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

ABSTRACT

Introduction

Duodenal 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 covered

This 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 opinion

Comprehensive 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.

KEYWORDS:

• Celiac disease
• gluten
• challenge
• children
• diagnosis
• tetramers
• drug

Article highlights

• It is essential to perform comprehensive diagnostic evaluations for celiac disease before introducing any dietary gluten restrictions.

• Gluten challenge continues to have an important role in situations in which a gluten-free diet has already been initiated before appropriate investigations or when the celiac disease diagnosis is otherwise inconclusive.

• Due to limited scientific evidence, the timing, duration, and amount of gluten used in the challenge should be determined according to individual assessment and joint decision-making.

• It is important for clinicians to recognize that there are still significant limitations in the utilization and interpretation of the gluten challenge.

• More studies with standardized protocols and outcome measures are warranted to determine best practices in the implementation of the challenge.

• Recent pharmaceutical studies have driven the development of more sensitive immunological methods and other outcome measures that may help to shorten or even eliminate the need for gluten challenge.

Declaration of interest

K Kurppa and P Laurikka have received lecture fees from Thermo Fisher and Finnish celiac disease societies, and K. Kurppa also consultancy fees from Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors of this study were supported by the Foundation for Pediatric Research and the Competitive State Research Financing of the Expert Area of Tampere University Hospital. The funders had no role in the writing of this article or in the decision to submit it for publication.