Epidemiology and pathogenesis of celiac disease and non-celiac gluten (wheat) sensitivity

While in the past, celiac disease (CD) was considered the only clinical entity caused by the ingestion of gluten-containing grains, now there is evidence that a spectrum of gluten-related disorders, including also wheat allergy and non-celiac gluten (wheat) sensitivity (NCGS/NCWS), exists. The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. CD is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype [human leukocyte antigen (HLA)-DQ2 and HLA-DQ8 genes] and autoantibodies (antitissue transglutaminase and antiendomysial). NCGS/NCWS is diagnosed in individuals who do not have CD or wheat allergy but who, like CD patients, may experience intestinal symptoms, extraintestinal symptoms, or both, related to ingestion of gluten-containing grains, with symptomatic improvement on their withdrawal. The clinical variability and the lack of validated biomarkers for NCGS/NCWS have as consequences unclear prevalence, difficult diagnosis and still fuzzy. Conversely, CD pathogenesis has been the object of intense studies thanks to its unique features, including genetic and environmental factors.