What diagnostic markers and treatment options are used for non-pulmonary tuberculosis (TB)?

From the Guidelines

Non-pulmonary tuberculosis (TB) is diagnosed through a combination of clinical evaluation, imaging, and microbiological confirmation, with treatment typically following the same principles as pulmonary TB, using a standard first-line regimen consisting of isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months, followed by isoniazid and rifampin for 4-7 additional months. Diagnostic markers include tissue biopsy with histopathology showing granulomatous inflammation, acid-fast bacilli (AFB) smear microscopy, culture of Mycobacterium tuberculosis from affected sites, nucleic acid amplification tests (NAATs) like GeneXpert MTB/RIF, and elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 1.

The total treatment duration varies by site: 6 months for lymph node, skin, and pleural TB; 9-12 months for bone/joint, CNS, and disseminated TB. Adjunctive treatments may include surgical intervention for abscess drainage, spinal stabilization, or joint debridement, and corticosteroids (e.g., dexamethasone or prednisone) for TB meningitis or pericarditis to reduce inflammation. Drug resistance must be considered, with modified regimens including second-line drugs like fluoroquinolones, aminoglycosides, and newer agents such as bedaquiline and delamanid for MDR-TB cases, as recommended by the World Health Organization in 2020 1.

Some key points to consider in the diagnosis and treatment of non-pulmonary TB include:

• The use of rapid molecular tests as the initial test to diagnose pulmonary TB and to simultaneously detect rifampicin resistance 1
• The importance of drug susceptibility testing (DST) to ensure that the treatment regimen is effective and to prevent amplification of resistance to other effective new anti-TB medicines 1
• The need for regular monitoring of liver function, vision (with ethambutol), and therapeutic response throughout treatment 1
• The consideration of adjunctive treatments, such as surgical intervention and corticosteroids, to reduce inflammation and improve outcomes in certain cases of non-pulmonary TB.

Overall, the diagnosis and treatment of non-pulmonary TB require a comprehensive approach that takes into account the specific characteristics of the disease, the patient's overall health, and the potential risks and benefits of different treatment regimens.

From the FDA Drug Label

Patients with Extra Pulmonary Tuberculosis The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimen is effective Because of the insufficient data, military tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children should receive 12 month therapy. Bacteriologic evaluation of Extra pulmonary tuberculosis may be limited by the relative in accessibility of the sites of disease. Thus, response to treatment often must be judged on the basis of clinical and radiographic findings The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease. Surgery may be necessary to obtain specimens for diagnosis and to treat such processes as constrictive pericarditis and spinal cord compression from Pott’s Disease Corticosteroids have been shown to be of benefit in preventing cardiac constriction from tuberculous pericarditis and in decreasing the neurologic sequelae of all stages of tuberculosis meningitis, especially when administered early in the course of the disease.

Diagnostic markers and treatment options for non-pulmonary tuberculosis (TB)

• The treatment of non-pulmonary TB is based on the same principles as pulmonary TB, with a 6 to 9 month short-course regimen often effective.
• However, the diagnosis and treatment of non-pulmonary TB can be more complex due to the relative inaccessibility of the sites of disease.
• Clinical and radiographic findings are often used to judge response to treatment.
• Surgery and corticosteroids may be necessary as adjunctive therapies.
• The duration of treatment may be longer for certain forms of non-pulmonary TB, such as military tuberculosis, bone/joint tuberculosis, and tuberculous meningitis in infants and children, which may require 12 months of therapy 2.

From the Research

Diagnostic Markers for Non-Pulmonary Tuberculosis

• The diagnosis of non-pulmonary tuberculosis (TB) can be challenging due to non-specific symptoms and diverse radiological presentations 3.
• Microbiological exams, such as acid-fast bacilli smear and cultural-isolation of Mycobacterium tuberculosis, are currently used for diagnosis, but may take several weeks to attain results 3.
• Biochemical (adenosine deaminase) and molecular techniques (nucleic acid amplification tests) are also approved for TB diagnosis and can provide rapid diagnostic information 3.
• Interferon-gamma release assays (IGRAs) have been shown to be more sensitive and specific than the tuberculin skin test (TST) for detecting latent TB infection, especially in individuals with active TB infection 4, 5.

Treatment Options for Non-Pulmonary Tuberculosis

• The treatment of choice for most patients with latent TB infection is 9 months of isoniazid therapy 6.
• For active TB, combination therapy with isoniazid, rifampin, pyrazinamide, and ethambutol should be initiated for a 2-month "intensive phase", followed by isoniazid and a rifamycin product for a 4- to 7-month "continuation phase" 6.
• Directly observed therapy should be used to ensure adherence to treatment 6.
• IGRAs have been investigated for monitoring the response to treatment for TB, but the results are inconsistent and their utility for this purpose remains uncertain 7.