目的:别嘌呤醇引起的药物反应伴嗜酸性粒细胞增多和全身症状(DRESS)是一种罕见但严重且可能危及生命的药物超敏反应综合征。在这项研究中,我们的目的是调查临床特征,治疗结果,以及别嘌呤醇诱导DRESS的预后因素。
方法:检索中国2000年1月至2021年8月发表的别嘌醇致DRESS病例报告。万芳,VIP,和PubMed数据库进行分析。
结论:本研究包括52例患者,由41名(78.8%)男性和11名(21.2%)女性组成(M:F=3.7:1)。平均年龄为56.1±17.1岁(范围:18-86岁)。平均潜伏期为24.6±15.0天(范围:1-63天)。大多数患者出现发烧,皮肤喷发,嗜酸性粒细胞增多,淋巴结病,和面部水肿。36/52(69.2%)患者显示两个或多个内脏器官受累。肝脏和肾脏损伤是最常见的内脏表现。肺部受累(34.6%),心脏受累(25.0%)和胃肠道受累(21.2%)是相对鲜为人知但严重的并发症.2/52(3.8%)患者表现出神经系统受累,表现为白质脑病或周围神经病变。2/52(3.8%)患者出现继发性噬血细胞淋巴组织细胞增多。1/52(1.9%)患者发生纯红细胞再生障碍性贫血,1/52(1.9%)患者发生无痛性甲状腺炎。在18/52(34.6%)患者中测试了HLA*B58:01等位基因。16/18(88.9%)例阳性。48/52(92.3%)患者接受全身性糖皮质激素治疗。16/52(30.8%)患者治愈,23/52(44.2%)患者部分康复,13/52(25.0%)患者死亡。感染性休克,消化道出血和多器官功能衰竭是死亡的主要原因。高龄,潜在的心血管疾病,慢性肾脏病和高剂量别嘌呤醇,感染和内脏器官受累(包括肾脏,心,肺和胃肠道)是死亡的危险因素。
结论:我们探索了临床特征,中国52例别嘌醇诱导的DRESS患者的治疗结果和预后因素。种族,尤其是汉族,HLA-B*58:01等位基因阳性是迄今为止最明显的危险因素。高龄,潜在的心血管疾病,慢性肾脏病和高剂量别嘌呤醇,感染和内脏器官受累(包括肾脏,心,肺和胃肠道)与较差的预后相关。早期识别和停药对DRESS的管理至关重要。对于患有严重疾病的患者,推荐使用皮质类固醇作为一线治疗.然而,需要进一步的研究来解决DRESS早期诊断的诊断标准,以及制定标准化的皮质类固醇治疗方案。
OBJECTIVE: Allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious and potentially life-threatening drug hypersensitivity syndrome. In this study, we aimed to investigate the clinical features, treatment outcomes, and prognostic factors of allopurinol-induced DRESS.
METHODS: Case reports of allopurinol-induced DRESS published by
China from January 2000 to August 2021 were retrieved from CNKI, Wan Fang, VIP, and PubMed databases for analysis.
CONCLUSIONS: This study included 52 patients, consisting of 41 (78.8%) males and 11 (21.2%) females (M:F = 3.7:1). The mean of age was 56.1 ± 17.1 years (range: 18-86 years). The mean of latency periods was 24.6 ± 15.0 days (range:1-63 days). Most patients presented with fever, cutaneous eruption, eosinophilia, lymphadenopathy, and facial edema. 36/52 (69.2%) patients showed two or more internal organs involved. Liver and kidney injuries were the most common visceral manifestation. Pulmonary involvement (34.6%), cardiac involvement (25.0%) and gastrointestinal involvement (21.2%) were relatively less known but severe complications. 2/52 (3.8%) patients showed nervous system involved, presenting as leukoencephalopathy or peripheral neuropathy. 2/52 (3.8%) patients presented with secondary hemophagocytic lymphohistiocytosis.1/52 (1.9%) patient developed pure red cell aplasia and 1/52 (1.9%) patient developed painless thyroiditis. HLA*B 58:01 allele was tested in 18/52 (34.6%) patients. 16/18 (88.9%) cases were positive. 48/52 (92.3%) patients were treated with systemic corticosteroids. 16/52 (30.8%) patients were cured, 23/52 (44.2%) patients received partial recovery, and 13/52 (25.0%) patients were died. Septic shock, gastrointestinal bleeding and multiple organ failure were the leading causes of death. Advanced age, underlying cardiovascular disease, chronic kidney disease and high dose of allopurinol, infection and internal organ involvement (including kidney, heart, lung and gastrointestinal tract) were risk factors for death.
CONCLUSIONS: We explored clinical features, treatment outcomes and prognostic factors of 52 allopurinol-induced DRESS cases in
China. Ethnicity, especially Han Chinese, and positive HLA-B*58:01 allele are the clearest risk factors so far. Advanced age, underlying cardiovascular disease, chronic kidney disease and high dose of allopurinol, infection and internal organ involvement (including kidney, heart, lung and gastrointestinal tract) were associated with poorer outcomes. Early identification and discontinuation of the causative drug are crucial to the management of DRESS. For patients with severe disease, corticosteroids are recommended as the first-line therapy. However, further studies are needed to address diagnostic criteria of DRESS for early diagnosis, as well as to develop standardized corticosteroid treatment regimens.