Food allergy, anaphylaxis, dermatology, and drug allergy
Esophageal remodeling in pediatric eosinophilic esophagitis

https://doi.org/10.1016/j.jaci.2006.10.016Get rights and content

Background

Eosinophils are associated with airway remodeling in asthma, but studies have not yet determined whether eosinophilic esophagitis (EE) is associated with esophageal remodeling.

Objective

We performed quantitative immunohistochemical analysis of remodeling changes in esophageal biopsy specimens from children with and without EE to evaluate if there were changes in the esophagus of pediatric patients with EE akin to airway remodeling. In addition, we determined whether the esophagus of patients with EE had increased levels of expression of TGF-β1 and its signaling molecule, phosphorylated SMAD2/3 (phospho-SMAD2/3).

Methods

To determine esophageal levels of eosinophilic inflammation, fibrosis, and vascular activation, endoscopically obtained esophageal biopsy specimens from 7 patients with EE (5 strictured, 2 nonstrictured), 7 with gastroesophageal reflux disease, and 7 normal patients were processed for immunohistology, trichrome staining, and assessment of levels of expression of TGF-β1, phospho-SMAD2/3, and vascular cell adhesion molecule 1.

Results

Esophageal biopsies in patients with EE demonstrated increased levels of subepithelial fibrosis and increased expression of TGF-β1 and its signaling molecule phospho-SMAD2/3 compared with gastroesophageal reflux disease and normal control patients. In addition, esophageal biopsies in patients with EE demonstrated an increased vascular density and an increased expression of the vascular endothelial adhesion molecule, vascular cell adhesion molecule 1.

Conclusion

Previously unrecognized esophageal remodeling changes analogous to aspects of airway remodeling are detectable in the subepithelial region of the esophagus in pediatric patients with EE.

Clinical implications

Pediatric patients with EE demonstrate increased fibrosis, vascularity, and vascular activation in the esophagus that may contribute to stricture formation and potentially provide a basis for stratifying patients with EE on the basis of disease severity and/or prognosis.

Section snippets

Patient selection

An EE database was compiled at Children's Hospital San Diego of all patients meeting criteria for EE and an equal number of patients with gastroesophageal reflux disease (GERD).3 The biopsy used in this study was the first biopsy that demonstrated EE in the patient. EE was defined histologically as greater than 20 eosinophils per hpf on ×400 light microscopy. Patients with GERD were children who underwent diagnostic endoscopic esophageal biopsy for complaints of vomiting and pain consistent

Patient characteristics

The mean age of patients with EE (n = 7), patients with GERD (n = 7), and patients with a normal esophagus (n = 7) was 10.5, 8.4, and 11.2 years, respectively (Table I). All children with EE were male, whereas 57% of children with GERD and 86% of normal children were male. All of the patients with EE complained of dysphagia, whereas none of the patients with GERD or normal patients complained of dysphagia. Five of 7 patients with EE were known to be atopic (71%), 2 of 7 patients with GERD were

Discussion

In this study we have demonstrated the novel finding that several structural features associated with allergen-induced airway remodeling in patients with asthma are also occurring in the esophagus of pediatric patients with EE, especially in the subset of patients who have esophageal strictures. However, even nonstrictured patients with EE had increased fibrosis and vascularity compared with patients with GERD and normal patients, suggesting that the remodeling process is occurring even in the

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    Supported by the American Academy of Allergy, Asthma & Immunology Education and Research Trust (ERT) Clinical Research Grant (S.S.A.), National Institutes of Health T32 Training award AI 007469 (S.S.A.), and National Institutes of Health grant AI 38425 (D.H.B.).

    Disclosure of potential conflict of interest: S. S. Aceves has received grant support from the American Academy of Allergy, Asthma and Immunology Clinical ERT. D. H. Broide has received grant support from the National Institutes of Health. The other authors have declared that they have no conflict of interest.

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