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Enteropathy-associated t-cell lymphoma (EATL) is a rightly feared complication of coeliac disease (CeD) often presenting as the first manifestation of CeD or a complication of preexisting refractory coeliac disease type 2 (RCD2).1 Cording et al in Gut have provided in exquisite detail the molecular landscape of RCD2 and the resultant EATL.2 It provides not so much of a road map to guide us, but rather a sketch of what has gone wrong in this severe complication of CeD. The sequence of CeD leading to RCD2 and finally to EATL provides a rare opportunity for so much confusion. Is RCD2 a chronic inflammatory disease? Most certainly yes. Is it a lymphoma? Perhaps not yet? Thanks to this paper and another recent paper we have a clearer picture of the genotoxic somatic aberrations that occur in and cause expansion and spread of these rare lineage cells.3 Short of the often-lethal lymphoma, RCD2 itself produces substantial morbidity and even mortality.4 Intraepithelial lymphocytes (IELS) can be quite cytotoxic causing significant damage to the epithelium that has persisted despite a gluten-free diet. These aberrant IELS drive the destructive nature of the disease and its cytotoxicity.
The face of RCD2 for the gastroenterologist: gastroenterologists looking after these patients are often faced with an ill patient who has very advanced malnutrition as well as a propensity to infection.5 This face of CeD requires the clinician to confirm preexisting CeD, then detect and treat concurrent conditions such as small intestinal bacterial overgrowth, exocrine pancreatic insufficiency, microscopic colitis, motility changes, lactose or other maldigestive problems. Vigorous management of nutritional deficiencies including protection of bone health is crucial.5 Often, gastroenterologists will institute an anti-inflammatory approach to the disease on the basis that it has produced chronic inflammation. In the author’s experience, the early and …
Collaborators Joseph A. Murray.
Contributors JAM is the sole author and contributor of this invited commentary. He was invited to write the commentary by EE-O, editor-in-chief.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests JAM received study grants from Nexpep/ImmusanT, National Institutes of Health, Immunogenix, Takeda Pharmaceutical, Allakos, Oberkotter, and Cour; consultancy fees from Bionix, Lilly Research Laboratory, Johnson & Johnson, Dr. Schar USA, UCB Biopharma, Celimmune, Intrexon Corporation, Chugai Pharma, Kanyos and Boehringer Ingelheim; holds patents licensed to Evelo Biosciences; and receives royalties from Torax Medical.
Provenance and peer review Commissioned; internally peer reviewed.
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