**3.2. Other factors**

Results of HIV and AIDS research also emphasize the importance of T-cell response. Several working groups have shown, that the prevalence of tuberculous pleurisy in HIV-infected patients with TB is strikingly correlated with their CD4+ blood lymphocyte count. In one series pleuri‐ sy prevalence in individuals with a count of > 200 cells/ml was 27 % as compared to 10 % in those with a count of < 200 cells/ml [25]. The data support the view, that the clinical expression of exudative pleural effusion requires a largely intact cellular immune system and features pleurisy as a high activity response in a still immunocompetent individual. In epidemiologic terms one would conclude that pleural effusion should be more frequent in the still immunocompetent host than in patients with AIDS. In reality however in most HIV-high-prevalence countries like South Africa, Uganda and Zimbabwe the percentage of thoracic TB-patients with pleural effusion is reportedly higher in HIV+ patients [26]. As an explanation the situation is probably blurred

**Figure 1.** Mechanisms and immunogenesis of tuberculous pleurisy: the three stages of protective immune response. IFN: interferon; TNF: tumor necrosis factor; IL: interleukin; PMN: polymorphonuclear granulocyte; X: undefined cell;

by a variable and poorly defined immune status in HIV+ individuals.

MΦ: macrophage, MTB: mycobacterium tuberculosis; PPD purified protein derivative

270 Tuberculosis - Current Issues in Diagnosis and Management

The mechanisms of fluid accumulation and of abundant protein leakage to the pleura with often extensive fibrin deposits in tuberculous pleurisy have so far not been fully elucidated. In actual fact pleuritis exudativa tuberculosa generally presents with the highest protein levels commonly seen in exudative conditions. The intensity of inflammation and a proportionately increased vascular permeability would provide a satisfying explanation [25, 27] although at least in animal models, no such significantly altered vascular permeability could be demon‐ strated [12]. Current opinion holds that grossly impeded lymphatic protein clearance from the pleura due to altered parietal lymphatic channels is probably of tantamount importance.

Again the *entry mechanism* of mycobacteria to the pleura has remained unclear. It is usually assumed that the release of infectious material from a ruptured subpleural TB-lesion is the most common mechanism. While this is likely to occur in more or less extensive pulmonary TB, it would not explain the frequent association of tuberculous pleuritis with an – at least radiographically – unaffected lung. There are also no convincing data yet to quantify the contribution of a purported hematogenous or lymphogenous contribution. One might reasonably speculate that different patterns of pleural tuberculous involvement are operative which might correspond to the different clinical settings of primary, post-primary and reactivated TB.

*Caseous tuberculous pleuritis or specific empyema* is nowadays a rare condition which is believed to be the result of longstanding or chronic infection of the pleura, when either caseous material gains access to the pleura or chronic pleuritis develops on the background of impaired local defence such as pre-existing fibrous damage of the pleura or as a sequel and complication of artificial pneumothorax, oleothorax or other TB-specific surgery dating back to the prechemotherapy era. Correspondingly there is usually an extremely long history often with a remarkable paucity or even absence of symptoms. Penetration to deeper chest wall structures (specific abscess) and ultimately transcutaneous discharge (empyema necessitans) or creation of a specific bronchopleural fistula, as not infrequently seen in the pre-chemotherapeutic era, may complicate this condition [27]. Putrid discharge from a thoracic mass or putrid expecto‐ ration with or without haemoptysis may ultimately advert to the condition.
