title: Changes in Presentation of Celiac Disease in Ireland From the 1960s to 2015.
abstract: OBJECTIVE
  Celiac disease is an immune-mediated enteropathy characterized with high heterogeneity in presentation among genetically predisposed individuals. In recent years, a change in the phenotypic presentation of celiac disease has been reported. We studied clinical presentation, from 1960 through 2015, in Ireland, which has a high incidence of celiac disease.
  
  
  METHODS
  We performed a retrospective analysis of medical charts from patients diagnosed with celiac disease at 5 secondary referral centers in Ireland from 1960 through 2015 (n = 749; median age, 56 years; age range, 18-91 years). The cohort was divided into 5 groups based on year of diagnosis (≤1985, 1986-1995, 1996-2005, 2006-2010, or 2011 and later). We collected findings from clinical presentation at diagnosis; serology tests; small intestinal biopsy analyses; and patients' demographic, clinical, and family data. Presentations at diagnosis were classified according to the Oslo criteria as follows: classical (patients presenting with malabsorption), nonclassical (no signs or symptoms of malabsorption at presentation), or subclinical (below the threshold of clinical detection). The primary outcome was change in clinical presentation of celiac disease over time.
  
  
  RESULTS
  Of the 749 patients studied, 512 were female and 237 were male (ratio of 2.2:1). Female patients were diagnosed at younger ages than male patients (42 vs 47 years, respectively; P = .004), and had more immune-mediated conditions than male patients (35.7% for female patients vs 21.5% for male patients; P < .001). For patients diagnosed as adults (after the age of 18 years), the median age of diagnosis increased from 34.0 years during the period ≤1985 to median ages of 44-46 years after 1985 (P < .002). A smaller proportion of patients presented with classical features of celiac disease after 2010 (48.4%) than ≤1985 (85.2%); the proportion of patients with nonclassical or subclinical celiac disease increased from 14.8% ≤1985 to 51.6% after 2010 (P = .006 for each). Biopsies categorized as Marsh 3c decreased, from 52.2% in the period 1996-2005 to 22.5% in the period after 2010 (P = .003). The prevalence of associated thyroid disease has decreased during the study period, from 36.6% ≤1985 to 17.1% after 2010 (P = .039), whereas body mass index at diagnosis increased from 21.5 kg/m2≤1985 to 24.8 kg/m2after 2010 (P < .001).
  
  
  CONCLUSIONS
  We found the clinical presentation of celiac disease changed significantly in Ireland from 1960 through 2015. The age of presentation in adulthood increased over this time period, as did the proportions of patients with nonclassical or subclinical disease.
authors.affiliation: Trinity Translational Medicine Institute & Department of Clinical Medicine, Trinity Centre for Health Science, St James's Hospital, Dublin, Republic of Ireland. Electronic address: domingup@tcd.ie.
authors.forename: Patricia
authors.initials: P
authors.lastname: Dominguez Castro
authors.affiliation: Department of Clinical Medicine, University College Hospital Galway, Galway, Republic of Ireland.
authors.forename: Grace
authors.initials: G
authors.lastname: Harkin
authors.affiliation: Department of Clinical Medicine, The Adelaide and Meath Hospital, Dublin, Republic of Ireland.
authors.forename: Mary
authors.initials: M
authors.lastname: Hussey
authors.affiliation: Connolly Hospital Blanchardstown, Blanchardstown, Dublin, Republic of Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Christopher
authors.affiliation: Department of Clinical Medicine, University College Hospital Galway, Galway, Republic of Ireland.
authors.forename: Clifford
authors.initials: C
authors.lastname: Kiat
authors.affiliation: Trinity Translational Medicine Institute & Department of Clinical Medicine, Trinity Centre for Health Science, St James's Hospital, Dublin, Republic of Ireland.
authors.forename: Jun
authors.initials: J
authors.lastname: Liong Chin
authors.affiliation: Trinity Translational Medicine Institute & Department of Clinical Medicine, Trinity Centre for Health Science, St James's Hospital, Dublin, Republic of Ireland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Trimble
authors.affiliation: Department of Clinical Medicine, The Adelaide and Meath Hospital, Dublin, Republic of Ireland.
authors.forename: Deirdre
authors.initials: D
authors.lastname: McNamara
authors.affiliation: Gastrointestinal Unit, Mater Misericordiae University Hospital, Eccles Street, Dublin, Republic of Ireland.
authors.forename: Padraic
authors.initials: P
authors.lastname: MacMathuna
authors.affiliation: Department of Clinical Medicine, Mayo General Hospital, Castlebar, County Mayo, Republic of Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Egan
authors.affiliation: Department of Clinical Medicine, The Adelaide and Meath Hospital, Dublin, Republic of Ireland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ryan
authors.affiliation: Trinity Translational Medicine Institute & Department of Clinical Medicine, Trinity Centre for Health Science, St James's Hospital, Dublin, Republic of Ireland.
authors.forename: David
authors.initials: D
authors.lastname: Kevans
authors.affiliation: Connolly Hospital Blanchardstown, Blanchardstown, Dublin, Republic of Ireland.
authors.forename: Richard
authors.initials: R
authors.lastname: Farrell
authors.affiliation: Department of Clinical Medicine, University College Hospital Galway, Galway, Republic of Ireland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Byrnes
authors.affiliation: Trinity Translational Medicine Institute & Department of Clinical Medicine, Trinity Centre for Health Science, St James's Hospital, Dublin, Republic of Ireland.
authors.forename: Nasir
authors.initials: N
authors.lastname: Mahmud
authors.affiliation: Trinity Translational Medicine Institute & Department of Clinical Medicine, Trinity Centre for Health Science, St James's Hospital, Dublin, Republic of Ireland.
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002446:Celiac Disease / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
keywords: Autoimmune Disease; BMI; Environmental Factors; Epidemiology; Gluten