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病例漫谈99:胸部结核的罕见临床表现:更好地了解该病症的必要性 [复制链接]

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Background

Tuberculosis is one of the most common systemicinfectious disease, and a major public health problem all over the world. Ithas several forms of presentation and clinical manifestations and remains animportant cause of preventable death in the adult population. An uncommon formof pulmonary tuberculosis is endobronchial tuberculosis, which accounts forabout 10–40% of the cases of active tuberculosis. It may be complicated bytracheobronchial stenosis, and fistula formation is an unusual complication,mainly in the region of the pleura and less frequently in the oesophagus (BEF).Increased risk of acquiring these rare complications occurs largely inimmunocompromised people (e.g., HIV, malignancies, and patients undergoingimmunesuppressi-

vetherapy). In these cases, the diagnosis is often missed or delayed.

背景

肺结核是最常见的全身性传染病之一,也是全球主要公共卫生问题之一。该病症有多种表现形式和临床表现,仍是引起成人死亡的重要原因之一。肺结核的一种罕见表现形式是支气管内膜结核,约占肺结核病例的10-40%。该病症可能并发气管支气管狭窄,瘘管是一种少见的并发症,多数形成于胸膜区,少数形成于食道(BEF)。这种罕见并发症多发于免疫功能受损的患者(如艾滋病患者、恶性肿瘤患者和接受免疫抑制治疗的患者),且诱发风险更高。在这些病例中,往往会发生诊断失误或延误。


Tubercular lymphadenitis can also lead to fistulaformation through a process of caseum necrosis and opening of a fistula betweenthe bronchus and oesophagus.

结核性淋巴结炎通过酪状碎屑坏死及支气管和食管之间的瘘管开放的过程同样会导致支气管食管瘘的形成。


The purpose of this article is to discuss a case reportof thoracic tuberculosis that showed an unusual presentation, emphasizing theimportance of an early diagnosis in order to reduce both the risk of mortalityand prevent the spread of infection to the community.

这篇文章旨在探讨一例有罕见临床表现的胸椎结核病例,并强调早期诊断对于降低死亡率及预防群体感染的重要性。


Case Report

An immunocompetent 73-year-old Caucasian man who is anex-smoker of 42 pack-years, presented in the past 6 months with a history ofaccessional nonproductive cough that appeared during meals, especially afteringestion of liquids, and a significant weight loss of 10 kg in a year. He hadno fever, dyspnea, night sweats, chest pain, or hemoptysis. There was no familyhistory of tuberculosis or previous contact with a TB patient. He had nosignificant past medical or surgical history and prior to the onset of coughingduring meals, remarkable respiratory symptoms were not reported.

病例报告

病例报道了一例73岁,免疫功能正常的白人男性患者,有42年吸烟史,已戒烟。在过去6个月里,患者在饮食过程中伴有干咳,在食用液体食物时尤其明显。同时在一年内患者暴瘦了10公斤。患者无发热、呼吸困难、盗汗、胸痛和咯血症状。患者家族没有结核病史,本人也从未接触过结核患者。既往无任何与该病症有关的用药史或手术史,干咳症状出现之前无明显呼吸系统症状。


During the first 6 months, on the basis of a clinicalsuspicion of gastroesophageal reflux, he was initially, treated by a generalpractitioner, with a standard dose of proton pump inhibitors (PPI) therapy. Dueto the lack of a treatment response, in June 2013, he underwent a bariumcontrast swallow test. The chest X-ray examination performed with a bariumcontrast showed the presence of a fistula extending from the lower tract of theesophagus to the right main bronchus (Figure 1), without evidence of activeparenchymal lung infiltrates or pleural involvement.

6个月内怀疑为胃食管反流,全科医生给予标准剂量的质子泵抑制剂(PPI)进行治疗。由于治疗效果不佳,20136月,他接受了钡餐造影检查。钡剂造影胸部X线检查的结果表明患者存在一个从食管下道延伸到右侧主支气管的瘘道(图1),无肺部软组织浸润或胸膜受累的迹象。

Figure 1. Fistula demonstrated by barium contrast swallowfrom

the middle third and lower third of the esophagus to theright main bronchus.

1. 钡餐造影法可见从食管中下1/3到右主支气管的瘘道。


He was then endoscopically treated by application ofmetal clips in the esophagus for fistula closure. No chest CT scan wasperformed in this first phase of the diagnostic process.

随后患者行内镜食管瘘金属圈夹闭。第一阶段的诊断未进行胸部CT扫描。


For persistence of cough, on July 2013 the patient wassent to our Clinic where, after chest CT scan, he underwent a flexiblefiberoptic bronchoscopy in an outpatient setting.

20137月,患者因持续性咳嗽再次入院,在经胸部CT扫描后,在门诊部进行了支气管镜检查。


Routine blood investigation results were normal; only anincrease of PCR (3.45 mg/dl) was found. Serum QuantiFERON testing was positive(2.41 IU/mL). The remaining systemic examination revealed no abnormality.

患者血常规检测正常;仅PCR3.45毫克/升)检测结果偏高。血清 QuantiFERON结果呈阳性(2.41 IU /毫升),其他全身检查未见异常。


The chest CT scan “with contrast” showed a significantenlargement of mediastinal lymph nodes (Figure 2A) that caused trachealcompression with deflection to the right side and reduction of its lumen forpresence of an endoluminal vegetating lesion. Several other enlarged lymphnodes were seen in the right supraclavicular and axillary area, but there wasno associated parenchymal infiltrates.

胸部CT对比扫描表明纵隔淋巴结肿大(图2A),进而造成气管右侧受压迫,管腔空间缩小,引发腔内增殖病变。右侧锁骨和腋窝区也发现了淋巴结肿大,但无并发性软组织浸润。

Figure 2. (A) CT scan of chest (coronal view)pre-antitubercolosis treatment showing a mediastinal lesions.

(B) CT scan of chest (coronal view) during antitubercolosistreatment showing regression of mediastinal lesions.

2.(A) CT扫描(冠状面)显示为抗结核治疗前纵膈内淋巴结肿大

(B) CT扫描(冠状面)显示抗结核治疗后纵膈淋巴结缩小。



Bronchoscopy revealed a mild inflammation of thebronchial mucosa and the presence of different vegetating lesions in thecarina, on the medial wall of the main bronchi, and on the lateral wall of theintermedius bronchus (Figure 3).

支气管镜检查结果显示支气管粘膜有轻度炎症,同时隆突、主支气管内壁和中间支气管侧壁均有不同程度的增殖性病变(3)

Figure 3. Bronchoscopic view showing a vegetatinglesions.

3. 支气管镜下视图显示增殖性病变


Histopathology revealed moderate chronic granulomatousinflammation characterized by the presence of lymphocytes,
histiocytes, and Langhans-type giant cells. Bronchialaspirate test results for routine culture, fungal, and AFB (acid-fast bacilli)were negative.

组织病理学检查提示中度慢性肉芽肿性炎症,该病症以存在淋巴细胞、组织细胞和朗格汉斯型巨细胞为特征。常规培养,真菌和AFB(抗酸杆菌)的支气管抽吸试验结果均为阴性。


The patient was re-evaluated after a week byesophagoscopy and bronchoscopy, mainly for worsening symptoms and for thereevaluation of the fistula. The first reconfirmed the persistence ofbronchoesophageal fistula, so further endo-clips were placed. Thebronchoscopy control showed that the vegetating lesions had increased in size,so a laser treatment was performed with lumen desobstruction. Bronchialaspirate testing confirmed the presence of a marked lymphocytic and histiocyticinflammatory infiltrate with giant cells and granulomatous component withoutcentral necrosis. Results of a microscopic examination and molecular test (PCR)for Koch’s bacillus were negative.

一周后,由于病情恶化同时为了再评价瘘道的状况,患者进行了食管镜和支气管镜检查,对病情做出再评估。首次确定患者患有持久性食管支气管瘘,并安置了深度内镜夹。支气管镜对比检查显示增殖性病变区扩大,固以激光治疗法疏通管腔。支气管抽吸检查证实存在伴随巨细胞的显著性淋巴细胞和组织细胞炎症渗透和无中央坏死的肉芽肿性成分。科赫氏芽孢杆菌的显微镜检查和分子检测(PCR)结果均为阴性。


Based on the pathological pattern, we decided to start astandard antitubercular treatment with isoniazid 300 mg daily, rifampin 600 mgdaily, pyrazinamide 1500 daily, and ethambutol 1200 mg daily. The patient wasplaced in isolation with negative pressure inside the room.

基于病理学特点,我们决定给予患者标准抗结核治疗:异烟肼300毫克/天,利福平600毫克/天、吡嗪酰胺1500毫克/天和乙胺丁醇1200毫克/天。病人被安排住在负压隔离监护病房。


After 40 days, the culture of the first bronchoscopicbiopsy demonstrated the growth of Mycobacterium tuberculosis (Lowenstei-Jensenmedium and Bactec Mycobacteria Growth Indicator Tube (MGIT) 960 TB System). Thedrug susceptibility test did not show any resistance to the first-line drugs.Our patient continued anti-tuberculous treatment for 2 months, followed byrifampicin and isoniazid treatment for the following 4 months.

40天后,首次支气管镜检培养证实结核分枝杆菌的生长(Lowenstei-Jensen培养基和分枝杆菌生长指示管(MGIT960 TB系统)。药敏试验未表现出对一线药物的任何耐药性。患者进行了持续2个月的抗结核治疗,而后接受了4个月的利福平和异烟肼治疗。


During antitubercular treatment, symptoms progressivelyimproved. CT and bronchoscopy performed 2 months later showed regression oflymph node enlargement (Figure 2B) and the disappearance of intraluminallesions in the tracheobronchial tree. Bronchoscopy also showed thebronchoesophageal fistula closure (Figure 4).

抗结核治疗过程中症状逐渐减轻。2个月后行CT和支气管镜检查显示淋巴结缩小(图 2B)和支气管腔内病变消失。支气管镜也显示支气管食管瘘闭合(图4)。

Figure 4.Bronchoscopic view: scar tissue of the fistula.

4. 支气管镜下视图:肛瘘的疤痕组织


At 6-month and 1-year follow-up, physical andbronchoscopy examinations did not show evidence of recurrence, a chest CT scanat 1 year demonstrated no evidence of mediastinal lymphadenopathy, and symptomsof patient were resolved. The final diagnosis was “bronchoesophageal fistula inendobronchial tuberculosis and mediastinal lymphadenopathy”.

6个月和1年的随访中,身体检查和支气管镜检查均未发现复发迹象,1年后胸部CT扫描未显示纵隔淋巴结肿大,病人的症状得以解除。最终诊断为支气管内膜结核和纵隔淋巴结肿大的食管支气管瘘


Discussion

Bronchoesophageal or tracheoesophageal fistula isextremely rare in adults. It is more frequently a congenital condition;otherwise, the acquired forms, are usually secondary to primary neoplasm(benign, malignant, or metastatic), infectious diseases (tuberculosis,histoplasmosis, actinomycosis, and syphilis), traumatic events (sequels ofsurgical procedures), and connective tissue diseases. Broncho-esophagealfistula (BEF) in adults is commonly due to malignancy, mainly oesophaguscarcinoma and, less frequently, lymphoma, carcinoma of the lungs or trachea.Benign BEF is a rare condition. The fistula has a short course and usually thecommunication is pervious, permitting the passage of air in the stomach andliquids in the airways. The clinical symptoms and signs that occur as a resultof attempted oral feeding are closely related to the size of the fistula andare characterized by chest pain, dyspnea, barking cough, cyanosis, hemoptysis,and sputum production; in some cases episodes of pneumonia and otherrespiratory infections can occur through a mechanism of “aspiration”.

讨论

支气管食管或气管食管瘘极少发生于成人。该病症多为先天性疾病;若后天形成,则通常继发于原发性肿瘤(良性,恶性,或转移性)、传染性疾病(结核病、组织胞浆菌病、放线菌病、梅毒),创伤性(手术后遗症)和结缔组织疾病。成年支气管食管瘘(BEF)的发生通常是由于恶性肿瘤,主因为食管癌,少数为淋巴瘤、肺部或气管肿瘤。临床少见良性BEF。瘘道具有病程短、可透过胃中的空气和气道中的液体的特点。进食时出现的临床症状及体征与瘘口的大小密切相关,表现为胸痛、呼吸困难、犬吠样咳嗽,发绀,咯血和咳痰;在某些病例中出现的肺炎和其他呼吸道感染是通过一种吸入机制所致。


Endobronchial tuberculosis (EBTB), defined as“tuberculous infection of the tracheobronchial tree with microbial andhistopathological evidence”, is a particular form of TB. Described for thefirst time by Mortem in 1698, represents about 10–40% of cases of active TB.It’s more common in young adults, with a female predominance, and only 15% inelderly patients. Often dangerous for its consequences (trachea andbronchostenosis, recurrent pneumonia, atelectasis and respiratory failure) ispotentially an important source of infection spread in the community. Itspathogenesis remains unclear; however, different mechanisms have been suggestedand the more plausible are: direct implantation of Mycobacterium tuberculosis(Mt) in the bronchus after their inhalation, or direct extension of infectionfrom parenchymal lesions or erosion and infiltration from adjacent mediastinallymph nodes into the bronchus.

支气管内膜结核(EBTB)是指伴随有微生物和组织病变的支气管树的结核感染,是结核病的一种特殊形式。1698年,Mortem首次描述了支气管内膜结核,提出此疾病约占活动性肺结核的10~40%。年轻人更易出现支气管内膜结核病,其中以女性居多,老年人仅占所有患者的15%。该病引起的危险性后果(气管和支气管狭窄、复发性肺炎、肺不张、呼吸衰竭)可能是群体性感染的重要传染源。其发病机制目前尚不清楚;但研究人员已经提出了许多不同的机制,其中较合理的几个观点为:直接吸入结核分枝杆菌(Mt)至支气管,或实质性病变的感染扩大,或从相邻纵隔淋巴结到支气管的侵蚀和浸润。


The mediastinal tuberculous lymphadenitis is rare in theabsence of simultaneous lung involvement in immunocompetent adultswhile it maybe observed more frequently in HIV-positive patients and in developingcountries with high rates of TB just as it is in sub-Saharan Africa.

结核性纵隔淋巴结炎极少发生于免疫功能正常且未有肺部病症的成年人,多发于HIV阳性患者以及肺结核发病率较高的发展中国家例如撒哈拉以南非洲地区。


During primary TB, tubercle bacillus reaches themediastinal or hilar lymph nodes causing lymph node enlargement but theparenchymal infiltrate in an immunocompetent subject may resolve withoutsequels at conventional radiography. Mycobacterium tuberculosis may stayinactive (dormant) for many years inside the lymph nodes and becomes activeagain during decreased immune status, as for example in the elderly.

在原发性肺结核中,结核杆菌感染纵隔或肺门淋巴结,引发淋巴结肿大,但实质浸润的患者如果免疫功能正常,那么在未行常规X线摄影的情况下该症状也可能消除。结核分枝杆菌可能在淋巴结内以不活跃状态(休眠)潜伏多年,在免疫状态下降时,例如在老年人身上会再次激活。


Our clinical case was characterized by severalcriticisms:

我们的临床案例指出了如下几个观点:


• The considerable delay with which the patient has beensubject to a chest CT scan and bronchoscopy. Bronchoscopy should be donepromptly in the case of a fistula suspicion. The cough during meals wouldsuggest the presence of a bronchoesophageal fistula and this suspicion involvesthe assessment of the cause.

患者治疗耽误主要在胸部CT扫描及支气管镜检查。一旦有瘘管的可疑症状,就应及时进行支气管镜检查。就餐时咳嗽暗示存在支气管食管瘘,也能用于评估疾病病因。


• Usually, it is thought that microbiological examinationof bronchial aspirate and BAL are positive for Mycobacterium tuberculosis inpatients with EBTB, and that examination provides a good diagnostic yield. Astudy conducted by Ozkaya et al. highlights the difficulty of thebacteriological diagnosis of EBTB based on BAL analysis, bronchial aspirate, orsputum analysis, and showed that a high diagnostic yield was obtained throughthe histopathologic examinations of bronchial biopsies, confirmed in ourclinical case.

通常认为有EBTB类分枝杆菌结核病患者的支气管抽吸和支气管肺泡灌洗液的微生物检查呈阳性,而这项检查有利于得到好的诊断率。由Ozkaya等人进行的研究强调了支气管内膜结核基于支气管肺泡灌洗液分析,支气管抽吸或痰液分析的细菌学诊断面临的困境,同时本临床病例证实,较高的诊断率是通过支气管活检的组织病理学检查获得的。


• Chest x-ray, performed on our patient in the firstinstance, did not pose a suspicion of TB. There were no direct signs such asparenchymal consolidation, or pneumonia and/or excessive gastric and intestinalgasification as expression of communication between the oesophagus and airway,specific lesions of active TB or inactive as scarring; complications ofendobronchial TB (recurrent pneumonia or atelectasis) or mediastinum lymph nodeenlargement. In fact, up to 20% of patients with EBTB have a normal chestradiograph.

在第一次就诊时,患者进行的胸部X光检查未显示结核病的可疑症状。没有如实质合并,肺炎和/或食道和气道之间过度的胃肠道气化,活动性结核或非活性疤痕的特异性病变等直接迹象;也没有支气管内膜结核并发症(复发性肺炎或肺不张)或纵隔淋巴结肿大。事实上,超过20%EBTB患者胸片检查正常。


• The presence of non-specific symptoms such as cough,only present during meals, simulated a gastro-esophageal reflux disease. Infact, despite the bronchial obstruction, the patient didn’t have any symptomsof endobronchial tuberculosis. EBTB, may sometimes present with a veryinsidious onset and, in some cases, it may simulate other pathologicalconditions such as bronchogenic carcinoma or bronchial asthma. This symptom canmimic many diseases, misleading the doctor for a proper diagnosis. Moreover,several studies showed that, in the elderly, the classic signs and symptoms ofTB, such as fever, weight loss, night sweats, and hemoptysis and sputumproduction are sometimes absent compared to young adult.

一些非特异性症状,如进食时咳嗽,会误判为胃食管反流病。事实上,尽管患者支气管受阻,仍不会表现任何支气管内膜结核的症状。支气管内膜结核有时会呈现较长的潜伏期,在某些情况下,它也可能表现为其他疾病如肺癌或支气管哮喘。这种症状可以掩盖许多疾病,进而误导医生的准确诊断。此外,一些研究表明,老年人较年轻人更不会表现出经典的结核病体征和症状,如发热、消瘦、盗汗、咯血、咳痰。


• Pathogenesis of bronchoesophageal fistula in thisspecific case report remains difficult to interpret. It may be secondary toendobronchial tuberculosis, through a mechanism of erosion of the bronchialwall, involvement of mediastinal lymph nodes and then fistula formation into theesophagus. However, the absence of parenchymal involvement, makes unlikely thismechanism. Much more probable, was a reactivation of a primary infection inperitracheal and peribronchial lymph nodes, as a consequence of animmunodepression state, subsequent lymph node erosion intooesophagus and bronchus and fistulization with a consequent implantation of Mtin the bronchial mucosa and secondary endobronchial TB onset. Similar studiesshow that both mechanisms are uncommon or rare complications of thoracic tuberculosis.As far as we know, no cases have been reported in the literature withsimultaneous combination of bronchoesophageal fistula, endobronchialtuberculosis without parenchymal involvement, mediastinal tuberculouslymphadenitis in the elderly.

这个具体的病例报告中食管支气管瘘的发病机制目前尚难以解释。可能是继发于支气管内膜结核,通过对支气管壁的侵蚀作用、累及纵隔淋巴结,而后在食管形成瘘。然而,这一作用过程不能缺少实质的参与。更可能的机制是气管和支气管周围淋巴结的感染复发,而后产生免疫抑制应答,继而淋巴结侵蚀食管,支气管和食瘘,在支气管粘膜产生结核分枝杆菌和二次支气管结核。类似的研究表明,这两种机制都是少见或罕见的胸椎结核并发症。据我们所知,文献中尚未报道并发支气管食管瘘,无实质性累及的支气管内膜结核和纵隔淋巴结核的老年患者。


Despite the delay and the mismanagement, the patient hasresponded optimally to a standard treatment with isoniazid, rifampicin,pyrazinamide and ethambutol for 2 months, followed by isoniazid and rifampicinfor a further 4 months. The 1-year follow-up showed healing of tuberculosis,without evidence of recurrence.

尽管治疗受到拖延且处理失当,给予患者标准剂量治疗还是得到了最佳疗效,其治疗方式为服用异烟肼,利福平、吡嗪酰胺和乙胺丁醇2个月,而后进一步服用异烟肼和利福平4个月。随访1年的结果显示,肺结核已愈合且无复发迹象。


Conclusions

Bronchoesophageal fistula is a rare manifestation of acommon disease such as tuberculosis.

结论

支气管食管瘘是肺结核等常见疾病的罕见临床表现。


We know that early diagnosis and proper treatment maymodify the natural course of this disease and increase the rate of healing.Therefore, if not treated, severe complications may occur, endangering thepatient’s life.

众所周知,早期诊断和合理治疗可以改变这种疾病的自然病程,提高治愈率。因此,如果不及时治疗,患者可能会出现严重的并发症,并危及其生命。


The difficulty of this case report, associated with thelow level of knowledge of the illness and its serious complications, caused adiagnostic delay, deferring the start of an effective antitubercular treatment.

对该疾病及其严重并发症知识的欠缺造成了本病例报告中的困境,耽误了诊断,也拖延了抗结核治疗的开展。


We can not forget that a normal chest radiograph and thepresence of nonspecific symptoms do not exclude the diagnosis of tuberculosis,but even the best early detection is of no use if subsequent treatment isinadequate, or downright wrong.

我们应牢记正常胸片和非特异性症状并不能排除肺结核的可能,如果后续治疗不充分或者完全错误,即使最佳的早期检测也于事无补。



Medicool医库软件 王露黔 赵美凤 编译

原文来自 Am J Case Rep

最后编辑百里小溪 最后编辑于 2016-07-11 15:07:04
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