Two cases in a rural BC family practice demonstrate the challenge of diagnosing extrapulmonary tuberculosis. Both cases were resolved successfully, but only after some initial diagnostic confusion. Primary care physicians need to be more aware of the possibility that patients in some high-risk populations (including aboriginal Canadians, immigrants from TB-prevalent parts of the world, and HIV-infected individuals) may present with extrapulmonary tuberculosis.
Physicians in family practice clinics and emergency departments should always consider extrapulmonary TB in their differential diagnoses, particularly when working with immigrants, aboriginal Canadians, immunocompromised patients, and HIV-infected individuals.
The presentation of extrapulmonary tuberculosis (TB) can challenge the diagnostic skills of clinicians and lead to a delay in the diagnosis and management of the disease. Two case reports of extrapulmonary tuberculosis illustrate this problem. Neither case involved HIV infection, although such co-morbidity is common. The first case demonstrates the difficulty of diagnosing tuberculous spondylitis and the second case involves tuberculous meningitis.
In May 1998 a 79-year-old aboriginal female presented to a physician in rural practice with back pain that had become progressively worse over the course of 1 year. She related all her symptoms to a fall 1 year before presentation, and had been treated conservatively for this back pain for 6 months. Finally it became necessary to admit her to hospital.
The patient had no cough or fever on admission. She had, however, a previous history of exposure to a tuberculosis patient. On examination she had a normal gait but was in distress with back pain. The pain seemed to come in waves and was not radiating. She had localized tenderness over the lower part of the spine. She had no motor weakness or sensory abnormalities in her lower limbs. Reflexes were difficult to elicit, but there was no neurological deficit. A complete blood count was normal, the erythrocyte sedimentation rate was 40 mm/hr, and a chest radiograph was normal.
Diagnosis moved forward when lumbar spine radiographs revealed a grossly destructive lesion at L1 that suggested tuberculous spondylitis. Further diagnostic workup at a tertiary care centre included a CT scan-guided needle biopsy of the vertebral body that showed granulomatous changes. Both Gram and Ziehl-Neelsen stains were negative, but a culture of cerebrospinal fluid (CSF) confirmed the presence of Mycobacterium tuberculosis, which proved sensitive to first-line antituberculosis drugs.
The patient completed 9 months of supervised treatment with an initial induction phase of 300 mg isoniazid, 600 mg rifampin, and 1.5 g pyrazinamide, followed by isoniazid and rifampin alone in the continuation phase.
In March 1997 a 27-year-old aboriginal female was admitted to a rural hospital with headache that had endured and worsened for 2 to 3 weeks before admission. She was known to suffer from migraine headaches that required frequent management in hospital. She also had a previous history of exposure to an active case of tuberculosis and had had a positive test result for tuberculosis. She had been on isoniazid preventive therapy for 1 year, but her compliance was uncertain.
On the day of admission she experienced a severe throbbing headache. On examination she was alert and oriented to time, place, and person. She was afebrile and her neurological examination was normal. She had no focal neurological deficit and was negative for Kernig’s sign. She had no neck stiffness and appeared well. On the evening of admission her temperature climbed to 38.5°C and she exhibited a decreased level of consciousness.
When the patient was transferred to a regional hospital for further investigation, an initial CT scan of her brain was normal. Lumbar puncture revealed slightly cloudy CSF, evidence of elevated WBC (688) with mainly lymphocytes, a very low CSF glucose of 0.3 g/l, and an elevated protein. A Ziehl-Neelsen stain of her CSF was negative.
Once a presumptive diagnosis of tuberculous meningitis was made, the patient was treated with 900 mg ethambutol, 600 mg pyrazinamide, 600 mg rifampin, and 300 mg isoniazid. After the presence of M. tuberculosis was confirmed by culture, this regimen was continued daily for 6 months.
In 1997 there were 413 confirmed new cases of tuberculosis in British Columbia, corresponding to an incidence rate of 10.5 per 100 000 population. This peak in incidence was attributed to an influx of immigrants in the previous years.
Extrapulmonary tuberculosis represented 28% of all active cases of tuberculosis in BC in the year 1996–1997. The most common sites of extrapulmonary tuberculosis were the lymphatic system (16%), bone and joints (2%), genitourinary system (2%), and meninges and central nervous system (1%).
The frequency of occurrence of tuberculous spondylitis and meningitis is low. However, the direct and indirect costs are enormous and the complications and sequelae of the disease are serious. These can be appreciably reduced through early diagnosis and management of cases.
Physicians in family practice clinics and emergency departments should always consider extrapulmonary TB in their differential diagnoses, particularly when working with immigrants, aboriginal Canadians, immunocompromised patients, and HIV-infected individuals. The incidence of extrapulmonary TB is significantly higher in HIV-infected individuals, with 50% of HIV-AIDS patients exhibiting extrapulmonary TB compared with only 10% to 15% of tuberculous patients who are not infected with HIV. Because of this connection, HIV testing is recommended for any individual diagnosed with extrapulmonary TB.
Although the Mantoux test should be done in all cases of suspected TB, the clinician should remember that a negative response does not rule out TB. The test, which is read 48 to 72 hours after injecting 0.2 mL of tuberculin using 5 TU (PPD) intradermally on the volar aspect of the arm, may be negative in immunocompromised persons. Similarly the test may be positive in persons from high-prevalence countries as a result of simple infection in the absence of active disease. For a definitive diagnosis of TB, it is necessary to obtain positive smears and/or cultures from appropriate body fluids.
The gold standard for the diagnosis of tuberculous meningitis remains lumbar puncture, followed by culturing for M. tuberculosis, which can take 2 to 8 weeks. Because CSF M. tuberculosis smears are frequently negative, therapy must be started while awaiting the results. In high-prevalence countries, such as India, the following clinical and laboratory findings are considered indicative of TB: prodromal symptoms >7 days, focal deficits, optic atrophy, abnormal movements, and CSF leukocytes with <50% polymorphs. This last finding has a high predictive value in the diagnosis of tuberculous meningitis in children. A somewhat similar clinical definition of TB in adults is described by other authors. Such simple clinical definitions are useful for early diagnosis of tuberculous meningitis and should be available to primary care physicians working in communities where TB is prevalent.
The gold standard for the diagnosis of tuberculous spondylitis is CT scan-guided needle biopsy of spinal lesions, followed by culturing for M. tuberculosis. MRI can also be helpful in the early detection of TB of the spine, but is not readily available in all parts of British Columbia. Bone scans have a limited role in the diagnostic workup, and standard X-rays may be somewhat useful but not diagnostic.
The decline in the number of TB cases in North America and Europe has led to reduced awareness of tuberculosis. Many physicians have completed their medical training with little formal education regarding TB, and many have minimal or no involvement in the diagnosis or treatment of active cases of TB. In one study, the absence of pulmonary symptoms and the advanced age of the patient were found to be the most significant factors resulting in the physician’s failure to suspect TB.
Canada receives some 250,000 immigrants a year, the majority of whom come from communities with a high prevalence of TB. Approximately 60% to 70% of TB cases occur in foreign-born Canadians and 20% in aboriginal Canadians. Because it is increasingly likely that primary care physicians will see patients who are at high risk of having TB, it is important that these physicians receive continuing medical education on tuberculosis.
In both cases described here, the absence of drug resistance and the full compliance of each patient resulted in successful treatment. The patient with tuberculous spondylitis (Case 1) responded well to her 9 months of drug therapy. After her treatment ended she still had some back pain, but was functioning well overall.
The patient with tuberculous meningitis (Case 2) responded very slowly to therapy and experienced significant nausea and vomiting. A repeat CT scan of her brain showed mild enlargement of the ventricular system, suggesting potential obstruction of CSF outflow. This was subsequently treated with steroids, which are useful for reducing the production of CSF and decreasing the basilar inflammation commonly associated with tuberculous meningitis.[8,9] After a year of treatment she made an excellent recovery.
The two cases discussed here highlight the need for increased awareness of TB in general and extrapulmonary TB in particular. Improved early recognition of TB is essential in minimizing morbidity, eliminating TB transmission, and reducing health care costs.
Any physician working with members of high-risk populations, such as HIV-infected individuals, aboriginal Canadians, and immigrants, should consider the possibility of extrapulmonary TB. The initial presentation of a tuberculosis patient is likely to involve a primary care physician. Thus, primary care physicians not only need to have a high index of suspicion for TB, they also need to maintain a greater awareness of the changing epidemiolgic conditions and varied presentation of the disease.
Dr Germa thanks Dr Tekle-Mariam Ayele and Dr Elwood for their pre-submission review of the manuscript.
1. Division of Tuberculosis Control, BC Centre for Disease Control. 1998 Annual Report. Vancouver: BC Centre for Disease Control, 1998. http://www.bccdc.org/content.php?item=33 (retrieved 5 December 2001).
7. Mathur P, Sacks L, Auten G, et al. Delayed diagnosis of pulmonary tuberculosis in city hospitals. Arch Intern Med 1994;154:306-310. PubMed Abstract
8. Schoeman JF, Van Zyl LE, Laubscher JA, et al. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Pediatrics 1997;99:226-231. PubMed Abstract
9. Escobar JA, Belsey MA, Duenas A, et al. Mortality from tuberculous meningitis reduced by steroid therapy. Pediatrics 1975;56:1050-1055.PubMed Abstract
Fikre Germa, MD, CCFP(EM) and J. Mark FitzGerald, MB, MD, FRCP, FRCPI
Dr Germa is clinical preceptor, Emergency Medicine at the UBC Family Practice Residency Program, Chilliwack General Hospital, and has done rural family physician locums at various locations in British Columbia. At the time of writing, Dr FitzGerald was the director of the Aboriginal TB Control Program at the BC Centre for Disease Control; he is now the director of Clinical Epidemiology and Evaluation at the Vancouver General Hospital.
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