A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications.

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCGS.

Background: Noninvasive serologic tests have shown high diagnostic accuracy for celiac disease (CD) in selected populations. Our aim was to determine prospectively the performance of CD-related serology in individuals undergoing intestinal biopsy because of clinical suspicion of small-bowel disorders. Methods: We enrolled 141 unselected consecutive adult patients attending a small-bowel disease clinic. Patients underwent endoscopy and biopsy; serum samples were obtained at that time for measurements of anti–tissue transglutaminase (a-tTG), IgA and IgG anti–deamidated gliadin-related peptide (a-DGP), and IgA antiactin antibodies (AAAs). Characterization of patients was based on histological criteria (Marsh type II lesion or greater). Results: The prevalence of CD was 42.5%. Sensitivity, specificity, and positive and negative predictive values were >90% for most assays. Diagnostic accuracy based on ROC curve analysis was similar for all assays [area under the curve (95% CI): 0.996 (0.967–0.998) for a-tTG, 0.995 (0.964–0.998) for IgA a-DGP, 0.989 (0.954–0.999) for IgG a-DGP, 0.996 (0.966–0.998) for blended conjugated of IgA + IgG a-DGP in a single assay, and 0.967 (0.922–0.990) for AAA]. The combinations of 2 tests, IgG a-DGP plus IgA a-tTG or the single blended conjugate detecting IgA + IgG a-DGP plus IgA a-tTG had 100% positive and negative predictive values if concentrations of both tests in either combination were above or below the cutoff. Conclusions: In a population with high pretest probability, the newly developed a-DGP tests have diagnostic accuracy that is at least equivalent to that of established assays.

AIM: To establish the diagnostic performance of several serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential serological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.