A fatal case of spinal tuberculosis mistaken for metastatic lung cancer: recalling ancient Pott's disease
© Ringshausen et al; licensee BioMed Central Ltd. 2009
Received: 10 September 2009
Accepted: 20 November 2009
Published: 20 November 2009
Tuberculous spondylitis (Pott's disease) is an ancient human disease. Because it is rare in high-income, tuberculosis (TB) low incidence countries, misdiagnoses occur as sufficient clinical experience is lacking.
We describe a fatal case of a patient with spinal TB, who was mistakenly irradiated for suspected metastatic lung cancer of the spine in the presence of a solitary pulmonary nodule of the left upper lobe. Subsequently, the patient progressed to central nervous system TB, and finally, disseminated TB before the accurate diagnosis was established. Isolation and antimycobacterial chemotherapy were initiated after an in-hospital course of approximately three months including numerous health care related contacts and procedures.
The rapid diagnosis of spinal TB demands a high index of suspicion and expertise regarding the appropriate diagnostic procedures. Due to the devastating consequences of a missed diagnosis, Mycobacterium tuberculosis should be considered early in every case of spondylitis, intraspinal or paravertebral abscess. The presence of certain alarm signals like a prolonged history of progressive back pain, constitutional symptoms or pulmonary nodules on a chest radiograph, particularly in the upper lobes, may guide the clinical suspicion.
In 2007, one-fifth of 5,020 tuberculosis (TB) cases reported to the responsible German authority (Robert Koch Institute) were extrapulmonary, mainly lymphatic (9.1%) disease manifestations, but only 0.8% of all adult TB cases were spinal TB . Even though spinal TB is scarce in countries with a low incidence of TB, it is an ancient human disease. While the characteristic clinical features of tuberculous spondylitis were first described in the medical literature by Sir Percivall Pott in 1779 (Pott's disease) , spinal TB has been identified in Egyptian mummies dating back to 3000 B. C. by typical skeletal lesions and consecutive DNA analysis . A delay in diagnosis and timely initiation of treatment of aggressive TB manifestations like central nervous system (CNS) TB or vertebral TB may cause severe and irreversible neurologic sequelae including paraplegia, even if antimycobacterial chemotherapy is available [4, 5]. Moreover, as evidence of either previous or current pulmonary TB is found in approximately half the reported patients, a delay in diagnosis may lead to further significant exposure of contacts, particularly endangering health care workers and thus highlighting TB's potential as a nosocomial and occupational disease .
We report a fatal case of a patient with Pott's disease, who was misdiagnosed and irradiated for metastatic lung cancer of the spine. Subsequently, the patient progressed to CNS TB, and finally, disseminated TB before the accurate diagnosis was established after an in-hospital course of approximately three months including numerous health care related contacts and procedures .
Given the progressive back pain and supposed spinal instability, the patient was referred to another external hospital, where a palliative irradiation of the upper thoracic spine was initiated and a cumulative dose of 36 Gy was applied over three consecutive weeks. However, the patient's condition deteriorated and he soon developed paresthesia and paralysis of both lower limbs. At this point, magnetic resonance imaging (MRI) of the spine revealed an extensive intraspinal abscess, which resulted in compression of the upper thoracic spinal cord. Hence, the patient was immediately referred to the neurotraumatological service of our university hospital for surgical treatment.
When the patient was finally referred to the pulmonary department for further evaluation of the initially suspected metastatic lung cancer on February 28th 2007, he had developed a new brachiofacially accentuated, right-sided hemiparalysis and aphasia. Now, MRI of the brain revealed multiple fresh ischemic bihemispheric and pontine lesions. Again, infectious endocarditis was ruled out.
The patient was febrile with a temperature of 39.3°C despite an antimicrobial regime consisting of Imipeneme/Cilastatin, Vancomycin, Ciprofloxacin, and Metronidazole, which had been administered for the past two weeks. At this time, the major findings on physical examination included cachexia, signs of respiratory distress (a respiratory rate of 25/min, productive cough, but insufficiently coughing up), moderate fluid overload (bilateral basal pulmonary rales, peripheral edema), and a dorsal paravertebral reddish and fluctuating swelling at the site of prior surgery, but no meningeal signs. Furthermore, we observed oral candidiasis and a unilateral segmental herpes zoster rash at the lower back that both indicated relevant immunosuppression. Now, routine laboratory studies showed markedly increased inflammatory activity (CRP 22 mg/dL), but a normal white blood count of 4,900/μL. HIV serology was negative. Remarkably, the interferon-γ release assay QuantiFERON®-TB Gold In-Tube was negative (IFN 0.189 IU/mL).
Summary of microbiological results
TB Culture †
Spinal tumor mass
Morning fasting gastric acid‡
There are some important lessons this fatal case teaches. The clinical diagnosis of TB, particularly extrapulmonary TB, requires a certain extent of clinical suspicion and expertise regarding the adequate diagnostic tests. Along with Staphylococcus aureus and a few other bacteria, MTB is still an important cause of spondylitis, intraspinal or paravertebral abscess. In TB low incidence countries spinal TB is mainly a disease of the elderly, resulting from endogenous reactivation of infectious foci that spread during the initial bacteremia. Pott's disease most often affects the lower thoracic and lumbar spine, while disease of the upper thoracic and cervical spine is potentially more disabling [4, 9, 10]. The most common cause of delay in the diagnosis of Pott's disease is failure to consider the diagnosis. Hence, skeletal TB should always be considered in patients with focal bony abnormalities and a chest radiograph compatible with prior or active TB.
Our patient showed a combination of alarm signals (progressive back pain over several months, presence of a pulmonary nodule of the left upper lobe, night sweats and weight loss), which should have prompted further work-up in order to enforce a definite diagnosis. Back pain is the typical presenting symptom of early Pott's disease, but signs or symptoms of systemic infection are often missing. Constitutional symptoms, fever, and weight loss are unspecific and present in less than 40% of spinal TB cases. Due to the subtle nature of symptoms, diagnostic evaluations are often not initiated until the process is advanced. However, establishing the correct diagnosis is challenging and misdiagnoses may occur in up to 41% of cases . Hence, a significant proportion of patients present with neurological impairment in advanced stages of disease [4, 12]. The early changes of spinal TB are particularly difficult to detect by routine radiographs of the spine. CT and MRI scans of the spine are considerably more sensitive and should be obtained whenever an infectious process is suspected .
CT-guided percutaneous biopsy of the vertebral body is an effective and safe diagnostic procedure for spinal lesions of unclear origin [14, 15]. The consecutive microbiological and histological work-up including PCR may help to establish a rapid diagnosis as PCR results are usually available within one or two working days. In this context, PCR is an extremely useful tool for the guidance of further diagnostic steps and treatment decisions, particularly if the initiation of antimicrobial chemotherapy is crucial. Nevertheless, it should be mentioned that PCR has a limited sensitivity, particularly in AFB smear negative specimens, and that TB culture of clinical specimens remains the gold standard for the confirmation of active TB infection and the assessment of mycobacterial resistance .
Combining radical surgery with a standard triple or quadruple antimycobacterial chemotherapy produces the most favourable outcomes and a more rapid neurological recovery [4, 10], while a conservative, nonsurgical approach may be warranted in patients without advanced neurological deficits [9, 17].
Furthermore, our case emphasizes that IGRAs are of limited value in the context of severely ill patients, where false negative results occur secondary to the host's anergy. IGRAs were developed as immunological diagnostics for the diagnosis of TB infection rather than TB disease, and data on the sensitivity of these assays in critically ill patients and patients with severe immunosuppression and advanced or disseminated active TB is sparse .
There were important implications of the delayed diagnosis for the health care workers (HCWs) at our institution. Two-hundred and two HCWs were evaluated, 158 subjects were screened for the nosocomial transmission of TB, and 143 subjects were eventually analyzed within a recently published contact investigation . However, this study concluded that, fortunately, major nosocomial TB transmission from the source case did not occur. Nevertheless, the present case illustrates the increased risk of occupational TB transmission in health care [6, 19].
Finally, the following basic implications for the general clinical practice emerge from this fatal case: a) whenever possible, aim at establishing a definite diagnosis before initiating treatment, particularly if cancer is suspected, and immediate or extensive therapeutic implications arise; b) easily treatable causes of disease should always be thoroughly considered and regularly re-evaluated, if applicable; c) copying and pasting medical diagnoses without critical reflection endangers patients and should therefore be strictly rejected.
Awareness is the key point of diagnosing Pott's disease, an ancient but nowadays rare manifestation of extrapulmonary TB. Due to the devastating consequences of a missed diagnosis, MTB should be considered early in every case of spondylitis, intraspinal or paravertebral abscess. The presence of certain alarm signals like a prolonged history of progressive back pain, constitution symptoms or pulmonary nodules on a chest radiograph, particularly in the upper lobes, may guide the clinical suspicion. CT-guided percutaneous biopsy of the affected vertebral body and the consecutive microbiological and histological work-up including PCR may contribute to rapidly establishing the correct diagnosis.
Written informed consent was obtained from the patient's widow for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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