Guideline sources The following summarized guidelines for the evaluation and management of extrapulmonary tuberculosis are prepared by our editorial team based on guidelines from the European Bone and Joint Infection Society (EBJIS 2023), the U.S. Preventive Services Task Force (USPSTF 2023), the French Society of Infectious Diseases (SPLIF 2023), the Canadian Thoracic Society (CTS 2022), the World Health Organization (WHO 2022; 2021; 2020; 2017), the Neurocritical Care Society (NCS 2020), the European Association of Nuclear Medicine (EANM/ESNR/ESCMID 2019), the Infectious Diseases Society of America (IDSA/ATS/CDC 2017; 2016), the European Society of Cardiology (ESC/EACTS 2015), the Infectious Diseases Society of America (IDSA 2015; 2008), and the British Thoracic Society (BTS 2010). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Guidelines 1. Screening and diagnosis Screening for latent tuberculosis: As per USPSTF 2023 guidelines, obtain screening for latent tuberculosis infection in populations at increased risk. B https://web.pathway.md/diseases/recSbGzA8a48XKtDL 1/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway As per WHO 2020 guidelines, obtain systematic testing for latent tuberculosis infection in patients initiating anti-TNF treatment, receiving dialysis, preparing for an organ or hematological transplant, or having silicosis. E Show 3 more As per ATS 2017 guidelines, obtain an IGRA rather than a tuberculin skin test in 5 years old patients meeting the following criteria: likely to be infected with Mycobacterium tuberculosis low or intermediate risk of disease progression it has been decided that testing for latent tuberculosis infection is warranted history of BCG vaccination or it is expected that the individual is unlikely to return to have the TST read. A Show 4 more 2. Diagnostic investigations Specimen collection (general principles): make every effort to collect clinical samples for both mycobacteriologic (AFB smear, culture, NAAT) and histopathologic tests. E Specimen collection, bone and joint: As per EBJIS 2023 guidelines, collect synovial fluid for mycobacteriologic analysis (AFB stain, mycobacterial culture, and NAAT) in patients with suspected tuberculous arthritis, such as a subacute or chronic course of arthritis (weeks to months or even years), especially in patients living in or previously living in endemic areas or with a prior history of tuberculosis. B As per SPLIF 2023 guidelines, collect less invasive samples (respiratory or lymph node) preliminary before considering disco-vertebral biopsy in patients with suspected spinal tuberculosis. E Fluid specimen analysis (general principles): consider obtaining an analysis for counts and chemistries on amenable fluid specimens collected from sites of suspected extrapulmonary tuberculosis. C Fluid specimen analysis (pleural fluid): obtain an analysis for cell count and differential, protein, glucose, pH, LDH, and cytology on pleural effusion/pleural fluid in patients with suspected tuberculosis. E Fluid biomarkers: As per ATS 2017 guidelines: Consider obtaining adenosine deaminase level measurement on fluid collected from patients with suspected pleural, meningeal, peritoneal, or pericardial tuberculosis. C Consider obtaining free interferon-gamma level measurement on fluid collected from patients with suspected pleural or peritoneal tuberculosis. C As per CTS 2010 guidelines, consider obtaining surrogate markers (such as adenosine deaminase) as rule-out tests for pleural tuberculosis in low-incidence countries. C Acid-fast bacilli smear (general principles): consider obtaining AFB smear microscopy on specimens collected from sites of suspected extrapulmonary tuberculosis. C https://web.pathway.md/diseases/recSbGzA8a48XKtDL 2/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway Acid-fast bacilli smear (pleural fluid): obtain AFB smear on pleural effusion/pleural fluid in patients with suspected pleural tuberculosis. E Acid-fast bacilli smear (synovial fluid): obtain AFB smear on synovial fluid specimens in patients with suspected tuberculous arthritis. B Mycobacterial culture, general principles: As per CTS 2022 guidelines, prioritize obtaining mycobacterial culture if the specimen is insufficient for all testing, given it has the highest diagnostic yield and allows for gold- standard phenotypic drug testing. E As per CDC/IDSA/ATS 2017 guidelines: Obtain mycobacterial cultures on specimens collected from sites of suspected extrapulmonary tuberculosis. B Submit one culture isolate from each mycobacterial culture-positive patient to a regional genotyping laboratory for genotyping. B Mycobacterial culture (pleural fluid): obtain Gram stain and culture on pleural effusion/pleural fluid in patients with suspected pleural tuberculous. E Mycobacterial culture (synovial fluid): obtain mycobacterial culture on synovial fluid specimens in patients with suspected tuberculous arthritis. B Nucleic acid amplification testing: As per EBJIS 2023 guidelines, obtain an NAAT on synovial fluid specimens in patients with suspected tuberculous arthritis. B As per WHO 2021 guidelines, consider obtaining Xpert MTB/RIF in lymph node aspirate, C lymph node biopsy, C pleural fluid, C peritoneal fluid, C pericardial fluid, C synovial fluid, C or urine specimens C rather than smear microscopy/culture as an initial diagnostic test in adult and pediatric patients with signs and symptoms of extrapulmonary tuberculosis. C Show 3 more As per ATS 2017 guidelines, consider obtaining an NAAT on specimens collected from sites of suspected extrapulmonary tuberculosis. C Blood/skin tests: As per EANM 2019 guidelines, obtain a purified protein derivative skin test and an IGRA in patients with suspected spondylodiscitis and risk factors for Mycobacterium tuberculosis. B As per IDSA 2015 guidelines, consider obtaining a purified protein derivative skin test or an IGRA in patients with subacute native vertebral osteomyelitis at risk for Mycobacterium tuberculosis (originating or residing in endemic regions or having risk factors). C Testing for pulmonary tuberculosis: test for pulmonary tuberculosis to assess infectiousness and potentially assist with diagnosis in patients with presumed extrapulmonary tuberculosis. E 3. Diagnostic procedures https://web.pathway.md/diseases/recSbGzA8a48XKtDL 3/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway Tissue biopsy (general principles): perform a histological examination of specimens collected from sites of suspected extrapulmonary tuberculosis. B Tissue biopsy (pleural biopsy): Send pleural biopsies for both histological examination and culture to improve the diagnostic sensitivity for tuberculosis. B Prefer thoracoscopic pleural biopsies to yield positive mycobacterial culture (and therefore drug sensitivity) results. B Tissue biopsy (synovial biopsy): perform a synovial biopsy for culture and histopathological analysis in patients with suspected tuberculous arthritis. B 4. Medical management Setting of care: As per WHO 2017 guidelines, consider offering the following treatment administration options in patients on tuberculosis treatment: community- or home-based directly observed treatment over health facility-based directly observed treatment or unsupervised treatment C directly observed treatment administered by trained lay providers or health-care workers over directly observed treatment administered by family members or unsupervised treatment C video-observed treatment over directly observed treatment when the video communication technology is available and can be appropriately organized and operated by healthcare providers and patients. C As per ATS 2016 guidelines, consider delivering directly observed treatment rather than self- administered therapy for routine treatment of patients with all forms of tuberculosis. C Management of tuberculous lymphadenitis (antimycobacterial therapy): consider administering standard anti-tuberculosis therapy for 6 months in patients with treating drug- susceptible tuberculous lymphadenitis. C Management of tuberculous lymphadenitis (surgery/drainage): perform surgical/drainage procedures for the relief of discomfort caused by enlarged nodes or tense, fluctuant nodes in patients with tuberculous lymphadenitis. E Management of pleural tuberculosis (antimycobacterial therapy): consider administering standard anti-tuberculosis therapy for 6 months in patients with drug-susceptible pleural tuberculosis. C Management of pleural tuberculosis (adjunctive corticosteroids): avoid administering routine adjunctive corticosteroids in patients with pleural tuberculosis. D Management of pleural tuberculosis (thoracentesis): Avoid performing routine therapeutic thoracentesis/chest tube drainage for pleural tuberculosis-associated effusions. D Consider performing therapeutic thoracentesis on a case-by-case basis to relieve symptoms of significant dyspnea. E https://web.pathway.md/diseases/recSbGzA8a48XKtDL 4/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway Management of tuberculous pericarditis, antimycobacterial therapy: As per CTS 2022 guidelines, consider administering standard anti-tuberculosis therapy for 6 months in patients with drug-susceptible tuberculosis pericarditis. C As per EACTS/ESC 2015 guidelines, initiate empiric anti-tuberculosis therapy for exudative pericardial effusion in patients living in endemic areas, after excluding other causes. B Show 2 more Management of tuberculous pericarditis, adjunctive corticosteroids: As per CTS 2022 guidelines, consider administering initial adjunctive corticosteroids in all human immunodeficiency virus-negative patients with tuberculosis pericarditis. C Show 2 more As per WHO 2017 guidelines, consider administering initial adjuvant corticosteroids in patients with tuberculous pericarditis. C As per CDC/IDSA/ATS 2016 guidelines, do not administer routine initial adjunctive corticosteroids in patients with tuberculous pericarditis. D As per EACTS/ESC 2015 guidelines: Consider administering adjunctive corticosteroids in human immunodeficiency virus- negative patients with tuberculous pericarditis. C Avoid administering corticosteroids in human immunodeficiency virus-positive patients with tuberculous pericarditis. D Management of tuberculous pericarditis (intrapericardial urokinase): consider administering intrapericardial urokinase to reduce the risk of constriction in patients with effusive tuberculous pericarditis. C Management of tuberculous pericarditis, pericardiectomy: As per CTS 2022 guidelines, consider performing early pericardiectomy in patients with recurrent pericardial effusions or persistently elevated central venous pressures despite the removal of pericardial fluid and the use of anti-tuberculosis drugs. E As per EACTS/ESC 2015 guidelines, perform pericardiectomy if the patient is not improving or is deteriorating after 4-8 weeks of anti-tuberculosis therapy. B Management of tuberculous meningitis, antimycobacterial therapy: As per CTS 2022 guidelines, consider initiating empiric therapy immediately in patients with high suspicion of tuberculosis meningitis while awaiting diagnostic results. E Show 3 more As per IDSA 2008 guidelines, initiate 4-drug antituberculous therapy in patients with tuberculous meningitis. B Management of tuberculous meningitis, adjunctive corticosteroids: As per CTS 2022 guidelines, administer a course of corticosteroids guided by disease severity in all patients presenting with tuberculosis meningitis. B As per NCS 2020 guidelines, administer corticosteroids to reduce mortality in patients with tuberculosis meningitis. B Consider continuing corticosteroids for 2 two weeks. B As per WHO 2017 guidelines, administer initial adjunctive corticosteroids with dexamethasone or prednisolone tapered over 6-8 weeks in patients with tuberculous https://web.pathway.md/diseases/recSbGzA8a48XKtDL 5/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway meningitis. B As per IDSA 2008 guidelines, administer adjunctive dexamethasone in patients with tuberculous. meningitis. B Management of abdominal tuberculosis: consider administering standard anti-tuberculosis therapy for 6 months in patients with drug-susceptible abdominal tuberculosis. C Management of genitourinary tuberculosis: Consider administering standard anti-tuberculosis therapy for 6 months in patients with drug- susceptible genitourinary tuberculosis. C Consider administering isoniazid and rifampin for a minimum of 9 months in patients with BCG disease, given inherent pyrazinamide resistance. C Management of bone and joint tuberculosis, antimycobacterial therapy: As per EBJIS 2023 guidelines, initiate anti-tuberculosis therapy alone in patients with early tuberculosis arthritis. B Show 3 more As per CTS 2022 guidelines, consider administering standard anti-tuberculosis therapy for 6 months in patients with drug-susceptible bone and joint tuberculosis with extension to 9-12 months in patients with markers of increased risk of failure/relapse; a diagnostic biopsy sample smear positive for AFB and/or elevated ESR/CRP at the planned end of treatment. C Management of bone and joint tuberculosis, surgery: As per EBJIS 2023 guidelines: Avoid performing surgical intervention in the active phase of tuberculosis arthritis. Consider performing debridement and synovectomy only in exceptional cases with large abscesses, significantly devitalized bone, or showing inadequate response to medical management. D Consider performing surgical management with excisional arthroplasty or arthrodesis in patients with substantial joint destruction, ankylosis, deformity, significant loss of function, or chronic pain after tuberculosis arthritis. B As per CTS 2022 guidelines: Avoid performing routine surgical intervention as part of treatment for spinal tuberculosis. Consider performing surgery for spinal tuberculosis in patients with progressive neurologic deterioration and in < 15 years old patients with significant kyphosis. D Avoid performing surgical intervention as part of the treatment of joint tuberculosis. Consider performing surgery to prevent the extension of disease and to provide relief of pain and immobility after control of infection is established. D Management of ocular tuberculosis: consider administering standard anti-tuberculosis therapy for 6 months in patients with drug-susceptible (suspected or confirmed) intraocular tuberculosis. C Management of skin tuberculosis: consider administering standard anti-tuberculosis therapy for 6 months in patients with drug-susceptible tuberculosis of the skin, including tuberculids. C Management of disseminated tuberculosis: https://web.pathway.md/diseases/recSbGzA8a48XKtDL 6/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway Consider initiating empiric anti-tuberculosis treatment in severely ill or significant immunocompromised patients while waiting for mycobacterial culture confirmation. E Consider administering standard anti-tuberculosis therapy for 6 months in patients with drug- susceptible disseminated tuberculosis without CNS involvement. Consider extending treatment to 9-12 months in immunocompromised patients if the predisposing condition is not modified (such as patients with human immunodeficiency virus not receiving antiretroviral therapy or continuation of immunosuppressive therapy). C Management of tuberculoma (antimycobacterial therapy): consider administering standard anti-tuberculosis therapy for 9-12 months in patients with drug-susceptible tuberculoma and spinal arachnoiditis because of the severity of the disease and the risk of morbidity with inadequate treatment. E Management of tuberculoma (adjunctive corticosteroids): avoid administering adjunctive corticosteroids routinely in patients with CNS tuberculoma without meningitis. D 5. Specific circumstances Patients with HIV infection: As per WHO 2022 guidelines, initiate antiretroviral therapy as early as possible (within the first 8 weeks) following the initiation of antituberculosis treatment in all patients with human immunodeficiency virus infection and drug-resistant tuberculosis requiring second-line antituberculosis drugs, irrespective of the CD4 cell count. B As per WHO 2017 guidelines, initiate antiretroviral therapy in all patients with tuberculosis and human immunodeficiency virus infection, regardless of the CD4 cell count. Initiate tuberculosis treatment first, followed by antiretroviral therapy as soon as possible within the first 8 weeks of treatment. A . Initiate antiretroviral therapy within the first 2 weeks of initiating tuberculosis treatment in human immunodeficiency virus infection-positive patients with profound immunosuppression, such as CD4 counts < 50 cells/mm . As per ATS 2016 guidelines, initiate antiretroviral therapy during tuberculosis treatment in patients coinfected with human immunodeficiency virus, ideally starting within the first 2 weeks of tuberculosis treatment in patients with CD4 counts < 50 cells/ L and by 8-12 weeks of tuberculosis treatment in patients with CD4 counts 50 cells/ L. A 6. Patient education Patient support: As per WHO 2017 guidelines, provide health education and counseling on the disease and treatment adherence in patients receiving tuberculosis treatment. B Show 2 more As per ATS 2016 guidelines, consider offering case management interventions (such as patient education/counseling, field/home visits, integration/coordination of care with specialists and medical home, patient reminders, and incentives/enablers) in addition to curative interventions in patients with tuberculosis. C https://web.pathway.md/diseases/recSbGzA8a48XKtDL 7/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway Clinical findings Symptoms Past medical history Abdominal pain BCG therapy Agitation Human immunodeficiency virus infection Amenorrhea Immunocompromising condition Back pain Pulmonary tuberculosis Back stiffness Blurred vision Cardiac exam Bone pain Chest pain Pericardial friction rub Constipation Abdominal exam Cough Diarrhea Abdominal distension Dysphagia Ascites Dysuria Hepatomegaly Epigastric pain Palpable abdominal mass Fever Splenomegaly Flank pain Floaters and flashes Genitourinary exam Headache Scrotal mass Hematuria Hoarseness Lymphatic exam Limb weakness Axillary lymphadenopathy Loss of appetite Cervical lymphadenopathy Malaise Inguinal lymphadenopathy Menstrual irregularity Submandibular lymphadenopathy Muscle spasms Nausea Supraclavicular lymphadenopathy Night sweats Nocturia Odynophagia Imaging findings Personality or behavioral changes Abdominal lymphadenopathy Photophobia Cardiomegaly Pleuritic chest pain Pericardial effusion RUQ pain Pericardial thickening Seizure Pleural effusion Shortness of breath Suprapubic pain Urinary frequency Urinary urgency Vaginal bleeding Vaginal discharge Vision loss Vomiting https://web.pathway.md/diseases/recSbGzA8a48XKtDL 8/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway Weight loss Neurological exam Altered mental status Cauda equina syndrome Focal neurologic deficits Limb paresis Meningismus Respiratory exam Dullness to percussion Pleural friction rub Musculoskeletal exam Kyphosis Muscle atrophy Skeletal deformity spinal ROM Gynecologic exam Adnexal mass Uterine enlargement Integument exam Draining sinus tract Jaundice Studies 2022 SHINE In children with non-severe, symptomatic, presumed drug-susceptible tuberculosis, 4 months treatment was noninferior to 6 months treatment with respect to treatment failure or disease recurrence at 72 weeks. Anna Turkova et al. N Engl J Med. 2022 Mar 10. 2018 Rifampin in latent TB In patients with latent tuberculosis infection, 4-month regimen of rifampin, as compared with 9- month regimen of isoniazid, was not inferior for the prevention of active tuberculosis. In rifampin group, among 3443 patients, confirmed active tuberculosis and clinically diagnosed active tuberculosis developed in 4 and 4 patients, respectively, during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) for confirmed active tuberculosis and for confirmed or clinically diagnosed tuberculosis were < 0.01 cases per 100 person-years (95% CI -0.14 to 0.16) and < 0.01 cases per 100 person-years https://web.pathway.md/diseases/recSbGzA8a48XKtDL 9/11 6/29/23, 4:21 AM Extrapulmonary tuberculosis Pathway (95% CI -0.23 to 0.22), respectively. The upper boundaries of the 95% CI for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75% in cumulative incidence. The difference in the treatment-completion rates was 15.1% (95% CI 12.7-17.4). The rate differences for adverse events of grade 3-5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) for all events and hepatotoxic events were -1.1% (95% CI -1.9 to -0.4) and -1.2% (95% CI -1.7 to -0.7), respectively. Menzies D et al. N Engl J Med. 2018 Aug 2. Show 1 more References 1. Tunkel AR, Glaser CA, Bloch KC et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Aug 1;47 3 303 27. Open 2. Christen Ravn, Jeroen Neyt, Natividad Benito et al. Guideline for management of septic arthritis in native joints SANJO . 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