Pleural Effusion Secondary to Fungal Infections, Actinomycosis, and Nocardiosis
In this chapter, pleural disease resulting from fungal infections is discussed. Although fungal diseases account for less than 1% of all pleural effusions, it is important to identify correctly patients with fungal disease of the pleura because effective treatment is available. Actinomycosis and nocardiosis are also included in this chapter because they produce a chronic disease similar to that caused by the fungi, although they actually are bacteria.
ASPERGILLOSIS
Occasionally, the pleural space becomes infected with the Aspergillus species of fungus. The usual infecting organism is Aspergillus fumigatus (1), but other species such as Aspergillus niger may also be responsible (2). Pleural aspergillosis is uncommon, but 13 cases were observed in one institution during a recent 5-year period (3).
Clinical Manifestations
Pleural aspergillosis usually occurs in one of two settings. Most commonly, it occurs in patients who were treated in the past with artificial pneumothorax therapy for tuberculosis (2,3,4). Such patients have signs and symptoms of a chronic infection, including weight loss, malaise, a low-grade fever, and a chronic, productive cough (1). The chest radiograph reveals increasing degrees of pleural thickening and usually an air-fluid level in the pleural space indicating the presence of a bronchopleural fistula (1). Fungus balls, although uncommon, may be evident radiographically either in the lungs or the pleural space (1,5).
The second situation in which pleural aspergillosis occurs is postoperatively after lobectomy or pneumonectomy for lung cancer, tuberculosis, or aspergillosis (3,4,6). A bronchopleural fistula is almost invariably present. The clinical picture is similar to that of a pleural bacterial infection after lung resection (see Chapter 12). On rare occasions, the pleural fluid becomes infected with aspergillus in the immunosuppressed patient with systemic aspergillosis (7). One report cited two patients with pleural effusion complicating allergic bronchopulmonary aspergillosis (8), but the relationship between the pleural effusion and the allergic aspergillosis was not convincing.
Diagnosis
The diagnosis of pleural aspergillosis should be suspected in any patient with a history of artificial pneumothorax therapy for tuberculosis who has a chronic pleural infection, particularly when a bronchopleural fistula is present. Similarly, the diagnosis should be suspected in any patient with a pleural infection after lung resection. The diagnosis is confirmed by the demonstration of aspergillus on fungal cultures of the pleural fluid. The presence of brown clumps containing fungal hyphae in the pleural fluid suggests the diagnosis (4). Patients with pleural aspergillosis almost always have positive precipitin blood tests for antibodies against aspergillus (1,4). Aspergillus antigens can also be demonstrated in the pleural fluid
by radioimmunoassay (10). The presence of calcium oxalate crystals in the pleural fluid suggests an infection due to A. niger (2). The presence of the blackpigmented spores of A. niger can impart a black color to the pleural fluid (11).
by radioimmunoassay (10). The presence of calcium oxalate crystals in the pleural fluid suggests an infection due to A. niger (2). The presence of the blackpigmented spores of A. niger can impart a black color to the pleural fluid (11).
Treatment
The optimal treatment for pleural aspergillosis is early excision of the involved pleura with resection of the upper lobe or the entire ipsilateral lung, if necessary (1). When this definitive surgical treatment is undertaken, itraconazole or voriconazole should be administered systemically before and after the operation because the incidence of postoperative pleural infection with aspergillus is high if systemic antifungal drugs are not administered (1,12,13). The reason for performing this extensive operation is that the infection is likely to invade and destroy the underlying lung. The longer the surgical procedure is postponed, the more severe the damage to the underlying lung and the more debilitated the patient becomes (1). The bronchopleural fistulas are often difficult to manage and frequently require muscle transpositions or omentoplasty (3). Even if there is no bronchopleural fistula, muscle transpositions are sometimes necessary because the pleural space cannot be obliterated with just the damaged underlying lung (3).
Some patients with pleural aspergillosis are too debilitated to undergo a surgical procedure, or their pleural aspergillosis is a complication of pulmonary resection. In such patients, a chest tube should be inserted, and the pleural space should be irrigated daily with amphotericin B or nystatin (4,5,14). The usual dose of amphotericin B is 25 mg, and the usual dose of nystatin is 75,000 U (5). After instillation of the antifungal agents, the chest tube is clamped for an hour. In addition voriconazole and micafungin should be given as they penetrate the pleural space well (15). One patient with an aspergillus empyema was cured with the combination without chest tubes (15). An open-drainage procedure (see Chapter 12) can be performed for the patient’s comfort (5). Although this treatment takes many months, it is successful in most patients (4,5,14).
BLASTOMYCOSIS
Infection with Blastomyces dermatitidis is frequently associated with pleural disease. In one series of 118 patients with pulmonary blastomycosis, 4 (3%) had pleural effusions (16). In a more recent study of 63 cases with proven pulmonary blastomycosis, 13 of the patients (21%) had a pleural effusion. The effusions in this series were small and caused only mild-to-moderate blunting of the costophrenic sulci (17). However, an occasional patient with pleural blastomycosis has an effusion that occupies more than 50% of a hemithorax (18).
Patients with pleural blastomycosis have signs and symptoms similar to those with tuberculous pleuritis (see Chapter 13). In addition to the pleural effusion, there may be an associated parenchymal infiltrate (19,20). With pleural blastomycosis, the pleural fluid is an exudate containing predominantly lymphocytes or polymorphonuclear leukocytes (18,19,20). The pleural fluid glucose level is normal, and the lactate dehydrogenase (LDH) level is usually not higher than the upper limits of normal for serum (18). Microscopic examination of the pleural fluid at times reveals the budding yeasts typical of B. dermatitidis (18). Pleural biopsy may reveal noncaseating granulomas (19,20). Therefore, one should consider the diagnosis of blastomycosis in patients with a clinical picture suggestive of tuberculous pleuritis, and one should obtain fungal cultures of the pleural fluid in all such patients. The complement-fixation test is the most widely used test for the serologic diagnosis of blastomycosis; however, its clinical value is limited because fewer than 25% of culture-proven cases are detected using this method (21). There is no commercially available skin test for blastomycosis.
Patients with pleural blastomycosis should be treated with itraconazole 400 mg/day for 6 months, ketoconazole 400 to 800 mg/day for 6 months, or amphotericin B with a total dose of 2 g. It appears that the treatment of choice is itraconazole (12,22), which cures virtually all immunocompetent individuals with pulmonary blastomycosis. Amphotericin B remains the drug of choice for all forms of blastomycosis in the immunosuppressed host (12,22).
COCCIDIOIDOMYCOSIS
Coccidioides immitis is an infectious fungus endemic to southwestern United States, particularly the San Joaquin Valley in California. The disease is acquired by inhaling the light, fluffy, and infectious arthrospores produced by the mycelial form growing in appropriate soil. Once inhaled, the arthrospores develop into the yeast form that produces disease in humans. Pleural disease of two types occurs in association with coccidioidomycosis (23). The first type is a pleural effusion associated with the primary benign
infection and may or may not have concomitant parenchymal involvement. The second type occurs when a coccidioidal cavity adjacent to the pleura ruptures to produce a hydropneumothorax with a bronchopleural fistula.
infection and may or may not have concomitant parenchymal involvement. The second type occurs when a coccidioidal cavity adjacent to the pleura ruptures to produce a hydropneumothorax with a bronchopleural fistula.
Primary Infection
The pleura is frequently involved in primary infections with C. immitis. As many as 70% of patients have pleuritic chest pain, and approximately 20% have blunting of the costophrenic angles radiologically (24). Approximately 7% of all symptomatic patients with primary coccidioidomycosis have pleural effusions (24). However, on one study (25), 22 of 146 patients (15%) hospitalized with coccidioidomycosis had a pleural effusion. Patients with pleural effusions secondary to coccidioidomycosis are almost always febrile, and more than 80% have pleuritic chest pain (24). Approximately 50% of patients have either erythema nodosum or erythema multiforme (24). The chest radiograph reveals parenchymal infiltrates in addition to the pleural effusion in approximately 50% of patients. The pleural effusion varies in size, but it often occupies more than 50% of the hemithorax (24). In one series of 28 patients, all pleural effusions were unilateral (24).
Pleural fluid analysis reveals an exudate that usually contains predominantly small lymphocytes (24). Although approximately 50% of patients have peripheral eosinophilia, pleural fluid eosinophilia is uncommon and occurred in only 1 of 15 patients in one series (24). However, in another series (25) the mean percentage of eosinophils in the pleural fluid was 10.3%. The pleural fluid glucose level is almost always above 60 mg/dL (24), and the pH is normal unless the patient has an empyema, which occurred in 5 of 15 patients (33%) in one series (25). The pleural fluid cultures are positive for C. immitis in approximately 20% of patients, but cultures of pleural biopsy specimens are positive in almost all patients (24). In one series, eight of eight pleural biopsy cultures were positive, and cocci spherules were identified in six of eight specimens (24). The pleural biopsy may reveal caseating or noncaseating granulomas (24). The cocci skin tests are usually positive, and the mean complement fixation (CF) titer 6 weeks after the onset of symptoms is 1:32 (24).
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