结核病患者药物性皮疹的特征及临床疗效影响因素分析

目的 研究抗结核药物治疗后出现药物性皮疹患者的临床特征,分析这些皮疹患者的疗效影响因素.方法 将2008年1月至2010年5月入住上海市肺科医院102例出现药物性皮疹的肺结核患者纳入研究.统计研究对象出现皮疹后的体征、实验室检查、影像学表现,随访其治疗后的痰结核菌及胸片病灶吸收情况.采用stepwise回归法进行疗效影响因素分析.结果 在102例患者中,男62例,女40例,年龄16~81岁,平均年龄（38.41±17.74）岁;初治患者86例,复治患者16例;皮疹前抗结核治疗中位时间为10 d;皮疹消退后治疗中位时间为8个月;应用抗结核药物0～7种,平均为（3.71±1.77）种;皮疹发生的频率由高到低依次为上肢79.2%,胸部75.0%,背部70.8%,下肢64.6%,腹部60.4%,颜面部12.8%;最常见的过敏药物为：利福平40.0%、异烟肼13.3%、乙胺丁醇12.2%;11.76%的药物性皮疹患者合并谷丙转氨酶升高,中位数为206.50 U/L,5.88%的患者合并胆红素增高,为（75.10±37.5）μmol/L;13.73%的患者合并白细胞下降,为（2.97±0.64）×109/L,29.41%的患者合并发热,为（39.09±0.44）℃;疗程结束时,病灶好转者占78.43%;稳定者占11.76%,恶化者占9.80%;共46例（45.10%）患者有空洞存在,疗程结束时空洞的好转率为34.78%,闭合率为47.83%,恶化率为4.35%;治疗前痰结核菌涂片阳性患者52例（50.98%）,培养阳性患者24例（23.53%）,疗程结束时的阴转率可达92.31%;回归分析结果 显示：肝功能损伤、白细胞下降、停抗结核药物天数、复治、老龄为负相关因素,而结核抗体阳性、CD4值为正相关因素.结论 高热、肝功能损伤、白细胞下降为药物性皮疹结核病患者的常见并发症.疗程结束时的痰结核菌阴转率接近标准方案的水平,但病灶的吸收率及空洞的关闭率不够理想.合并肝功能损伤、白细胞下降、停抗结核药物天数长、复治、老龄为预后不良因素,增强患者的免疫力可能有助于提高疗效.

Characteristics of tuberculosis patients with drug rash and relative factors affecting curative effect

Objective To study the characteristics of tuberculosis patients with drug-induced rash, analyze the relative factors affecting curative effect. Methods From January 2008 to May 2010,102 tuberculosis inpatients with drug rash were enrolled in this study. Clinical features, laboratorial examinations, imaging findings were described. At the end of the follow-up, rates of sputum negative conversion, cavity closure and lesions absorbance were statistically analyzed. Stepwise regression analysis was conducted to find out the prognostic factors. Results One hundred and two patients including 86 untreated and 16 re-treated cases were involved, among which were 62 males and 40 females,with an average age of （38.41 ± 17.74）years. Rash broke out in an average time of 10 days after taking medicine. Therapeutic period after rash subsided was 8 months. Regimes included （ 3.71± 1.77 ） kinds of drug,ranging from 0 to 7. Predilection sites of the rash （from high to low）were upper limb （79. 2% ）, breast （ 75.0% ） , back （ 70. 8% ）, lower limbs （ 64. 6% ） , abdomen （ 60.4% ）, face （ 12. 8% ）. The most common allergy drugs were rifampin （40. 0% ）, isoniazid （ 13.3% ）, ethambutol （ 12. 2% ）. Among all the cases, 11.76% with increased serum alanine aminotransferase, the mean was 206. 50 U/L,5.88% with elevated serum bilirubin, the mean was（75.10 ±37.5） μmol/L; 13.73% with leucopenia,the mean was（2. 97 ±0. 64） × 10^9/L,29.41% with fever; the mean was （ 39.09 ± 0. 44 ） ℃. At the end of treatment, lesions improving accounted for 78.43% ; Stabilizeraccounted for 11.76%, deterioration accounted for 9. 80%. In 46 （45. 10% ） patients with cavities, the improvement rate was 34.78% ,closure rate was 47.83%, deterioration rate was 4. 35%. After treatment, the sputum conversion rate was 92.31% in 52 （ 50. 98% ） smear-positive and 24 （ 23.53% ） culture-positive cases. Regression analysis showed that hepatic dysfunction, leucopenia, time of anti-tuberculosis drugs withdrawal, re-treatment and aging were negatively correlated factors, while tuberculosis antibody, CD4 valueshad positive correlation with outcome. Conclusions High fever, hepatic dysfunction, leucopenia are common complications in tuberculosis patients with rash. At the end of therapy, spit negative rate is close to the level of standard regimen, but the absorption rate of lesions and cavities are less than ideal. Hepatic dysfunction, leucopenia, time of anti-tuberculosis drugs withdrawal, re-treatment and aging are poor prognostic factors ,while enhance the patient＇s immune system may help to improve the therapeutic effect.