Andrès Emmanuel, Mourot-Cottet Rachel, Maloisel Frédéric, Keller Olivier, Vogel Thomas, Séverac François, Tebacher Martine, Gottenberg Jacques-Eric, Weber Jean-Christophe, Kaltenbach Georges, Goichot Bernard, Sibilia Jean, Korganow Anne-Sophie, Herbrecht Raoul
Departments of Internal, Strasbourg University Hospitals, Strasbourg 67000, France.
Departments of Onco-hematology, Strasbourg University Hospitals, Strasbourg 67000, France.
J Clin Med. 2017 Sep 26;6(10):92. doi: 10.3390/jcm6100092.
Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital.
Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France).
Mean patient age was 52.2 years old (range: 18-93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 × 10(9)/L (range: 0-0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 × 10(9)/L) was 7.5 days (range: 2-21), which was reduced to 0.7 days (range: 2-16) ( = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died.
Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of "daily medication" exposure.
尽管在发热性中性粒细胞减少症的预防和治疗方面取得了重大进展，但它仍然是癌症化疗最令人担忧的并发症。然而，在肿瘤学领域之外，目前关于非化疗药物引起的发热性中性粒细胞减少症的数据很少。我们在此报告了76例与非化疗药物相关的发热性中性粒细胞减少症患者的数据，这些患者在大学医院的转诊中心接受了随访。
回顾性分析了76例特发性药物性发热性中性粒细胞减少症患者的数据。所有病例均取自法国斯特拉斯堡大学医院进行的一项关于粒细胞缺乏症的队列研究。
患者平均年龄为52.2岁（范围：18 - 93岁），性别比（女/男）为1.6，86.8%的患者存在多种合并症。最常见的致病药物为：抗生素（37.4%）、抗甲状腺药物（17.2%）、抗精神病药和抗癫痫药（13.1%）、非甾体抗炎药和镇痛药（8%）以及血小板聚集抑制剂（8%）。住院时的主要临床表现包括单纯发热（30%）、咽痛、急性扁桃体炎和鼻窦炎（18.4%）、确诊的肺炎（18.4%）、败血症（14.5%）和感染性休克（6.6%）。中性粒细胞计数最低点的平均值为0.13×10⁹/L（范围：0 - 0.48）。住院期间，22例患者（28.9%）临床症状恶化，需要入住重症监护病房。所有患者均立即接受了广谱抗生素治疗，45例（59.2%）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7.5天（范围：2 - 21天），使用造血生长因子后缩短至0.7天（范围：2 - 16天）（P = 0.089）。89.5%的患者预后良好，8例死亡。
与肿瘤学和骨髓抑制性化疗情况一样，特发性发热性中性粒细胞减少症通常很严重，约40%的患者表现为严重肺炎、败血症和感染性休克，死亡率为10%。与化疗相关的发热性中性粒细胞减少症一样，现代及时管理（立即进行广谱抗生素治疗、造血生长因子）可能降低感染相关死亡率。所有从业者都应意识到这种潜在的副作用，即使在“日常用药”情况下也可能发生。
