title: Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience.
abstract: BACKGROUND
  Coeliac disease may be regarded as refractory disease (RCD) when symptoms persist or recur despite strict adherence to a gluten-free diet. RCD may be subdivided into types I and II with a phenotypically normal and aberrant intraepithelial T-cell population, respectively. RCD I seems to respond well to azathioprine/prednisone therapy. RCD II is usually resistant to any known therapy and transition into enteropathy-associated T-cell lymphoma (EATL) is common.
  
  
  OBJECTIVE
  To provide further insight into RCD and the development of EATL, by reporting on long-term survival and risk of transition of RCD into EATL in a large cohort of patients with complicated coeliac disease.
  
  
  METHODS
  Retrospective comparison of responses to therapy in four groups of patients with complicated coeliac disease: 43, RCD I; 50, RCD II (total), of whom 26 with RCD II developed EATL after a period of refractoriness to a gluten-free diet (secondary EATL) and 13 were EATL patients without preceding history of complicated coeliac disease (de novo EATL).
  
  
  RESULTS
  No coeliac-disease-related mortality was recognised in the RCD I group. The overall 5-year survival in the RCD I group it was 96%; in the RCD II (total) group was 58%; and in the RCD II group after developing EATL it was only 8%. The 2-year survival in the de novo EATL group was 20% versus 15% in secondary EATL group (p = 0.63). Twenty-eight (56%) of the 50 patients with RCD II died, 23 (46%) due to EATL, 4 due to a progressive refractory state with emaciation and 1 from neurocoeliac disease.
  
  
  CONCLUSIONS
  Remarkably, no patient with RCD I developed RCD II or EATL within the mean follow-up period of 5 years (range 2-15 years). A total of 52% of the RCD II patients developed EATL within 4-6 years after the diagnosis of RCD II. More aggressive and targeted therapies seem necessary in RCD II and EATL.
authors.affiliation: VU University Medical Centre, Department of Gastroenterology, P.O. Box 7057, 1005 MB Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Al-Toma
authors.forename: W H M
authors.initials: WH
authors.lastname: Verbeek
authors.forename: M
authors.initials: M
authors.lastname: Hadithi
authors.forename: B M E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: C J J
authors.initials: CJ
authors.lastname: Mulder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002446:Celiac Disease / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D004812:Epidemiologic Methods; D005260:Female; D005983:Glutens / Q000008:administration & dosage; D006801:Humans; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D005983:Glutens