2.2 Extrapulmonary tuberculosis

 

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.

 

Due to relative immunodeficiency, young children, HIV-infected persons and malnourished patients are more at risk of developing extrapulmonary tuberculosis (EPTB).

 

Approximately 16% of global TB cases are classified as EPTB, although this figure varies according the local epidemiology [1] Citation 1. World Health Organization. Global Tuberculosis Report 2020. Geneva: World Health Organization; 2020.
https://apps.who.int/iris/rest/bitstreams/1312164/retrieve .

 

A patient with EPTB may also have pulmonary involvement (PTB), 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 persons.

 

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, a lymph node specimen should be collected and tested (Chapter 3).
Lymph nodes usually disappear 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 persons. It is a medical emergency. Any delay in diagnosis or treatment will result in irreversible neurological sequelae or death [2] 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://doi.org/10.1186/s12890-019-0966-8 .

TB meningitis typically has a subacute insidious course over days or weeks. Symptoms include headache, irritability, fever, vomiting and altered consciousness, 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.

A CSF specimen should be collected and tested (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 [3] Citation 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.
https://doi.org/10.1186/s12879-018-3456-3 .

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.

Arthritis

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

Osteitis 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 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. There are usually few constitutional symptoms such as fever, night sweats, malaise and weight loss.
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 for urinary infection.

A urine specimen should be collected and tested (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 [4] 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.
https://doi.org/10.1186/1471-2334-9-44 . 
Constitutional symptoms such as fever, night sweats, malaise and weight loss may be present. Accumulation of ascites may mask weight loss.

Ascitic fluid specimen can be collected and tested. Medical imaging can contribute to diagnosis (Chapter 3).

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 with large effusion. 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 be present. 
Effusion can progress to tuberculous empyema, with purulent fluid containing large numbers of bacilli. TB empyema is often associated with thickened, scarred and calcified pleura.
Pleural fluid specimen can be collected and tested. Medical imaging can contribute to diagnosis (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.
Medical imaging is key 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.