Dupilumab for STAT3-Hyper-IgE Syndrome With Refractory Intestinal Complication
Dupilumab for STAT3-Hyper-IgE Syndrome With Refractory Intestinal Complication
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DOI：
10.1542/peds.2021-050351
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发表时间：
2021-09-01
期刊：
影响因子：
8
通讯作者：
Chung, Wen-Hung
中科院分区：
文献类型：
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作者：
Lu, Chun-Wei;Lee, Wen-, I;Chung, Wen-Hung
STAT3 高免疫球蛋白 E 综合征 (STAT3-HIES) 是一种罕见的原发性免疫缺陷综合征，其特征是血清免疫球蛋白 E 水平升高、湿疹、反复皮肤和呼吸道感染以及多种胃肠道 (GI) 问题。 60% 的患者有胃肠道表现，如胃食管反流病、吞咽困难、腹痛、肠道运动障碍、肠穿孔、嗜酸性食管炎和腹泻。到目前为止，还没有有效的治疗方法可以有效控制该综合征的各个方面。在本报告中，我们介绍了一名 21 岁男性的病例，尽管他从 2 岁起就接受了积极的抗生素和类固醇治疗，但仍患有无法检测到的致病性难治性腹泻，该腹泻持续超过 21 天。通过二代测序诊断出STAT3 Int10(-2)A > G剪接突变引起的STAT3-HIES。患者自10岁起就反复出现肠道和结肠穿孔。他接受了多次手术和连续全身静脉注射免疫球蛋白治疗来控制胃肠道症状。然而，每天发生超过5至6次的顽固性腹泻、严重的湿疹性皮炎和频繁形成的脓肿仍然威胁着他的生命。每三周服用 300 毫克 Dupilumab 来控制他的皮肤问题，但患者的腹泻也完全消退。因此，dupilumab 似乎不仅可以有效治疗皮肤炎症，还可以有效治疗传统免疫调节剂难治的 STAT3-HIES 胃肠道表现相关炎症。
STAT3 hyper-immunoglobulin E syndrome (STAT3-HIES) is a rare primary immunodeficiency syndrome characterized by elevated serum immunoglobulin E levels, eczema, recurrent skin and respiratory tract infections, and several gastrointestinal (GI) problems. GI manifestations, such as gastroesophageal reflux disease, dysphagia, abdominal pain, gut dysmotility, bowel perforation, eosinophilic esophagitis, and diarrhea, have been reported in 60% of patients. Until now, there was no efficient treatment that could effectively manage all aspects of the syndrome. In this report, we present the case of a 21-year-old man who suffered from undetectable pathogenic refractory diarrhea that persisted >21 days despite aggressive antibiotic and steroid treatment since he was 2 years old. STAT3 Int10(-2)A > G splicing mutation-caused STAT3-HIES was diagnosed by next-generation sequencing. The patient had suffered recurrent intestinal and colon perforations since he was 10 years old. He had received multiple surgeries and continuous systemic intravenous immunoglobulin therapy to manage his GI symptoms. However, refractory diarrhea occurring >5 to 6 times per day with severe eczematous dermatitis and frequent abscess formation remained threats to his life. Dupilumab 300 mg every 3 weeks was prescribed to control his skin problems, but the patient's diarrhea also completely subsided. As such, it appears that dupilumab may not only effectively treat the skin inflammation but also the GI manifestation-related inflammation of STAT3-HIES refractory to traditional immunomodulators.