长期服用糖皮质激素和(或)免疫抑制剂合并奴卡菌病的临床预后分析

Clinical and prognostic characteristics of nocardiosis in patients with long-term glucocorticoid and/or immunosuppressive agent therapy

目的回顾性分析长期服用糖皮质激素和(或)免疫抑制剂合并奴卡菌病患者的临床特征、诊疗及预后。方法入选我院近5年来长期服用糖皮质激素和(或)免疫抑制剂患者明确诊断奴卡菌病的病例7例。奴卡菌病诊断标准:体液(痰液、血液、胸腔积液、脓液)和(或)组织学(皮肤活检、肺活检)细菌培养结果为奴卡菌。播散性奴卡菌病诊断标准:奴卡菌病培养阳性,同时累及≥2个器官的化脓性感染。结果 7例患者中男性5例(71%),女性2例(29%),平均(56.1±11.6)岁。3例原发病为肾病综合征,4例为自身免疫性疾病,均接受了长期激素和(或)免疫抑制剂治疗。5例院外曾给予抗感染治疗,但治疗效果不佳。发生感染时免疫抑制治疗的中位疗程6个月(IQR 5~9)。入院时糖皮质激素的平均剂量(21.0±8.8)mg。7例均存在肺奴卡菌病,其中5例为播散性奴卡菌病(1例为皮肤播散至肺部、腹腔、腹膜后,1例为皮肤播散至肺部、颅内,1例为肺部播散至颅内,1例为肺部播散至皮肤,1例为皮肤播散至肺部)。中位播散时间2个月。6例病程中出现中高热,最高体温平均(39.5±0.7)℃。7例均有咳嗽、咳痰,3例呼吸困难,2例胸痛,1例咯血。5例皮肤奴卡菌病表现为皮下脓肿,其中1例还合并关节脓肿。2例颅内感染患者出现视物模糊,其中1例伴有癫痫。7例(100%)患者均CRP升高,平均(114±140)mg/L。降钙素原平均水平为0.4(IQR 0.14~0.64)μg/L,仅1例(1/6,17%)升高。6例(6/7,86%)淋巴细胞比例降低,其中5例低于10%。2例(2/2,100%)患者的CD4^+计数<200/μl,CD4^+/CD8^+比值明显下降。IgG平均水平(7 650±2 269)mg/L。白蛋白平均水平(30.6±6.6)g/L。肺部CT常见改变为空洞5例(71%)、结节5例(71%)、斑片影5例(71%)、磨玻璃影5例(71%)。各种类型体液及组织细菌培养阳性率分别为:肺组织活检(1/1,100%)、脓液(3/3,100%)、胸腔积液(2/4,50%)、痰培养(3/7,43%)及血培养(2/6,33%)。磺胺和(或)利萘胺为基础的治疗方案有效率71%,2例(29%)死亡,2例(29%)停药后复发。结论奴卡菌病是一种机会性感染,误诊率高,易全身播散,易复发。组织活检及无菌体液培养阳性率较高。早期诊断与合理治疗方案是改善预后、减少播散与复发的关键。

Objective To retrospectively analyze the clinical and prognostic features, and diagnosis and treatment strategies of nocardiosis in patients undergoing long-term glucocorticoid and/or immunosuppressive agent therapy. Methods Seven cases with confirmed diagnosis of nocardiosis who received long-term glucocorticoid and/or immunosuppressive agent therapy during the past 5 years in our hospital were reviewed. Nocardiosis diagnostic criteria： Nocardia presented in bacteria culture of various body fluids （ sputum, blood, hydrothorax, pus） and/or biopsy specimens （ skin biopsy, lung biopsy）. Disseminated nocardiosis diagnostic criteria： Nocardia culture was positive with nocardiosis involving two or more organs. Results Five patients were male （71%） and 2 were female （29%） with a mean age of 56.1 ± 11.6 years. All the patients received long-term immunosuppressive therapy for nephrotic syndrome （3 cases） and autoimmune diseases （4 cases）. Pre- admission anti- infective treatment was given in 5 cases, but the effect was poor. The median duration of therapy at diagnosis of nocardiosis was 6 months （IQR 5 to 9）. The average dose of glucocorticoids on admission was 21.0 ± 8.mg. All 7 cases had pulmonary nocardiosis, among which 5 cases （71%） had disseminated nocardiosis. The median disseminating time was 2 months. Six cases presented high fever in the disease course with an average highest temperature of 39.5 ± 0.7℃. All of the patients had cough and sputum, with dyspnea in 3 cases, chest pain in 2 cases,and hemoptysis in 1 case. Five cases had skin nocardiosis of subcutaneous abscess, of which 1 case also had joint abscess. Two patients with intracranial infections had blurred vision, of which 1 case had epilepsy. CRP was elevated in 7 patients （100%）, with an average of 11. 4 ± 14.0 mg/dl. The procalcitonin had an average level of 0.4 ng/ml （ IQR 0.14 to 0.64）, and increased in only 1 case （ 1/6, 17% ）. Lymphocytes decreased in 6 cases （6/7, 86% ）, and were less than 10% in 5 of them. In 2 patients （2/2, 100% ）, CD4＋ count was less than 200/ul, and the ratio of CD4＋/CD8＋ decreased significantly. The average IgG level was 765.0 ± 226.9 mg/dl, and the average albumin level was 30.6 ± 6.6 g/L. Lung CT scan showed pulmonary cavity in 5 cases （71%）, nodules in 5 cases （71%）, patchy shadow in 5 cases （71%）, and ground glass opacities in cases （71%）. The positive rates of bacterial culture from various body fluids and tissues were as follows： lung biopsy （1/1, 100% ）, pus （3/3, 100% ）, hydrothorax （43%）, and blood culture （2/6, 33% ）. lid-based treatment regimens were effective （ 71% ）, while 2 （ 29% ） died and 2 （ 29% ） relapsed after treatment discontinuation. Conclusions Nocardiosis is an opportunistic infection with a high rate of misdiagnosis, and is subject to dissemination and relapse. Tissue biopsy specimens and sterile humoral fluids culture had higher positive rates. Early diagnosis and rational treatment are key for improving its prognosis and reducing its spread and recurrence.