High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders

J Allergy Clin Immunol. 2013 Aug;132(2):378-86. doi: 10.1016/j.jaci.2013.02.030. Epub 2013 Apr 19.


Background: Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling.

Objective: We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs).

Methods: We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features.

Results: We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; χ(2)1 = 112.0; P < 10(-3)) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs.

Conclusion: There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD.

Keywords: BMI; Body mass index; CCHMC; CTD; Cincinnati Children's Hospital Medical Center; Connective tissue disorder; EDS; EGID; EMR; Ehlers-Danlos syndrome; Electronic medical record; EoE; Eosinophilic esophagitis; Eosinophilic gastrointestinal disorder; FBN1; Fibrillin-1 gene; GERD; Gastroesophageal reflux disease; Informatics for Integrating Biology & the Bedside; JHS; Joint hypermobility syndrome; LDS; Loeys-Dietz syndrome; MFS; Marfan syndrome; PPI; Proton pump inhibitor; connective tissue disorders; eosinophil; eosinophilic gastrointestinal disease; hypermobility syndrome; i2b2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Collagen Type VIII / genetics
  • Connective Tissue Diseases / complications
  • Connective Tissue Diseases / epidemiology
  • Connective Tissue Diseases / genetics
  • Ehlers-Danlos Syndrome / complications*
  • Ehlers-Danlos Syndrome / epidemiology
  • Ehlers-Danlos Syndrome / genetics
  • Eosinophilic Esophagitis / complications*
  • Eosinophilic Esophagitis / epidemiology*
  • Eosinophilic Esophagitis / genetics
  • Esophagus / metabolism
  • Female
  • Humans
  • Male
  • Marfan Syndrome / complications*
  • Marfan Syndrome / epidemiology
  • Marfan Syndrome / genetics
  • Prevalence
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • COL8A2 protein, human
  • Collagen Type VIII
  • RNA, Messenger