AGA InstituteAmerican Gastroenterological Association (AGA) Institute Technical Review on the Diagnosis and Management of Celiac Disease
Section snippets
Pathology
Although celiac disease has consequences for many organs, the site of maximum impact is the proximal small intestine, which is where dietary gluten first encounters the mucosal immune system. Over the past 50 years, celiac disease has become defined by this small intestinal damage. Our understanding of the spectrum of injury and its consequences has increased substantially over the past several years. There are varying degrees of inflammation and architectural changes that occur at presentation
Pathogenesis
Recent information has illuminated our understanding of the basic mechanisms that lead to the development of celiac disease. We briefly summarize these advances to provide a pathophysiologic context for the more detailed analysis of questions of immediate importance to clinical practice. Furthermore, such pathophysiologic insights into the disease suggest potential therapeutic alternatives that ultimately may be substitutes or adjuncts to the GFD. A full review of the processes that lead to the
Aim of the Technical Review
The aim of this technical review on celiac disease is to address specific areas of clinical importance relevant to practicing gastroenterologists and primary care practitioners who see and detect most cases of celiac disease. The major focus is on adults, although some data from studies on children are also included for completeness. The specific issues related to celiac disease in childhood have been recently addressed.11
Methods
This technical review was conducted using standard systematic review methodology to address several key content areas regarding celiac disease: use of serologic testing in diagnosis, use of HLA-DQ2/DQ8 testing in diagnosis, prevalence of celiac disease in the general population and in groups of individuals presumed to be at increased risk for celiac disease, complications of celiac disease, benefits of a GFD, promoting adherence to a GFD, and maintaining adherence to a GFD. The specific
Diagnosis of Celiac Disease
The diagnostic approach to detecting celiac disease has undergone important changes in recent years. This reflects the development and application of serologic tests, particularly the EMA and tTG antibody tests, as an initial screen for this disease. Serologic tests are largely responsible for the recognition that celiac disease is not a rare disease. Moreover, with the recognition of a relatively high prevalence of celiac disease in the US population (∼1:100) has come increased recognition of
Epidemiology
Celiac disease has been classified into 4 phenotypes,30 as described in Table 3. “Classic” celiac disease is dominated by the symptoms and sequelae of gastrointestinal malabsorption. “Atypical” celiac disease is characterized by few or no gastrointestinal symptoms, with extraintestinal manifestations predominating.30 Of note, atypical celiac disease is more prevalent than classic celiac disease, which could call into question the use of these terms. “Silent” celiac disease is used when
Prevalence of Celiac Disease in the General Population
Much of the data on the prevalence of celiac disease in the general population has come from western European countries, where celiac disease previously was believed to be more common than in other parts of the world, including the United States. However, it is now apparent that celiac disease is also common in the United States, Eastern Europe, and many other countries with the exception of Japan.31, 32, 33, 34
The prevalence of celiac disease varies greatly across and within different
Mortality
Mortality associated with celiac disease has been assessed in several cohort studies230, 231, 232, 233, 234, 235 and a survey. Among the cohort studies, included patients had biopsy-proven celiac disease, and the majority had symptomatic celiac disease. The death rate in patients with celiac disease was higher than that of a standardized population rate or of a control population in all but one study.236 In the remaining studies, the standardized mortality rate (SMR; the ratio of the number of
Protection From NHL
Compliance with a GFD is likely protective against NHL in patients with celiac disease. Holmes et al reported a significant risk reduction of NHL in patients on a strict GFD (SIR, 44.4) versus those who did not adhere to a GFD (SIR, 100).246 Others reported that a cohort of 383 patients with celiac disease with a very high prevalence of strict adherence to a GFD did not have a significantly increased risk of NHL compared with the general population (SIR, 2.66; 95% CI, 0.07–14.8).242 Also, a
Promoting Adherence to a GFD
The treatment of celiac disease is lifelong adherence to a GFD. The preceding sections have discussed the benefits of identifying and treating patients with celiac disease. However, changes in dietary habits are difficult to maintain, and there are many barriers to continued compliance with a GFD. Adding to the difficulty of assessing any proposed intervention is the lack of certainty as to how best to measure compliance with a GFD.
Existing evidence suggests a positive correlation between
Monitoring Adherence to a GFD
Patients with celiac disease should be evaluated at regular intervals by a health care team including a physician and a dietician. These visits can be used to assess, by history, a patient’s compliance with a GFD and to reinforce the importance of such compliance. Beyond this, there are no clear guidelines as to the optimal means to monitor adherence to a GFD. Symptom improvement alone may not offer an accurate assessment of adherence to a GFD as judged by interview or by biopsy,278 and this
Continued or Relapsing Symptoms in Treated Celiac Disease
Patients with known celiac disease can continue to have or redevelop symptoms despite being on a GFD. It is important to review the original diagnosis to ensure that it is accurate, and a repeat small intestinal biopsy may be indicated in patients with a poor response to a GFD. These symptoms may be due to incompletely healed celiac disease, an associated condition, a complication, or a second unrelated diagnosis.297 Persistent or intermittent symptoms due to deliberate or inadvertent ingestion
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This literature review and the recommendations therein were prepared for the AGA Institute Clinical Practice and Economics Committee. The paper was approved by the Committee on August 21, 2006, and by the AGA Institute Governing Board on September 25, 2006.
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M.F.K. is supported by National Institutes of Health grants DK35108 and DK58960 and a grant from the William K. Warren Foundation, and J.A.M. is supported by National Institutes of Health grants DK 71003 and DK 57892.