title: Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.
abstract: BACKGROUND
  Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients.
  
  
  OBJECTIVE
  To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy.
  
  
  METHODS
  221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded.
  
  
  RESULTS
  130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II-III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p = 0.002). Marsh I relatives had more severe abdominal pain (p = 0.006), severe distension (p = 0.047) and anaemia (p = 0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%).
  
  
  CONCLUSIONS
  The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.
authors.affiliation: Department of Gastroenterology, Hospital Mútua de Terrassa, Universitat de Barcelona, Plaça Dr Robert no. 5, 08221 Terrassa, Barcelona, Catalonia, Spain. mestevecomas@telefonica.net
authors.forename: M
authors.initials: M
authors.lastname: Esteve
authors.forename: M
authors.initials: M
authors.lastname: Rosinach
authors.forename: F
authors.initials: F
authors.lastname: Fernández-Bañares
authors.forename: C
authors.initials: C
authors.lastname: Farré
authors.forename: A
authors.initials: A
authors.lastname: Salas
authors.forename: M
authors.initials: M
authors.lastname: Alsina
authors.forename: P
authors.initials: P
authors.lastname: Vilar
authors.forename: A
authors.initials: A
authors.lastname: Abad-Lacruz
authors.forename: M
authors.initials: M
authors.lastname: Forné
authors.forename: M
authors.initials: M
authors.lastname: Mariné
authors.forename: R
authors.initials: R
authors.lastname: Santaolalla
authors.forename: J C
authors.initials: JC
authors.lastname: Espinós
authors.forename: J M
authors.initials: JM
authors.lastname: Viver
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001284:Atrophy; D001323:Autoantibodies / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology; D002446:Celiac Disease / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000473:pathology; D004751:Enteritis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D005192:Family Health; D005195:Family Relations; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D007223:Infant; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D011503:Transglutaminases