Ramírez Elena, Medrano-Casique Nicolás, Tong Hoi Y, Bellón Teresa, Cabañas Rosario, Fiandor Ana, González-Ramos Jessica, Herranz Pedro, Trigo Elena, Muñoz Mario, Borobia Alberto M, Carcas Antonio J, Frías Jesús
Department of Clinical Pharmacology, La Paz University Hospital-Carlos III, IdiPAZ, School of Medicine, Autonomous University of Madrid, Madrid, Spain.
Institute for Health Research, La Paz University Hospital-Carlos III, IdiPAZ, Madrid, Spain.
Br J Clin Pharmacol. 2017 Feb;83(2):400-415. doi: 10.1111/bcp.13096. Epub 2016 Oct 12.
We conducted a prospective evaluation of all eosinophilic drug reactions (EDRs) through the Prospective Pharmacovigilance Program from Laboratory Signals at Hospital to find out the incidence and distribution of these entities in our hospital, their causative drugs, and predictors.
All peripheral eosinophilia >700 × 10 cells l detected at admission or during hospitalisation, were prospectively monitored over 42 months. The spectrum of the localised or systemic manifestation of EDR, the incidence, the distribution of causative drugs, and the predictors were analysed.
The incidence of EDR was 16.67 (95% Poisson confidence interval [CI]: 9.90-25.98) per 10 000 admissions. Of 274 cases of EDR, 154 (56.2%) cases in 148 patients were asymptomatic hypereosinophilia. In the remaining 120 (43.8%) cases, there was other involvement. Skin and soft tissue reactions were detected in 36 (13.1%) cases; visceral EDRs in 19(7.0%) cases; and drug-induced eosinophilic cutaneous and visceral manifestations were detected in the remaining 65 (23.7%) cases, 64 of which were potential drug reaction with eosinophilia and systemic symptoms (DRESS). After adjusting for age, sex, and hospitalisation wards, predictors of symptomatic eosinophilia were earlier onset of eosinophilia (hazard ratio [HR], 10.49; 95%CI: 3.13-35.16) higher eosinophil count (HR, 8.51; 95%CI: 3.28-22.08), and a delayed onset of corticosteroids (HR, 1.34; 95%CI: 1.01-1.73). A higher eosinophil count in patients with DRESS was significantly associated with greater impairment of liver function, prolonged hospitalisation, higher cumulative doses of corticosteroids, and if hypogammaglobinaemia was detected, a reactivation of human-herpesvirus 6 was subsequently detected.
Half (53.3%, 64/120 cases) of symptomatic EDRs were potential DRESS. The main predictor of severity of EDR was an early severe eosinophilia.
我们通过医院实验室信号前瞻性药物警戒计划对所有嗜酸性粒细胞药物反应（EDR）进行了前瞻性评估，以了解这些反应在我院的发生率、分布情况、致病药物及预测因素。
对入院时或住院期间检测到的所有外周嗜酸性粒细胞增多>700×10⁹/L的情况进行了为期42个月的前瞻性监测。分析了EDR的局部或全身表现谱、发生率、致病药物分布及预测因素。
每10000例入院患者中EDR的发生率为16.67（95%泊松置信区间[CI]：9.90 - 25.98）。在274例EDR病例中，148例患者的154例（56.2%）为无症状性嗜酸性粒细胞增多。其余120例（43.8%）有其他受累情况。36例（13.1%）出现皮肤和软组织反应；19例（7.0%）出现内脏EDR；其余65例（23.7%）出现药物性嗜酸性粒细胞皮肤和内脏表现，其中64例为潜在的伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS）。在调整年龄、性别和住院病房因素后，症状性嗜酸性粒细胞增多的预测因素为嗜酸性粒细胞增多出现较早（风险比[HR]，10.49；95%CI：3.13 - 35.16）、嗜酸性粒细胞计数较高（HR，8.51；95%CI：3.28 - 22.08）以及糖皮质激素开始使用延迟（HR，1.34；95%CI：1.01 - 1.73）。DRESS患者中较高的嗜酸性粒细胞计数与肝功能损害加重、住院时间延长、糖皮质激素累积剂量较高显著相关，并且如果检测到低丙种球蛋白血症，则随后会检测到人类疱疹病毒6再激活。
有症状的EDR中有一半（53.3%，64/120例）为潜在的DRESS。EDR严重程度的主要预测因素是早期严重嗜酸性粒细胞增多。
