title: Clinical characteristics and long-term outcome of patients with refractory sprue diagnosed at a single institution.
abstract: BACKGROUND
  Refractory sprue (RS) is a rare and severe celiac-like enteropathy not responding to a strict gluten-free diet. Although prognosis is generally poor, little is known about the long-term outcome of patients.
  
  
  OBJECTIVE
  to report baseline characteristics and long-term outcome of a series of patients diagnosed and treated in a single institution.
  
  
  METHODS
  We report a retrospective cohort of 25 consecutive patients (15 females; mean age 46 yr; range 28-71) diagnosed with RS based on the presence of a non-responsive celiac-like enteropathy. All patients were intensively treated with a gluten-free diet, steroids, nutritional support and immunosupression.
  
  
  RESULTS
  Clinical and biological characteristics of patients suggest that, at least, 24 patients had clear evidences of celiac disease. HLA DQ2/DQ8 genes were present in all the 24 patients typed and autoimmune enteropathy was excluded in all. According to the genotyping, 12 patients had a polyclonal lymphocyte population (RS type I) and 13 exhibited monoclonal TCR-gamma gene rearrangements (RS type II). Sixteen patients had evidence of ulcerative jejunitis (UJ) (7 in RS type I and 9 in type II). Overall median follow-up time after diagnosis of RS was 29 mo/patient (range 7 to 204) (45 mo for type I and 24 mo for type II). Overall mortality was 48% (12 patients), 6 in each type. Eight patients with UJ (50%), 3 with lymphoma (two T-cell and one B-cell type) and 4 (44%) without ulcers died during follow-up. The causes of death were sepsis in the context of a progressive deterioration but without overt malignancies (n=5), vascular causes (n=3) and severe malnutrition (n=1). Three- and 5-yr survival rate after diagnosis of RS for the overall population was 60% and 56%. There was no differences between type I (67%, 58%) and type II RS patients (54% for both periods). Patients with UJ had lower but non-significant 3- and 5-yr survival rates (56% and 50%, respectively) compared with patients without ulcers (78% and 66%). Survivors had a favorable outcome. While 11 patients persists asymptomatic, two other cases still have mild diarrhea and one low body weight.
  
  
  CONCLUSIONS
  We confirm that RS is a severe celiac disease-related disorder with very high mortality. Diagnosis of overt lymphoma (12%) in our long-term follow-up was not as frequent as was reported by other groups. A proportion of patients persist in good health for a long time irrespective of the nature of the IEL infiltration or the presence of UJ.
authors.affiliation: Small Bowel Section, Department of Medicine, Carlos Bonorino Udaondo Gastroenterology Hospital, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mauriño
authors.forename: Sonia
authors.initials: S
authors.lastname: Niveloni
authors.forename: Alejandra C
authors.initials: AC
authors.lastname: Cherñavsky
authors.forename: Emilia
authors.initials: E
authors.lastname: Sugai
authors.forename: Horacio
authors.initials: H
authors.lastname: Vázquez
authors.forename: Silvia
authors.initials: S
authors.lastname: Pedreira
authors.forename: Natalia
authors.initials: N
authors.lastname: Periolo
authors.forename: Roberto
authors.initials: R
authors.lastname: Mazure
authors.forename: Edgardo
authors.initials: E
authors.lastname: Smecuol
authors.forename: María L
authors.initials: ML
authors.lastname: Moreno
authors.forename: Néstor
authors.initials: N
authors.lastname: Litwin
authors.forename: Fabio
authors.initials: F
authors.lastname: Nachman
authors.forename: Zulema
authors.initials: Z
authors.lastname: Kogan
authors.forename: Julio César
authors.initials: JC
authors.lastname: Bai
mesh_terms: D000328:Adult; D017677:Age Distribution; D001118:Argentina / Q000453:epidemiology; D002446:Celiac Disease / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017678:Sex Distribution; D011503:Transglutaminases / Q000097:blood
chemical_list: D011503:Transglutaminases