Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally prescribed to ameliorate symptoms associated with acute pain and chronic inflammatory diseases such as arthritis. Recent epidemiologic studies and clinical trials indicate that use of NSAIDs and cyclooxygenase (COX)-2 selective inhibitors are associated with a reduced risk of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase enzymes are the best known targets of NSAIDs; this diverse class of compounds blocks conversion of arachidonic acid to prostanoids. Prostaglandins and other eicosanoids derived from COX-1 and COX-2 are involved in a variety of physiologic and pathologic processes in the gastrointestinal tract. Recent efforts to identify the molecular mechanisms by which COX-2-derived prostanoids exert their proneoplastic effects have provided a rationale for the possible use of NSAIDs alone or in a combination with conventional or experimental anticancer agents for the treatment or prevention of gastrointestinal cancers.

To address the issue of screening children for celiac disease, current evidence has been summarized and placed within the context of 8 established criteria for childhood screening. Screening all children for celiac disease is not recommended at this time. Areas with gaps in knowledge are identified as areas in need of further study. These include the timing of screening, defining the natural history of screening-identified celiac disease, developing tools to predict disease onset and disease remission, and the risks of screening.

Celiac disease (CD) long has been associated with neurologic and psychiatric disorders including cerebellar ataxia, peripheral neuropathy, epilepsy, dementia, and depression. Earlier reports mainly have documented the involvement of the nervous system as a complication of prediagnosed CD. However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology. These include migraine, encephalopathy, chorea, brain stem dysfunction, myelopathy, mononeuritis multiplex, Guillain-Barre-like syndrome, and neuropathy with positive antiganglioside antibodies. The association between most neurologic syndromes described and gluten sensitivity remains to be confirmed by larger epidemiologic studies. It further has been suggested that gluten sensitivity (as evidenced by high antigliadin antibodies) is a common cause of neurologic syndromes (notably cerebellar ataxia) of otherwise unknown cause. Additional studies showed high prevalence of gluten sensitivity in genetic neurodegenerative disorders such as hereditary spinocerebellar ataxia and Huntington's disease. It remains unclear whether gluten sensitivity contributes to the pathogenesis of these disorders or whether it represents an epiphenomenon. Studies of gluten-free diet in patients with gluten sensitivity and neurologic syndromes have shown variable results. Diet trials also have been inconclusive in autism and schizophrenia, 2 diseases in which sensitivity to dietary gluten has been implicated. Further studies clearly are needed to assess the efficacy of gluten-free diet and to address the underlying mechanisms of nervous system pathology in gluten sensitivity.

Celiac disease (CD) is associated with intestinal lymphoma and other forms of cancer, especially adenocarcinoma of the small intestine, of the pharynx, and of the esophagus. Enteropathy-associated T-cell lymphoma (EATL) is a rare form of high-grade, T-cell non-Hodgkin lymphoma (NHL) of the upper small intestine that is specifically associated with CD. This NHL subtype arises in patients with either previously or concomitantly diagnosed CD. In a subgroup of patients, there is progressive deterioration of a refractory form of CD. EATL derives from a clonal proliferation of intraepithelial lymphocytes and is often disseminated at diagnosis. Extraintestinal presentations are not uncommon in the liver/spleen, thyroid, skin, nasal sinus, and brain. The outlook of EATL is poor. Recent studies indicated that (1) CD is associated with a significantly increased risk for NHL, especially of the T-cell type and primarily localized in the gut (EATL); (2) the CD-lymphoma association is less common than previously thought, with a relative risk close to 3; (3) CD screening is not required in patients with NHL of any primary site at the onset, unless suggested by specific findings (T-cell origin and/or primary gut localization). The risk of NHL associated with clinically milder (or silent) forms could be lower than in typical cases of CD. Several follow-up studies suggest that the GFD protects from cancer development, especially if started during the first years of life. Strict adherence to the GFD seems to be the only possibility of preventing a subset of rare but very aggressive forms of cancer.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains (including wheat, rye, and barley) in genetically susceptible individuals. CD is associated with HLA molecules DQ2 (90%-95%) and DQ8 (5%-10%), and in the continued presence of gluten the disease is self-perpetuating. CD is one of the most common lifelong disorders worldwide and is characterized by a variety of clinical presentations. These include the typical malabsorption syndrome (classic symptoms) and a spectrum of symptoms potentially affecting any organ or body system (nonclassic symptoms). Because CD often is atypical or even clinically silent, many cases go undiagnosed and are exposed to the risk of long-term complications. There is growing interest in the social aspects of CD because the burden of illness related to this condition is doubtless higher than previously thought.

Until recently, celiac disease (CD) was felt to be a rare disease in the United States. The aim of this study was to conduct a systematic review of the prevalence of CD in general Western populations and in populations at high risk for CD. Standard systematic review methodology was used. A literature search was conducted in MEDLINE (1966 to October 2003) and EMBASE (1974 to December 2003) databases. Qualitative and quantitative prevalence estimates were produced after assessing study heterogeneity. The prevalence of CD in general Western populations is close to 1% and is somewhat higher in certain Western European populations. The prevalence of CD in populations at risk for CD is as follows: 3%-6% in type 1 diabetic patients, up to 20% in first-degree relatives, 10%-15% in symptomatic iron-deficiency anemia (IDA), 3%-6% in asymptomatic IDA, and 1%-3% in osteoporosis. The prevalence of CD in patients suspected of having CD varied depending on the reasons for suspecting CD and on whether the study was conducted in a referral center. In general, the prevalence ranged from 5% to 15%, but was up to 50% in symptomatic patients evaluated in a tertiary referral center. CD is a common medical condition. The prevalence is higher still in high-risk groups. Clinicians in a variety of specialties should have a high index of suspicion for the diagnosis of CD and in particular need to pay close attention to the identified high-risk groups.

Celiac disease (CD) may be a much under recognized condition, in part because it is not considered in those patients at high risk or in clinical conditions that may be a manifestation of CD. Screening high-risk groups may reveal a higher prevalence than seen in the general population. Several diseases have been described to have an association with CD that may be greater than by chance alone. The presence of autoimmune conditions such as insulin-dependent diabetes mellitus (T1DM) or a family history of CD or dermatitis herpetiformis may increase the risk of coexisting CD. The prevalence of CD may be increased in certain patient groups, including the following: osteoporosis or low bone mass or iron-deficiency anemia. Many studies, including population-based work, suggest a prevalence of CD of 3%-7% of T1DM and 4%-10% of first-degree family members. Anemia and osteoporosis are common in patients with newly diagnosed CD. Conversely, CD is common in referral populations with those conditions but makes a relatively small contribution to the overall community prevalence of anemia or postmenopausal osteoporosis. Most screen-found patients tend to have little or no gastrointestinal symptoms. In conclusion, significant reservoirs of CD can be found in some at-risk groups, such as those with T1DM, family members, and referred patients with osteoporosis and anemia. It is not clear what impact CD has on the quality of life of these individuals.

Clinicians are increasingly utilizing noninvasive serologic tests for the diagnosis and screening of celiac disease (CD). The aim of this study was to conduct a systematic review of the diagnostic performance of serologic tests for the diagnosis and screening of CD. Standard systematic review methodology was used. A literature search was conducted in MEDLINE (1966 to October 2003) and EMBASE (1974 to December 2003) databases. A weighted mean of the sensitivity and specificity along with 95% confidence intervals and summary receiver operating characteristic (ROC) curves were calculated. The pooled specificity of endomyseal antibody (EMA)-monkey esophagus (ME) or EMA-human umbilical cord (HU) was close to 100% in adults and children. The pooled specificity of transglutaminase antibody (tTG)-guinea pig (GP) and tTG-human recombinant (HR) were between 95% and 99%. IgA-EMA-ME demonstrated sensitivities of 96% and 97% in children and adults, respectively. EMA-HU demonstrated a similar sensitivity of 97% in children but 90% in adults. The pooled sensitivity of tTG-GP in adults and children was 90% and 93%, respectively. The sensitivity of tTG-HR was 98% and 96%, respectively. The performance of antigliadin antibody was inferior to that of EMA and tTG. EMA and tTG offer high sensitivity and specificity. The sensitivity of these tests appears to be lower than reported when milder histologic grades are used to define CD (below 90%). If true, the nearly perfect negative predictive value of these tests would drop. The positive predictive value of these tests is likely lower than reported when the tests are applied in low-prevalence populations.

Celiac disease is a remarkable and common immune-mediated disorder determined by both the presence of characteristic HLA alleles (DQ2 and DQ8) and one of the best characterized environmental factors (gliadin) for any common autoimmune disease. The discovery of transglutaminase autoantibodies and the development of assays for these antibodies has allowed the identification of a large number of asymptomatic individuals with autoimmunity and intestinal biopsy evidence of celiac lesions. Further understanding of the sequelae of asymptomatic celiac disease, and the interaction between genetic susceptibility and environmental factors, are likely to alter fundamentally both genetic screening for celiac disease and its therapy.

A number of serologic tests are available commercially for identifying individuals who require an intestinal biopsy examination to diagnose celiac disease (CD). The aim of this study was to determine which test, or combination of tests, was most sensitive and specific for this purpose. We performed a literature review of studies that determined the sensitivity and specificity of serologic tests for CD. Studies that compared biopsy examination-confirmed cases of CD with controls with normal intestinal histology were selected for analysis. Sensitivities and specificities for the antigliadin tests were highly variable. Immunoglobulin (Ig)G-based antigliadin (AGA) tests generally were poor in both parameters whereas the IgA-based test was poorly sensitive but more specific. The IgA endomysium (EMA-IgA) and tissue transglutaminase (TTG-IgA) tests were both highly sensitive and specific with values for both parameters exceeding 95% in most studies. There were no identifiable differences between adults and children with respect to these tests. There was no evidence that a combination of tests was better than a single test using either the EMA IgA or TTG IgA. Either the EMA-IgA or TTG-IgA test is most useful for identifying individuals with CD. The variability and generally lower accuracy associated with the AGA tests make them unsuitable for screening purposes. There is no advantage to using a panel of tests as opposed to a single test. Because these data were obtained largely from studies conducted in a research setting, it is possible the tests will be less accurate when used in the clinical setting.

Celiac disease is a chronic enteropathy caused by intolerance to gluten. The true prevalence of this condition is much greater than previously recognized, with increasing numbers of silent cases being diagnosed. Population-based studies, using serologic screening, have indicated that the prevalence of celiac disease in Caucasian populations is .5%-1%. The pattern of incidence is changing, with a greater proportion of cases diagnosed later in adulthood. The pathologic lesion is characterized by a flattened small intestinal mucosa with a lymphocytic infiltrate, crypt hyperplasia, and villous atrophy. Absorptive function may be impaired and patients can experience gastrointestinal symptoms and malabsorption leading to development of anemia, osteoporosis, or other complications. Untreated celiac disease is associated with significant morbidity and increased mortality, largely owing to the development of enteropathy-associated intestinal lymphoma. The pathologic changes and symptoms resolve when gluten is excluded from the diet for a sustained period.

A strict gluten-free diet (GFD) for life is the only treatment for celiac disease (CD). This article reviews (1) the impact of the GFD on the quality of life of individuals with CD and their families; (2) the causes of poorly controlled CD; (3) the access to and source and quality of information provided by health professionals and other groups; (4) management strategies, including nutritional assessment and education guidelines; (5) a variety of resources available to individuals and health professionals; (6) innovative educational initiatives and partnerships; and (7) specific recommendations to address the increasing numbers of people with CD and the growing need for gluten-free (GF) foods and further education about CD and the GFD. Successful management of CD requires a team approach, including the person with CD and his or her family, physician, dietitian, and celiac support group; an individualized approach; understanding of quality of life issues; use of evidence-based, current information and resources; and regular follow-up to monitor compliance, nutritional status, and additional information and support. The physician must clearly communicate, with a positive attitude, an overview of CD and strongly emphasize the importance of a GFD for life. It is essential that the physician initiate an immediate referral to a dietitian with expertise in CD for nutritional assessment, diet education, meal planning, and assistance with the adaptation to the challenging new gluten-free lifestyle. Good dietary compliance will reduce the risk of further complications and associated health care costs and improve quality of life in patients with CD.

Medical nutrition therapy is the only accepted treatment for celiac disease. This paper summarizes a review of scientific studies using the gluten-free diet, nutritional risk factors, controversial elements of the diet, and its implementation in treating celiac disease. Treatment for celiac disease requires elimination of the storage proteins found in wheat, rye, and barley. The inclusion of oats and wheat starch is controversial. Research supports that oats may be acceptable for patients with celiac disease and can improve the nutritional quality of the diet. However, use of oats is not widely recommended in the United States because of concerns of potential contamination of commercial oats. Studies assessing the contamination of commercial oats are limited. Research indicates no differences in patients choosing a strict wheat starch-containing, gluten-free diet vs. a naturally gluten-free diet. Factors other than trace gluten may be the cause of continued villous atrophy in some patients. The impact of nutrient malabsorption caused from untreated celiac disease is well documented. The diet and gluten-free products are often low in B vitamins, calcium, vitamin D, iron, zinc, magnesium, and fiber. Few gluten-free products are enriched or fortified, adding to the risk of nutrient deficiencies. Patients newly diagnosed or inadequately treated have low bone mineral density, imbalanced macronutrients, low fiber intake, and micronutrient deficiencies. Also troubling is the increased incidence of obesity seen in persons with celiac disease following a gluten-free diet. Because of the nutritional risks associated with celiac disease, a registered dietitian must be part of the health care team that monitors the patient's nutritional status and compliance on a regular basis.