Very early onset eosinophilic esophagitis is common, responds to standard therapy, and demonstrates enrichment for CAPN14 genetic variants

Lyles, John L.; Martin, Lisa J.; Shoda, Tetsuo; Collins, Margaret H.; Trimarchi, Michael; He, Hua; Kottyan, Leah C.; Mukkada, Vincent A.; Rothenberg, Marc E.

doi:10.1016/j.jaci.2020.10.017

Cited by 33 publications

(11 citation statements)

References 45 publications

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“…Increased expression of CAPN‐14 is induced by IL‐13, which leads to disruptive effects on the esophageal epithelium by impairment of barrier integrity in association with loss of DSG‐1 expression. 5 , 41 , 42 , 43 A retrospective study by Lyle et al 44 recently suggested CAPN‐14 genetic variants being associated with earlier disease onset in pediatric EoE. In addition to this, longstanding eosinophilic inflammation is associated with esophageal remodeling and stricture formation.…”

Section: Discussionmentioning

confidence: 99%

Gene expression and clinical outcomes after dietary treatment for eosinophilic esophagitis: a prospective study

Rooij

Diks

Warners

et al. 2022

Neurogastroenterology Motil

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Background: Eosinophilic esophagitis (EoE) is an allergen-mediated disease and elimination diets have proven to be effective to obtain clinical and histological remission.However, the effect of elimination diets on specific EoE transcripts and their clinical correlates is relatively unknown. The main aim of the study was to evaluate the effect of dietary treatment (four-food elimination diet [FFED]) with or without addition of amino acid-based formula (AAF) on a variety of pro-/anti-inflammatory, epithelial/ barrier function and remodeling/fibrosis-related markers of disease activity and clinical correlates (eosinophils, symptoms, and endoscopic signs) in adult EoE patients. Methods:We conducted an analysis of biopsy samples and data collected during a randomized controlled trial with an elimination diet in adult patients with active EoE (≥15 eosinophils [eos] per high-power field [hpf]). Demographics, symptoms (SDIscore), endoscopic signs (EREFS) and peak eosinophil counts/hpf were recorded at baseline and after 6 weeks of treatment. Transcripts of 10 indicated genes were measured (qPCR) and compared to clinical correlates at baseline and after treatment. Key Results: Forty patients (pooled FFED + FFED + AAF) (60% male, age 34.5 (interquartile range [IQR] 29-42.8 years) completed the diet. Peak eosinophil counts/ hpf, symptoms and endoscopic signs were significantly decreased after 6 weeks dietary treatment. DSG-1 levels were significantly upregulated from baseline to week 6, whereas IL-13, CAPN-14, IL-5, IL-10, CCL-26, POSTN, TSLP, CPA-3, and TGFβ were significantly downregulated after 6 weeks of diet (all; <0.01). Prior to treatment, upregulation of CAPN-14 and lower levels of DSG-1 were associated with clinical fibrotic phenotypes, whereas upregulation of IL-10 was linked to food impaction phenotypes. Conclusion:These findings strongly suggest that elimination diets, besides a clinical and histological response, are associated with a broad transcriptional response at the level of the esophageal epithelium.How to cite this article: de Rooij WE, Diks MAP, Warners MJ, Ampting MTJV, van Esch BCAM, Bredenoord AJ. Gene expression and clinical outcomes after dietary treatment for eosinophilic esophagitis: a prospective study.

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Section: Discussionmentioning

confidence: 99%

Gene expression and clinical outcomes after dietary treatment for eosinophilic esophagitis: a prospective study

Rooij

Diks

Warners

et al. 2022

Neurogastroenterology Motil

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“…However, LD residue on clothing could be particularly hazardous to newborns, whose pH is already high, ranging from 6.3 to 7.5 [ 101 ], the skin barrier more fragile, and whose immature immune system is more vulnerable to dysregulation from exposure to microbial protases and other LD ingredients. Indeed, very early onset of EoE in the first year of life is a common presentation [ 102 ]. A prophylactic daily moisturization until 6 months of age prevents AD in high-risk newborns, suggesting that skin hydration in this critical time may have a protective effect [ 103 ].…”

Section: Discussionmentioning

confidence: 99%

Laundry detergent promotes allergic skin inflammation and esophageal eosinophilia in mice

et al. 2022

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The prevalence of allergic diseases is on the rise, yet the environmental factors that contribute to this increase are still being elucidated. Laundry detergent (LD) that contains cytotoxic ingredients including microbial enzymes continuously comes into contact with the skin starting in infancy. An impaired skin barrier has been suggested as a route of allergic sensitization. We hypothesized that exposure of skin to LD damages the skin barrier resulting in systemic sensitization to allergens that enter through the impaired skin barrier. Mouse skin samples exposed in vitro to microbial proteases or LD exhibited physical damage, which was more pronounced in neonatal skin as compared to adult skin. Exposure of the skin to microbial proteases in vitro resulted in an increase in the levels of interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). BALB/c wild type mice epicutaneously exposed to LD and ovalbumin (OVA) showed an increase in levels of transepidermal water loss, serum OVA-specific immunoglobulin (Ig) G1 and IgE antibodies, and a local increase of Il33, Tslp, Il4 and Il13 compared with LD or OVA alone. Following intranasal challenge with OVA, mice epicutaneously exposed to LD showed an increase in allergen-induced esophageal eosinophilia compared with LD or OVA alone. Collectively, these results suggest that LD may be an important factor that impairs the skin barrier and leads to allergen sensitization in early life, and therefore may have a role in the increase in allergic disease.

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“…Another genetic risk factor is the expression of calpain 14 (CAPN14), which is a calcium-activated intracellular regulatory protease that is overexpressed in esophageal epithelial cells in EoE [ 28 , 29 ]. Its expression is also higher following the exposure of the esophageal epithelial progenitor cell line to IL-13 (100 ng/mL) [ 28 ].…”

Section: Eoe Risk Factorsmentioning

confidence: 99%

Eosinophilic Esophagitis—What Do We Know So Far?

Wąsik

Małecka-Wojciesko

2023

JCM

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Eosinophilic esophagitis is a Th-2 antigen-mediated disease in which there is an influx of eosinophils to all layers of the esophagus, triggering an inflammatory response. Chronic inflammatory process causes esophageal remodeling, leading to difficulties in swallowing. Food impaction, heartburn, and chest pain are other characteristic (but not pathognomonic) symptoms in adults. Although the disease has only been described since in the early 1970s, its incidence and prevalence are rapidly growing, especially in Western countries. According to the diagnostic guidelines, there should be at least 15 eosinophils visible per high-power field in biopsies obtained from different sites in the esophagus upon endoscopy with relevant esophageal symptoms. Other diseases that can cause esophageal eosinophilia should be ruled out. Eosinophilic esophagitis treatment may be challenging; however, new methods of management have recently emerged. The currently used proton pump inhibitors, topical corticosteroids, and elimination diet are combined with biological treatment. New methods for disease diagnostics and clinical course assessment are also available. This review presents current knowledge about the disease, supported by the latest research data.

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Very early onset eosinophilic esophagitis is common, responds to standard therapy, and demonstrates enrichment for CAPN14 genetic variants

Cited by 33 publications

References 45 publications

Gene expression and clinical outcomes after dietary treatment for eosinophilic esophagitis: a prospective study

Gene expression and clinical outcomes after dietary treatment for eosinophilic esophagitis: a prospective study

Laundry detergent promotes allergic skin inflammation and esophageal eosinophilia in mice

Eosinophilic Esophagitis—What Do We Know So Far?

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