTIVE: The reader will be more aware of the symptoms of celiac disease and available diagnostic tests.
Charles O. Elson, MD, no conflicts of interest
Nearly 3 million people in the United States suffer from celiac disease, yet most remain undiagnosed, according to a recently convened consensus panel assembled by the National Institutes of Health (NIH) and led by UAB gastroenterologist Charles O. Elson III, MD. Until recently, epidemiologists believed celiac disease occurred in 1 of 3000 Americans; prevalence is now estimated at 1 in 300.
"Physicians need to be aware of how common celiac disease is in the general population. If they fail to recognize the need for celiac testing, patients will continue to suffer needlessly," Elson says.
To arrive at the recently revised estimate of the prevalence of celiac disease, the NIH panel charged an independent research group to analyze the quality of existing celiac disease studies in current literature and determine the frequency of the condition. After reviewing the data, the panel reported findings at a June 2004 consensus conference.
Singling Out Symptoms
The chief characteristic of celiac disease is chronic inflammation of the small intestinal mucosa that may cause atrophy of intestinal villi and malabsorption syndromes. "Symptoms may develop in childhood or adult life and include diarrhea, abdominal cramping, pain, or bloating, but symptoms can mimic a wide range of other illnesses, such as irritable bowel syndrome, or may present as constipation," Elson says.
Recent epidemiologic studies have shown that adult-onset, extraintestinal forms of celiac disease are much more frequent than the familiar malabsorptive presentation (Lancet. 2003;362:383-391 and N Engl J Med. 2002;346:180-188). These can included iron deficiency anemia, elevated transaminases, infertility, and psychiatric and neurologic syndromes. Obesity does not exclude diagnosis.
"Celiac disease is easy to miss, therefore, anyone with symptoms that could be celiac disease should be evaluated," he says. "Left untreated, celiac disease can lead to vitamin and mineral deficiencies, anemia, osteoporosis, infertility, neuropsychiatric conditions, and possibly, non-Hodgkin lymphoma. The condition also is strongly associated with the chronic, itchy rash dermatitis herpetiformis."
Difficult Diagnosis
Among patients screened for celiac disease, the condition was probably missed before the availability of the current highly sensitive and specific tests, Elson notes. "Antigliadin antibody assays are not as specific as current tests, and endoscopies performed without simultaneous small intestinal biopsies may have failed to identify disease. Further complicating the diagnosis, some adults with the condition initially present without gastrointestinal symptoms, or with nonclassical or extraintestinal symptoms, such as anemia, osteopenic bone disease, or tetany," he says.
Some celiac disease patients exhibit no symptoms that would lead a clinician to suspect the disorder. Latent celiac disease, typically found when patients are asymptomatic but have positive serologic testing without villous atrophy, may eventually develop into symptomatic or histologic changes. Silent celiac disease occurs in asymptomatic patients who have both positive serology and villous atrophy.
Specific Testing
"Greater awareness and improved serological testing will dramatically improve celiac diagnosis," Elson says. Because celiac disease has been perceived as rare, clinicians have not traditionally performed aggressive testing. But, in adults and children aged 5 years and older, current serological testing, notably the IgA antihuman tissue transglutaminase (TTG) and IgAendomysial antibody immunofluorescence (EMA) tests, are highly sensitive and specific.
"If a patient has a positive celiac disease antibody test with TTG or EMA, a biopsy of the proximal small bowel should be performed," Elson says. "With concordant positive serology and biopsy results, celiac disease can be presumed and definitively confirmed if a gluten-free diet resolves patient symptoms."
Evaluating Risk
Celiac disease is characterized by genetic risk factors HLA-DQ2 and HLA-DQ8 and environmental triggers of specific peptides in barley, wheat, and rye. In addition to a family history of celiac disease, risk factors include type 1 diabetes and Down syndrome, and the condition is strongly associated with Turner syndrome, Williams syndrome, selective IgA deficiency, and autoimmune endocrinopathies.
If serology results are indeterminate but celiac disease is suspected, genetic testing has a high negative predictive value and will stratify patients into risk groups. More than 97% of individuals with celiac disease carry the HLA-DQ2 and/or HLA-DQ8 marker, compared with 40% of the general population.
People suspecting intolerance to gluten or wheat who have removed such products from their diet without first consulting a physician will be advised to resume gluten products before serologic testing. "Patients who stop eating wheat products may find their symptoms disappear, but because of the variety of differential diagnoses, celiac disease cannot be inferred, and the tests for celiac disease do not work if the immune response to gluten is inactive due to dietary changes," he explains. Patients who choose not to undergo a gluten challenge may elect genetic testing.
Successful Treatment
"Celiac disease is caused by an immune response to gluten, so a gluten-free diet is an effective treatment," Elson says. Six to 12 months after starting a gluten-free diet, clinical remission and histologic recovery of small intestinal mucosa is assumed to occur, although large studies are not available to support this conclusion. Anecdotal evidence suggests children may respond more quickly than adults to a gluten-free diet.
However, adherence to a lifelong gluten-free diet can be difficult, especially when patients are not aware of all the food products that may contain triggers, Elson counsels. Furthermore, some people with celiac disease seem able to tolerate limited amounts of gluten, while others are extremely sensitive, reacting adversely to oat products that have been cross-contaminated during processing.
"The American Dietetic Association is currently developing objective evidence that will help devise a standard definition of a gluten-free diet. Clinicians should regularly monitor celiac disease patients and counsel them on the importance of lifelong diet adherence. We also strongly recommend patients meet with a dietitian or nutritionist with extensive knowledge of celiac disease," he says.
Persistent elevated serologic levels may suggest lack of adherence to a gluten-free diet or unintended gluten ingestion. If patients fail to respond to dietary intervention, they should be reevaulated, according to new NIH panel guidelines.
Clinicians should consider and treat vitamin and mineral deficiencies, including iron, calcium, phosphorus, folate, B12, and fat-soluble vitamins, especially in newly diagnosed celiac disease patients, who may also benefit from osteoporosis screening, given its prevalence in this particular population. When dermatitis herpetiformis is present, the antibiotic dapsone may speed treatment while initiating dietary intervention.
Celiac disease support groups, such as those found at www.celiac.com, help patients connect with dietitians, find fellow sufferers, and link to gluten-free resources, including cookbooks and foods.
In closing the 2-day NIH celiac disease consensus conference, experts recommended furthering research into alternatives to gluten-free diets, exploring possibilities for prevention in infancy, analyzing the cost-effectiveness of testing the general population for celiac disease, identifying celiac frequency in ethnic populations, and developing animal models to dissect pathogenic mechanisms of the disease.
Until such research elucidates many of the unresolved issues surrounding this prevalent disorder, clinicians are advised to use the following acronym to underscore treatment after a confirmed diagnosis of celiac disease:
C - Consultation with a skilled dietitian
E - Education about the disease
L - Lifelong adherence to a gluten-free diet
I - Identification and treatment of nutritional deficiencies
A - Access to an advocacy group
C - Continuous long-term follow up.
"Much like thyroid disease or hemochromatosis, which may present with a vague array of symptoms, celiac disease must be considered when certain conditions are present," Elson concludes. "Alleviating unnecessary suffering, preventing complications, and improving quality of life for these patients is our goal."
NIH Panel Consensus statement available at
http://consensus.nih.gov/cons/118/118cdc_intro.htm
For more information
Dr. Charles Elson
1.800.UAB.MIST
mist@uabmc.edu
Published in UAB Insight, Winter 2005