Spinal tuberculosis in post‐liver transplantation patients: case reports

X.F. Lou, R.H. Wu, S.Z. Xu, X.J. Lin. Spinal tuberculosis in post‐liver transplantation patients: case reports.
Transpl Infect Dis 2010: 12: 132–137. All rights reserved Abstract: Recipients of solid organ transplantation are, because of immunosuppressive therapy, disposed to opportunistic infections including tuberculosis (TB). Spinal TB is a rare complication after transplantation but it is serious with high mortality. We report 3 cases of spinal TB in Chinese recipients of orthotopic liver transplant whose first complaint was back pain. These 3 cases were diagnosed by magnetic resonance imaging and percutaneous biopsy. After treatment with isoniazid, rifampicin, streptomycin, and ethambutol for >1 year, symptoms of 2 patients improved noticeably, but 1 patient died of liver failure and severe mixed pulmonary infection. Diagnosis and treatment regimens of spinal TB are discussed.     

器官移植术后结核病25例临床分析并文献复习

目的 探讨器官移植术后结核病的临床特征、诊断和治疗。方法 分析总结了25例器官移植术后结核病的临床资料并进行了文献复习。结果 68％（17／25）的患者起病时症状轻微，主要表现为发热、咳嗽、乏力和胸闷，肺结核、胸膜炎、血行播散性结核、淋巴结核和肾结核较为常见，72％（18／25）的患者侵犯2个以上器官。影像学多为范围广泛的软性病灶、粟粒结节、胸腔积液、肺门纵隔淋巴结增大和空洞。细菌学和组织学检查有助于诊断。平均确诊时间为38d，治疗总有效率为76％（19／25）。因极度免疫功能低下和肝肾功能损害，无法使用抗结核药物是影响器官移植术后结核病预后的重要因素。结论 应对免疫抑制并发的结核病引起高度重视，正确诊断和及时处理是降低其死亡率的重要手段。     

器官移植患者术后肺部感染23例临床分析

目的探讨器官移植术后肺部感染临床特点，提高其诊治水平。方法回顾分析23例器官移植术后肺部感染的临床资料。结果23例患者中18治愈，2例呼吸衰竭死亡，1例移植肾切除，2例肾功能减退。病原体主要有细菌、病毒、真菌、结核杆菌等，多为混合感染。结论器官移植术后肺部感染早期临床症状、体征不典型，因此临床应加强对器官移植术后肺部感染的认识，力争做到早期诊断，及时采取有效的综合治疗，是降低病死率的关键。     

Clinical features and outcome of tuberculosis in solid organ transplant recipients

BACKGROUND:: Taiwan is an area with moderate to high incidence of Mycobacterium tuberculosis infection. The risk of M tuberculosis infection in transplantation recipients is considered to be significant. Our aim in this study was to investigate the clinical spectrums of M tuberculosis-infected transplantation recipients in a southeast Asian country, Taiwan. METHODS:: We retrospectively analyzed the demographic data, clinical features, treatment, and outcome of M tuberculosis infection in kidney, heart, and liver transplant recipients from May 1996 to April 2005 at the National Taiwan University Hospital. RESULTS:: Fifteen patients who had received solid organ transplantation developed tuberculosis (kidney = 6, heart = 7, liver = 2). The median duration from transplantation to diagnosis of tuberculosis was 31 months. The cumulative incidence of post-transplantation tuberculosis was 2.0% (15/760), ie, approximately 3 times that of the general population. Ten patients (66.7%) had pulmonary tuberculosis, 1 (6.7%) had extrapulmonary tuberculosis, and 4 (26.7%) had disseminated tuberculosis. Nine patients completed the anti-tuberculosis treatment; the median treatment duration was 12 months (pulmonary: 9 months; extrapulmonary: 13.5 months). No treatment failure was noted in patients receiving the complete treatment course. The graft failure and mortality rates of post-transplantation tuberculosis were 13.3% each (2/15). The tuberculosis-associated mortality rate was 6.7% (1/15). CONCLUSIONS:: Cumulative incidence of tuberculosis was slightly higher in transplant recipients than in the general population in Taiwan. Conventional 4-combined anti-tuberculosis regimen for 12 months can treat the potentially fatal infection successfully in post-transplantation tuberculosis patients without recurrence.     

Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation

Solid organ transplantation(SOT)is the best treatment option for end-stage organ disease.Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection,particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis.Active tuberculosis(TB)after SOT is a significant cause of morbidity and mortality.Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection(LTBI)due to the effects of long-term immunosuppressive therapy.Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation.Isoniazid with vitamin B6 supplementation is the treatment of choice.However,liver transplantation(LT)candidates and recipients have an increased risk of isoniazid-induced liver toxicity,leading to lower treatment completion rates than in other SOT populations.Fluoroquinolones(FQs)exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid.In the present review,we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.     

脊柱结核内固定术后复发探讨（附23例报告）

目的 探讨脊柱结核内固定术后复发原因及处理方法。方法 回顾性分析23例脊柱结核内固定术患者的发病及治疗经过以及复发后的表现和再治疗经过。重新调整抗结核药物治疗，并且用药时间为18～30个月；19例行手术病灶清除术及重新植骨，其中2例内固定物取出1例重新行内固定手术；4例单纯行瘘管清创换药。结果 23例患者19例治愈，术后安置病灶引流管相应延长到3-14天；2例耐药术后又瘘管形成，经局部换药及调整结核药物治疗，2年后痊愈，平均用药时间增加6～12个月；2例内固定取出后绝对卧床6～8个月。结论 脊柱结核内固定术后复发是严重的并发症，它影响结核的治疗和预后以及结核的播散问题；规范抗结核治疗和正确的手术时机和方法的选择应引起高度重视；及时调整抗结核药物治疗及瘘管换药和局部结核病灶的进一步清除是治愈结核复发的关键；内固定物取出不是治愈结核的关键条件。     

Paradoxical worsening of tuberculosis in a heart–lung transplant recipient

We report on a heart-lung transplant recipient who presented with pulmonary tuberculosis (TB) 2.5 months after transplantation and then developed a paradoxical reaction after 4 months of adequate anti-TB treatment. She eventually recovered with anti-TB and high-dose steroid treatments. METHODS: Using sequential bronchoalveolar lavages, we assessed the inflammatory response in the lung and investigated the alveolar immune response against a Mycobacterium tuberculosis antigen. RESULTS: The paradoxical reaction was characterized by a massive infiltration of the alveolar space by M. tuberculosis antigen-specific CD4(+) T cells and by the presence of a CD4(-)CD8(-) T lymphocyte subpopulation bearing phenotypic markers (CD16(+)/56(+)) classically associated with NK cells. CONCLUSION: This case report illustrates that even solid organ transplant recipients receiving intense triple-drug immune suppression may be able to develop a paradoxical reaction during TB treatment. Transplant physicians should be aware of this phenomenon in order to differentiate it from treatment failure.     

Aspergillus vertebral osteomyelitis after simultaneous kidney–pancreas transplantation

Abstract: Aspergillus osteomyelitis is a rare complication of invasive aspergillosis after organ transplantation. This is the report of a 46‐year‐old man who underwent a simultaneous pancreas and kidney transplantation, complicated by an Aspergillus osteomyelitis and diskitis of the lumbar spine. Prompt diagnosis with needle biopsy, followed by antifungal therapy using caspofungin, a new antifungal agent recommended for the treatment of refractory aspergillosis, in combination with amphotericin B and an early surgical intervention led to clinical resolution of the infection. Reported cases of spinal aspergillosis after transplantation are reviewed in terms of clinical presentation, risk factors, therapeutic options, and outcome.     

脊柱结核早期误用激素治疗107例分析

目的 探讨糖皮质激素的应用对脊柱结核发展及治疗影响。方法 回顾性分析我院收治的107例脊柱结核患者早期误用糖皮质激素与同期215例未用激素治疗的脊柱结核患者比较其症状、体征、治疗的结果及预后。结果 脊柱结核患者早期误用激素，造成患者发热重、脓肿大，病变部位多发及骨破坏加重，同时需延长用药时间、加大药量，术后并发症多及治愈时间延长。结论 脊柱结核患者应用糖皮质激素促使结核病情加重，影响治疗效果和预后。     

脊柱结核抗结核药物化学治疗的思考

脊柱结核是最常见的肺外结核之一,随着现代影像学、实验室诊断技术的不断进步,脊柱结核的确诊率逐年增高。脊柱结核的治疗原则以抗结核药物化学治疗为根本,营养支持、手术治疗为辅助。作者就脊柱结核化学治疗的特点、时机、方案制定、药物选择、疗程、局部化学治疗、停药指征等进行阐述,为临床治疗提供参考。     

Chemotherapeutic treatment for spinal tuberculosis.

AIM: To evaluate whether 6 months of chemotherapy for patients with spinal tuberculosis prevents relapse as effectively as more than 6 months of chemotherapy. METHOD: Literature review. Medline search including references, from January 1978 to November 2000. Inclusion criteria for publications: diagnosis of spinal tuberculosis confirmed bacteriologically and/or histologically, or probable on the basis of clinical and radiological parameters; treatment regimen (whether or not in combination with surgery) included isoniazid (H), rifampicin (R) and pyrazinamide (Z); follow-up period after completion of treatment of 12 months or more. Exclusion criteria: patients with relapse who had previously been treated adequately for tuberculosis. OUTCOME PARAMETERS: Relapse rate. RESULTS: Four publications were found with HRZ regimens of 6 months' duration and 10 publications with HRZ regimens of >6 months' duration. A number of patients had received HRE (E = ethambutol) for > or = 9 months. In the results, no distinction was made between treatment groups. HRZ for 6 months led to a relapse rate of 0% (0/56, 95%CI 0.0-6.4); follow-up after surgical intervention ranged from 6 to 108 months. HRZ for > or = 9 months (> or = 119 patients) or HRE for > or = 9 months (< or = 71 patients) led to a relapse rate of 2% (4/218, 95%CI 0.6-5.0); follow-up after surgical intervention was 6-168 months. Despite the small number of studies, 6 months of therapy is probably sufficient for patients with spinal tuberculosis.     

Liver transplantation and tuberculosis

Although liver transplantation in Japan has rapidly expanded its indication to adult patients, our experience and measures in posttransplant tuberculosis is still limited. Early posttransplant patients under immunosuppressants generally have a higher risk for tuberculosis and the risk in liver recipients follows that in lung recipients. Rejection treatment is one of the risk factors for infection, dissemination, and mortality of tuberculosis. Drug-induced liver injury by anti-tuberculotic drugs and their interaction with immunosuppressants, combined infection, and increased susceptibility to rejection in posttransplant tuberculosis are major obstacles in the treatment. Evidence-based consensus in the diagnosis and treatment of posttransplant tuberculosis, as well as establishment of speedy and reliable screening method in potential organ donors, are in a pressing need.     

器官移植肺

器官移植的生存率与有无并发症及是否能有效的控制并发症密切相关，肺部由于其自身特点最易出现并发症。本文探讨了器官移植术后肺部常见的并发症——急性呼吸窘迫综合征、肺部感染(包括细菌、结核、真菌、病毒、原虫)和肿瘤的临床特点和防治措施，为临床医生早期诊断和及时、有效地防治肺部并发症提供参考，从而提高器官移植患者的生存率。     

Tuberculosis of the bone marrow: clinico-pathological study of 22 cases from Saudi Arabia.

OBJECTIVE: To study the clinical and pathological patterns of tuberculosis (TB) involving the bone marrow in a tertiary care setting. METHODS: A retrospective study of cases of bone marrow TB diagnosed and treated at King Faisal Specialist Hospital and Research Center from 1990 to 2002. The main criterion for inclusion was the isolation of Mycobacterium tuberculosis from a bone marrow specimen. RESULTS: We identified 22 patients with culture-proven M. tuberculosis infection of the bone marrow. Underlying conditions found in this series include solid organ transplantation in 4 patients (18%), HIV infection in 2 (9%), and diabetes in 3 (14%). No risk factor was identified in 12 patients (55%). Histopathological findings were reported as granuloma in 19 patients (86%) and caseating granuloma in 3 (14%). The outcome was favourable for 11 patients (50%), while 10 (45%) died during hospitalisation and one was lost to follow-up. For patients who completed their regimens, the duration of treatment was 12 months. CONCLUSION: The isolation of M. tuberculosis from a bone marrow specimen is an indication of disseminated disease which carries a high mortality rate and requires prompt initiation of appropriate treatment.     

Unsuccessful treatment of four patients with acute graft-vs-host disease after liver transplantation

AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation.METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed.RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are required for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.     

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-γ based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking.     

前路病椎切除植骨内固定治疗脊柱结核

目的　探讨经脊柱前路结核病灶清除的同时植骨内固定的可行性和必要性 ,以及对脊柱结核的治疗效果。方法　 1998年 2月～ 2 0 0 0年 8月采用脊柱前路病椎切除加植骨 ,并采用Orion或Z plate钢板进行椎体固定。共治疗 12例脊柱结核 ,观察植骨融合及矫正畸形情况和结核病灶愈合情况。结果　经平均 10个月的随访 ,12例患者脊柱结核均治愈 ,植骨与受骨区全部骨性融合 ,融合时间平均为 5 8个月 ,后凸矫正角度平均 16°。全组病例切口均一期愈合。无手术并发症。结论　本方法可经脊柱前路作较彻底的病灶清除 ,并较好地进行脊柱矫形和椎管减压 ,完成脊柱稳定性重建 ,有利于患者早期离床活动和脊柱结核治愈率的提高。     

手术联合置管冲洗引流病灶治疗脊柱结核的Meta分析

目的：系统分析手术联合置管冲洗引流病灶治疗脊柱结核的治疗效果。方法：两位研究者独立对数据库包括中国知网、万方数据知识服务平台、维普数据库、PubMed、EMbase、Cochrane Library进行文献检索,收集关于手术联合置管冲洗引流病灶治疗脊柱结核的随机对照试验 (RCT) 与回顾性研究。语种限中、英文。两位研...     

肾上腺结核的多层螺旋CT诊断

目的 探讨肾上腺结核的多层螺旋CT平扫及增强表现特征,以提高该病的CT诊断水平。 方法 对经临床证实的13例肾上腺结核患者的CT表现特征进行回顾性分析。 结果 13例中,男性8例,女性5例;年龄20～58岁,平均42岁。肾上腺结核累及双侧共12例,单侧1例。肾上腺肿块样增大10例,轻度或中度增大3例,轮廓完整。肾上腺密度均匀增高1例,不均匀增高12例。周边强化11例。4例患者经抗结核治疗后复查CT,其中1例双侧增大的肾上腺体积缩小或恢复正常,其内低密度消失,9例患者行手术治疗,而且术前术后进行了抗结核治疗。早期肾上腺结核 CT 表现为肾上腺体积增大,并见密度不均匀的扁圆形肿块9例,增强扫描后肿块周边强化,其内见线样明显强化的正常肾上腺组织分隔,边缘清楚。晚期肾上腺结核表现为腺体萎缩及钙化4例。8例患者伴有肾上腺外结核,包括肺结核4例、泌尿系结核2例、脊柱结核1例,同时伴有肺结核、左肾结核及脊柱结核1例。 结论 肾上腺结核的CT具有特征性表现,当发现全身多脏器结核,同时发现肾上腺上述影像变化,则要考虑肾上腺结核的诊断,为临床治疗及疗效判断提供指导。     

Psychological response and quality of life after transplantation: a comparison between heart, lung, liver and kidney recipients

PRINCIPLES: Various non-specific questionnaires were used to measure quality of life and psychological wellbeing of patients after organ transplantation. At present cross-organ studies dealing specifically with the psychological response to a transplanted organ are non-existent in German-speaking countries. METHODS: The Transplant Effects Questionnaire TxEQ-D and the SF-36 Quality of Life Questionnaire were used to examine the psychological response and quality of life of 370 patients after heart, lung, liver or kidney transplantation. The organ groups were compared with regard to psychosocial parameters. RESULTS: 72% of patients develop a feeling of responsibility for the received organ and its function. This feeling is even stronger towards the patient's key relationships i.e. family, friends, the treatment team and the donor. 11.6% worry about the transplanted organ. Heart and lung patients report significantly fewer concerns than liver and kidney patients. Overall, only a minority of patients report feelings of guilt towards the donor (2.7%), problems in disclosing their transplant to others (2.4%), or difficulties in complying with medical orders (3.5%). Lung transplant patients show significantly better adherence. CONCLUSIONS: A feeling of responsibility towards those one is close to and towards the donor is a common psychological phenomenon after transplantation of an organ. Conscious feelings of guilt and shame are harboured by only a minority of patients. The fact that heart and lung patients worry less about their transplant might have primarily to do with the greater medical and psychosocial support in this group.