The role of gluten challenge in the diagnosis of celiac disease: a review

IntroductionDuodenal biopsy is the gold standard in the diagnosis of celiac disease, with increasing utilization of serology. A gluten challenge may be required, for example, when dietary gluten reduction precedes appropriate diagnostic evaluations. Evidence on the best challenge protocol is currently sparse. Pharmaceutical trials in recent years may have provided new insights into the challenge and advanced the development of novel sensitive histological and immunological methods.Areas coveredThis review outlines the current perspectives on the use of gluten challenge in the diagnosis of celiac disease and explores future directions in this area.Expert opinionComprehensive elimination of celiac disease before dietary gluten restriction is essential to avoid diagnostic uncertainties. Gluten challenge continues to have an important role in certain clinical scenarios, although it is important to understand its limitations in the diagnostic evaluation. The evidence so far permits no unequivocal recommendation considering the timing, duration, and amount of gluten used in the challenge. Thus, these decisions should be made on a case-by-case basis. Further studies with more standardized protocols and outcome measures are called for. In the future novel immunological methods may help to shorten or even avoid gluten challenge.