Celiac disease, non-celiac wheat sensitivity, wheat allergy: clinical and diagnostic aspects

In recent years, wheat- and gluten-free diets have increased in demand due to reported increases in various conditions reported to be driven by ingredients of these food products. Celiac disease, wheat allergy and non-celiac wheat sensitivity constitute the three main categories of wheat-related disorders. Celiac disease is a well-characterized immune-mediated disease caused by immune reaction against specific gliadin epitopes, the main protein in wheat. Screening studies of samples collected over time bring evidence that there is a true increase in prevalence not only driven by increased testing activity. Clinical presentation of CeD is diverse and there is an increased risk of autoimmune co-morbidities. Wheat allergy consists of IgE- and non-IgE-mediated reactions, driven by Th2-cells directing eosinophil and basophil responses. Rapid IgE-mediated reactions are characterized by specific IgE antibodies in conjunction with symptoms originating especially from the respiratory and gastrointestinal tract. There is an increased risk of other allergies and the majority recover during adolescence. Non-IgE-mediated wheat allergy is a less-well defined condition, which is often diagnostically challenging due to a longer interval between exposure and symptoms and lack of non-invasive biomarkers. In this condition, wheat as a trigger needs to be established by exclusion followed by dietary challenge. Non-celiac wheat sensitivity, despite being the most recently recognized, has the highest reported prevalence among the three wheat-related entities. It remains, however, particularly poorly characterized due to unclear pathophysiology and lack of diagnostic markers. This narrative review will scrutinize the shared and distinct clinical features of the three wheat-related conditions, focusing on epidemiology, clinical presentation, co-morbidities, diagnosis, treatment and prognosis.