Diagnosis of coeliac disease by flow cytometry of intraepithelial lymphocytes: a new 'gold' standard?

Objective: The analysis of intraepithelial lymphocytes (IELs) by flow cytometry of duodenal biopsies-the 'IEL' lymphogram-has been proposed as a diagnostic test for coeliac disease. However, its clinical applicability has been limited due to variability in methods and definitions. This study set out to define useful parameters for the application of the IEL lymphogram to the diagnosis of coeliac disease. Design: Flow cytometry was performed on 117 sets of duodenal biopsies in 107 adult patients with active coeliac disease, long-term coeliac disease on a gluten free diet and a control group. The initial 95 samples were used for hypothesis generation for the subsequent samples comprising 12 patients with coeliac disease and 10 controls. Results: Rather than using single linear cut-offs for CD3 and T-cell receptor γδ (TCRγδ)+ve IELs, a discriminant function was identified as %CD3+ve IELs+2x(%TCRγδ+IELs)>100. This differentiated coeliac disease from control biopsies in the hypothesis generating group. These results were replicated in the validation group and found to be independent of histology in patients on long-term gluten free diet up to 12 years (combined sensitivity, 98.5%; specificity, 97.7%). Conclusions: Flow cytometric analysis of IELs is a highly sensitive and specific adjunct to serology and histological examination for the diagnosis of coeliac disease, even in individuals with coeliac disease following a gluten free diet who exhibit normal duodenal histology.

How to manage adult coeliac disease: perspective from the NHS England Rare Diseases Collaborative Network for Non-Responsive and Refractory Coeliac Disease.

Adult coeliac disease (CD) affects approximately 1% of the population. Most patients diagnosed will respond to a gluten-free diet; however, up to 30% may have persisting symptoms. Such patients may have ongoing issues associated with adherence, non-responsive CD or refractory CD. This article provides a clinical overview of how to manage this group of patients with persisting symptoms, including an investigational algorithm and details of how to contact the National Health Service England Rare Diseases Collaborative Network for Non-Responsive and Refractory Coeliac Disease. We hope this will be a valuable source of contemporary information for all UK gastroenterologists and internationally.

The Long and Short of IT: intestinal failure-associated liver disease (IFALD) in adults-recommendations for early diagnosis and intestinal transplantation.

Intestinal failure-associated liver disease (IFALD) often presents in adults unexpectedly with advanced disease. Non-invasive tests can be falsely reassuring. Patients with 'ultrashort' intestine (<20 cm) ending in a stoma are at particular risk of developing IFALD, which may occur rapidly. Recent experience and studies suggest that IFALD can be reversed by isolated intestine transplant occurring before the development of high grade fibrosis or cirrhosis. Post-transplant survival is superior for isolated intestinal grafts compared with liver containing intestinal grafts; waiting time and waiting list mortality is higher for a combined graft, and donor liver supply is limited. Therefore, the aim of clinicians treating patients with intestinal failure should be to identify IFALD early and refer to an intestinal transplant centre while isolated intestine transplantation can be contemplated and before the liver disease has progressed to a stage requiring consideration of combined liver and intestinal transplantation.