Extra-pulmonary tuberculosis

Peter Davies,
Director tuberculosis research unit
Liverpool

Definition
Extra-pulmonary tuberculosis (EPTB) refers to disease outside the lungs. It is sometimes confused with non-respiratory disease. Disease of the larynx for example, which is part of the respiratory system, is respiratory but extra-pulmonary.

Incidence
Accurate data on the incidence of disease is difficult to find except in countries where good national data is available. There is wide variation between series depending on the region studied and the ethnic groups. In the UK the White population present with an extra-pulmonary site in 15% of cases but those of Bangladeshi, Pakistani or Indian ethnic origin present with an extra-pulmonary site in up to 50% of cases.
Patients with HIV positive disease present with more than 50% extra-pulmonary disease

Development of extra-pulmonary disease

At the time primary infection occurs (see article elsewhere on web site)blood or lymphatic spread of tubercle bacilli to parts of the body outside the lung may occur. In the fully immunocompetent host these bacteria are probably destroyed. If some immune deficit is present some may concentrate at a particular site where they may lie dormant for months or years before causing disease.
Bacteria may be coughed from the lungs and swallowed. By this route they may enter the lymph nodes of the neck or parts of the gastro-intestinal (GI) tract.
Before milk was routinely pasteurised cattle infected with M. bovis, the bovine variant of tuberculosis could pass disease to humans who drank infected milk. Transmission by this route would also give rise to GI diseases.

Sites
The commonest sites are listed as follows

Lymph glands and abscesses particularly around the neck.
Orthopaedic sites such as bones and joints. The spine is affected in about half such cases.
GU tract. In women uterine disease is probably the most common while in men the epididymis is the site most frequently affected. Both sexes are affected by renal , ureteric or bladder disease equally.
Abdomen. This may affect the bowel and or peritoneum.
Meningitis, which may be rapidly fatal if not, treated in time
Pericardium causing constriction to the heart
Skin. which can take a number of forms, most notably Lupus vulgaris where changes of the facial skin was supposed to give patients a wolf-like appearance.

Clinical presentation
Clinical presentation is characteristically chronic with pain and swelling being the principal features.

Lymph glands of the neck may develop singly or in chains. They become swollen painful and may have a rubbery texture. They may break down to give abscess formation. These may discharge onto the skin giving a very unsightly combination of swelling a pus around the neck. This was the old fashioned scrofula, which was said to be cured by a touch from the King. (It was therefore also named the King's evil)

Bony disease causes pain and swelling of the affected part. Spinal disease may cause paraplegia if enough of the vertebrae are destroyed to cause instability of the spine.

Abdominal disease characteristically causes pain and constipation. If advanced it may cause complete obstruction of the bowel.

Tuberculous meningitis (TBM) may cause a wide variety of symptoms. A single cranial nerve my be affected resulting in double vision. There may be mental confusion developing over days or weeks. If not detected and treated coma may develop. If treated soon enough recovery may be complete but long term sequelae are likely if the treatment is delayed. TBM has the highest mortality of all complications of tuberculosis.

Diagnosis
The clinical picture should give an indication of the diagnosis. In the ethnic minority groups this is readily considered but because extra-pulmonary tuberculosis is so unusual in the white population it may not be considered and therefore missed.
The diagnosis at any site should be confirmed by obtaining specimens for bacteriology wherever possible. This means that fluid aspirated or biopsies taken should be placed in a medium such as saline which will not kill the bacteria.
Too often still biopsy specimens are placed in formalin so that bacteriological confirmation including sensitivity testing cannot be done.

Treatment
Treatment is as for pulmonary disease with isoniazid, rifampicin, pyrazinamide and ethambutol for two months followed by isoniazid and pyrazinamide for four months, except for CNS disease when treatment should be continued for a full year. Steroids may be used in pericardial and meningeal disease.
Surgery is usually unnecessary especially where lymph glands and abscess are pesent as long term discharging sinuses may result. Surgery is sometimes necessary in spinal TB where there is instability and may be needed to overcome strictures in GU or GI disease. Occasionally pericardectomy may be required when pericardial disease causes tamponade.
It is surprising how the most destructive lesion can be healed with drug treatment alone.

Further Reading

Humphries M.J, Lam W.K. Non-respiratory tuberculosis in Clinical Tuberculosis 2nd Edtn: Edit P.D.O.Davies Chapman and Hall London 1998. Pp 175-204.
A very readable short account

David Schlossberg Tuberculosis 4th Edition Springer_Verlag 1998
The most comprehensive review..

Kumar D, Watson JM, Charlett A et al. Tuberculosis in England and Wales in 1993: results of a national survey. Thorax 1997;52:1060-7
The incidence of EPTB in England and Wales