Recent advances in refractory coeliac disease: a review

Abstract

Coeliac disease (CD) is an immune-mediated disease of the small intestine caused by intolerance to gluten. Removal of gluten from the diet results in a return to normal health for the majority of patients. A significant proportion of patients do not respond to a gluten-free diet and are considered to be suffering from refractory coeliac disease (RCD). Two types of RCD are now recognized: type 1 RCD is characterized by a polyclonal population of intraepithelial lymphocytes (IELs) with a normal immunophenotype, and type 2 RCD shows monoclonal IELs with an aberrant immunoprofile. Patients with RCD have a high risk of complications such as ulcerative jejunitis (UJ) and enteropathy-type T-cell lymphoma (ETTL). RCD2 may represent an early stage in the development of overt lymphoma. The diagnosis of RCD, therefore, has important implications, but remains a challenging area. In this paper we review the latest developments in RCD, including the diagnostic approach and a discussion of the key clinical, histological, immunohistochemical and molecular features of RCD and its complications.

Persistence of elevated deamidated gliadin peptide antibodies on a gluten‐free diet indicates nonresponsive coeliac disease

“…22 Early detection of RCD is critical because of the increased risk of ulcerative jejunitis, enteropathy-associated T-cell lymphoma (EATL) and non-Hodgkin’s lymphomas, epithelial neoplasms, oesophageal and pharyngeal squamous cell carcinomas, and concomitant autoimmune diseases. 24,38 RCD diagnosis depends on the exclusion of other possible causes of villous atrophy and increased IELs. The only definitive test for RCD requires detection of an abnormal IEL phenotype specific to RCD type II.…”

Celiac disease: From pathophysiology to treatment

“…Several refractory patients (roughly, 5%-30%) never respond to a gluten-free diet[59], others initially responded but have a recurrence of symptoms and intestinal damage. Two different sub-types of refractory celiac disease have been recognized: “Type 1”, showing a normal intraepithelial lymphocytes count and “type 2” presenting aberrant intraepithelial lymphocytes[29].…”

“…This morphological pattern is very similar to the condition of collagenous colitis described in the colon, where the thickness of the connective band best highlighted with Masson’s trichrome is more than 15 nanometers, although this is a very rare event described in the literature; (4) Refractory sprue: This condition is depicted as collagenous sprue although can be identified by immunohistochemical staining, demonstrating that T lymphocytes, which in normal conditions express CD3 and CD8, in this case present only the expression of CD3 and not of CD8; (5) Ulcerative jejunoileitis: Extensive ulceration of the intestinal mucosa, and involving ileum and jejunum. It presents around 50 years old with chronic diarrhea, steatorrhoea and complications of intestinal ulceration (perforation, haemorrhage or obstruction)[59]; (6) Non-Hodgkin lymphoma: Recent data suggests an association between celiac disease and Non-Hodgkin lymphoma[80]; (7) Small bowel adenocarcinoma: Even rare, a connection between carcinoma of the small bowel and celiac disease is known since 1958[81]. The etiologic factors predisposing to malignancy in celiac disease are uncertain.…”

Ulcerative jejunitis in a child with celiac disease

“…Histological findings can vary due to patchy distribution or varying degrees of villous atrophy [4]. Furthermore, intraepithelial lymphocytosis, crypt hyperplasia and villous atrophy can be seen in other conditions affecting the small bowel, such as giardiasis, Crohn’s disease, autoimmune and allergic enteropathies [1,4,9]. A diagnostic dilemma arose in this case in that the serology was borderline positive as the patient is IgA deficient.…”