In this module we will learn about
Various forms of Extra Pulmonary Tuberculosis
After penetration into the organism through the respiratory route, M. tuberculosis can settle and multiply in any organ during the primary infection, before development of the specific immune response. After this, tubercle bacilli can multiply at any time when there is a decrease in the host’s immune capacity to contain the bacilli in their implantation sites. The specific signs and symptoms will depend on the affected organ or system, and are characterized by inflammatory or obstructive phenomenon Systemic symptoms are much less frequent than in pulmonary TB, except in the disseminated form of the disease.
The majority of the extra pulmonary forms of TB affect organs with suboptimal conditions for bacillary growth. For this reason, the extra pulmonary disease generally has an insidious presentation, a slow evolution and paucibacillary lesions and/or fluids. Access to the lesions through secretions and body fluids is not always possible, and for this reason, invasive techniques may be necessary in many cases to obtain material for diagnostic investigation. Tissues and/or body fluids should be submitted to laboratory examination, in particular bacteriological culture for mycobacteria and histopathological analysis.
Imaging studies provide valuable information for the diagnosis of extra pulmonary TB, although specific radiological patterns are not observed. Nevertheless, the chest X-ray is mandatory for the evaluation of evidence of primary infection lesions, which provide a good verification to support the diagnosis
1) Pleural Tuberculosis
This is the most common form of extra pulmonary TB, and can either result
- from the rupture of a primary sub-pleural lung focus (evident or not on conventional chest X-ray)
- Or be secondary to lymphohematogenic dissemination.
The presence of a pleural TB effusion has also been related to hypersensitivity
Most cases occur several months after the primary infection, and frequently the patient relates having contact with an active pulmonary TB case in the two years preceding the current episode. The simultaneous presence of active pulmonary TB may be related to recent infection followed by disease. The onset of the disease may be insidious or abrupt, with fever, systemic complaints, dyspnea, dry coughs ,and pleuritic thoracic pain.
The physical examination shows signs characteristic of pleural effusion.
The pleural effusion is generally unilateral and moderate, and can easily be detected by conventional chest X-ray examination.
Left sided Pleural effusion
Pleural tap is advised in patients with the above mentioned clinical presentation and radiological findings unless contraindicated.
At the time of diagnostic tap therapeutic aspiration should also be attempted if effusion is massive (to relieve patient symptoms and to prevent the sequelae of Pleural tuberculosis like pleural thickening, calcifications, fibro thorax and chronic persistent effusion)
The gross appearance of the pleural fluid and its odor should always be recorded. This helps in differential diagnosis of fluid. Send fluid sample for detailed report (DR) of biochemical and microscopic examination.
Yellow or Straw-colored fluid, with more than 2.9gm/dl proteins,cell counts ranging from 1000 to 5000 /mm3 with predominant lymphocytosis and less than 5% mesothelial cells in a young person is suggestive of tuberculosis. In such cases register the patient, start ATT, and refer patient back to PHC.
Patients having clear fluid, hemorrhagic fluid or pus are referred for further investigations, like pleural biopsy, for diagnosis.
Patient with tuberculous empyema and bronchopleural fistula need chest intubation and therefore should be referred to tertiary care facilities for further management,
The determination of adenosine deaminase (ADA), an enzyme liberated by activated lymphocytes is an important auxiliary method in the diagnosis of pleural TB This examination has a sensitivity and specificity above 90%.
The differential diagnosis for pleural effusions includes
- para-pneumonic pleural effusions,
- malignant diseases
- Especially in young women, collagen vascular diseases.
Most of the time, the effusion is resolved, even if not treated, leaving minimal or no radiological sequelae. Nevertheless, there is a high risk of reactivation of pulmonary TB in the following years if pleural TB is not adequately treated with anti-tuberculosis drugs.
NTP Pakistan has suggest an algorithm how to approach case of suspected pleural effusion
2. Peripheral TB lymphadenitis:
The lymph nodes at any site of the body may be involved but the cervical nodes are the most commonly affected. The typical signs and symptoms are unilateral, painless, non-tender neck mass/es sometime associated with constitutional symptoms. During the course of illness, the nodes may become fluctuant and drain spontaneously resulting in sinus tract formation.
Diagnosis of tuberculous lymphadenitis is based on either examination (cytological and/or bacteriological) of aspirated specimen (Fine needle aspiration) and/or biopsy. ( excision or incision).
Fine needle aspiration (FNA) is diagnostic in about 60% of cases. This is a simple technique which can be performed as an out door procedure
Interpretation of results of FNA
Needle aspiration of lymph node
Gross examination of aspirated material
Chronic granulomatous Tuberculosis lymphadenitis
Smear for cytology
Smear for AFB
- If diagnosis is established as tuberculous lymphadenitis, register the patient start ATT, if diagnosis is other than TB, manage accordingly.
- When diagnosis is not established on aspiration. Repeat FNAC. If it is again inconclusive, refer the patient to surgeon for excision biopsy of the lymph node for diagnosis; ensure follow up of patient with biopsy report.
- Lymph node can decrease in size, can remain static in size or may increase in size during the course of treatment. This does not indicate treatment failure
- If the lymph node persists after completion of anti tuberculosis treatment, just reassure the patient.
- If the lymph node increases in size after completion of full course of ATT. Repeat FNAC, subject the aspirated material for AFB smear.
3. Miliary tuberculosis
Miliary TB results from the massive hematogenic dissemination of the TB bacillus during the primary infection. Its onset may be either insidious or abrupt, depending on the bacillary load and/or the host immune situation, with unvaccinated infants, elderly and immunodeficient patients being the most susceptible
Symptoms include fever, anorexia, weight loss, and asthenia. Other specific symptoms depend on the organs affected, and involvement of the central nervous system occurs in 30 % of cases.
Physical Examination is non-specific, and the patient can present with variable degrees of wasting, fever, tachycardia and toxemia. The observation of bacilli on smear microscopy examination is rare, and culturing mycobacteria provides a higher probability of bacteriological confirmation of the diagnosis of TB.
Chest X-ray shows a characteristic diffuse, bilateral and symmetrical micro nodular infiltrate. Other characteristic TB lesions can be found simultaneously, such as cavities, focal parenchymatous collapse, and pleural effusion. Bilateral involvement is highly suggestive of miliary dissemination.
X-ray chest of miliary TB
4. Renal Tuberculosis
Renal TB is rare in children and predominantly affects individuals in the fourth decade of life. Renal disease occurs after a long latency period and is frequently secondary to hematogenous dissemination. The localization is almost always bilateral, but can be asymmetric. The lesions often start in the renal cortex and progress slowly toward the central region. Dissemination can occur to the bladder and even to the genital system.
Symptoms and signs vary in duration and severity. The patient generally complains of dysuria, polacyuria, and lumbar pain, whereas systemic symptoms occur less frequently. Frequently, the disease presents as a urinary infection that does not respond to routine broad-spectrum antimicrobial treatment. Purulent urine is frequently found, with urine culture negative for common germs (aseptic pyuria).Hematuria occurs in 10 % to 15 % of the cases. Excretory urography can either be normal or present a wide variety of alterations that include parenchymatous cavities, dilatation of the pyelocalicial system, renal calcifications of irregular contours, decreased capacity of the urinary bladder, and multiple ureter stenoses Due to the high association between renal TB and urinary bladder TB, cystoscopy is indicated.
In the Cystoscopy, edema and diffuse hyperemia are observed, which are more intense around the orifice (golf hole sign), often accompanied by irregular ulcerations and/or infiltrates and vegetations.
In these cases biopsy is indicated.
Infertility is associated hysterosalpingogram, reveals proximal dilatations of the fallopian tubes (“rigid pipe stem" appearance) and distal enlargements/constrictions (“beaded"appearance).
When the urine culture is positive for M. tuberculosis. The diagnosis is confirmed Culture of three to six specimens of first morning urine are together as reliable as the culture of a single 24-hour urine sample.
5. Tuberculosis of the central nervous system
The compromise of the central nervous system occurs in two basic forms:
- intracranial tuberculoma.
Since the introduction of modern chemotherapy and especially massive BCG vaccination, a lower proportion of the mining encephalitis has been observed, but the frequency of this form of TB is higher among young adults with HIV/AIDS
The clinical manifestations are due to the inflammatory process induced by the mycobacterial infection, and the symptoms depend on the site and intensity of inflammation.
Granulomas can be located in the
- cerebral cortex (TUBERCULOMA)
- in the meninges (MENINGITIS)
Symptoms: Meningoencephalitis generally has an insidious onset and a slowly progressive course, with symptoms including apathy, lethargy, fever, and mental disturbances such as irritability, understanding difficulties, personality alterations, disorientation, and progressive mental confusion. Vertigo, migraine and vomiting can also be observed.
Physical examination are related to the stage of the disease and the affected area, such as cranial nerve involvement (the most affected are the 2nd , 3rd ,4th, and 8th nerve pairs), focal neurological deficits, and signs of meningeal and cerebellar irritation.
The cerebrospinal fluid is generally clear, with a predominance of lymphocytes, an increase in proteins and a decrease in glucose levels. Microscopic examination for AFB is generally negative and cultures are positive in only 15 % to 30 % of cases.
- other infectious meningitis,
- vascular pathologies,
- the collagen vascular disease sarcoidosis,
- metastatic carcinoma,
- acute hemorrhagic leucoencephalopathy,
Intracranial tuberculoma, the clinical manifestations depend on the location of the lesion, which generally grows slowly. When there is no compromise of the sub-arachnoid space, the cerebrospinal fluid is normal and the computerized tomography exhibits a mass, which is generally difficult to differentiate from neoplasia
6. Osteo-articular tuberculosis
Involvement of the osteoarticular system is most commonly found in children and the elderly, and is generally secondary to hematogenous seeding, but can also occur as a consequence of lymphatic dissemination or direct spread from a contiguous lesion. Bone involvement consists of osteomyelitis, and arthritis can occur either by extension of the osseous lesion to the joint or by direct hematogenic inoculation.
The most frequent sites of bone involvement are
- vertebrae (Pott’s disease)
- proximal extremities of the long bones.
Spinal TB frequently affects more than one vertebra. With evolution, it presents a wedged flattening and gibbous formation that can be associated with a paravertebral cold abscessParesthesia and paraplegia are reported when the cervical and upper thoracic area are affected.
Image on X-ray is characterized by erosion of the anterior vertebral body margins with no preservation of the intervertebral space. The definitive diagnosis should be obtained by biopsy for culture and histopathological analysis
The peripheral joints most frequently affected by TB are the hip and the knee. Pain,with or without movement limitation, fever and systemic symptoms are frequent.
Monoarticular involvement is much more frequent than multiarticular disease. The diagnosis of osteoarticular TB is usually delayed because this etiology is often overlooked in the differential diagnosis of joint disease.
Cold abscesses occurring in the advanced phase of osteoarticular TB can develop into cutaneous fistulae, which are frequent in this form of the disease. The diagnosis is established by puncture, biopsy, histopathological examination, and culture
7. Other extra pulmonary localizations
Tuberculous involvement of other tissues, such the eye, skin (lupus vulgaris), genital, and digestive tract, may also be the result of hematogenous dissemination, but there are other possible routes of infection.
Can be acquired by the oral route and in countries with a high prevalence of bovine TB. Before the generalization of milk pasteurization, this was a rather common form of zoonotic TB (produced by Mycobacterium bovis), particularly in infants.
Eye and skin TB may be the consequence of accidental inoculation, particularly among medical and veterinary professionals,
Monitoring extra pulmonary tuberculosis
Clinical assessment is often the only means available for judging progress in extra-pulmonary and smear-negative pulmonary tuberculosis. Weight gain is a valuable indicator in such cases. Another way is to assure regular intake of medicine. Like sputum negative cases, the out come in these cases is reported as ‘treatment completed’.
Relapsed extra pulmonary tuberculosis
More than 80% of the relapses occur with drug-susceptible organisms. 80–90%. These cases can be treated successfully for eight months with five drugs, including rifampicin, during the intensive phase and three drugs in the continuation phase. Every effort should be made to obtain the material from the lesions and subject it for bacteriology.