Starting from a pulmonary localisation (primary infection), M. tuberculosis can spread to other organs during a silent phase, usually soon after primary infection (Chapter 1). Active TB can develop in many other parts of the body, particularly in lymph nodes, meninges, bones and joints, kidneys, genital organs and the abdominal cavity.
Extrapulmonary tuberculosis (EPTB) can develop at any age. Due to relative immunodeficiency, young children, HIV-infected and malnourished patients are more at risk of developing EPTB.
Approximately 15% of global TB cases are classified as EPTB, although this figure varies according the local epidemiology
World Health Organization. Global Tuberculosis Report 2020. Geneva: World Health Organization; 2020.
A patient with EPTB may also have pulmonary involvement, which should be searched for whenever EPTB is diagnosed or suspected.
Table 2.3 at the end of this chapter summarises the characteristics of EPTB.
2.2.1 Lymph node tuberculosis
Lymph node TB is common, particularly in certain areas of Africa and Asia, and especially in children and HIV-infected patients.
The presentation of lymph node TB is a non-inflammatory adenopathy. Nodes are cold and painless, multiple (usually bilateral) or single, evolving in a chronic mode towards softening and fistulisation. Cervical localisation is most frequent. Axillary and mediastinal localisations are also common. Other sites may be involved.
Diagnosis may be clinical, but whenever possible, fine needle aspiration should be performed (Chapter 3 and Appendix 7).
Adenopathy usually disappears within 3 months of treatment initiation. Paradoxical reactions may occur at the beginning of treatment (appearance of abscesses, fistulas or other lymph nodes), but a change in the treatment is not required.
Differential diagnoses include malignancies (lymphoma, leukaemia, ear/nose/throat tumours, Kaposi sarcoma) and other infections (bacterial, viral, non-tuberculosis mycobacteria, toxoplasmosis, HIV infection, syphilis, African trypanosomiasis).
2.2.2 Tuberculous meningitis
TB meningitis is a serious form of TB that affects the meninges. It is most common in children under 2 years and in HIV-infected patients. It is a medical emergency. Any delay in diagnosis or treatment will result in irreversible neurological sequelae or death  Citation 2. Wang, M.G., et al., Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis. BMC Pulm Med, 2019. 19(1): p. 200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833188/pdf/12890_2019_Article_966.pdf .
TB meningitis typically has a subacute insidious course over days or weeks. Symptoms include headaches, irritability, fever, vomiting and altered mental status, which worsen if treatment is delayed. The meningeal syndrome (stiff neck, hypotonia in infants, photophobia and headache) is present in most cases. Third cranial nerve palsy (oculomotor paralysis) may occur.
Diagnosis is assisted by examination of cerebrospinal fluid (Chapter 3).
The main differential diagnoses are other forms of meningitis.
2.2.3 Tuberculosis of bones and joints
Up to 40% of patients with TB of bones and joints have concurrent PTB
Qian, Y., et al., Characteristics and management of bone and joint tuberculosis in native and migrant population in Shanghai during 2011 to 2015. BMC Infect Dis, 2018. 18(1): p. 543.
Spinal TB (spondylodiscitis or Pott's disease)
TB can affect vertebrae and intervertebral disks, causing destruction and deformation of the spine. The thoracic spine is the most frequently affected.
Localised back pain may precede by several months the appearance of the first radiological anomalies (destruction of an inter-vertebral disk).
A spinal prominence (gibbus) due to destruction and deformity of the vertebral bodies may be felt.
Paravertebral cold abscesses and/or neurological complications can develop.
A missed diagnosis of thoracic or cervical spinal TB can result in paralysis.
TB most frequently causes a chronic mono-arthritis, starting insidiously, with little or no pain and accompanied by joint destruction. The joints most often affected are the hips, knees, elbows and wrists.
Osteitis is the least common presentation of TB of the bones. It may be a primary osteitis or an osteitis secondary to TB arthritis. Typically, long bones are affected. Cold abscesses may occasionally occur. Like arthritis, it is distinguished from common bacterial infections by the presence of mild symptoms, despite bone and joint destruction.
The diagnosis is based on the patient’s history, clinical examination and radiography, as biopsy and culture are difficult to perform in many settings. A history of prolonged and insidious osteitis or arthritis associated with a deterioration of the general physical condition favours TB aetiology, as opposed to bacterial osteomyelitis or brucellosis. The patient may have a history of non-response to antibiotics.
2.2.4 Urogenital tuberculosis
Renal involvement is frequent and may be asymptomatic for a long period, with a slow development of signs and symptoms: painful urination (dysuria), urinary urgency and frequency (pollakiuria), including during the night (nocturia); back/abdominal pain; tenderness/swelling of the testes or epididymitis or haematuria. General physical condition is generally preserved.
Diagnosis is suspected in the presence of pyuria (white blood cells in the urine) and micro- or macroscopic haematuria, which does not respond to antibiotics. Examination of the urine helps with diagnosis (Chapter 3).
In men, genital localisation is secondary to renal involvement. Signs are most often epididymitis with scrotal pain.
In women, genital tract infection can also occur by a hematogenous path. Signs are non-specific: pelvic pain, leucorrhoea and abnormal vaginal bleeding. Infertility is often the reason leading women to seek medical attention.
Extension may be found in the peritoneum, with resulting ascites.
2.2.5 Abdominal tuberculosis
Abdominal TB commonly presents as ascites resulting from the peritoneal localisation of the infection.
Abdominal mass (often in the right lower quadrant), pain and diarrhoea may be present. The frequency of chronic ascites in tropical regions, with its many different causes, makes this relatively uncommon form of TB difficult to diagnose  Citation 4. Sinkala, E., et al., Clinical and ultrasonographic features of abdominal tuberculosis in HIV positive adults in Zambia. BMC Infect Dis, 2009. 9: p. 44.
Diagnosis is assisted by examination of the ascitic fluid via paracentesis (Chapter 3).
Constitutional symptoms (fever, night sweats, malaise and weight loss) may be present. Accumulation of ascites may mask weight loss.
2.2.6 Tuberculous pleural effusion
Tuberculous pleural effusion is one of the most common forms of EPTB.
It is often asymptomatic, especially if less than 300 ml. Shortness of breath and chest pain (often unilateral) occur when the effusion is large. Sputum production and cough are present in the case of concurrent PTB, which is common.
Constitutional symptoms such as fever, night sweats, malaise and weight loss may also be present.
Effusion can progress to tuberculous empyema, characterised by purulent fluid containing large numbers of bacilli. Tuberculous empyema is often associated with thickened, scarred and calcified pleura.
Diagnosis is assisted by examination of the pleural fluid via paracentesis and chest x-ray (CXR). See Chapter 3.
2.2.7 Tuberculous pericardial effusion
Clinical signs of a tuberculous pericardial effusion include chest pain, shortness of breath, oedema of the lower limbs and sometimes ascites.
Clinical examination may show pericardial friction rub, raised jugular pressure and tachycardia.
CXR and ultrasound are key elements for diagnosis (Chapter 3).
Pericardiocentesis may be necessary in the event of acute heart failure with haemodynamic compromise. It must be performed by experienced personnel in well-equipped hospitals, and when possible, under direct visualisation with ultrasound.
2.2.8 Cutaneous tuberculosis
The clinical presentation of cutaneous TB is chronic, painless, non-pathognomonic lesions, ranging from small papula and erythema to large tuberculomas.
The diagnosis is based on culture from a biopsy.
- 1.World Health Organization. Global Tuberculosis Report 2020. Geneva: World Health Organization; 2020.
- 2.Wang, M.G., et al., Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis. BMC Pulm Med, 2019. 19(1): p. 200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833188/pdf/12890_2019_Article_966.pdf
- 3.Qian, Y., et al., Characteristics and management of bone and joint tuberculosis in native and migrant population in Shanghai during 2011 to 2015. BMC Infect Dis, 2018. 18(1): p. 543.
- 4.Sinkala, E., et al., Clinical and ultrasonographic features of abdominal tuberculosis in HIV positive adults in Zambia. BMC Infect Dis, 2009. 9: p. 44.