Musculoskeletal infection with M tuberculosis accounts for 1–5% of cases of tuberculosis (TB) and can produce spondylitis (Pott disease), arthritis, osteomyelitis, tenosynovitis, bursitis, and pyomyositis. In developing countries, where the prevalence of TB is high, musculoskeletal TB remains an important source of morbidity and mortality, particularly among children. In the developed world, musculoskeletal TB is uncommon and largely affects adults. Immigrants from countries where TB is prevalent account for a substantial proportion of musculoskeletal TB in the United States and Europe. Musculoskeletal infection has been reported in HIV-infected persons and in patients whose TB reactivated in the setting of anti-tumor necrosis factor therapy. Tuberculosis is a reportable disease and suspected or proven cases should be reported to local public health authorities.
Spinal Tuberculosis (Pott Disease)
- Back pain.
- Radiographic evidence of spondylitis or spondylodisciitis.
- Identification of M tuberculosis in aspirates or biopsy specimens of skeletal lesions.
Tuberculosis of the spine accounts for approximately 50% of musculoskeletal TB. The thoracic and lumbar vertebrae are most often affected; the cervical spine is involved in less than 10% of cases. Organisms reach the vertebrae either by hematogenous spread (at the time of initial infection or during reactivation) or through lymphatic spread from renal, pleural, or other foci of disease. Most patients do not have active TB at sites outside the skeleton. Pulmonary TB, which is the most common form of concomitant extraskeletal disease, occurs in less than 20% cases.
Infection usually begins within the body of a vertebra and then extends to involve adjacent vertebrae and disks; however, “skipping” to noncontiguous vertebrae is not rare. Soft-tissue involvement is common, and paravertebral cold abscesses develop in about 75% of cases. Isolated involvement of the posterior elements is unusual (5% in one large series).
The most common presenting complaint is pain localized to the spine. The pain typically is not relieved by rest and may be present for months or longer before the patient seeks medical attention. In contrast to pulmonary TB, constitutional symptoms (weight loss, fever, and night sweats) occur in only 50% of cases.
Radicular pain is common. Approximately 50% of patients have lower extremity weakness at presentation; these figures are higher in case series from the developing world. Compression of either the cauda equina or the spinal cord by an inflammatory mass or abscess is the leading cause of neurologic compromise. Meningitis and meningomyelitis are less common. Severe spinal instability can lead to compression or ischemia of the cord.
Destruction of the anterior vertebral body can result in severe angular kyphosis: the gibbus deformity of Pott disease. Paravertebral cold abscesses can track from the lumbar vertebrae along the psoas muscle and present as inguinal masses or can extend from the thoracic spine into the pleural space. Fistulae occur in a small number of patients. In a small percentage of cases, bone can become superinfected with pyogenic organisms.
Routine laboratory investigations are of little diagnostic help. Patients may or may not manifest a peripheral leukocytosis. There usually is a moderate elevation in the erythrocyte sedimentation rate (ESR), but in 10% of cases the ESR is <20 mm/hour.
Plain radiographs can be normal early in the course of disease but then demonstrate evidence of spondylitis, including osteolysis, a combination of lytic and sclerotic lesions, and bony destruction that classically is confined to the vertebral body. Although initially there may be relative preservation of the intervertebral disk, disk narrowing is common later in the disease course. CT and MRI reveal changes earlier than plain radiography, provide greater detail of the extent of bony involvement, and can reveal paraspinal abscesses not suspected on clinical grounds. MRI permits prompt detection of compression of the spinal cord or cauda equina and is the preferred imaging technique in cases with signs or symptoms of neurologic compromise.
Most patients (75–90%) have a positive reaction to purified protein derivative (PPD). In one recent series from India, the sensitivity of an interferon-gamma release assay for TB was 84%. Cultures of material obtained by percutaneous needle aspiration of paraspinal abscesses, percutaneous needle biopsy of spinal lesions, and open surgical biopsy are positive for M tuberculosis in 70–90% of reported cases. Smears of biopsy material reveal acid-fast bacilli in a lower percentage (20–25%) than do smears of aspirates of paraspinal abscesses (60%). Biopsies reveal characteristic caseating granulomas in 70%. These percentages on the yields of culture, staining, and histopathology may be inflated by the relatively strict case definitions of the studies. The bacillary burden in spinal TB is low, and some writers with extensive clinical experience in endemic areas estimate that the false-negative rates of aspirates and biopsies approach 50%. Nucleic acid amplification tests may facilitate earlier diagnosis but have only been studied in small numbers of patients with spinal TB, and these tests are not approved by the Food and Drug Administration for diagnosis of extrapulmonary tuberculosis. In patients with extraspinal disease suggestive of tuberculosis, identification of M tuberculosis at another site is sufficient to establish the diagnosis of spinal TB.
Pyogenic or fungal osteomyelitis or neoplasm can cause disease that is clinically indistinguishable from tuberculous spondylitis. Pyogenic vertebral osteomyelitis generally has a more acute presentation and is more often associated with fever and clinical toxicity than spinal TB. Blood cultures are positive for Staphylococcus aureus, streptococci, or enteric Gram-negative organisms in approximately 50% of cases of pyogenic vertebral osteomyelitis; but in up to 25% of cases, routine bone and blood cultures will not yield an organism. Imaging studies cannot reliably differentiate pyogenic and tuberculous spondylitis. Noncaseating granulomas, which occasionally are the only histologic evidence of spinal TB, can be seen on biopsy specimens of vertebral osteomyelitis due to Brucella or fungi (either of which can mimic spinal TB clinically). Certain imaging features, such as the presence of paravertebral abscesses, can help distinguish spinal TB from neoplastic disease, but these are not always present.
Antimicrobial therapy is the cornerstone of treatment for spinal TB. Unless there is strong suspicion of resistance to first-line drugs, most authorities recommend a 6- to 9-month course of therapy with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months followed by isoniazid and rifampin for 4–7 months.
When cultures and histopathologic studies fail to yield a definitive diagnosis, empiric therapy for tuberculosis should be considered, especially for foreign-born individuals from areas where M tuberculosis is endemic, those with evidence of past tuberculosis, or individuals who test positive for tuberculin skin tests or interferon-gamma release assays for TB.
The role for surgical intervention is controversial. Uncomplicated cases generally respond well to antituberculous therapy alone. A randomized trial conducted by the Medical Research Council found no additional benefit of surgery over medical therapy alone, but critics of these studies point out that there was a trend toward greater spinal instability in the medically treated groups and that patients with extensive disease were excluded. Surgery is indicated for patients with persistent neurologic deficits and spinal cord compression, with severe spinal instability, or with ongoing infection despite appropriate antibacterial therapy. A neurosurgeon or orthopedist should evaluate all patients with signs or symptoms of neurologic compromise or with spinal instability or deformity.
Complications of spinal TB include destruction of vertebral bodies and disks with consequent spinal deformities and instability; paraparesis or paraplegia; and tracking of paravertebral cold abscesses to distant sites in the chest, abdomen, groin, and neck.
- Usually monoarticular with predilection for hip or knee.
- Periarticular abscesses and sinus tracts in late stages of disease.
- Culture of M tuberculosis from synovial fluid or biopsy.
- Demonstration of caseating granulomas on synovial biopsy.
Tuberculous arthritis is the second most common form of musculoskeletal TB. Tuberculous arthritis is seen mostly in children and young adults who live in developing countries. In nonendemic regions, tuberculous arthritis tends to affect older persons. The hip is most often involved, followed by the knee. Any joint may be infected, however, and infection of non–weight-bearing joints and the sacroiliac joints were prominent in a recent European series. The great majority of cases (85%) of tuberculous arthritis are monoarticular; oligoarticular TB is an uncommon but well-recognized condition.
Tuberculous arthritis usually develops from adjacent TB osteomyelitis but also can be initiated by hematogenous spread directly to the synovium. Because M tuberculosis does not produce collagenases, joint destruction is more insidious than in septic arthritis due to pyogenic organisms.
The classic presentation is that of a monoarthritis with pain, stiffness, and gradual loss of function over weeks to months. Some patients seek medical attention after years of symptoms. Approximately 15%, however, have an acute presentation that mimics septic arthritis or microcrystalline disease.
Constitutional symptoms such as fever, night sweats, and weight loss are present in only 50% of patients. Most patients do not have active TB elsewhere, and the chest radiograph may be normal.
On examination, there is swelling with or without warmth of the affected joint. Pain limits motion, particularly when the hip is involved. Cold abscesses and draining sinus tracts may be present in those with long-standing disease.
A mild anemia is common. Peripheral leukocytosis is variable. Most patients have an elevated ESR.
The classic radiographic changes of tuberculous arthritis are juxta-articular osteopenia, bony erosions at the periphery of the joint, and gradual narrowing of the joint space (Phemister triad). CT and MRI detect changes earlier than plain radiography and can better visualize the extent of bony destruction. MRI is superior to CT for the detection of para-articular abscesses, sinus tract formation, and other soft-tissue abnormalities.
The great majority (>90%) of patients have a positive reaction to PPD, but false-negative tests can occur in immunocompromised patients. Synovial fluid analysis reveals inflammatory fluid; cell counts vary but usually are in the range of 10,000–20,000 cells/mcL with a predominance of neutrophils. Smears of synovial fluid reveal acid-fast bacilli in only 20% of cases, but 80% of cultures of synovial fluid grow M tuberculosis. Synovial biopsies yield positive cultures (>90%) and compatible histopathology (>90%) and are the test of choice when there is clinical suspicion of tuberculous arthritis and smears of synovial fluid are unrevealing. The sensitivity and specificity of nucleic acid amplification tests are not yet known for tuberculous arthritis.
Infection with M tuberculosis should be suspected in any patient with an unexplained, chronic inflammatory monoarthritis. Fungal infections and non-tuberculous mycobacterial infections can have a similarly indolent course. The chronic nature of the infection may cause confusion with the spondyloarthropathies, particularly when there is sacroiliac joint involvement or in the unusual patient with oligoarticular involvement. Conversely, acute presentations of tuberculous arthritis can lead to a misdiagnosis of septic arthritis or crystal-induced arthritis. Noncaseating granulomas can be observed in synovial biopsy specimens from patients with sarcoidosis, Crohn disease, foreign body reactions, gout (rarely), brucellosis, and infections due to fungi or atypical mycobacteria.
Antimicrobial therapy is the primary treatment. Six- to 9-month regimens of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months followed by isoniazid and rifampin for 4–7 months are recommended for tuberculosis of bone and joint (see http://www.thoracic.org/statements/). Drainage or joint lavage is necessary if there is thick purulent material in the joint. Occasionally, surgical intervention is required for debridement of extensive foci of osseous infection or for drainage of cold abscesses. Arthroplasty has been successful for patients with joint destruction.
Untreated infection leads to pannus formation that erodes cartilage and subchondral bone, eventually destroying the joint. Para-articular cold abscesses and draining sinus tracts develop in long-standing disease; the latter can be superinfected with pyogenic organisms.
Other Forms of Musculoskeletal TB
Spinal TB and tuberculous arthritis account for the great majority of cases of musculoskeletal TB. Although TB can cause tenosynovitis of the hand and wrist, olecranon bursitis, and trochanteric bursitis, infections of tenosynovium and bursae are more common with non-tuberculous mycobacterial species than with M tuberculosis. Tuberculous osteomyelitis of the phalanges can produce dactylitis, particularly in children.
Poncet disease is a polyarthritis seen with extra-articular TB. The failure to isolate M tuberculosis from involved joints led to the concept that Poncet disease is a reactive arthritis, but this hypothesis has been questioned.
Primary tuberculous myositis is rare and typically affects the psoas muscle. Muscle also can be infected secondarily by sites in joints or bone.
Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society, Centers for Disease Control and Prevention, and the Infectious Diseases Society. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med.
[Joint statement by the Centers for Disease Control and Prevention, the American Thoracic Society, and the Infectious Diseases Society of America on the treatment of tuberculosis.]
Kumar R, Das RK, Mahapatra AK. Role of interferon gamma release assay in the diagnosis of Pott disease. J Neurosurg Spine.
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