Gastrointestinal adverse events are common during oral immunotherapy (OIT) for food allergy and range from immediate IgE-mediated reactions to non-anaphylactic clinical presentations. This review aims to summarize recent findings on non-anaphylactic eosinophil-associated gastrointestinal adverse events during OIT. Two clinical presentations of non-anaphylactic eosinophil-associated gastrointestinal adverse events during OIT are identified, each with a different paradigm for treatment, and distinguished by their time of onset. In the first clinical entity, characterized by its onset early in the course of treatment, patients present with abdominal pain, nausea, and/or vomiting. The symptoms become evident typically within weeks to months of starting OIT. These symptoms, however, are not temporally related to the time of dose administration, as in the case of immediate IgE-mediated anaphylactic reactions. While esophageal biopsies, when performed, can demonstrate eosinophilic esophagitis (EoE), baseline esophageal eosinophilia has also been observed in food allergic patients prior to OIT. A potential non-invasive biomarker, the peripheral absolute eosinophil count (AEC), often rises during these reactions and subsides after dose reduction and subsequent resolution of symptoms. OIT can usually then be resumed, albeit at a slower pace, without a recurrence of symptoms. Risk factors for development of symptoms early during OIT include a high starting dose and a baseline AEC of greater than 600. The second, and much less frequently encountered, non-anaphylactic gastrointestinal adverse event related to OIT, presents months to years after initiating OIT. In this latter group, patients present with the classical clinical symptoms and endoscopic findings of EoE. In contrast to the acute onset group, peripheral eosinophilia is usually not observed in these cases. This OIT-associated EoE has shown good response to standard EoE treatment approaches of proton pump inhibitors or swallowed steroids. Most patients with eosinophil-associated adverse reactions are able to continue OIT and remain desensitized. Treatment approaches depend on the specific subtype of these reactions and relate to the stages of OIT treatment.

胃肠道不良事件在食物过敏的口服免疫治疗 (OIT) 过程中很常见，范围从直接 IgE 介导的反应到非过敏性临床表现。本综述旨在总结 OIT 期间非过敏性嗜酸性粒细胞相关胃肠道不良事件的最新发现。确定了 OIT 期间非过敏性嗜酸性粒细胞相关胃肠道不良事件的两种临床表现，每种都有不同的治疗模式，并根据发病时间进行区分。在第一个临床实体中，其特征是在治疗过程的早期发作，患者出现腹痛、恶心和/或呕吐。这些症状通常在开始 OIT 后数周至数月内变得明显。然而，这些症状在时间上与给药时间无关，就像 IgE 介导的即时过敏反应一样。虽然食管活检可以证实嗜酸性粒细胞性食管炎 (EoE)，但在 OIT 之前的食物过敏患者中也观察到基线食管嗜酸性粒细胞增多。外周绝对嗜酸性粒细胞计数（AEC）是一种潜在的非侵入性生物标志物，在这些反应期间通常会上升，并在剂量减少和症状缓解后消退。然后通常可以恢复 OIT，尽管速度较慢，并且症状不会复发。OIT 早期出现症状的危险因素包括高起始剂量和大于 600 的基线 AEC。第二种与 OIT 相关的非过敏性胃肠道不良事件（较少遇到）在开始 OIT 后数月至数年出现。在后一组中，患者出现 EoE 的典型临床症状和内镜检查结果。与急性发病组相反，在这些病例中通常观察不到外周嗜酸性粒细胞增多。这种与 OIT 相关的 EoE 对质子泵抑制剂或吞咽类固醇的标准 EoE 治疗方法显示出良好的反应。大多数出现嗜酸性粒细胞相关不良反应的患者能够继续 OIT 并保持脱敏。治疗方法取决于这些反应的具体亚型，并与 OIT 治疗的阶段相关。