University of North Carolina, Chapel Hill, North Carolina.
Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Clin Gastroenterol Hepatol. 2022 Mar;20(3):535-545.e15. doi: 10.1016/j.cgh.2021.05.053. Epub 2021 Jun 2.
BACKGROUND & AIMS: Eosinophilic gastritis (EG) and eosinophilic duodenitis (EoD), characterized by chronic gastrointestinal (GI) symptoms and increased numbers or activation of eosinophils and mast cells in the GI tract, are likely underdiagnosed. We aimed to determine rates of EG and EoD and number of biopsies required to optimize detection using screening data from a randomized trial of lirentelimab (AK002), an antibody against siglec-8 that depletes eosinophils and inhibits mast cells. We also characterized endoscopic features and symptoms of EG and EoD.
Subjects with moderate-to-severe GI symptoms, assessed daily through a validated patient-reported outcome questionnaire, underwent endoscopy with a systematic gastric and duodenal biopsy protocol and histopathologic evaluation. EG diagnosis required presence of ≥30 eosinophils/high-power field (eos/hpf) in ≥5 hpfs and EoD required ≥30 eos/hpf in ≥3 hpfs. We analyzed diagnostic yields for EG and EoD and histologic, endoscopic, and clinical findings.
Of 88 subjects meeting symptom criteria, 72 were found to have EG and/or EoD (EG/EoD), including patients with no prior diagnosis of EG/EoD. We found that GI eosinophilia was patchy and that examination of multiple biopsies was required for diagnosis-an average of only 2.6 per 8 gastric biopsies and 2.2 per 4 duodenal biopsies per subject met thresholds for EG/EoD. Evaluation of multiple nonoverlapping hpfs in each of 8 gastric and 4 duodenal biopsies was required to capture 100% of EG/EoD cases. Neither endoscopic findings nor symptom severity correlated with eosinophil counts.
In an analysis of patients with moderate-to-severe GI symptoms participating in a clinical trial of lirentelimab for EG/EoD, we found eosinophilia to be patchy in gastric and duodenal biopsies. Counting eosinophils in at least 8 gastric and 4 duodenal biopsies is required to identify patients with EG/EoD, so they can receive appropriate treatment. (ClinicalTrials.gov, Number: NCT03496571).
嗜酸粒细胞性胃炎（EG）和嗜酸粒细胞性十二指肠炎（EoD）的特征是慢性胃肠道（GI）症状和胃肠道中嗜酸性粒细胞和肥大细胞数量增加或激活，这些疾病可能诊断不足。我们旨在通过 lirentelimab（AK002）的一项随机试验的筛查数据来确定 EG 和 EoD 的发生率以及需要进行多少活检以优化检测，lirentelimab 是一种针对 siglec-8 的抗体，可耗尽嗜酸性粒细胞并抑制肥大细胞。我们还描述了 EG 和 EoD 的内镜特征和症状。
具有中度至重度 GI 症状的受试者，通过经过验证的患者报告结局问卷每天进行评估，接受内镜检查，并进行系统的胃和十二指肠活检以及组织病理学评估。EG 的诊断需要在≥5 个高倍视野（hpf）中至少有≥30 个嗜酸性粒细胞/高倍视野（eos/hpf），EoD 需要在≥3 个 hpf 中至少有≥30 eos/hpf。我们分析了 EG 和 EoD 的诊断收益以及组织学、内镜和临床发现。
在符合症状标准的 88 名受试者中，有 72 名被发现患有 EG 和/或 EoD（EG/EoD），其中包括以前没有 EG/EoD 诊断的患者。我们发现胃肠道嗜酸性粒细胞增多是斑片状的，需要检查多个活检才能诊断-每个受试者平均只有 2.6 个胃活检和 2.2 个十二指肠活检符合 EG/EoD 的标准。需要评估每个受试者的 8 个胃活检和 4 个十二指肠活检中的多个非重叠 hpf，才能捕获 100%的 EG/EoD 病例。内镜检查结果和症状严重程度均与嗜酸性粒细胞计数无关。
在一项针对 lirentelimab 治疗 EG/EoD 的临床试验中，我们对有中度至重度 GI 症状的患者进行了分析，发现胃和十二指肠活检中的嗜酸性粒细胞增多是斑片状的。至少检查 8 个胃活检和 4 个十二指肠活检以识别 EG/EoD 患者，以便他们可以接受适当的治疗。（临床试验.gov，编号：NCT03496571）。
