背景:非食道嗜酸性粒细胞性胃肠道疾病(非EoE-EGID)是一种罕见的疾病,其中嗜酸性粒细胞渗入食道以外的胃肠道部分;但是,近年来,非EoE-EGID患者的数量一直在增加.由于其反复复发的慢性过程,它可能会导致营养不良导致发育迟缓,尤其是儿科患者。没有针对非EoE-EGID的既定治疗方法,需要长期全身性皮质类固醇给药。虽然dupilumab的疗效,抗IL-4/13受体单克隆抗体,对于嗜酸性粒细胞性食管炎,据报道,只有少数报告证明其在非EoEEGID中的疗效.
方法:一个13岁的男孩发展为十二指肠溃疡的非EoE-EGID,以鸡蛋为扳机.他成功地接受了无鸡蛋饮食治疗,质子泵抑制剂,和白三烯受体拮抗剂.然而,15岁时,他出现了上腹痛恶化和进食困难。血液分析显示嗜酸性粒细胞增多;红细胞沉降率升高;C反应蛋白水平升高,总免疫球蛋白E,胸腺和活化调节趋化因子。上消化道内镜显示十二指肠溃疡伴明显的粘膜嗜酸性粒细胞浸润。胃肠道症状甚至在开始使用全身性类固醇后仍然存在,很难减少类固醇的剂量。由于特应性皮炎加重,开始皮下注射dupilumab。三个月后,胃肠道症状消失,5个月后,十二指肠溃疡消失,粘膜嗜酸性粒细胞计数减少。六个月后,全身性类固醇停药,十二指肠溃疡仍无复发。卵挑战测试结果为阴性;因此,停止无蛋饮食.dupilumab治疗后,血液嗜酸性粒细胞计数和血清IL-5,IL-13和eotaxin-3水平降低。血清IL-5和eotaxin-3水平保持在正常范围内,尽管口服泼尼松龙停药后血液嗜酸性粒细胞计数再次增加。
结论:dupilumab抑制IL-4R/IL-13R介导的信号传导可能会改善非EoE-EGID患者的腹部症状以及内镜和组织学表现,导致停止全身类固醇给药和对致病食物的耐受性。
BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few
reports have demonstrated its efficacy in non-EoE EGIDs.
METHODS: A 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.
CONCLUSIONS: Suppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.