Gastroenterology

Gastroenterology

Volume 148, Issue 6, May 2015, Pages 1175-1186
Gastroenterology

Celiac Disease: Clinical Spectrum and Management
Advances in Diagnosis and Management of Celiac Disease

https://doi.org/10.1053/j.gastro.2015.01.044Get rights and content

Celiac disease is an autoimmune disorder that is induced by dietary gluten in genetically predisposed individuals. It has a prevalence of approximately 1% in many populations worldwide. New diagnoses have increased substantially, owing to increased awareness, better diagnostic tools, and probable real increases in incidence. The breadth of recognized clinical presentations continues to expand, making the disorder highly relevant to all physicians. Newer diagnostic tools, including serologic tests for antibodies against tissue transglutaminase and deamidated gliadin peptide, greatly facilitate diagnosis. Tests for celiac-permissive HLA-DQ2 and HLA-DQ8 molecules are useful in defined clinical situations. Celiac disease is diagnosed by histopathologic examination of duodenal biopsy specimens. However, according to recent controversial guidelines, a diagnosis can be made without a biopsy in certain circumstances, especially in children. Symptoms, mortality, and risk for malignancy each can be reduced by adherence to a gluten-free diet. This treatment is a challenge, however, because the diet is expensive, socially isolating, and not always effective in controlling symptoms or intestinal damage. Hence, there is increasing interest in developing nondietary therapies.

Section snippets

Clinical Features

The clinical manifestations of celiac disease are classic (signs and symptoms of malabsorption including diarrhea, steatorrhea, weight loss, or growth failure), nonclassic and symptomatic (with evident gastrointestinal and/or extraintestinal symptoms), or asymptomatic.1 Celiac disease has diverse manifestations and associations, so it is important for all physicians to be aware of its many potential clinical presentations. With greater awareness more patients are being diagnosed—particularly

Diagnosis

The rate of diagnosis of celiac disease is increasing worldwide, in part owing to a greater appreciation of the variability in clinical presentation. Until the 1950s, celiac disease was diagnosed based on clinical observations focused on malabsorptive features. The development of the peroral intestinal biopsy (1955−1956) produced a substantial change in the diagnostic paradigm. Since that time, gluten-dependent enteropathy, based on histologic assessment of intestinal mucosa, has been the

Treatment

The only available therapy for celiac disease is the GFD, which usually reduces clinical symptoms and morbidity and increases nutritional parameters including body weight and bone density.54, 55, 56, 57 However, studies have reported low patient satisfaction, high costs, and continued symptoms and histologic signs of intestinal damage, indicating that the GFD is not always optimal.58, 59, 60, 61, 62, 63 Nonetheless, the concept that the GFD is an ideal therapy has contributed to the lack of

Monitoring

Celiac disease is a lifelong inflammatory condition that affects multiple organ systems, so patients should be followed up routinely. There are no differences in recommendations for monitoring symptomatic vs asymptomatic patients. Based on expert consensus, at the time of diagnosis, patients should be evaluated for common co-existing autoimmune conditions, such as thyroid and liver diseases, as well as deficiencies in iron, vitamin D, and vitamin B12. It also is important to consider zinc,

Nonresponsive Celiac Disease

Nonresponsive celiac disease (NRCD) can be defined as persistent or recurrent symptoms, signs, or laboratory findings consistent with active celiac disease, despite at least 12 months of treatment with the GFD.1, 60, 72, 80 A substantial proportion of patients with celiac disease develop NRCD (7%–30% in different series of studies). NRCD has multiple and diverse etiologies; a thorough and systematic evaluation is needed to determine the correct diagnosis and management plan for each patient (

Refractory Celiac Disease

Refractory celiac disease (RCD) can be defined as persistent or recurrent small-intestinal villous atrophy with symptoms of malabsorption, despite 12 months or more of a strict GFD, in the absence of an overt lymphoma or another condition that causes villous atrophy.1 RCD makes up a small subset (approximately 10%) of NRCDs and occurs in 1% to 2% of patients with celiac disease.60, 72, 83 Severe diarrhea and weight loss in patients with NRCD increase the risk for RCD.

RCD is characterized by the

Malignancy

The mortality risk is increased in adult celiac patients (hazard ratio, 1.31; 95% confidence interval, 1.13–1.51 in one study) as a result of an increased risk for fatal malignancy.90, 91 Mortality risk was highest shortly after diagnosis and in those with active malabsorption and enteropathy, suggesting a beneficial effect of the GFD.79, 90, 91, 92 Celiac disease was first associated with small-intestinal adenocarcinoma, and then with non-Hodgkin’s lymphoma, and, more specifically,

Future Directions

The past decade has deepened our appreciation of the protean manifestations of celiac disease, which presents at all stages of life, has a diverse geographic distribution, and is a common autoimmune disease. Advances in our understanding of pathogenesis and genetic factors that affect risk have led to the development of and refinements to diagnostic tools. Challenges for the next decade include reducing the burden of treatment by providing easier access to inexpensive gluten-free foods and

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    Conflicts of interest Dr Ciarán P. Kelly has acted as a consultant and scientific advisor to Alba Therapeutics, Alvine Pharmaceuticals, and Immunosant. Dr Daniel A. Leffler has acted as a consultant and/or received research support from Alba Therapeutics, Alvine Pharmaceuticals, INOVA diagnostics, Genzyme, Coronado Biosciences, Ironwood Pharmaceuticals, GI Supply, Glenmark Pharmaceuticals. The remaining authors disclose no conflicts.

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