From the Guidelines
Refractory coeliac disease is characterized by persistent villous atrophy and increased intraepithelial lymphocytes, with type II being a low-grade intra-epithelial lymphoma with aberrant IELs lacking surface CD3 and CD8 expression. The histopathological findings of refractory coeliac disease (RCeD) can be classified into two types: type I and type II, based on the number of aberrant intraepithelial lymphocytes (IELs) and clonal rearrangement of the T cell receptor (TCR) 1.
Key Histopathological Features
- Persistent villous atrophy
- Increased intraepithelial lymphocytes (IELs)
- Aberrant IELs in type II, which can be identified by immunohistochemistry (IHC) and flow cytometry
- Aberrant IELs in type II make up 20% or more of total IELs on flow cytometry and more than 50% on IHC 1
Classification and Prognosis
- Type I: normal phenotype of IELs with surface expression of CD3 and CD8
- Type II: abnormal clonal population of IELs lacking surface CD3 and CD8 expression while retaining intracellular CD3 expression, considered a low-grade intra-epithelial lymphoma 1 Management of RCeD should be done in tertiary or national referral centres with specific experience in this rare form of CeD. The severity of villous atrophy can be classified using the Marsh-Oberhuber classification, with most RCeD patients showing Marsh 3 lesions (partial to total villous atrophy) 1. Immunohistochemistry and flow cytometry are essential for distinguishing between RCeD types I and II, which is crucial for treatment decisions and prognosis assessment, as type II has a significantly worse prognosis with higher mortality rates.
From the Research
Histopathological Findings of Refractory Coeliac Disease
The histopathological findings of refractory coeliac disease (RCD) are characterized by:
- Persisting villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes despite a strict gluten-free diet for more than 12 months 2
- Abnormal intraepithelial lymphocyte (IEL) population with lack of surface expression of usual T-cell markers (CD3-CD8 and/or the T-cell receptor (TCR)) on IELs associated with T-cell clonality pattern, suggesting the presence of an early enteropathy-associated T-cell lymphoma (EATL) in a subgroup of patients with RCD 3
- Increased intraepithelial lymphocytes (IELs) in the small bowel 3
Classification of Refractory Coeliac Disease
RCD can be classified into two types based on the T-cells in the intra-epithelial lymphocyte (IEL) morphology:
- Type 1: normal IEL phenotype 4, 2, 5
- Type 2: abnormal (clonal) IEL phenotype, defined by the presence of aberrant T-cells detected by immunophenotyping by flowcytometric analysis or immunohistology of the intestinal mucosa 4, 2, 5
Complications of Refractory Coeliac Disease
Severe complications of RCD include: