From the AGA Journals

Topical steroid might improve mucosal integrity in eosinophilic esophagitis

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Topical steroid may improve mucosa in EoE

In the past year, the topic of mucosal integrity in eosinophilic esophagitis has garnered growing attention. Epithelial permeability defects have been described in the pathogenesis of GI disorders, including inflammatory bowel disease and celiac sprue, as well as allergic disorders such as atopic dermatitis. In EoE, both experimental as well as clinical studies have shown an eosinophil-predominant inflammatory response to specific antigens, particularly common food allergens. Increased permeability may predispose genetically susceptible individuals to swallowed allergen penetration through the esophageal epithelium. Beneath the epithelial barrier, antigens have access to antigen presenting cells, including dendritic cells, leading to both allergic sensitization and perpetuation of the TH-2 chronic inflammatory response.

Dr. Ikuo Hirano

The article by Dr. Katzka and his colleagues supports the concept of epithelial barrier defects in EoE through the demonstration of reduced immunohistochemical expression of filaggrin, zonula occludens-3, and claudin-1, important tight junction proteins. Expression was increased in EoE patients treated with topical steroids. Similarly, the study by Dr. van Rhijn and his associates identified impaired mucosal integrity in EoE by a variety of techniques that included electron microscopic demonstration of dilated intercellular spaces, electrical tissue impedance as an in vivo biomarker, and in vitro transepithelial molecular flux in an Ussing chamber. Furthermore, they found that proton pump inhibitor therapy partially restored mucosal permeability defects to a greater degree in patients with PPI-responsive esophageal eosinophilia, compared with patients with EoE. These two studies substantiate studies from the Cincinnati group that previously identified reduced mRNA expression of filaggrin in esophageal mucosal biopsies as well as reduced expression of the intercellular adhesion molecule, desmoglein 1.

In spite of these novel data, the exact role of altered esophageal epithelial permeability in the pathogenesis of EoE is yet unclear. The reversibility of the defect with medical therapy argues against defective cell junction proteins as an intrinsic abnormality. Furthermore, the location of antigen presentation in EoE may occur through other routes such as the small intestine, nasal epithelium, or skin. In the meantime, these studies provide an important advance in our understanding of EoE and open the door to novel therapeutic approaches.

Dr. Ikuo Hirano, AGAF, is professor of medicine at Northwestern University, Chicago. He reported no conflicts of interest.




Topical steroid therapy improved some indicators of mucosal integrity in patients with eosinophilic esophagitis, but proton pump inhibitor therapy did not, according to two studies reported in the November issue of Clinical Gastroenterology and Hepatology.

The first study found that topical fluticasone therapy at a dose of 880 mcg twice daily for 2 months helped correct esophageal spongiosis, or dilated intercellular space, in patients with eosinophilic esophagitis (EoE). Spongiosis scores for treated patients were significantly lower than for untreated patients (0.4 vs. 1.3; P = .016), said Dr. David Katzka at the Mayo Clinic in Rochester, Minn. and his associates (Clin. Gastroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.039]).

In the study, histologic analyses also showed that improved spongiosis scores in treated patients correlated with increased density of two tight junction proteins, filaggrin (P = .001) and zonula occludens-3 (P = .016), said the investigators. These proteins might help regulate antigenic penetration of the esophageal mucosa and also could permit migration of white blood cells, they said. “Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment,” the researchers concluded. But they also noted that their study did not examine the same patients before and after steroid therapy and did not look at desmosomes, intercellular junctions that past research has suggested might be affected in EoE.

For the second study, Dr. Bram van Rhijn and his associates at the Academic Medical Center in the Netherlands compared endoscopies of 16 patients with dysphagia and suspected (unconfirmed) EoE with 11 controls, both at baseline and after 8 weeks of high-dose esomeprazole treatment. Esophageal mucosal integrity was “severely impaired” in patients with confirmed EoE and in those with proton pump inhibitor–responsive eosinophilia (PPRE), the researchers said (Clin. Gasteroenterol. Hepatol. 2014 [doi:10.1016/j.cgh.2014.02.037]).

In both forms of disease, molecules as large as 40,000 daltons were able to pass through the compromised esophageal mucosa, Dr. Bram van Rhijn and his associates reported. “This size is similar to the size of most plant and animal food allergens to which EoE patients are sensitized,” they added. Esophageal permeability might increase the rate of immune exposure to allergens, thereby mediating EoE and PPRE, they said.

On mucosal functional tests, both EoE and PPRE were associated with reduced transepithelial electrical resistance and lower electrical tissue impedance, most notably in patients with EoE (P less than .001 for both, compared with controls), the investigators reported. Proton pump inhibitor treatment partially reversed these changes in patients with PPRE but showed no effect for patients with EoE, they said. This finding suggests that acid reflux might play a role in PPRE, but not in EOE, they concluded.

Dr. Katzka and his associates disclosed no funding sources and reported having no conflicts of interest. Dr. Rhijn and his associates were supported by the Netherlands Organization for Scientific Research. Two of Dr. Rhijn’s coauthors reported financial relationships with AstraZeneca, Endostim, Medical Measurement Systems, Shire, and GlaxoSmithKline.