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Tuberculous synovitis frequently presents as a monoarthritis of weight-bearing joints such as the hip, knee, or ankle. Owing to its low incidence in developed countries, the diagnosis is often delayed for months to years. Early diagnosis with a synovial biopsy permits prompt antituberculous therapy and substantially improves the prospect of preservation of joint structure and function. Initial treatment typically includes combination therapy with four drugs (isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol) because of the frequency of isoniazid resistance. Antimicrobial therapy should be of at least 9 months’ duration, longer in immunocompromised hosts. Partial synovectomy and other surgical procedures should be restricted to joints with severe cartilage destruction, large abscesses, joint deformity, multiple drug resistance, or atypical mycobacteria.
Tubercular bacilli reach the joint space via the blood stream through subsynovial vessels, or indirectly from epiphyseal (more common in adults) or metaphyseal (more common in children) lesions, which erode into the joint space. Articular cartilage destruction begins peripherally and the weightbearing surfaces are preserved for a few months, providing the potential for good functional recovery with effective treatment in patients with early disease.
The disease may start in bone or in the synovial membrane, but one rapidly infects the other. The initial focus starts in the metaphysis in childhood or at the end of the bone in adults. An example of articular tuberculosis of the typical osseous areas of predilection for hip disease.
Osseous Changes and Tubercular Sequestra
After the infection, marked hyperemia and severe osteoporosis occur. The softened bone easily yields under the effect of gravity and muscle action, leading to compression, collapse, or deformation. Necrosis also may be caused by ischemic infarction of segments of bone.
Sequestration gives the appearance of coarse sand and rarely produces a radiologically visible sequestrum. Because of loss of nutrition, the adjacent articular cartilage or the intervening disc degenerate and also may become separated as sequestra. Some of the radiologically visible smaller sequestra in tuberculous cavities may result from calcification of caseous matter.

The Future Course of Tubercle
Before the availability of antitubercular drugs, the 5–year followup mortality of patients with osteoarticular tuberculosis was approximately 30.Modern antitubercular agents have changed the outlook considerably. Depending on the sensitivity pattern, host resistance, and the stage of the lesion at the inception of treatment, the tuberculous lesion may behave as follows. It may resolve completely; the disease may heal with residual deformity and loss of function; the lesion may be walled off completely and the caseous tissue may calcify; low-grade chronic fibromatous granulating and caseating lesion may persist (grumbling disease); and the infection may spread locally by contiguity and systematically by the blood stream
DIAGNOSIS OF TB INFECTION
| Methods |
| Tuberculin Skin Test (TST) |
| Interferon Gamma Release Assays (IGRAs) |
| Enzyme-Linked Immunosorbent Assays (ELISA) |
| Bacteriology |
| Radiology |
| Computed Tomography (CT) |
| Magnetic Resonance Imaging (MRI) |
| Polymerase Chain Reaction (PCR) |
| Synovial fluid examination |
| Synovial biopsy |
Blood
A relative lymphocytosis, low hemoglobin, and increased erythrocyte sedimentation rate often are found in patients with the active stage of disease. An increased erythrocyte sedimentation rate, however, is not necessarily proof of activity of the infection. Its repeated estimation at 3- to 6-month intervals gives an index of the activity of the disease.
Mantoux Test
As a rule, a positive reaction is present in a patient infected with tuberculosis for more than 1 month. A negative test, in general, rules out the disease. The tuberculin test rarely may be negative although active tuberculosis is present, such as in immune deficiency states.
Biopsy
Whenever there is doubt (particularly in the early stages) it is mandatory to prove the diagnosis by obtaining a biopsy specimen of the diseased tissue (granulations, synovium, bone, lymph nodes, or margins of tuberculous ulcers). Microscopic examination of an aspiration, core biopsy, needle biopsy, or open biopsy will reveal typical tubercles in patients who are not treated. Epithelioid cells surrounded by lymphocytes, even without central necrosis or peripheral foreign-body giant cells, are adequate histologic evidence of tuberculosis in a patient who is suspected to have the disease. At the time of open biopsy of a joint or bone, the orthopaedic surgeon should do therapeutic synovectomy or curettage. The infections of bone and joint that present as granulomatous lesions in order of frequency are tuberculosis, mycotic infection, brucellosis, sarcoidosis, and tuberculoid leprosy.
Guinea Pig Inoculation
The tuberculous pus, joint aspirate, or diseased material may be injected intraperitoneally into a guinea pig. Examination in positive cases shows tubercles on the peritoneum 5 to 8 weeks later. Although it currently is not considered a cost-effective test, it perhaps is the most reliable proof of tuberculosis.
Smear, Culture, and Serology
The material prepared for guinea pig inoculation also may be submitted for smear and culture examination for acid-fast bacilli. In superficial joints, one may be able to aspirate synovial fluid. Analysis of synovial fluid does not provide pathognomonic information; however, in general the leukocyte count is elevated to approximately 20,000 mm3, there is a lowered glucose level, and poor mucin. Clear synovial aspirate is not an appropriate material for microbiologic investigation; however, it is an excellent material for polymerase chain reaction and nucleic acid probes.

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Principles of Treatment of Osteoarticular Tuberculosis
Modern drugs promote the healing of sinuses, ulcers, and abscesses in patients previously unresponsive to extensive surgery. They also eliminate the danger of postoperative miliary and meningeal disease caused by dissemination of the tuberculous infection.
Death caused by uncontrolled disease, meningitis, miliary tuberculosis, amyloidosis, paralysis, and crippling now is rare. If a patient is diagnosed early and treated vigorously, healing can be accomplished without residual joint ankylosis or deformity.
With the use of modern drugs, the indications for surgery have become universally more selective and directed toward the prevention and correction of deformities, and the improvement in function of the diseased joints. At the stage of tuberculous arthritis, if abscess formation has not occurred, the natural outcome generally is a fibrous ankylosis. If an abscess discharges and sinuses develop, the outcome may be a bony ankylosis. The prognosis in articular tuberculosis depends on the stage of the disease. when the specific treatment is started. Concomitant disease must be treated and hospitalization is necessary only for patients with complications, or for patients requiring traction under supervision to correct deformities.
| Category of treatment | Category of TB cases | Anti-TB drug regimens | |
| Intensive phase | Continuation phase | ||
| I | New Patient Regimen New smear-positive PTB Smear-negative PTB with extensive Parenchymal involvement Severe forms of EPTB other than TB meningitis | 2HRZE | 4HR |
| II | New Patient Regimen Smear-negative PTB without extensive P Parenchymal involvement Less severe forms of EPTB (e.g., TB cervical adenitis) | 2HRZ | 4HR |
| III | New Patient Regimen TB meningitis | 2HRZSa | 4HR |
| IV | Retreatment regimen Previously treated smear-positive PTB (relapse, treatment after interruption or treatment failure) If low risk for MDR-TB or risk unknown, continue with retreatment regimen If high risk for MDR-TB, use MDR-TB regimen below | 2HRZES/1HRZE | 5HRE |
| V | MDR Regimen MDR-TB | Individualized regimens |
Table 2: Treatment regimens for tuberculosis recommended by the WHO . Other regimens are recommended for the treatment of TB meningitis, including replacing streptomycin with ethionamide and treating for 9-12 months.
E: Ethambutol; EPTB: Extra-Pulmonary Tuberculosis; H: Isoniazid; HIV: Human Immunodeficiency Virus; MDR-TB: Multi-Drug Resistant Tuberculosis; PTB: Pulmonary Tuberculosis; R: Rifampicin; S: Streptomycin; Z: Pyrazinamide; 2HRZ 4HR: Denotes a Two-month Intensive Phase of Daily Isoniazid, Rifampicin, and Pyrazinamide followed by a Four-month Continuation Phase of Daily Isoniazid and Rifampicin

Rest, Immobilization, and Braces
In the active stage of disease, the joints are rested in the position of function using removable splints. Prolonged immobilization can lead to spontaneous ankylosis when joints are grossly destroyed. Patients with early disease are allowed 1 to 2 hours of intermittent, guarded active and assisted exercises while taking antitubercular drugs, with the aim of retaining a useful range of movement in the functional arc of the involved joint. Traction helps to correct deformity and to rest the diseased part. Gradual ambulation is encouraged with the help of suitable braces approximately 3 months after the start of treatment while healing is progressing. As the disease heals and pain subsides, weightbearing and activity are permitted. If there is steady progress, activity is increased within the limits of discomfort. The use of a brace is discontinued gradually after approximately 2 years.
Treatment of Abscess, Effusion, and Sinus
Palpable and large joint effusions are aspirated and 1000 mg of streptomycin alone or combined with injectable isoniazid (300 mg) is instilled at each aspiration. Local concentrations of antibiotics after parenteral administration may make this local instillation unnecessary. Open drainage of an abscess is indicated if aspiration fails. Radiologically visible paravertebral abscess shadows do not need to be drained, unless decompression is done in patients with paraplegia or when diseased vertebrae are debrided. A prevertebral abscess in the cervical region is drained if it causes difficulty in swallowing or breathing. Drainage of a large paravertebral abscess also may be considered when its radiologic size increases markedly despite treatment.
A majority of ulcers and sinuses heal within 6 to 12 weeks under the influence of systemic antitubercular drugs. Less than 1% of patients with sinuses require longer treatment and excision of the tract, with or without debridement. Sinus ramification always is greater than can be appreciated and complete surgical excision therefore is impractical.
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Antitubercular Chemotherapy
Combination chemotherapy should be used for an adequate length of time. Most of the antitubercular drugs potentially are toxic and resistance or intolerance to the drugs should be suspected when a patient fails to respond.
Multidrug Resistant Tuberculosis and Patients Who do not Respond
If the disease is caused by organisms resistant to isoniazid and rifampicin (multidrug resistant tuberculosis), if the disease is not controlled within 4 to 5 months, or if despite multidrug therapy, more active tuberculous lesions appear, one has to resort to second line drugs or potential antituberculous drugs. The situation is desperate in patients who do not respond. Immunomodulation in conjunction with drugs may be used in such patients. A favorable response was reported in approximately 85% of patients.
Pending the availability of better immunomodulation techniques.the current author has evolved the following outline during the past 12 years to upgrade cell-mediated immunity. In brief, 150 mg of levamisol is given at night for 3 days at weekly intervals for a total of 45 tablets. Four injections are administered once a month. The first and second infections are 0.1 mL intradermal (Bacillus Calmett-Guérin) injections and the third and fourth are intramuscular DPT injections (diphtheria vaccine + tetanus vaccine + Bordetella pertussis 20,000 million per 0.5 mL).
Surgery in Patients with Tuberculosis of Bones and Joints
No surgery is a substitute for a prolonged course of antitubercular drugs. A trial of conservative treatment is justified in most patients before surgery is contemplated. Nonoperative treatment usually is adequate in patients with pure synovial tuberculosis, low-grade or early arthritis of any joint, and even advanced (Stage III or IV) arthritis, especially in the upper extremity.
Surgery only should be considered once the general condition of the patient is stabilized by drug therapy, before the development of drug resistance. In general, a minimum of 1 to 4 weeks of therapy is advisable before any major surgical intervention.
Relapse of Osteoarticular Tuberculosis or Recurrence of Complications
The incidence of relapse or recurrence is unknown because these complications may occur at any period during the lifetime of a patient, whether the initial treatment included excisional surgery. Reactivation may occur in 2% to 5% of patients as late as 20 years or more after apparent healing.
The causes of reactivation include prolonged use of systemic cortisone therapy, malnutrition, the development of diabetes or an immune deficiency state, or a surgical procedure or injury to the previously infected area. Dormant bacilli persisting in tissue for years may start multiplying under such circumstances.
Tuberculosis of the Spine
Vertebral tuberculosis accounts for 50% of all cases of skeletal tuberculosis. In the majority of patients, the disease typically started in the paradiscal region. Narrowing of the disc often is the earliest radiologic finding. Any reduction in disc space, if it is associated with a loss of definition of the paradiscal margins of the vertebrae, suggests tuberculosis and occurs before the appearance of frank osseous destruction. These changes usually are evident only after infection has been present for 3 to 6 months, although advanced imaging may detect changes at approximately 6 weeks.
Most cases of tuberculosis of the spine heal without surgical intervention. However, uncertainty about the diagnosis, progressive bone destruction, and neurologic symptoms despite chemotherapy are definite indications for surgery in the active stage of disease.

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