The 5 Ws of a gluten challenge for gluten-related disorders

Gluten-related disorders (GRDs) are gradually emerging as epidemiologically relevant diseases, with a global prevalence estimated to be approximately 5% in the population. Conditions related to gluten ingestion include celiac disease (CD), wheat allergy (WA), and nonceliac gluten sensitivity (NCGS). Although mediated by different pathogenic pathways, these 3 conditions share similar clinical manifestations and can present a difficult differential diagnosis. The gluten challenge (GC) is an important diagnostic tool for GRDs, but there is great variability in regards to deciding which patients should be challenged, what amount of gluten should be used, what the GC duration should be, when and where the GC should occur, and, sometimes, why to conduct a GC. This review summarizes the current knowledge about the desirable characteristics of GCs in the 3 main GRDs following a 5 Ws approach-that is, the 5 main journalistic questions: who, what, when, where, why. The answers will help to determine the correct use of the GC in diagnosing GRDs.