An algorithm for the diagnosis and treatment of eosinophilic esophagitis in adults, 2024 update
Authors: Marc Pfefferlé, Thomas Greuter
Journal: Allergy (2024)

Eosinophilic esophagitis (EoE) is a chronic Th2-mediated inflammatory disease of the esophagus.1 Accurate and fast diagnosis together with an adequate and effective treatment is necessary to decrease symptoms, improve quality of life and prevent development of complications.2 Here, we provide an updated algorithm for diagnosing and treating EoE. EoE needs to be suspected in any individual with solid-food dysphagia. Patients should undergo esophagogastroduodenoscopy (EGD) irrespective of the presence or absence of risk factors for EoE (Figure 1). However, EoE has to be considered also in patients with a non-classical presentation (reflux, nausea-vomiting or burning sensation in the esophagus). Although endoscopic appearance of the esophagus judged by the EoE Endoscopic Reference Score (EREFS) can adequately predict the presence of EoE, proper diagnosis can only be established with the detection of at least 15 eosinophils per high power field in esophageal biopsies.3, 4 Given the patchy nature of the disease, at least five biopsies are needed (two–three biopsies from the distal and the proximal esophagus).5 The use of the EoE histological scoring system EoE-HSS is encouraged.6 Other conditions potentially associated with esophageal eosinophilia should be ruled out depending on clinical pre-test probability (Table S1). Non- or semi-invasive biomarkers are an unmet need in EoE management. At least, cytosponge and esophageal string tests have shown promising results, but did not make it into clinical practice. Assessment of esophageal distensibility by EndoFLIP is recommended when available, particularly in patients with suspected fibrosis. If clinical presentation suggests EoE, but eosinophilic infiltration is absent or low and the patient is not under anti-eosinophil treatment or diet, the diagnosis of an EoE variant needs to be considered. These variants include EoE-like esophagitis, lymphocytic esophagitis and non-specific esophagitis.7 Capturing EoE variants is important given the risk for progression to EoE over time.8 All therapeutic strategies in EoE aim at achieving clinical and histological remission and at preventing the development of complications. First-line treatments are PPI (with a potential role for potassium-competitive acid blockers, PCAB), topical corticosteroids (TCS, in Europe budesonide orodispersible tablet BOT 2 × 1 mg, in the US budesonide oral suspension 2 × 2 mg) and empirical elimination diet (Figure 2). The choice between PPI and TCS is made at the physician's discretion, although some countries require a PPI trial before TCS due to health insurance-related issues. For elimination diet, a step-wise approach is favored as it is less restrictive than a six-food elimination diet (FED).9 Of note, a simple 1-FED (dairy products) appears to be equally effective than a 6-FED.10 In severe cases, medication should probably be chosen over dietary approaches, although no clear evidence exists for this approach. Irrespective of the therapeutic strategy, response to treatment should be checked after 6–12 weeks with repeat EGD with esophageal biopsy sampling.11 When remission is achieved, anti-eosinophil treatment should be maintained. If inflammation is ongoing (in the absence of pseudorefractory disease, Table S2), the therapeutic regimen should be changed. There is no scientific evidence for combination therapy such as PPI + TCS or medication + diet. For treatment refractory patients, the anti IL4/13 antibody Dupilumab should be used.12 This therapy is also an appealing first-line option in case of intolerance/contraindications of PPI/TCS or presence of other Th2-mediated disease. If inflammation is controlled, but symptoms persist, presence of a fibrostenotic phenotype should be considered. Fibrosis can be suggested clinically (ongoing symptoms), endoscopically (presence of rings/strictures) or by using EndoFLIP. These patients benefit from gentle (repetitive) endoscopic dilations (until a diameter of 18 mm). There is no need for anti-inflammatory treatment before dilation if indicated, but EoE treatment should be established in all patients. Due the frequent discrepancy between clinical and histological disease activity, long-term follow-up with EGD every 1–2 years is recommended, even in the absence of ongoing symptoms.13 Given the chronicity of the disease, indefinite maintenance treatment is required in all patients and patients should be discouraged from stopping their treatment.14 This work was supported by grants from the Swiss National Science Foundation to TG (grant no. P2ZHP3_168561). This work was further supported by the Swiss EoE foundation, a young investigator award from the Swiss Society of Gastroenterology to TG, a research grant from the Novartis Foundation for Medical-Biological Research to TG, a research award from the Swiss IBDnet to TG, and a training grant from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) to TG. CEGIR (U54 AI117804) is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), and is funded through collaboration between the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and NCATS. CEGIR is also supported by patient advocacy groups including the American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Disease (CURED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). The work was further supported by grants from the Swiss EoE Foundation and the University of Zurich. TG has consulting contracts with Sanofi-Regeneron, Janssen, BMS, Takeda, Abbvie, and Falk Pharma GmbH, received travel grants from Falk Pharma GmbH, Abbvie, Takeda, and Vifor, speaker's fee from Norgine and an unrestricted research grant from Novartis. MP reports no conflicts of interest. No new data was generated for this article. Table S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.