Pulmonary and extrapulmonary tuberculosis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Tuberculosis is one microbiological disease with different anatomical decisions. Pulmonary cavitation determines infectiousness and respiratory sampling; meningitis changes urgency, total duration and adjunctive steroid use; spinal disease raises stability and cord questions; lymph-node or pleural disease often depends on correctly divided tissue. The site must therefore appear in the problem representation before treatment is prescribed.

Diagnosis, treatment and health protection proceed together. Smear burden and cough inform immediate transmission risk, molecular testing accelerates M tuberculosis and rifampicin-resistance detection, and culture supplies the complete susceptibility record. Notification on suspicion enables coordinated contact work without treating the laboratory as the only route into public health.

A six- or twelve-month regimen is a monitored programme, not a static drug list. Weight change, renal and hepatic function, vision, neuropathy, pregnancy, HIV therapy and interacting medicines can alter safe exposure. Missed doses or apparent failure require a specialist review of adherence, absorption, resistance and diagnosis; adding one drug to a failing regimen is unsafe.

Key points

Pulmonary TB creates transmission risk; extrapulmonary TB may present through lymph nodes, pleura, meninges, spine, abdomen, genitourinary tract, pericardium or disseminated organ disease.
Use epidemiology as probability, not a gate: exposure, residence in a high-incidence setting, immune suppression, homelessness, detention and previous treatment matter, but disease can occur without a disclosed classic risk.
For suspected pulmonary TB, NICE recommends multiple deep-cough sputum specimens for smear and culture, preferably three with one early-morning sample; add rapid molecular identification and resistance testing.
An acid-fast smear identifies mycobacteria, not M tuberculosis. Maintain the protective pathway until molecular and culture evidence distinguishes TB from NTM.
For lymph-node, pleural, meningeal, bone or other disease, plan unfixed tissue or fluid for mycobacterial culture and molecular testing as well as a separate histology specimen.
Drug-susceptible TB without central-nervous-system involvement usually receives 2 months of rifampicin, isoniazid, pyrazinamide and ethambutol, followed by 4 months of rifampicin and isoniazid; add pyridoxine for people at increased neuropathy risk.
Central-nervous-system TB uses the same four-drug first 2 months followed by rifampicin and isoniazid for 10 further months, plus high-dose corticosteroid tapered over 4 to 8 weeks.
Rifampicin induces many metabolic pathways; isoniazid, rifampicin and pyrazinamide can injure liver; ethambutol can damage optic nerve; renal impairment changes pyrazinamide and ethambutol dosing.
In England, TB notification is routine within 3 days unless the case is urgent, such as suspected MDR disease, a healthcare worker or a cluster; notify on suspicion and use the current nation-specific route.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Airborne M tuberculosis

Aerosols from untreated pulmonary or laryngeal disease carry bacilli to a new host, especially during prolonged indoor contact with poor ventilation.

Recent progression

Newly acquired infection can progress directly to active pulmonary or disseminated disease, particularly in young children and people with impaired cellular immunity.

Reactivation

HIV, anti-TNF therapy, transplantation, undernutrition, diabetes, renal failure and ageing weaken granuloma control and permit latent bacilli to multiply.

Drug-resistant transmission

Resistance may be acquired during inadequate therapy or transmitted initially; previous treatment and contact history help identify the need for rapid resistance assessment.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Macrophage survival
Inhaled bacilli reach alveoli and persist within macrophages by disrupting normal intracellular killing, allowing early local replication.
2
Granulomatous containment
T-cell-mediated immunity recruits activated macrophages into granulomas that limit spread without reliably sterilising every viable organism.
3
Caseation and cavitation
Loss of immune containment produces caseous necrosis; erosion into airways forms high-burden cavities that amplify cough-mediated transmission.
4
Haematogenous seeding
Bacilli entering blood can establish meningitis, miliary lung disease, vertebral infection, renal lesions and other extrapulmonary foci.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Potentially infectious pulmonary TBRed flag

Weeks of cough, weight loss, fever, night sweats or haemoptysis accompany upper-zone, nodular or cavitary change, especially with exposure or epidemiological risk.

Tuberculous meningitisRed flag

Subacute headache, fever, neck stiffness, cranial neuropathy, confusion or reduced consciousness may coexist with hyponatraemia and requires urgent CSF, neuroimaging and treatment planning.

Spinal or skeletal TBRed flag

Persistent focal back pain, constitutional illness, vertebral destruction, deformity, weakness or sphincter change raises spinal infection and possible cord compression.

Pleural or lymph-node TB

Unilateral exudative effusion or chronic nodes may be paucibacillary; fluid alone can be insensitive and tissue frequently provides better culture and histological yield.

Disseminated or miliary diseaseRed flag

Fever, weight loss, cytopenia, organomegaly, diffuse micronodules or multi-organ abnormalities in pregnancy or immune suppression can signal haematogenous spread.

Resistance-enriched historyRed flag

Previous incomplete or failing treatment, contact with resistant TB, prior therapy abroad or origin from a high-resistance setting requires rapid molecular resistance testing and expert regimen design.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Chest radiograph followed by targeted CTFirst step
Why
Find pulmonary disease, cavitation, nodes, miliary spread and a safe route to sample.
Interpretation and limitations
Radiology changes probability and infection-control planning but is not organism proof. Immunosuppressed patients may have non-cavitary, lower-zone or initially subtle appearances.
02
Three respiratory specimens for smear and culture
Why
Measure acid-fast burden, grow the organism and obtain full susceptibility.
Interpretation and limitations
Prefer spontaneous deep-cough samples, including one early-morning specimen; induced sputum or bronchoscopy follows specialist risk assessment. Label suspected TB before transport.
03
Rapid M tuberculosis complex and resistance assay
Why
Accelerate species identification and detect important resistance, particularly rifampicin resistance.
Interpretation and limitations
A positive result can guide early action. A negative result cannot exclude paucibacillary pulmonary or extrapulmonary disease, and culture remains essential.
04
Site-specific fluid or tissue
Why
Diagnose nodal, pleural, meningeal, bone, abdominal, pericardial or genitourinary TB.
Interpretation and limitations
Agree allocation before the procedure: fresh material for mycobacterial culture and molecular testing, separate fixed tissue for histology, plus chemistry or cell studies suited to the compartment.
05
Baseline toxicity and interaction assessment
Why
Make four-drug therapy safe before the first doses and establish monitoring comparators.
Interpretation and limitations
Record weight; FBC; renal and liver profile; visual acuity and colour discrimination; neuropathy risk; pregnancy; alcohol and hepatitis history; and every prescription, supplement and recreational substance.
06
HIV and immune-status evaluation
Why
Identify immune suppression that changes presentation, drug interactions, ART timing and opportunistic-infection risk.
Interpretation and limitations
Offer HIV testing through routine consent and result follow-up. Coordinate rifamycin and antiretroviral selection with a TB-HIV specialist rather than stopping effective ART casually.
07
Public-health and adherence assessment
Why
Define contacts, infectious environments and practical threats to completing treatment.
Interpretation and limitations
The TB team establishes the infectious period and contact priorities. Housing, language, work, transport, substance use and medicine access require supportive solutions, not punitive assumptions.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Non-tuberculous mycobacteria

Acid-fast organisms may be environmental NTM; molecular identification, repeated culture and the clinical syndrome separate diagnoses with very different treatment and public-health implications.

Malignancy

Lung cancer and lymphoma can produce weight loss, nodes, effusion or cavitation; adequate tissue is required because cancer and tuberculosis may coexist.

Fungal or bacterial cavitation

Chronic pulmonary aspergillosis, septic emboli and lung abscess share cavity and haemoptysis patterns but differ in exposure, tempo and microbiology.

Inflammatory granulomatous disease

Sarcoidosis and vasculitis can resemble TB clinically and histologically; infection evidence must be sought before immunosuppression is started.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Pulmonary suspicionProtect, sample and reportFirst stepSymptoms and imaging make pulmonary or laryngeal tuberculosis credible.

1Place the patient in the locally approved airborne pathway, minimise unnecessary movement and involve infection prevention and the specialist TB team.
2Send multiple respiratory samples for smear, molecular testing and culture plus baseline safety tests; begin treatment before culture when the clinical diagnosis is strong or illness is life threatening.
3Report suspected active TB through the current national route and telephone urgently when resistance, healthcare work or a possible cluster raises immediate public-health concern.

02Non-CNS diseaseDeliver the usual six-month structureActive drug-susceptible TB is diagnosed without central-nervous-system involvement.

1Start daily weight-banded rifampicin, isoniazid with pyridoxine, pyrazinamide and ethambutol for 2 months under the TB service.
2When susceptibility and response permit, stop pyrazinamide and ethambutol and continue rifampicin with isoniazid for 4 further months.
3Use the same standard duration for most nodal, pleural and bone or joint disease; new nodes or residual enlargement alone do not automatically justify extension.

03CNS or pericardial diseaseAdd the site-specific duration and steroidTuberculosis involves meninges, brain or spinal cord, or causes active pericardial disease.

1For CNS TB, give the four-drug phase for 2 months then rifampicin and isoniazid for 10 months, modified by susceptibility.
2Offer dexamethasone or prednisolone at high dose from treatment start and taper over 4 to 8 weeks; use urgent neurosurgical assessment when raised intracranial pressure is present.
3For adult pericardial TB, NICE recommends prednisolone 60 mg daily at treatment start with gradual withdrawal 2 to 3 weeks later, alongside cardiac assessment for tamponade or constriction.

04Resistance or toxicityProtect the remaining active drugsMolecular resistance, severe adverse effect, interrupted delivery or poor microbiological response emerges.

1Contact an experienced drug-resistant TB service and never add a single medicine to a regimen that may be failing.
2AlternativeRepeat culture and susceptibility, verify administered doses and absorption, and identify interactions, renal or hepatic change and alternative diagnoses.
3Build a complete effective regimen and revise isolation, monitoring and contact actions according to susceptibility and response, not a fixed number of treatment days.

05CompletionDemonstrate cure and retain the recordThe planned course is approaching completion or has been interrupted.

1Review symptoms, weight, adherence, radiology and culture conversion where relevant and reconcile the actual number and spacing of doses received.
2Document organism, complete susceptibility, anatomical sites, regimen, adverse effects and treatment outcome in hospital and primary-care records.
3Give recurrence and urgent haemoptysis advice and ensure latent-infection and contact pathways remain owned after the index treatment ends.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Treats drug-susceptible active TB with multiple active mechanisms while susceptibility is established and organism burden falls.

Rifampicin, isoniazid, pyrazinamide and ethambutol intensive phase

Use specialist daily weight bands approximating rifampicin 10 mg/kg, isoniazid 5 mg/kg, pyrazinamide 25 mg/kg and ethambutol 15 mg/kg for 2 months.

Rifampicin is a potent inducer affecting contraception, anticoagulants, antiretrovirals, anticonvulsants and transplant drugs; isoniazid inhibits some metabolism and causes neuropathy; rifampicin, isoniazid and pyrazinamide are hepatotoxic; pyrazinamide and ethambutol require renal review, and ethambutol requires visual safety monitoring.

Eradicates persistent drug-susceptible organisms after the four-drug intensive phase.

Rifampicin and isoniazid continuation phase

Give rifampicin 10 mg/kg up to 600 mg and isoniazid 5 mg/kg up to 300 mg orally once daily for the site-specific continuation period.

Continue formal interaction, liver, neuropathy and adherence review throughout. The usual continuation is 4 months without CNS disease and 10 months for CNS disease; resistance, interruption or absorption failure changes the plan.

Reduces isoniazid-related peripheral neuropathy in pregnancy, malnutrition, diabetes, HIV, renal disease, alcohol dependence and other susceptible states.

Pyridoxine with isoniazid

Give pyridoxine 10 mg orally once daily for people at increased neuropathy risk, using a specialist treatment dose if neuropathy develops.

It does not prevent every neuropathy and must not delay assessment of new sensory or motor symptoms. Confirm the dose when treating established neuropathy and avoid unnecessarily high long-term exposure.

Reduces inflammatory injury when tuberculosis affects the central nervous system or pericardium, alongside effective antimycobacterial treatment.

Adjunctive corticosteroid for CNS or pericardial TB

For CNS TB use the NICE stage-based high-dose dexamethasone or prednisolone taper over 4 to 8 weeks; for adult pericardial TB start prednisolone 60 mg daily and withdraw gradually after 2 to 3 weeks.

This is site-specific adjunctive therapy, not routine steroid for pulmonary TB. Monitor glucose, mental state, gastrointestinal and secondary-infection risk and check rifampicin induction, which lowers corticosteroid exposure; use the specialist TB protocol.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Major haemoptysis

Cavities can erode bronchial vessels or form pulmonary-artery pseudoaneurysms, causing life-threatening bleeding that requires airway protection and interventional planning.

Neurological disability

Meningeal inflammation, infarction, hydrocephalus or spinal compression can leave cranial neuropathy, weakness, cognitive injury and long-term rehabilitation needs.

Pericardial compromise

Pericardial inflammation and effusion can cause tamponade acutely or constrictive physiology later, requiring cardiac imaging and sometimes drainage or surgery.

Post-tuberculous lung disease

Fibrosis, volume loss, bronchiectasis and residual cavities cause chronic breathlessness, recurrent infection, haemoptysis and susceptibility to fungal colonisation.

Transmission and acquired resistance

Delayed detection exposes contacts, while incomplete or functionally weak treatment permits persistent disease and selection of additional resistance.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Reweigh regularly and confirm that each medicine still matches the specialist weight band, renal function and the delivered fixed-dose formulation.
Ask actively about anorexia, nausea, abdominal pain, jaundice and dark urine and check liver tests promptly; follow the TB service's thresholds for holding and sequentially reintroducing hepatotoxic drugs.
Record baseline acuity and colour discrimination and stop ethambutol pending urgent TB and ophthalmic advice if visual acuity, red-green discrimination or central vision changes.
Assess neuropathy at baseline and during isoniazid, ensure appropriate pyridoxine and investigate rather than masking progressive symptoms.
Repeat respiratory culture at specialist-defined points for initially culture-positive pulmonary disease; persistent positivity triggers adherence, exposure, resistance and absorption review.
Review contraception, anticoagulation, antiretroviral, anticonvulsant, steroid, opioid and transplant-drug interactions whenever rifampicin starts, stops or changes.
Track CNS examination, sodium and imaging or pericardial haemodynamics according to site, and monitor steroid toxicity during the taper.
Update notification, contact investigation, isolation and outcome records with the TB service while applying the correct legal route for the UK nation.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Acid fast is not species

Microscopy can reveal organism burden rapidly, but only molecular testing and culture distinguish M tuberculosis complex from environmental NTM and establish susceptibility.

Tissue allocation is irreversible

A lymph node placed entirely in formalin cannot be cultured. The procedural plan must preserve fresh material before the sample leaves the bedside.

Site controls the clock

Most active TB without CNS involvement uses six months, whereas CNS disease uses twelve months and adds an early tapering corticosteroid regimen.

Rifampicin has an offset

Induction develops and wanes over time, so interacting medicines may need adjustment both when rifampicin begins and after it is stopped.

New nodes can be paradoxical

Lymph nodes may enlarge during otherwise effective treatment; review adherence, resistance and alternative diagnoses before extending therapy or declaring failure automatically.

Infectivity is assessed, not timed

Cough, smear burden, cavities, susceptibility, effective therapy and vulnerable contacts all matter; a universal two-week rule is unsafe.

11Common pitfallsFrequent interpretation and management errors.

01
Treating an acid-fast smear as definitive proof of M tuberculosis.
02
Submitting all biopsy tissue in fixative and losing culture and susceptibility yield.
03
Using the six-month pulmonary schedule for CNS disease.
04
Starting rifampicin before checking hormonal contraception, anticoagulation, ART, anticonvulsants and transplant medicines.
05
Continuing ethambutol through new colour or central visual change.
06
Adding one drug to possible resistant or failing TB.
07
Calling all TB notifications urgent in England or, conversely, waiting for culture before routine statutory reporting.