KS is one of the more common causes of a pleural effusion in patients with AIDS. KS occurs almost exclusively in male homosexual patients with AIDS (4). Human herpesvirus 8 (HHV-8) is associated with the development of this malignancy. Although HHV-8 is necessary, additional factors not yet fully delineated need to be present for a person to develop KS (5,6). It is thought that HHV-8 is particularly likely to be spread by male homosexual contacts. In the past, KS occurred in 20% to 25% of individuals with AIDS (4). In recent years, there has been a precipitous decline in the prevalence of KS (5). For example, in the state of Washington, the prevalence of KS in the homosexual HIV-positive population was 6% in 1990, but had fallen to 2% by 1997 and apparently has fallen more in the next 3 years (5). It is likely that the decrease in the prevalence of KS is, at least in part, related to the introduction of the highly active antiretroviral therapy (HAART) (5).

Cutaneous violaceous plaques are the most common presentation of KS. At autopsy, 50% to 75% of patients with cutaneous KS have pulmonary involvement (5), but clinically apparent pulmonary involvement is less common during life (5). Most patients
with pleuropulmonary KS present with progressive shortness of breath, nonproductive cough, and fever. Patients with pulmonary KS generally have abnormal chest roentgenograms characterized by bilateral infiltrates (4). The incidence of pleural effusion with pulmonary KS is approximately 50% (4). Most patients with a pleural effusion due to KS also have bilateral parenchymal infiltrates (4). The pleural effusions may be unilateral or bilateral. Bilateral pleural effusions, focal airspace consolidation, intrapulmonary nodules and/or hilar adenopathy are very suggestive of KS (7). The computed tomography (CT) scans are somewhat characteristic with KS. In a review of 53 patients with pulmonary KS, 42 patients (79%) had nodules, 35 (66%) had bronchovascular bundle thickening, 28 (53%) had tumoral masses, and 29 (55%) had pleural effusions (8). The effusions were bilateral in 40 (76%) and were usually at least medium sized (8). Autopsy studies demonstrate multiple cherry red to purple lesions on the visceral surface but not on the parietal pleural surface (4).

The pathogenesis of the pleural effusions in KS is not conclusively defined. Approximately 20% of the pleural effusions with KS are chylothoraces, and, in these instances, the pleural effusion is probably due to involvement of the thoracic duct by the sarcoma (4). In the remaining patients, lymphatic blockade is probably not the responsible mechanism because the lymphatic drainage of the pleura is through the parietal pleura and KS does not involve the parietal pleura. It has been hypothesized that the effusion is due to the elaboration of vascular endothelial growth factor (VEGF) by the tumor (9). VEGF increases the permeability of the microvessels and is present in large quantities in AIDS-KS cell-derived conditioned media (10).

The diagnosis of pulmonary KS is usually established at bronchoscopy, which demonstrates erythematous or violaceous macules or papules in the respiratory tree (11). It is important to remember that many patients with pulmonary KS have a coexisting opportunistic infection (5). If the CT scan reveals ground-glass opacities, alternative diagnoses must be sought (8). The definitive diagnosis of pleural KS is not easy and is virtually one of exclusion. The pleural fluid is an exudate that is usually serosanguineous or hemorrhagic. The differential cell count shows a mononuclear cell-predominant pattern (4). In one series of 10 patients, the pleural fluid glucose and pH levels were normal in 9 patients but were reduced to 63 mg/dL and 7.02, respectively, in 1 patient (4). Cytologic examination of the pleural fluid is not helpful because the diagnosis requires a characteristic architectural appearance and not a particular neoplastic cell type (12). Mesothelial cells from patients with KS are infected with the HHV-8 virus (13). Needle biopsy of the pleura does not establish the diagnosis of KS because the parietal pleura is not involved (4). It is probable that the diagnosis could be established with thoracoscopy given the characteristic appearance of the KS lesions on the visceral pleura (4).

The prognosis of a patient with pleuropulmonary KS is poor. In one study, the average interval from diagnosis of pulmonary KS to death was 4 ± 3 months (4). The presence of the pleural effusion is a significant problem for many patients with pleuropulmonary KS. In one series, recurrent, massive, progressive effusions dominated the final days of a substantial percentage of patients and contributed significantly to the death of approximately 50% (4).

The treatment of the pleural effusion associated with KS is difficult. Tube thoracostomy with the instillation of tetracycline is usually not successful (4). If the diagnosis is made with thoracoscopy, pleural abrasion or parietal pleurectomy is probably the treatment of choice. Otherwise, the best alternatives are probably the insertion of a pleuroperitoneal shunt or an indwelling catheter (e.g., PleurX).

This rare lymphoma occurs almost exclusively in patients with HIV infection and is discussed in Chapter 11.

Community-acquired bacterial pneumonia (CAP) occurs frequently in patients with AIDS. It appears that patients with AIDS are probably more likely to develop pleural complications with their pneumonias than are other patients because they are more likely to have bacteremia with their pneumonia (14). Moreover, once there are bacteria in the pleural space, patients with low CD4⁺ counts probably have more trouble clearing the bacteria. When Staphylococcus aureus bacteria are injected intrapleurally in CD4⁺ knockout mice, there is a decreased pleural chemokine response, decreased neutrophil influx into the pleural space, and impaired bacterial clearance from the pleural fluid (15). In one series of 81 cases of community-acquired pneumonia, pleural effusion occurred in 21 (26%) patients (14). The pleural fluid was culture positive in 11 of these 21 (52%) patients. However, in a
more recent study of 1,415 patients hospitalized with HIV-associated CAP from 1995 to 1997 at 86 hospitals in seven metropolitan areas, the prevalence of pleural effusion was only 7.8% and the presence of a pleural effusion was not associated with a higher mortality (16). The distribution of organisms responsible for CAP in AIDS is similar to that of patients without AIDS (14). The management of the patient with AIDS and a parapneumonic effusion or an empyema is the same as that for any patient with a parapneumonic effusion (see Chapter 12). HIV-positive patients with empyema and CD4⁺ counts less than 200/mm³ more commonly have complex empyemas that require open decortication and drainage (17).

Although pleural effusions due to Pneumocystis jiroveci account for only a small percentage of pleural effusions in patients with AIDS, they do occur. By 1993, a total of seven cases of pleural effusion due to P. jiroveci infection had been reported (18,19). In most cases, the diagnosis was established by visualization of Pneumocystis in pleural fluid stained with Gomori methenamine silver. All seven of the reported patients were receiving aerosolized pentamidine, and five of the seven had documented underlying P. jiroveci pneumonia. Two patients presented with primary pleural infection with Pneumocystis. It appears that Pneumocystis pleural disease is an anatomic extension of smoldering subpleural Pneumocystis pneumonia, and the prognosis is not worse than with pneumonia alone. Four of the seven patients with pleural Pneumocystis also had a bronchopleural fistula (18).

The pleural fluid is an exudate with pleural Pneumocystis. The pleural fluid lactate dehydrogenase (LDH) has been higher than 400 IU/L, and the ratio of the pleural fluid to serum LDH level has exceeded 1:0. Interestingly, the pleural fluid protein level has been below 3.0 g/dL, and the ratio of the pleural fluid to the serum protein has been below 0:50 in all patients. The pleural fluid glucose and pH levels are not reduced, and the differential cell count can reveal either neutrophils or mononuclear cells (18). The treatment of pleural Pneumocystis is the same as that of pulmonary Pneumocystis.

In some series, tuberculosis is the most common etiology for pleural effusions associated with AIDS (3). The clinical picture of tuberculous pleuritis in patients with and without AIDS is similar, but there are some differences. In patients with tuberculosis, some reports have demonstrated that a higher percentage of patients with AIDS have a pleural effusion (20), whereas others report a similar incidence (21). The percentage of cases of tuberculosis that have pleural effusions in patients with AIDS is higher in patients with CD4⁺ counts above 200 than in those with CD4⁺ counts below 200/mm³ (22).

The purified protein derivative (PPD) skin test is less frequently positive in patients with AIDS who have tuberculous pleuritis. In one series of patients with tuberculous pleuritis, the PPD was positive in 76% of patients without AIDS but in only 41% of patients with AIDS (23). The lower the CD4⁺ count, the less likely the PPD is to be positive. HIV-positive patients have a lower percentage of CD4⁺ lymphocytes and a higher percentage of CD8⁺ lymphocytes in their pleural fluid than do HIV-negative patients with tuberculous pleuritis (24). In patients without AIDS, the pleural fluid acid-fast bacilli (AFB) stain is only rarely positive (˜1%), but in one series, the AFB pleural fluid smear was positive in 15% of patients with AIDS (23). In another series, the pleural fluid smear was positive in 37% of patients with AIDS and a CD4⁺ count less than 200/mm³ (25). The pleural fluid cultures for AFB are more likely to be positive in patients with AIDS. In one study, the pleural fluid culture was positive in 75% and 24% of the HIV-positive and HIV-negative patients with BACTEC, respectively; with Lowenstein-Jensen medium, comparable numbers were 43% and 12%, respectively (26). The levels of pleural fluid interferon-gamma are higher in HIV-positive than in HIV-negative patients (24). The granuloma on pleural biopsy are less well formed in some patients with AIDS, and there are numerous AFB (27). Patients with poorly defined granuloma appear to respond less well to antituberculous therapy (27). The incidence of granuloma on pleural biopsy is comparable in patients with and without AIDS (23). The treatment of the patient with AIDS and tuberculous pleuritis is the same as the treatment of the HIV-negative individual. However, prednisone should not be given to the AIDS patient with tuberculous pleuritis because its administration is associated with a risk of developing KS (28).

Other opportunistic diseases such as cryptococcosis (29), histoplasmosis (30), nocardiosis (31), and
atypical mycobacteria (32) are at times responsible for a pleural effusion in patients with AIDS. In their terminal stages, some patients with AIDS develop hypoproteinemia and this may lead to a transudative pleural effusion (33). Patients with AIDS may also develop hypervolemia owing to heart failure or renal failure, which can lead to a pleural effusion (34). In one series, pancreatitis was the fifth leading cause of pleural effusion in patients with AIDS (1). The diagnosis and management of pleural effusions due to these different entities are described in the appropriate chapters in this book.

Patients with AIDS and pleural effusion should undergo a diagnostic thoracentesis. Studies on the fluid should include smears and cultures for bacteria, mycobacteria, and fungi; cytology with special consideration for primary effusion lymphoma; and either an interferon-gamma or an adenosine deaminase measurement for pleural tuberculosis. If the patient has a positive PPD (>5 mm) or if there are no mesothelial cells in the pleural fluid, chemotherapy with isoniazid and rifampin for 9 months is recommended. If the patient is receiving aerosolized pentamidine, silver stains of the pleural fluid should be obtained to rule out P. jiroveci.

If the diagnosis is not apparent after the thoracentesis and the patient has an exudative pleural effusion, what should be the next diagnostic procedure? Possible courses of action include a needle biopsy of the pleura, thoracoscopy, bronchoscopy, or observation. In general, a thoracoscopy is recommended, if any procedure is going to be done. With thoracoscopy one can establish the diagnosis of KS, other intrathoracic malignancies, tuberculous pleuritis, or other opportunistic pleural infections. In addition, a pleural abrasion or a partial parietal pleurectomy can be performed to prevent reaccumulation of the pleural fluid.