The gold standard for diagnosis of celiac disease (CD) requires both a duodenal biopsy showing villus blunting, crypt hyperplasia, and increased numbers of intraepithelial lymphocytes (IELs) and a subsequent small intestinal biopsy that shows resolution of these histological findings after the patient is put on a gluten-free diet (1). The development of new serological tests, however, have resulted in the current diagnostic standard of IgA anti–tissue transglutaminase (tTG), which is the autoantigen responsible for the development of endomysial antibodies.
In this case, the patient’s original diagnosis was by a biopsy and IgA anti-tTG. She was refractory, however, to her gluten-free diet (a situation that could be attributable to nonadherence to the diet). When this possibility is ruled out, a more concerning reason for a poor clinical response is that the patient may have a serious complication of celiac disease, enteropathy-associated T-cell lymphoma (EATL) or refractory CD. EATL is a clonal proliferation of IELs that historically has been diagnosed on the basis of biopsy and immunohistochemical analysis to determine the presence of abnormal T cells in the intestinal epithelium. This case study is one of the first to investigate the use of polymerase chain reaction (PCR) for T-cell receptor (TCR) gene rearrangements in EATL/refractory CD and demonstrates that this approach will detect a clonal rearrangement in intestinal biopsies. It is critical to note, however, that oligo- or monoclonal IEL populations can also be detected in the large majority of refractory CD (both type I and type II), and therefore differentiation between EATL and refractory disease is of limited use (2). Immunohistochemical analysis for T-cell surface receptors (CD3 and CD8) and histological appearance are more useful in the diagnosis of EATL or refractory CD. Serology is useful only in the initial diagnosis.
Grant/funding Support: None declared.
Financial Disclosures: None declared.
- © 2008 The American Association for Clinical Chemistry