布鲁氏菌性脊柱炎诊断及治疗专家共识
Expert consensus on the diagnosis and treatment of Brucella spondylitis
Corresponding authors:
Received: 2022-04-19
布鲁氏菌性脊柱炎近年来发病有不断增高的趋势,由于其早期的诊断率较低,常存在误诊误治的现象,造成后期治疗的难度成倍增加,患者致残。为规范布鲁氏菌性脊柱炎患者的诊疗流程,让更多业界同仁了解此类疾病的治疗细节,并在治疗时有据可依,中国防痨协会骨关节结核专业分会、西部骨结核联盟、华北骨结核联盟联合组织专家共同拟定了《布鲁氏菌性脊柱炎诊断及治疗专家共识》。本共识从布鲁氏菌性脊柱炎的流行病学特征开始论述,对其常见临床表现、实验室检查及诊断标准、治疗药物及手术治疗方法,以及预后等方面进行了深入的阐述与讨论。
关键词:
Brucellosis spondylitis has been increasing in recent years, because of the low early diagnosis rate, there is often the possibility of misdiagnosis and mistreatment, resulting in the difficulty of later treatment and disability of patients. In order to standardize the diagnosis and treatment process of patients with Brucella spondylitis, help more specialist to get the treatment details of such disease, and have evidence in the treatment, the Expert consensus on the diagnosis and treatment of Brucella spondylitis was jointly formulated by the Joint Tuberculosis Professional Branch of Chinese Antituberculosis Association, the Western China Bone Tuberculosis Union, the North China Union of Bone Tuberculosis. This consensus starts from the epidemiological characteristics of Brucella spondylitis, deeply expounds and discusses its common clinical manifestations, laboratory examination and diagnostic criteria, therapeutic drugs, surgical treatment methods, prognosis and so on.
Keywords:
本文引用格式
中国防痨协会骨关节结核专业分会, 中国华北骨结核联盟, 中国西部骨结核联盟.
The Joint Tuberculosis Professional Branch of Chinese Antituberculosis Association, The Western China Bone Tuberculosis Union, The North China Union of Bone Tuberculosis.
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布鲁氏菌病(又称布病、马尔他热、地中海弛张热、波状热)是由布鲁氏菌属的细菌侵入机体,引起的人兽共患的传染性变态反应性疾病[1]。其临床特征不典型、潜伏期较长,容易误诊和漏诊。该病是一种全身性疾病,可累及多个器官,其并发症容易对肝、血液、脾、神经、生殖等多个脏器和系统造成损害。
布鲁氏菌性脊柱炎是布鲁氏菌侵犯脊柱(椎间盘、椎体、肌肉)导致的脊柱感染性疾病,在国内外发生率报道不一,约占布鲁氏菌病患者的2%~53%,发热和脊柱局部疼痛是该病的主要临床症状[2]。该病若治疗不及时容易转化为慢性,严重影响患者生活质量和劳动能力;而且该病通常容易复发和出现并发症及后遗症。尽管目前布鲁氏菌性脊柱炎在临床越来越常见,然而大部分临床医师对其诊断和治疗认识不足,缺乏深入研究,有些观点尚未达成一致,临床诊疗欠规范。为此,中国防痨协会骨关节结核专业分会、中国华北骨结核联盟、中国西部骨结核联盟联合组织专家拟定《布鲁氏菌性脊柱炎诊断及治疗专家共识》。本共识对布鲁氏菌性脊柱炎的流行病学特征、常见临床表现、实验室检查及诊断标准、药物及手术治疗方法、预后等进行了深入的阐述。
病原学、传播途径及流行病学特征
一、病原学
布鲁氏菌病是一种自然疫源性疾病[5]。布鲁氏菌对感染宿主有一定的选择性。某种布鲁氏菌经常感染的宿主,最适合细菌在其体内寄生和繁殖,致病较重,这样的宿主称为最适宿主。例如,羊种布鲁氏菌感染羊,羊就是其最适宿主;若因偶然机会羊种布鲁氏菌感染了牛或其他动物,则这些宿主被称为转移宿主。此外,同种布鲁氏菌间具有干扰现象。在感染人和畜的寄生过程中即存在着布鲁氏菌属内种间的干扰现象,毒力强的菌种能干扰毒力弱的菌种,微小、透明、无色的光滑型(S)菌能干扰粗糙型(R)菌。布鲁氏菌在其最适宿主内能干扰非最适菌。
二、传播途径
三、流行病学特征
布鲁氏菌性脊柱炎一年四季均可发病,但季节性较为明显。一般晚冬和早春开始发病,夏季进入发病高峰期,秋季以后发病逐渐减少。该病具有地方流行性特点,遍及世界各地,以中东、西亚和南美洲最多,我国西北部、东北部、内蒙古、青藏高原等牧区发病率较高;农村地区发病高于城市,牧区高发,在发病高峰季节可呈暴发和流行之势[2]。人群普遍易感,男性多于女性,以中青年为多,与其职业特点有关。我国将其列为职业病,与被感染的牲畜或被污染的畜产品接触多者发病率高,如乳兽医、农牧民、皮毛入肉加工人员,取决于接触传染源机会的多少,各年龄组均有发病,主要是青壮年劳动力。尽管该病发生和流行在地理区域上不受限制,但由于接触机会不同,感染常存在地区差异。通常情况下,农牧区居民较城镇居民接触牲畜机会多,因此感染概率大。该病治愈后可获较强免疫力,因不同种布鲁氏菌之间存在交叉免疫,故再次感染者较少。
共识1:布鲁氏菌性脊柱炎是人体感染了布鲁氏菌而患的人畜共患疾病。人感染布鲁氏菌病主要为直接接触感染,如动物接产、屠宰、入肉加工等,病菌从接触处的破损皮肤进入人体,从而产生一系列的症状。
临床表现
布鲁氏菌病的潜伏期一般为l~3周,部分病例潜伏期更长,临床表现复杂、多样。该病按照发病时间分为急性期和慢性期,急性期病程在6个月以内,慢性期病程可超过6个月仍不痊愈[8]。其主要临床表现如下:
1.发热:典型病例表现为波状热,常伴有寒颤、头痛等症状,可见于各期病例。部分病例可表现为低热和不规则热型,且多发生在午后或夜间。
2.多汗:急性期病例出汗尤重,可湿透衣裤、被褥。
3.肌肉和关节疼痛:为全身肌肉疼痛和多发性、游走性大关节疼痛。部分慢性期病例还可有脊柱(腰椎为主)受累,表现为疼痛、畸形和功能障碍等。
4.乏力:几乎全部病例都有此表现。
5.肝、脾及淋巴结肿大:多见于急性期病例。
6.其他:男性病例可伴有睾丸炎,女性病例可伴卵巢炎;少数病例可有心、肾及神经系统受累表现。
布鲁氏菌病可侵犯全身各系统,常累及肝、脾、骨髓、淋巴结,还可累及骨、关节、血管、神经、内分泌及生殖系统等。典型病例表现为长期发热、多汗、疲乏无力、肌肉关节疼痛、淋巴结肿大、肝脾肿大,不典型病例以单一系统症状或以合并症的表现为主,如表现为肝炎、心内膜炎、腹膜炎、肺炎、脑膜炎、血液病等,病情轻重差异大,容易误诊。骨关节的损害是较常见的并发症,心内膜炎是少见但是最严重的并发症。
大量布鲁氏菌经消化道、呼吸道黏膜及皮肤侵入机体后,首先到达附近的淋巴结,突破淋巴防卫功能后进入血液循环,并不断释放内毒素,随之侵犯肝、脾、骨髓、关节等组织。主要病理改变为渗出、增生、肉芽肿形成,3种病理改变可以交替发生。
临床常见症状为发热(多为波状热)、多汗、关节痛、腰背酸痛、肌肉疼痛,骨关节损害以负重关节为主,病变常侵袭脊柱引起脊柱炎,多数患者以腰痛就诊,受侵部位出现持续性腰痛及下背痛,局部压痛,叩击痛,伴肌肉痉挛,脊柱活动受限,常处于固定姿势;有时局部淋巴结破溃后,出现腰大肌脓肿,甚至可因硬膜外脓肿而致截瘫。病变在脊柱不同部位表现为相应神经根放射痛或脊髓受压症状。易误诊为化脓性脊柱炎、脊柱结核或椎间盘突出症。实验室检查(病原体分离、试管凝集试验、补体结合试验、抗人球蛋白试验阳性)可以帮助确诊及鉴别诊断。
共识2:布鲁氏菌性脊柱炎多发于中青年,常累及腰椎,其次是胸椎;主要临床表现为发热、乏力、夜间盗汗、厌食、头痛、肝脾肿大、关节疼痛、腰背痛等全身及局部症状。
专科查体
布鲁氏菌性脊柱炎患者受累节段脊柱活动受限,病变节段棘突、椎旁压痛及叩击痛阳性;神经根或者脊髓受累时,则可能会出现病变相应神经支配区肢体放射性疼痛、肌力减弱、皮肤感觉减退、肌腱反射亢进等神经症状。患者一般很少出现脊柱后凸畸形,截瘫患者少见,可有关节同时受累。而脊柱结核常伴有体表可触及的椎旁脓肿形成,关节同时受累者少见,脊柱后凸畸形及神经功能障碍发生率较布鲁氏菌性脊柱炎高。
共识3:布鲁氏菌性脊柱炎专科查体主要是脊柱受损后出现的肢体疼痛等症状,无明显特异性。
实验室检查
一、一般实验室检查
白细胞计数多正常或偏低,淋巴细胞相对增多,有时可出现异形淋巴细胞,少数出现红细胞和血小板计数减少。可出现血红细胞沉降率、C反应蛋白升高等,累及肝脏者肝功能可有异常。
二、细菌培养
血液、骨髓、乳汁、子宫分泌物、脓性分泌物、关节液、脑膜炎患者的脑脊液等均可进行细菌培养;其中,血液最常用。该菌专性需氧,生长缓慢,在哥伦比亚血琼脂平板上35℃培养18~24h,出现较湿润、灰色、针尖大小菌落,48h后形成圆形、凸起、光滑、较小的灰色菌落,72h后逐渐增大。因此,布鲁氏菌培养应注意延长时间,以获得更高阳性率。
自动化培养系统的应用缩短了培养时间,可提高培养的敏感度。仪器阳性报警,在取培养物涂片染色时,推荐革兰染色和瑞氏染色法。若镜下见紫色球杆状、形似血小板样、多位于破坏细胞内的细菌,则可初步诊断;若未见细菌,应延长培养时间或重新送血培养。血培养阳性直接涂片疑似布鲁氏菌时,即可取培养物行脲酶反应。由于布鲁氏菌的致病性及既往实验室感染的报道,所有标本处理均应在二级以上的生物安全柜内进行。疑似布鲁氏菌在涂片染色前要用甲醇固定(以杀灭布鲁氏菌)再行涂片。
培养的敏感性取决于标本种类、培养方法和疾病分期,以及抗菌药物的使用。骨髓培养比血培养更加敏感。急性发热患者的血培养阳性率高于亚急性及慢性患者。应该指出,由于培养的低阳性率,阴性结果不能排除布鲁氏菌感染,治疗决策不应受阴性结果影响,应结合临床、流行病学史及血清学等各方面综合判断,给予诊断和治疗。
三、血清学检测
检测机体对菌体细胞膜上的光滑脂多糖(smooth-lipopolysaccharide,S-LPS)产生的抗体。发病初期IgM效价上升,约1周后IgG效价升高。在治疗有效的患者中,抗体水平逐渐下降,然后可长时间维持在一定的水平。复发时,布鲁氏菌特异性IgG和IgA可升高。
由于抗原的共同性,血清学检测会对某些革兰阴性菌种(如小肠结肠炎耶尔森菌O:9、大肠埃希菌O:157、霍乱弧菌及弯曲菌属等)产生交叉反应。由于产生抗体种类和效价随病程的变化而不同,且流行区背景效价的存在,抗体检测界值的确定是难题,难以顾全敏感度和特异度。故需要对所在地区的人群行背景效价的调查,建立正常区间。由于假阳性和假阴性的存在,建议同时采用两种以上血清学检测方法。
1.虎红平板凝集试验:方便快捷,可在5~10min内获得结果,呈现为阳性或阴性,推荐用作快速筛查试验。该方法基于S-LPS,在非暴露人群中敏感度高,假阳性率低。但流行区高背景抗体效价会影响其诊断价值,且由于其与其他革兰阴性菌的交叉反应,可出现假阳性结果。布鲁氏菌慢性感染和有并发症的患者可能出现较高的假阴性率。阳性结果须由其他血清学试验确认。我国应用的平板凝集试验,操作原理类似,亦用作初筛。
2.血清凝集试验:该试验是一种血清学定量试验。研究显示,血清凝集试验阳性检出的符合率为93.8%,滴度为1:80或更高提示布鲁氏菌病诊断;抗菌药物治疗4个月后滴度为1:160或更高,说明感染复发或耐药,其敏感度在急性期高于慢性期,但阴性者也不能排除布鲁氏菌病[9]。因此,血清凝集试验一般不单独使用,应与其他方法联合使用。
3.酶联免疫吸附试验(ELISA):现已较好地实现标准化,且检测迅速(4~6h),敏感度和特异度较高,可以针对性地检测不同抗体,包括非凝集性抗体。当其他检测均为阴性时,尤其推荐使用ELISA,其可用于疗效监测和急慢性、局灶、并发症感染的检测。ELISA和胶体金免疫层析法的特异度和敏感度均较高,且结果呈现快,胶体金免疫层析法可用于现场检验,ELISA适用于大样本检测。也有学者建议将ELISA与传统实验室检查相结合用于布鲁氏菌病的诊断,但是受到医院技术设备及试剂的影响,目前尚未作为临床常规检查。
4.布鲁氏菌病抗-人免疫球蛋白试验(Coomb试验):可同时检测凝集或非凝集性抗体,由此能更早产生阳性结果,且治疗恢复后保持阳性的时间也更长,敏感度高。其相较血清凝集试验,更适合用于慢性、有并发症、复发和持续性感染患者的检查,但对技术和设备要求较高。国内根据《WS 269—2007布鲁氏菌病诊断标准》判断标准定为:效价1:400并出现显著凝集及以上[10]。
四、分子生物学检测
五、其他检查
脑脊液检查适用于脑膜炎患者,可见脑脊液细胞(淋巴细胞为主)和蛋白质增加。心电图检测可示显P-R间期延长、心肌损伤、低电压等。肝功能、脑电图改变均属非特异性。
共识4:布鲁氏菌性脊柱炎的实验室检查主要有虎红平板凝集试验、血清凝集试验、ELISA、布鲁氏菌病抗-人免疫球蛋白试验、分子生物学检测,以及细菌培养等。
病理学检查
布鲁氏菌性脊柱炎的组织病理学检查一般在手术时进行,病理学检查能够清晰显示由布鲁氏菌破坏导致的细微变化,是其临床诊断的金标准。镜下病灶局部可见纤维组织和小血管增生,大量急、慢性炎症细胞浸润,包含嗜酸性粒细胞、中性粒细胞、单核细胞和淋巴细胞,部分病例可见增殖性结节、肉芽肿形成及类上皮细胞组成的结节状病灶,未见干酪样坏死,Gimesa染色通常可发现布鲁氏菌[19-20]。同时,组织病理检查可为布鲁氏菌对脊柱破坏的严重程度进行分期,从而根据不同时期病理表现为临床治疗提供参考。而典型的脊柱结核的病理变化为结核肉芽肿样改变(包括类上皮细胞、朗汉斯巨细胞、干酪样坏死等),不会出现中性粒细胞,抗酸染色一般为阳性,分子病理学可以进行菌种鉴定,借此可以对布鲁氏菌性脊柱炎与脊柱结核进行鉴别[21]。
共识5:布鲁氏菌性脊柱炎的病理学检查能够清晰显示由布鲁氏菌破坏导致的细微变化,Gimesa染色通常可发现布鲁氏菌。
影像学检查
一、X线检查
布鲁氏菌性脊柱炎患者胸部X线摄片(简称“胸片”)也可以有陈旧性肺结核的表现,但其比例较脊柱结核患者低,一般无活动性肺结核表现。布鲁氏菌性脊柱炎疾病早期常规X线摄片无特异性表现,仅部分表现为受累椎体密度增高,椎体关节面一般无明显的骨质破坏。X线检查需在发病后2个月或更长时间才可观察到其变化,表现为椎体边缘骨质轻度破坏,呈现不规则的虫蚀状或者锯齿状外观,同时,常伴有椎体边缘骨质硬化、增生性骨刺或者骨桥形成,呈现典型的“鸟嘴征”;也可伴有椎间小关节间隙变窄和关节面破坏。骨质修复反应强烈为布鲁氏菌性脊柱炎的典型特征。脊柱结核患者的椎间隙狭窄更明显,常伴有椎旁脓肿影,骨质增生及骨刺形成不如布鲁氏菌性脊柱炎明显。
二、CT检查
布鲁氏菌性脊柱炎的椎体骨质破坏部位多为相邻2个椎体的上下缘,病灶多表现为低密度灶,形状呈斑片状、圆形或者类圆形,以边缘型的骨质破坏最为常见。骨质破坏的早期表现为局部小的骨质疏松灶,数周以后病变部位明显扩大,病灶呈“虫蚀样”改变,较大病灶呈“岛屿状”,一般无死骨形成,慢性期病变椎体可见明显增生硬化现象,椎体密度明显升高,可有骨赘形成,一般无椎体压缩,少数伴有轻度的楔形变。晚期椎体边缘骨质增生,呈喙突状突出形成骨刺,甚至部分病例可见骨桥形成;骨破坏区域也可见反应性新生骨形成,该种影像表现被称为“花边椎”,这是布鲁氏菌性脊柱炎的特征性表现,可与脊柱结核相鉴别[22-23]。椎间盘的破坏多伴随着椎体骨质的破坏,可伴有椎间隙狭窄、终板增生和硬化。椎旁脓肿一般范围比较局限,脓肿很少超过受累椎体的范围,界限清楚,脓肿与椎体骨质破坏区相连,可挤压邻近的腰大肌,但布鲁氏菌性脊柱炎很少出现腰大肌脓肿。增生肥厚的骨膜和椎体之间仍然清晰可辨。韧带改变主要表现为棘间韧带和前纵韧带的钙化。椎小关节表现为椎小关节边缘虫蚀样的骨质破坏,关节面破坏毛糙,关节间隙逐渐变窄,最后形成关节骨性强直。脊柱结核患者的骨质破坏程度较布鲁氏菌性脊柱炎明显,常见死骨形成,椎旁及腰大肌脓肿形成。这可与布鲁氏菌性脊柱炎相鉴别。病程长者可见骨桥形成,但骨桥形成不如布鲁氏菌性脊柱炎明显。
三、MRI检查
MRI检查具有快速、准确、可重复的特点,是布鲁氏菌性脊柱炎早期首选的检查方法。布鲁氏菌性脊柱炎的早期,X线摄片和CT扫描常难以发现病灶,病变椎体多无明显形态学的改变。MRI增强扫描病灶呈明显均匀强化,所以MRI能早期发现布鲁氏菌性脊柱炎的局部病变[24-25]。随着病变的进展,骨质破坏逐渐加重,当累及整个椎体时,椎体呈长T1和长T2信号,但很少有死骨形成,一般椎体塌陷也不明显,极少有脊柱后凸畸形,这可与脊柱结核相鉴别。布鲁氏菌性脊柱炎累及椎间盘时,椎间盘可表现为长或者等T1和稍长T2信号影,增强扫描病灶边缘呈不均匀环形强化,一般椎间隙狭窄不明显,或者仅为小部分轻度狭窄。这可与脊柱结核进行鉴别,因为脊柱结核多表现为严重的椎间隙狭窄。布鲁氏菌性脊柱炎椎旁软组织可见程度不一的充血、水肿,边界欠清晰,形态欠规则,邻近的腰大肌受压,腰大肌内部分可有脓肿形成,一般无脓肿流注征象。这可与脊柱结核相鉴别。MRI能清晰显示椎旁及椎管内脓肿的大小及范围。其他的表现还有可伴有不同程度的椎小关节炎及韧带炎,表现为椎小关节间隙变窄,严重者椎小关节融合消失。病变累及韧带时,常表现为条索状长T1和短T2信号。
共识6:MRI检查是布鲁氏菌性脊柱炎早期首选的检查方法,扫描病灶呈明显均匀强化,能早期发现布鲁氏菌性脊柱炎的局部病变。布鲁氏菌性脊柱炎早期很少有死骨形成,一般椎体塌陷也不明显,极少有脊柱后凸畸形。“花边椎”是布鲁氏菌性脊柱炎CT扫描的特征性表现。
诊断
布鲁氏菌性脊柱炎的诊断目前主要结合患者的流行病学接触史、临床表现和实验室检查结果、影像学检查结果等进行综合判断。
1.流行病学表现:布鲁氏菌病在我国主要见于西北、内蒙古、东北等农牧区,易感人群为从事畜牧养殖业的牧民、接触含菌标本的实验室人员及饮用或食用未经灭菌的乳品及肉制品人群。
2.临床症状:(1)全身症状:发热、寒颤、头痛、多汗、乏力,肝、脾及淋巴结肿大,或伴男性睾丸炎及女性卵巢炎。(2)局部改变:关节肌肉疼痛、游走性疼痛及骨关节器质性损害;脊柱感染症状为胸部、腰背部持续剧烈疼痛,以腰背部疼痛多见,肌肉痉挛、局部压痛、叩击痛,伴活动受限,或见脓肿及神经根症状等。
部分布鲁氏菌性脊柱炎患者缺乏特异性临床症状,易与椎间盘突出症、脊柱结核等疾病相混淆。当前对血清学阴性的布鲁氏菌性脊柱炎的诊断仍存在难点,基于二代测序技术的病原微生物基因检测及PCR等检测技术有望进一步推动其诊断及治疗。
共识7:布鲁氏菌性脊柱炎的诊断目前主要结合患者流行病学接触史、临床表现和实验室检查结果、影像学检查结果等综合判断。二代测序技术有望进一步推动布鲁氏菌性脊柱炎的诊断及治疗。
治疗
一、药物治疗
布鲁氏菌性脊柱炎主要表现为发热、乏力及关节痛等感染中毒症状时期,主要采用联合抗生素保守治疗,且联合应用多西环素、利福平和链霉素等3种抗菌药物治疗效果较好。
二、手术治疗
布鲁氏菌性脊柱炎的手术时机存在争议。多数布鲁氏菌性脊柱炎患者依靠规范的抗布鲁氏菌病保守治疗均能获得满意疗效。但近年来临床工作中发现累积到脊柱的布鲁氏菌感染患者在急性发作期临床症状较重,因局部疼痛丧失生活能力患者不在少数,严重影响患者生活质量,其中不乏保守治疗效果不佳发展成为截瘫的患者。亦有在保守治疗后脊柱病变局部炎症控制但出现椎体失稳产生临床症状的患者。故在严格把握手术指征的基础上将手术时机前移可早期减轻患者疼痛,改善生活质量,缩短治疗疗程。
(一)手术入路的探讨
(二)后方入路手术优点
经后路病灶清除、髂骨取骨植骨融合、经椎弓根螺钉内固定手术内固定钉棒系统形成脊柱三柱稳定。费琦等[38]认为此类手术为一种安全有效的方法。由于其坚强固定作用对于病灶亦有预防扩散及复发作用,通过标准、万向螺钉对于脊柱矫形、复位及生理曲度的恢复均能提供较满意效果。由于腰椎椎管容积骨性容积较大,硬膜内神经分布较少,经后路病灶清除术中适度牵拉硬膜及神经根后神经反应轻,术后均无由于牵拉引起的相关神经根性疼痛症状及马尾神经损伤症状。由于各种角度的刮勺的出现,对于椎间复杂肉芽和脓肿的清除也均可获得满意效果,尤其椎管内的肉芽组织清理及双侧神经根周围的炎性组织清理效果均满意,术后随访患者均治愈,术前出现的相关神经损伤症状于术后均改善,其中大部分患者症状消失[39]。
(三)Quadrant通道辅助下的MIS-TLIF技术
随着脊柱微创技术的不断发展,Quadrant通道辅助下的MIS-TLIF技术被广泛应用于腰椎退行性疾病的手术治疗[40-41]。该技术采用肌间隙入路,通过一个可扩张撑开的通道,使术者精确到达手术区域,实现以往只有传统开放手术才能完成的腰椎管减压、滑脱复位、椎间植骨融合、椎弓根螺钉内固定等脊柱后路内固定融合手术的所有复杂操作。通过应用这一技术,不仅可以直达病变区域进行彻底清除病变组织,还保留了大部分的脊柱后柱结构及部分的椎板,可以很好地保护脊柱的稳定性。其采用肌间隙入路,无需广泛地剥离肌肉组织及软组织,尽可能对组织的保护达到最大化。有研究指出,布鲁氏菌性脊柱炎术后复发与脊柱的稳定性破坏有关,因此,配合经皮椎弓根螺钉内固定,脊柱可达到即刻稳定,为术后感染控制、植骨融合提供良好的力学基础[42]。
布鲁氏菌性脊柱炎的病理特性决定了其手术方式的多样性,结合目前脊柱手术的发展趋势,单一后路或前路手术均可达到病灶清除、重建脊柱稳定性及病变节段融合的目的。术者应根据自身技术特点实施对患者创伤最小的外科手术,内镜及通道下的微创手术值得多中心共同探索,也更加符合加速康复外科理念及当下患者的医疗需求。
三、注意事项
布鲁氏菌性脊柱炎患者手术切口为Ⅲ类切口,术后常规预防性使用抗生素与正常患者无区别。要根据患者症状、体征、实验室检查结果及具体情况决定抗生素使用时间;并发神经功能受损者需予营养神经的对症治疗。此外,术后严密关注点还包括患者生命体征及体位、手术切口的渗血及引流情况、脊髓神经功能恢复情况、康复训练、心理护理及生活护理,以及并发症的预防等。
共识8:布鲁氏菌性脊柱炎的药物治疗主要采用抗生素治疗,包括利福平、左氧氟沙星、多西环素、头孢曲松、链霉素等,利福平+多西环素联合治疗一般能取得良好效果。
共识9:布鲁氏菌性脊柱炎的手术治疗,一期后路或前路手术均可达到病灶清除、重建脊柱稳定性及病变节段融合的目的。术者应根据自身技术特点实施对患者创伤最小的外科手术,在严格把握手术指征的基础上将手术时机前移可早期减轻患者疼痛,改善生活质量,缩短治疗疗程。
总结与展望
布鲁氏菌性脊柱炎应引起足够重视,对患者的诊治在科学的角度上达成共识是一项艰巨的任务,尤其是在药物治疗及手术治疗方面有许多经验需要总结,仍有许多问题需要探讨与深入研究。未来,对布鲁氏菌性脊柱炎的防治研究应在以下方面进一步开展:(1)开展大规模多中心的流行病学研究,建立国家或地区性的登记系统和数据库;(2)疾病早期诊断技术及生物标志物的研究;(3)更为有效及规范的治疗方案的研究;(4)加强手术方式的进一步改善及规范化研究;(5)疾病防治措施的进一步落实与推广。本共识是对布鲁氏菌性脊柱炎患者临床诊治的初步探讨,因编者水平有限,难免存在疏漏和不足,尚需逐步完善。
执笔者 地里下提·阿不力孜 范俊 马良
编写组成员(排名不分先后) 地里下提·阿不力孜、高辉、唐伟、古甫丁、马良、盛杰(新疆医科大学第八附属医院);秦世炳、范俊、李元、董伟杰、兰汀隆、唐恺(首都医科大学附属北京胸科医院);艾克拜尔·哈力克(乌鲁木齐市卫生健康服务指导中心);蒲育、何敏(成都市公共卫生临床医疗中心); 张强(首都医科大学附属北京地坛医院);朱昌生(西安市胸科医院);朱德智、王文胜、张少华(内蒙古自治区第四医院);刘丰胜、贾晨光(河北省胸科医院);张文龙、鲍玉成(天津市海河医院);王锁柱(太原市第四人民医院);夏平(武汉市第一医院);王传庆(山东省胸科医院);石仕元(杭州市红十字会医院);谢伟、徐尚胜(青海第四人民医院);陈其亮、姚林明(陕西省结核病防治院)
利益冲突 所有作者均声明不存在利益冲突
作者贡献 地里下提·阿不力孜、秦世炳:酝酿和设计、起草文章、对文章知识性内容作批评性审阅;范俊、马良:采集数据、分析/解释数据、起草文章
参考文献
Human brucellosis
Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens. Molecular studies have shed new light on the pathogenesis of Brucella spp, and new technologies have permitted the development of diagnostic tools that will be useful in developing countries, where brucellosis is still a very common but often neglected disease. However, further studies are needed to establish optimum treatment regimens and local and international control programmes. This Review summarises current knowledge of the pathogenic mechanisms, new diagnostic advances, therapeutic options, and the situation of developing countries in regard to human brucellosis.
Major emerging and re-emerging zoonoses in China: a matter of global health and socioeconomic development for 1.3 billion
Human brucellosis in the People's Republic of China during 2005-2010
Brucellosis spondylitis
Osteoarticu-lar manifestations of human brucellosis: A review
Brucellosis is a common global zoonotic disease, which is responsible for a range of clinical manifestations. Fever, sweating and musculoskeletal pains are observed in most patients. The most frequent complication of brucellosis is osteoarticular involvement, with 10% to 85% of patients affected. The sacroiliac (up to 80%) and spinal joints (up to 54%) are the most common affected sites. Spondylitis and spondylodiscitis are the most frequent complications of brucellar spinal involvement. Peripheral arthritis, osteomyelitis, discitis, bursitis and tenosynovitis are other osteoarticular manifestations, but with a lower prevalence. Spinal brucellosis has two forms: focal and diffuse. Epidural abscess is a rare complication of spinal brucellosis but can lead to permanent neurological deficits or even death if not treated promptly. Spondylodiscitis is the most severe form of osteoarticular involvement by brucellosis, and can have single- or multi-focal involvement. Early and appropriate diagnosis and treatment of the disease is important in order to have a successful management of the patients with osteoarticular brucellosis. Brucellosis should be considered as a differential diagnosis for sciatic and back pain, especially in endemic regions. Patients with septic arthritis living in endemic areas also need to be evaluated in terms of brucellosis. Physical examination, laboratory tests and imaging techniques are needed to diagnose the disease. Radiography, computed tomography, magnetic resonance imaging (MRI) and bone scintigraphy are imaging techniques for the diagnosis of osteoarticular brucellosis. MRI is helpful to differentiate between pyogenic spondylitis and brucellar spondylitis. Drug medications (antibiotics) and surgery are the only two options for the treatment and cure of osteoarticular brucellosis.
Spinal brucellosis in Hulunbuir, China, 2011-2016
To investigate the demographic, epidemiological, clinical, and laboratory characteristics; treatment options; and outcome of human brucellosis with spine involvement at a major hospital in Hulunbuir, a brucellosis epidemic region of China. A total of 842 patients with human brucellosis treated in the Department of Brucellosis, Hulunbuir People's Hospital from January 2011 to December 2016 were included and analyzed in this study. The results of 67 brucellar spondylodiscitis (BS) cases were compared with those that were negative for spine involvements. The mean age of spinal brucellosis patients was 50.5±10.2 years (43 males and 24 females; age range 29-70). The risk factors for transmission are direct contact with animals, such as working in the farm, and consumption of unpasteurized milk or daily products. Back pain (92.5%), fever (85.1%), sweating (62.7%), and fatigue (52.8%) were the most common symptoms. Magnetic resonance imaging (MRI) was performed in all the patients with spondylodiscitis. The sites of involvement were lumbar (81.2%), thoracic (8.7%), cervical (4.3%), thoracolumbar (2.9%), and lumbosacral (2.9%). All isolates from blood culture were identified as, with 61% biovar 3 and 39% biovar 1 isolates. The antimicrobial therapy for BS lasted for at least 3 months. In the presence of paravertebral or epidural abscess, longer treatment was conducted to avoid possible sequelae. In endemic areas such as Hulunbuir, BS should be considered in patients with back pain and fever. MRI is a highly sensitive imaging modality that can be used to differentiate BS from other spinal infections. This study will be helpful to establish strategies for prevention, surveillance, and management of spinal brucellosis in China.
Brucellar spondylitis
布鲁菌病合并脊柱炎120例临床研究
全国结核分枝杆菌潜伏感染率估算专家共识
布鲁氏菌病诊疗指南(试行)
Tuberculous and Brucellar Spondylodiscitis: Comparative Analysis of Clinical, Laboratory, and Radiological Features
This was a retrospective study.The aim was to compare the clinical, laboratory, radiological, and evolutionary features of tuberculous spondylodiscitis (TS) and brucellar spondylodiscitis (BS).Clinical presentation of spondylodiscitis varies according to the underlying etiology, among which brucellosis and tuberculosis represent the primary cause, in endemic countries. Only a few studies have compared the characteristics between TS and BS.A retrospective study was conducted using the data of all patients hospitalized for TS and BS in the infectious diseases department between 1991 and 2018.Among a total of 117 patients, 73 had TS (62.4%) and 44 had BS (37.6%). Females were significantly more affected with TS than males (56.2% vs. 22.7%, p<0.001). Fever (72.7% vs. 45.2%, p=0.004) and sweating (72.7% vs. 47.9%, p=0.009) were significantly more frequent among patients with BS. The median erythrocyte sedimentation rate was significantly higher in the TS group (median, 70 mm/hr; interquartile range [IQR], 45-103 mm/hr) than in the BS group (median, 50 mm/hr; IQR, 16-75 mm/hr) (p=0.003). Thoracic involvement was significantly more frequent in the TS group (53.4% vs. 34.1%, p=0.04), whereas lumbar involvement was significantly more frequent in the BS group (72.7% vs. 49.3%, p=0.01). Initial imaging findings revealed significantly higher frequencies of posterior vertebral arch involvement, vertebral compaction, and spinal cord compression in the TS group. Percutaneous abscess drainage (20.5% vs. 2.3%, p=0.005) and surgical treatment (17.8% vs. 2.3%, p=0.01) were more frequently indicated in the TS group, with a significant difference.A combination of clinical, laboratory, and radiological features can be used to distinguish between TS and BS while these patients await diagnosis confirmation.
Seronegative brucellosis of the spine: A case of psoas abscess secondary to brucellar spondylitis
Polymerase chain reaction-based assays for the diagnosis of human brucellosis
Real-time PCR assays for diagnosing brucellar spondylitis using formalin-fixed paraffin-embedded tissues
Implications of laboratory diagnosis on brucellosis therapy
The role of CXCR3 and its ligands expression in Brucellar spondylitis
腰椎布氏菌性脊柱炎影像与病理观察
布氏杆菌性脊柱炎MRI征象与病理对照分析
Granulomatous infective spondylitis in a patient presenting with progressive difficulty in walking: the differential between tuberculosis and brucellosis
Characteristics of isolated spinal cord involvement in neurobrucellosis with no corresponding MRI activity: A case report and review of the literature
Discrimination of pyogenic spondylitis from brucellar spondylitis on MRI
Cervical spinal brucellosis: a diagnostic and surgical challenge
布氏杆菌性脊柱炎诊断与治疗研究进展
Current therapeutic strategy in osteoarticular brucellosis
Brucellosis is a common zoonotic disease with high morbidity. In the majority of human cases, the causative agent is B. melitensis. Infection is transmitted to humans by direct/indirect contact with the contaminated animal products (e.g., consumption of unpasteurized milk), infectious aerosols and aborted fetus. Brucellosis often affects middle-aged adults and young people. Patients with brucellosis tend to have non-specific symptoms, including fever, chills, night sweats, joint pain and myalgia. Brucellosis affects various organs and tissues. The osteoarticular system is one of the most commonly described affected systems in humans. In several clinical studies, the prevalence of Osteoarticular Brucellosis (OB) is reported as 2-77%. Most important osteoarticular clinical forms osteomyelitis, spondylitis, sacroiliitis, arthritis and bursitis. Spondylitis and spondylodiscitis are the most frequent complications. Spondylodiscitis often affects the lumbar (especially at the L4- L5 levels) and low thoracic vertebrae than the cervical spine. Back pain and sciatica radiculopathy are the most common complaints about patients. Sacroiliitis is associated with severe pain, especially back pain in affected individuals. Spinal destructive brucellar lesions are also reported in adults in previous studies. Brucellosis is diagnosed with clinical inflammatory signs (eg. tenderness, pain) of the affected joints together with positive serological tests and positive blood/synovial fluids cultures. Serological test measures the total amount of IgM/IgG antibodies. Standard agglutination test (SAT) titer ≥1:160 is in favor of brucellosis diagnosis. Enzyme-Linked Immunosorbent Assay (ELISA) and Polymerase chain reaction (PCR) are other types of diagnostic tests. Radiological assessments, such as joint sonography, computed tomography, magnetic resonance imaging, are the most helpful radiological methods to diagnose spinal brucellosis. The agents commonly used in the treatment of brucella spondylitis are doxycycline, streptomycin, gentamicin, ciprofloxacin, trimethoprim/sulfamethoxazole and rifampicin. The recommended regimens for treatment of brucella involve two or three antibiotics combinations. No standard treatment, physicians prescribe drugs based on conditions of the disease. Patients need a long-term (usually at three months) antibiotic therapy for mainly aiming to prevent relapses. Surgery may be required for patients with spinal abscess. This review focused on physicians' awareness for osteoarticular involvement, clinical presentation, diagnosis and current treatment of OB.Copyright: © 2019 by Istanbul Northern Anatolian Association of Public Hospitals.
Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal brucellosis [ISRCTN31053647]
Clinical Effect of Doxycycline Combined with Compound Sulfamethoxazole and Rifampicin in the Treatment of Brucellosis Spondylitis
Cervical spinal tuberculosis combined with brucellosis
Spinal stenosis caused by epidural and paraspinal abscess due to brucella Infection
Human brucellosis is a common zoonotic infectious disease in the world. Spinal epidural abscess development in brucellosis is a rare but serious complication. We aimed to discuss the clinical, radiological and serological findings of the spinal stenosis caused by epidural and paraspinal abscess due to brucella infection. Treatment of the abscess usually consists of surgical drainage, decompression and antibiotherapy. In our case, since the Brucellar spinal epidural abscess was diagnosed in the early period, it was improved with medical treatment without any surgical intervention. In the early diagnosis of the disease, serology and culture as well as magnetic resonance imaging are extremely important..
The application of surgical treatment in spinal brucellosis
Cervical Spine Spondylitis with an Epidural Abscess in a Patient with Brucellosis: A Case Report
布氏杆菌性脊柱炎的规范化诊断及外科标准化治疗
One-stage surgical management for lumber brucella spondylitis with anterior debridement, autogenous graft, and instrumentation
Surgical management for lumbar brucella spondylitis: Posterior versus anterior approaches
腰椎后路融合手术对失稳模型节段稳定性及相邻节段力学的影响
Single-stage transforaminal decompression, debridement, interbody fusion, and posterior instrumentation for lumbosacral brucellosis
Background: Spinal brucellosis is a less commonly reported infectious spinal pathology. There are few reports regarding the surgical treatment of spinal brucellosis in existing literature. This retrospective study was conducted to determine the effectiveness of single-stage transforaminal decompression, debridement, interbody fusion, and posterior instrumentation for lumbosacral spinal brucellosis.Methods: From February 2012 to April 2015, 32 consecutive patients (19 males and 13 females, mean age 53.7 +/- 8.7) with lumbosacral brucellosis treated by transforaminal decompression, debridement, interbody fusion, and posterior instrumentation were enrolled. Medical records, imaging studies, laboratory data were collected and summarized. Surgical outcomes were evaluated based on visual analogue scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopaedic Association (JOA) scale. The changes in C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), clinical symptoms and complications were investigated. Graft fusion was evaluated using Bridwell grading criteria.Results: The mean follow-up period was 24.9 +/- 8.2 months. Back pain and radiating leg pain was relieved significantly in all patients after operation. No implant failures were observed in any patients. Wound infection was observed in two patients and sinus formation was observed in one patient. Solid bony fusion was achieved in 30 patients and the fusion rate was 93.8%. The levels of ESR and CRP were returned to normal by the end of three months' follow-up. VAS and ODI scores were significantly improved (P < 0.05). According to JOA score, surgical improvement was excellent in 22 cases (68.8%), good in 9 cases (28.1%), moderate in 1 case (3.1%) at the last follow-up.Conclusions: Single-stage transforaminal decompression, debridement, interbody fusion, and posterior instrumentation is an effective and safe approach for lumbosacral brucellosis.
MIS-TLIF单侧与双侧椎弓根钉内固定治疗腰椎间盘突出症合并腰椎不稳的疗效比较
MIS-TLIF单侧固定与双边侧固定治疗单节段腰椎退行性疾病的疗效对比
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