Allergy testing in eosinophilic esophagitis
- Jonathan M Spergel, MD, PhD, FAAAAI
Jonathan M Spergel, MD, PhD, FAAAAI
- Professor of Pediatrics
- University of Pennsylvania School of Medicine
Eosinophilic esophagitis (EoE) was defined by a panel of experts as "a chronic, immune/antigen-mediated, esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation" . Allergy testing in EoE is warranted to identify and manage common comorbid atopic diseases (eg, asthma, allergic rhinitis) and to determine foods that may present a risk for acute allergic reactions/immediate-type allergy (this is a concern for many patients with EoE at baseline and also when eliminated foods are potentially reintroduced into the diet during treatment). It may also help identify EoE triggers.
The evidence supporting the role of allergies in EoE and the various types of allergy testing used are reviewed here. Other aspects of disease pathogenesis, clinical manifestations, general diagnostic evaluation, and treatment (including choosing a specific elimination diet) are reviewed separately. (See "Clinical manifestations and diagnosis of eosinophilic esophagitis" and "Treatment of eosinophilic esophagitis" and "Dietary management of eosinophilic esophagitis" and "Patient education: Eosinophilic esophagitis (The Basics)".)
EVIDENCE FOR ROLE OF ALLERGIES IN EoE
Several lines of evidence suggest that allergies play a significant role in EoE. An immune response to allergen/antigen is a primary factor in the pathogenesis of the disease, and there is evidence that both environmental allergies and food allergies are involved. In addition, the majority of patients with EoE are atopic, with asthma, allergic rhinitis, atopic dermatitis, and/or immunoglobulin E (IgE)-mediated food allergy.
Mechanistic studies — Evidence for allergies in EoE is supported by murine models that show that skin sensitization protocols can induce eosinophilic inflammation in the esophagus when that organ is challenged [2-4]. In addition, examination of esophageal samples has indicated that classic allergic cytokines and chemokines (interleukin [IL]-4, IL-5, IL-13, eotaxin-3) are involved in the pathogenesis of EoE [1,4-7]. Additional details on the pathogenesis of EoE are discussed separately. (See "Eosinophilic esophagitis (EoE): Genetics and immunopathogenesis", section on 'Pathogenesis'.)
Clinical response to dietary changes — The evidence for the role of food allergies in the pathogenesis of EoE is based upon the clinical response when patients are placed on various elimination diets, with resolution of symptoms and normalization of esophageal biopsies. The data are equally extensive and convincing in children and adults. This evidence is discussed in detail separately. (See "Dietary management of eosinophilic esophagitis", section on 'Role of food allergy in EoE'.)
- Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011; 128:3.
- Akei HS, Mishra A, Blanchard C, Rothenberg ME. Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology 2005; 129:985.
- Mondoulet L, Dioszeghy V, Larcher T, et al. Epicutaneous immunotherapy (EPIT) blocks the allergic esophago-gastro-enteropathy induced by sustained oral exposure to peanuts in sensitized mice. PLoS One 2012; 7:e31967.
- Mishra A, Wang M, Pemmaraju VR, et al. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology 2008; 134:204.
- Zhu X, Wang M, Mavi P, et al. Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice. Gastroenterology 2010; 139:182.
- Blanchard C, Mingler MK, Vicario M, et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol 2007; 120:1292.
- Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest 2006; 116:536.
- Ram G, Lee J, Ott M, et al. Seasonal exacerbation of esophageal eosinophilia in children with eosinophilic esophagitis and allergic rhinitis. Ann Allergy Asthma Immunol 2015; 115:224.
- Moawad FJ, Veerappan GR, Lake JM, et al. Correlation between eosinophilic oesophagitis and aeroallergens. Aliment Pharmacol Ther 2010; 31:509.
- Almansa C, Krishna M, Buchner AM, et al. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol 2009; 104:828.
- Wang FY, Gupta SK, Fitzgerald JF. Is there a seasonal variation in the incidence or intensity of allergic eosinophilic esophagitis in newly diagnosed children? J Clin Gastroenterol 2007; 41:451.
- Magnusson J, Lin XP, Dahlman-Höglund A, et al. Seasonal intestinal inflammation in patients with birch pollen allergy. J Allergy Clin Immunol 2003; 112:45.
- Onbasi K, Sin AZ, Doganavsargil B, et al. Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season. Clin Exp Allergy 2005; 35:1423.
- Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. J Allergy Clin Immunol 2003; 112:796.
- Spergel J, University of Pennsylvania School of Medicine, 2012, personal communication.
- Sugnanam KK, Collins JT, Smith PK, et al. Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis. Allergy 2007; 62:1257.
- Assa'ad AH, Putnam PE, Collins MH, et al. Pediatric patients with eosinophilic esophagitis: an 8-year follow-up. J Allergy Clin Immunol 2007; 119:731.
- Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007; 133:1342.
- Plaza-Martín AM, Jiménez-Feijoo R, Andaluz C, et al. Polysensitization to aeroallergens and food in eosinophilic esophagitis in a pediatric population. Allergol Immunopathol (Madr) 2007; 35:35.
- Spergel JM, Brown-Whitehorn TF, Beausoleil JL, et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J Pediatr Gastroenterol Nutr 2009; 48:30.
- Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005; 3:1198.
- Guajardo JR, Plotnick LM, Fende JM, et al. Eosinophil-associated gastrointestinal disorders: a world-wide-web based registry. J Pediatr 2002; 141:576.
- Arora AA, Weiler CR, Katzka DA. Eosinophilic esophagitis: allergic contribution, testing, and management. Curr Gastroenterol Rep 2012; 14:206.
- Roy-Ghanta S, Larosa DF, Katzka DA. Atopic characteristics of adult patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol 2008; 6:531.
- Kapel RC, Miller JK, Torres C, et al. Eosinophilic esophagitis: a prevalent disease in the United States that affects all age groups. Gastroenterology 2008; 134:1316.
- Ronkainen J, Talley NJ, Aro P, et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study. Gut 2007; 56:615.
- Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to treatment with fluticasone propionate. Gastrointest Endosc 2006; 63:3.
- Mahdavinia M, Bishehsari F, Hayat W, et al. Association of eosinophilic esophagitis and food pollen allergy syndrome. Ann Allergy Asthma Immunol 2017; 118:116.
- Alsalamah M, Makhajia M, Somers G, et al. Anaphylaxis to Milk After Elimination Diet for Eosinophilic Gastrointestinal Disease. Am J Gastroenterol 2016; 111:752.
- Spergel JM, Brown-Whitehorn T, Beausoleil JL, et al. Predictive values for skin prick test and atopy patch test for eosinophilic esophagitis. J Allergy Clin Immunol 2007; 119:509.
- Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol 2002; 109:363.
- Spergel JM, Brown-Whitehorn TF, Cianferoni A, et al. Identification of causative foods in children with eosinophilic esophagitis treated with an elimination diet. J Allergy Clin Immunol 2012; 130:461.
- Gonsalves N, Yang GY, Doerfler B, et al. Elimination diet effectively treats eosinophilic esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology 2012; 142:1451.
- Simon D, Straumann A, Wenk A, et al. Eosinophilic esophagitis in adults--no clinical relevance of wheat and rye sensitizations. Allergy 2006; 61:1480.
- Molina-Infante J, Martin-Noguerol E, Alvarado-Arenas M, et al. Selective elimination diet based on skin testing has suboptimal efficacy for adult eosinophilic esophagitis. J Allergy Clin Immunol 2012; 130:1200.
- Erwin EA, James HR, Gutekunst HM, et al. Serum IgE measurement and detection of food allergy in pediatric patients with eosinophilic esophagitis. Ann Allergy Asthma Immunol 2010; 104:496.
- Lucendo AJ, Arias A, Tenías JM, et al. Serum IgE-targeted elimination diets for treating eosinophilic esophagitis: things are not what they seem. Allergy 2014; 69:1567.
- van Rhijn BD, Vlieg-Boerstra BJ, Versteeg SA, et al. Evaluation of allergen-microarray-guided dietary intervention as treatment of eosinophilic esophagitis. J Allergy Clin Immunol 2015; 136:1095.
- Erwin EA, Kruszewski PG, Russo JM, et al. IgE antibodies and response to cow's milk elimination diet in pediatric eosinophilic esophagitis. J Allergy Clin Immunol 2016; 138:625.
- Wright BL, Kulis M, Guo R, et al. Food-specific IgG4 is associated with eosinophilic esophagitis. J Allergy Clin Immunol 2016; 138:1190.
- Heine RG, Verstege A, Mehl A, et al. Proposal for a standardized interpretation of the atopy patch test in children with atopic dermatitis and suspected food allergy. Pediatr Allergy Immunol 2006; 17:213.
- Spergel JM, Andrews T, Brown-Whitehorn TF, et al. Treatment of eosinophilic esophagitis with specific food elimination diet directed by a combination of skin prick and patch tests. Ann Allergy Asthma Immunol 2005; 95:336.
- Henderson CJ, Abonia JP, King EC, et al. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis. J Allergy Clin Immunol 2012; 129:1570.
- Molina-Infante J, Arias A, Barrio J, et al. Four-food group elimination diet for adult eosinophilic esophagitis: A prospective multicenter study. J Allergy Clin Immunol 2014; 134:1093.
- EVIDENCE FOR ROLE OF ALLERGIES IN EoE
- Mechanistic studies
- Clinical response to dietary changes
- Association with environmental allergies
- Atopic history
- FOOD ALLERGY TESTING IN EoE
- Skin prick testing
- Specific IgE testing
- Atopy patch testing
- Skin prick and atopy patch testing
- ENVIRONMENTAL ALLERGY TESTING IN EoE
- OUR APPROACH
- SUMMARY AND RECOMMENDATIONS