Novel approaches in the management of refractory celiac disease

Abstract

Celiac disease is a gluten-sensitive enteropathy, which commits the patient to a life-long gluten-free diet. This is sufficient to treat the overwhelming majority of patients. However, a small group of these patients, mainly those diagnosed above 50 years of age, fails to improve histologically and clinically upon elimination of gluten from the diet. These patients are regarded as suffering from refractory celiac disease. In a subgroup of these patients a pre-malignant intraepithelial lymphocyte population can be detected in the small intestinal mucosa (type II). These patients are at a high risk of developing an enteropathy-associated T-cell lymphoma (50–60% within 4–6 years), which has a very poor prognosis and a 5-year survival of only 8%. The therapeutic challenge in these refractory celiac disease type II patients is targeting the aberrant intraepithelial lymphocytes to eventually prevent enteropathy-associated T-cell lymphoma development. Although management of these patients is difficult and therapeutic options are currently limited, novel treatment modalities are being explored.

Keywords::

• 2-chlorodeoxyadenisine
• aberrant T lymphocyte
• antigen aberrancy
• autologous stem cell transplantation
• celiac disease
• enteropathy-associated T-cell lymphoma
• flow cytometry
• immunophenotyping
• intestinal γδ T cell
• refractory celiac disease

Acknowledgements

The authors thank Stijn van Weyenberg, for supplying his research data on the value of MRE in RCD patients. Furthermore, our gratitude goes out to nutritional team of the VU University Medical Center: Adje van Bodegraven, Job Peters and Nicolette Wierdsma, who were involved in constructing the flowchart for the diagnostic work-up of RCD patients and the research on intestinal energy absorption capacity in these patients.

Financial & competing interests disclosure

This work was partially supported by the Dutch Society for Gastroenterology (Gastrostart) and by unrestricted grant from AstraZeneca The Netherlands. 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.

No writing assistance was utilized in the production of this manuscript.

Notes

IEL: Intraepithelial lymphocyte.

Adapted with permission from [5].