Andrès Emmanuel, Mourot-Cottet Rachel, Maloisel Frédéric, Séverac François, Keller Olivier, Vogel Thomas, Tebacher Martine, Weber Jean-Christophe, Kaltenbach Georges, Gottenberg Jacques-Eric, Goichot Bernard, Sibilia Jean, Korganow Anne-Sophie, Herbrecht Raoul
Departments of Internal medicine.
Onco-hematology.
QJM. 2017 May;110(5):299-305. doi: 10.1093/qjmed/hcw220. Epub 2017 Jan 9.
Few data is currently available on neutropenia and agranulocytosis related to drug intake. We report here data on 203 patients with established idiosyncratic drug-induced agranulocytosis, followed up in a referral centre within a university hospital.
Data from 203 patients with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis in the Strasbourg University Hospital (Strasbourg, France) RESULTS: : The mean age was 61.6 years old (range: 18-95), the gender ratio (F/M) was 1.3. Several comorbidities were present in 63.5%. The most frequent causative drugs were: antibiotics (49.3%), especially ß-lactams and cotrimoxazole; antithyroid drugs (16.7%); neuroleptic and anti-epileptic agents (11.8%); antiviral agents (7.9%); and platelet aggregation inhibitors as ticlopidine and acid acetylsalicylic (6.9%). The main primary clinical manifestations during hospitalization included: isolated fever (26.3%); septicaemia (13.9%); documented pneumonia (13.4%); sore throat and acute tonsillitis (9.3%); and septic shock (6.7%). The mean neutrophil count at nadir was 0.148 x 10/L (range: 0-0.48). All febrile patients were treated with broad-spectrum antibiotics and 107 (52.7%) with hematopoietic growth factors. The mean duration of haematological recovery (neutrophil count ≥1.5 x 10/L) was 7.8 (range: 2-20). This mean duration was reduced to 2.1 days (range: 2-16) (p = 0.057) with hematopoietic growth factors. Outcome was favourable in 91.6% of patients; seventeen died. Thirty-seven patients (18.2%) required intensive care.
The present study demonstrated that idiosyncratic drug-induced agranulocytosis is a relative rare events; that antibiotics, antithyroid, neuroleptic and anti-epileptic agents, and platelet aggregation inhibitors are the main incriminated drug classes; that agranulocytosis typically serious, with at least 50% exhibiting severe sepsis and a mortality rate <10%; and that modern management of such disorder may reduce the infection-related mortality.
目前关于药物摄入相关的中性粒细胞减少症和粒细胞缺乏症的数据很少。我们在此报告203例确诊为特异质性药物性粒细胞缺乏症患者的数据，这些患者在一家大学医院的转诊中心接受随访。
对203例特异质性药物性粒细胞缺乏症患者的数据进行回顾性分析。所有病例均来自法国斯特拉斯堡大学医院关于粒细胞缺乏症的队列研究。结果：平均年龄为61.6岁（范围：18 - 95岁），性别比（女/男）为1.3。63.5%的患者存在多种合并症。最常见的致病药物为：抗生素（49.3%），尤其是β-内酰胺类和复方新诺明；抗甲状腺药物（16.7%）；抗精神病药和抗癫痫药（11.8%）；抗病毒药物（7.9%）；以及噻氯匹定和乙酰水杨酸等血小板聚集抑制剂（6.9%）。住院期间主要的初始临床表现包括：单纯发热（26.3%）；败血症（13.9%）；确诊肺炎（13.4%）；咽痛和急性扁桃体炎（9.3%）；以及感染性休克（6.7%）。中性粒细胞计数最低点时的平均值为0.148×10⁹/L（范围：0 - 0.48）。所有发热患者均接受了广谱抗生素治疗，107例（52.7%）接受了造血生长因子治疗。血液学恢复（中性粒细胞计数≥1.5×10⁹/L）的平均持续时间为7.8天（范围：2 - 20天）。使用造血生长因子后，该平均持续时间缩短至2.1天（范围：2 - 16天）（p = 0.057）。91.6%的患者预后良好；17例死亡。37例患者（18.2%）需要重症监护。
本研究表明，特异质性药物性粒细胞缺乏症是一种相对罕见的事件；抗生素、抗甲状腺药、抗精神病药和抗癫痫药以及血小板聚集抑制剂是主要的致病药物类别；粒细胞缺乏症通常较为严重，至少50%的患者表现为严重脓毒症，死亡率<10%；并且对这种疾病的现代管理可能会降低与感染相关的死亡率。
