甲巯咪唑致Graves病患者粒细胞缺乏症合并败血症的临床特征分析

Analysis on clinical characteristics of Graves′ disease patients with methimazole-induced agranulocytosis combined with septicemia

目的探讨甲巯咪唑致Graves病患者粒细胞缺乏症(粒缺症)合并败血症的临床特征。方法在既往对2000年1月至2015年12月因抗甲状腺药物所致粒缺症收住西安交通大学第一附属医院的Graves病患者临床资料进行回顾性分析的基础上,以其中服用甲巯咪唑后发生粒缺症合并败血症的7例患者(合并败血症组)为重点,从病历中重新提取相关数据,分析其临床表现、细菌学特征以及治疗和转归情况,并与55例未合并败血症的甲巯咪唑致粒缺症患者(未合并败血症组)比较,探索合并败血症患者的临床特征。结果合并败血症组7例患者均为女性,年龄20~56岁;3例合并甲亢性心脏病,1例合并甲亢危象;多器官感染者6例(化脓性扁桃体炎+肺部感染2例,化脓性扁桃体炎+胃肠道感染2例,化脓性扁桃体炎+肺部感染+颌下脓肿1例,化脓性扁桃体炎+肺部感染+牙周脓肿1例),单一肺部感染者1例。合并败血症组患者主要临床症状包括发热、咽痛、纳差和心悸等。合并败血症组患者中发生化脓性扁桃体炎、肺部感染及最小中性粒细胞绝对值(ANC)为0者占比均明显高于未合并败血症组[6/7比43.6%(24/55),5/7比21.8%(12/55),5/7比29.1%(16/55)],全组患者最小白细胞计数明显低于未合并败血症组[0.23(0.17,0.60)×10^9/L比0.92(0.50,1.47)×10^9/L],发热持续时间、粒缺症恢复时间和住院时间均明显长于未合并败血症组[13(7,21)d比6(3,9)d,(7±2)d比(5±3)d,29(17,37)d比14(9,21)d],差异均有统计学意义(P<0.05或P<0.01)。诊断粒缺症后均停用甲巯咪唑,经广谱抗菌药物、重组人集落刺激因子(rhG-CSF)以及糖皮质激素等药物治疗,7例患者败血症均得到有效控制,ANC恢复正常。结论服用甲巯咪唑后发生粒缺症合并败血症的Graves病患者常发生多器官感染,临床症状危重,治疗难度大。及早、合理地应用广谱抗菌药物,同时给予rhG-CSF和糖皮质激素治疗,有望改善患者预后。

Objective To explore the clinical characteristics of Graves′disease patients with methimazole-induced agranulocytosis combined with septicemia. Methods The study was based on a previous retrospective analysis of the clinical data in Graves′ disease patients admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2015 due to antithyroid drug-induced agranulocytosis and focused on the 7 patients who developed agranulocytosis combined with septicemia (septicemia group) after taking methimazole. Relevant data was re-extracted from the medical records of the 7 patients. The clinical characteristics of patients with septicemia were explored through the analysis on their clinical manifestations, bacteriological characteristics, treatment and outcomes, and the comparison of above contents with those of the 55 patients with methimazole-induced agranulocytosis without septicemia (non-septicemia group). Results Seven patients in the septicemia group were female, aged 20 to 56 years. Of the 7 patients, 3 combined with hyperthyroid heart disease, 1 combined with life-threatening thyrotoxicosis;6 patients with multiple organ infections (2 with suppurative tonsillitis and pulmonary infection;2 with suppurative tonsillitis and gastrointestinal infection;1 with suppurative tonsillitis, pulmonary infection, and submandibular abscess;1 with suppurative tonsillitis, pulmonary infection, and periodontal abscess) and 1 patient with pulmonary infection alone. The main clinical symptoms of patients with septicemia included fever, sore throat, anorexia, and palpitations. The proportions of patients with suppurative tonsillitis, lung infections, and the lowest absolute neutrophil count (ANC) value of 0 in the septicemia group were higher than those in the non-septicemia group [6/7 vs. 43.6%(24/55), 5/7 vs. 21.8%(12/55), and 5/7 vs. 29.1%(16/55)]. The minimum white blood cell count in patients in the septicemia group was significantly lower than those in the non-septicemia group[0.23 (0.17, 0.60)×10^9/L vs. 0.92 (0.50, 1.47)×10^9/L]. The duration of fever, recovery time of agranulocytosis, and hospitalization days in patients in the septicemia group were significantly longer than those in the non-septicemia group [13 (7, 21) d vs. 6(3, 9) d and 29 (17, 37) d vs. 14 (9, 21) d]. The differences were all statistically significant (P<0.05 or P<0.01). After the diagnosis of agranulocytosis, methimazole was stopped in all patients. Their septicemia was effectively controlled and ANC returned to normal after the treatments with broad-spectrum antibiotics, recombinant human colony-stimulating factor (rhG-CSF), and glucocorticoids. Conclusions Graves′disease patients, who developed agranulocytosis combined with septicemia after taking methimazole, often had multiple organ infections. Their clinical symptoms were critical and difficult to treat. The early and rational application of broad-spectrum antibacterial drugs and simultaneous treatments with rhG-CSF and glucocorticoids were expected to improve patients′outcomes.