Non-Responsive and Refractory Coeliac Disease: Experience from the NHS England National Centre

Abstract

We characterised the aetiology of non-responsive coeliac disease (NRCD) and provided contemporary mortality data in refractory coeliac disease (RCD) from our centre. We also measured urine gluten immunogenic peptides (GIPs) in patients with established RCD1 to evaluate gluten exposure in these individuals. Methods: This was a longitudinal cohort study conducted in Sheffield, UK. Between 1998 and 2019, we evaluated 285 adult (≥16 years) patients with NRCD or RCD. Patients with established RCD1 and persisting mucosal inflammation and/or ongoing symptoms provided three urine samples for GIP analysis. Results: The most common cause of NRCD across the cohort was gluten exposure (72/285; 25.3%). RCD accounted for 65/285 patients (22.8%), 54/65 patients (83.1%) had RCD1 and 11/65 patients (16.9%) had RCD2. The estimated 5-year survival was 90% for RCD1 and 58% for RCD2 (p = 0.016). A total of 36/54 (66.7%) patients with RCD1 underwent urinary GIP testing and 17/36 (47.2%) had at least one positive urinary GIP test. Conclusion: The contemporary mortality data in RCD2 remains poor; patients with suspected RCD2 should be referred to a recognised national centre for consideration of novel therapies. The high frequency of urinary GIP positivity suggests that gluten exposure may be common in RCD1; further studies with matched controls are warranted to assess this further.

A dietitian‐led coeliac service helps to identify and reduce involuntary gluten ingestion with subsequent reduction in the frequency of repeat endoscopies

“…This finding is comparable to a study whereby patients with and without histological remission had similar dietitian dietary adherence scores ( n = 44) 16 . This is also clinically useful to know, as it has previously been demonstrated, that the most common cause of persistent symptoms in CD is ongoing gluten exposure 24–27 . Thus, using a specialist dietitian assessment to help identify inadvertent gluten ingestion before considering a more invasive and costly endoscopy with repeat duodenal biopsies is likely to be safe and useful for many patients.…”

“…16 This is also clinically useful to know, as it has previously been demonstrated, that the most common cause of persistent symptoms in CD is ongoing gluten exposure. [24][25][26][27] Thus, using a specialist dietitian assessment to help identify inadvertent gluten ingestion before considering a more invasive and costly endoscopy with repeat duodenal biopsies is likely to be safe and useful for many patients. Despite this, the current recommendation for exploring persistent CD symptoms is that a dietitian assessment be offered after repeat duodenal biopsies have been performed.…”

Persistent villous atrophy predicts development of complications and mortality in adult patients with coeliac disease: a multicentre longitudinal cohort study and development of a score to identify high-risk patients

“…Overall, the prevalence of complications in the present study was higher than previously reported, although comparisons are difficult to make due to differences in clinical and demographic aspects, and duration of follow-up 30 34. It should be noted that roughly half of the complications in our cohort were due to refractory CD type 1, which is characterised by the best prognosis among the complications of CD, and for which it has recently been suggested that hidden gluten exposure may play a role 18 35. Unfortunately, in this regard, we cannot provide data on measurement of minimal traces of gluten given the retrospective nature of our study.…”

“…Identification of potential clinical targets in the follow-up of patients with CD is a crucial requirement for clinicians. Based on our results, this includes implementing strategies for obtaining and maintaining over time strict adherence to a GFD,9 control of persistent symptoms despite a GFD11 35 40 and obtaining deep mucosal healing. A substantial degree of overlap between these aspects is likely to exist.…”

Expanded T cell clones with lymphoma driver somatic mutations in refractory celiac disease

“…The immune response is amplified by capture and presentation of the deamidated peptides by intestinal plasma cells making autoantibodies to tissue transglutaminase 2 (TG2) ( 2 ) and by clonal expansion of CD8 T cells adopting an NK-like cytolytic phenotype ( 5–8 ). Treatment with a strict, lifelong gluten-free diet generally induces symptom resolution, normalisation of CD serology and healing of the enteropathy but up to 30% of patients experience non-responsive CD ( 9, 10 ).…”