Department of Nephrology, Key Laboratory of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Ministry of Health and Guangdong Province, Guangzhou, P.R. China.
Department of Nephrology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P.R. China.
J Clin Pharm Ther. 2022 Sep;47(9):1368-1378. doi: 10.1111/jcpt.13667. Epub 2022 Aug 16.
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.
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.
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.
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.
别嘌醇诱导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潜在危及生命的药物超敏综合征。本研究旨在探讨别嘌醇诱导的 DRESS 的临床特征、治疗结局和预后因素。
从中国知网、万方、维普和 PubMed 数据库中检索 2000 年 1 月至 2021 年 8 月期间发表的别嘌醇诱导的 DRESS 的病例报告进行分析。
本研究共纳入 52 例患者，其中男 41 例（78.8%），女 11 例（21.2%）（M:F=3.7:1）。平均年龄为 56.1±17.1 岁（范围：18-86 岁）。潜伏期的平均时间为 24.6±15.0 天（范围：1-63 天）。大多数患者表现为发热、皮疹、嗜酸性粒细胞增多、淋巴结肿大和面部水肿。36/52（69.2%）例患者有两个或两个以上的内脏器官受累。肝和肾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%）相对较少但较严重的并发症。2/52（3.8%）例患者出现神经系统受累，表现为白质脑病或周围神经病。2/52（3.8%）例患者出现继发性噬血细胞性淋巴组织细胞增生症。1/52（1.9%）例患者出现纯红细胞再生障碍，1/52（1.9%）例患者出现无痛性甲状腺炎。在 18/52（34.6%）例患者中检测了 HLA*B 58:01 等位基因。16/18（88.9%）例为阳性。48/52（92.3%）例患者接受全身皮质类固醇治疗。16/52（30.8%）例患者治愈，23/52（44.2%）例患者部分恢复，13/52（25.0%）例患者死亡。感染性休克、胃肠道出血和多器官功能衰竭是导致死亡的主要原因。高龄、基础心血管疾病、慢性肾脏病和别嘌醇高剂量、感染和内脏器官受累（包括肾脏、心脏、肺和胃肠道）是死亡的危险因素。
我们探讨了中国 52 例别嘌醇诱导的 DRESS 病例的临床特征、治疗结局和预后因素。种族，特别是汉族和 HLA-B*58:01 等位基因阳性是迄今为止最明确的危险因素。高龄、基础心血管疾病、慢性肾脏病和别嘌醇高剂量、感染和内脏器官受累（包括肾脏、心脏、肺和胃肠道）与不良结局相关。早期识别和停用致病药物是 DRESS 管理的关键。对于严重疾病患者，建议使用皮质类固醇作为一线治疗。然而，仍需要进一步的研究来制定 DRESS 的早期诊断的诊断标准，并制定标准化的皮质类固醇治疗方案。
