Mechanisms and management of refractory coeliac disease

Abstract

A small subset of patients with coeliac disease become refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. The most common cause of this condition is inadvertent gluten exposure, but concomitant diseases leading to villous atrophy should also be considered and excluded. After exclusion of these conditions, patients are referred to as having refractory coeliac disease, of which two categories are recognized based on the absence (type I) or presence (type II) of a clonal expansion of premalignant intraepithelial lymphocyte population with a high potential for transformation into an overt enteropathy-associated T-cell lymphoma. Type I disease usually has a benign course that can be controlled by mild immunosuppressive treatment, but type II can be more severe with cladribine with or without autologous stem cell transplantation effective as treatment. Patients who fail to respond to cladribine therapy, however, still have a high risk of malignant transformation. Insights into the immunophenotype of these cells and the recognition that type II disease is a low-grade, no-mass lymphoma opens avenues for new treatment strategies, including chemotherapeutic and immunomodulating strategies. This Review will provide an overview of refractory coeliac disease, discussing mechanisms, diagnosis and management.

Celiac disease diagnosis still significantly delayed – Doctor's but not patients’ delay responsive for the increased total delay in women

“…the persistence of symptoms despite a verified straight adherence to GFD over more than one year and exclusion of differential diagnosis for villous atrophy, corticosteroids or other immunosuppressive agents are advocated in combination with nutritional support, although there is no evidence based standard treatment approach [30][31][32]. The literature on epidemiology of RCD in CeD is scarse with no available global data [30]. However, percentage of patients ever having been treated with steroids and/or immunosuppressants appears to be in the magnitude of cumulative RCD incidence according to a north American study, where 4.0% of patients revealed to have true RCD (1.5% in the principal center in Boston) [33].…”

“…Apparently, only in patients with true refractory CeD (RCD), i.e. the persistence of symptoms despite a verified straight adherence to GFD over more than one year and exclusion of differential diagnosis for villous atrophy, corticosteroids or other immunosuppressive agents are advocated in combination with nutritional support, although there is no evidence based standard treatment approach [30][31][32]. The literature on epidemiology of RCD in CeD is scarse with no available global data [30].…”

Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review

“…Refractory celiac disease type I usually runs a benign course, but type II often progresses to overt intestinal lymphoma and premature death [117]. Such refractory cases are fortunately few in number; in a Finnish high-prevalence area, the prevalence of refractory celiac disease was 0.31 % among all diagnosed celiac disease patients [118].…”

Recent Advances in Celiac Disease

“…Type 1 RFD does not demonstrate abnormal intraepithelial lymphocyte populations and has a more benign course. Type 2 RFD is characterised by clonal expansion of an intraepithelial lymphocyte population with an aberrant phenotype -this may evolve into enteropathy associated T cell lymphoma, which carries a very poor prognosis [10].…”