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Resolution of Pleural Effusions^*

^* From the Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, Medical University of South Carolina, Charleston, SC.

Correspondence to: Steven A. Sahn, MD, FCCP, Division of Pulmonary and Critical Care Medicine, Allergy and Clinical Immunology, 96 Jonathan Lucas St, PO Box 250623, Charleston, SC 29425; e-mail: sahnsa{at}musc.edu

Key Words: AIDS • benign asbestos • congestive heart failure • coronary artery bypass • lupus pleuritis • organ transplantation • pancreatitis • parapneumonic effusions • pleural effusions • postcardiac injury syndrome • pulmonary embolism • rheumatoid pleurisy • sarcoidosis • spontaneous resolution • tuberculous pleurisy • uremic pleurisy

	Introduction

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Pulmonologists, internists, surgeons, and other medical specialists frequently encounter patients with pleural effusions. A plethora of articles have been written about the pathophysiology and pleural fluid (PF) characteristics that assist the physician in establishing a diagnosis and therapeutic plan for pleural diseases associated with effusions. In contrast, there is a paucity of information regarding the resolution time of a pleural effusion.

The purpose of this review is to present the available published data regarding the time course of resolution for nonmalignant pleural effusions in the most commonly encountered pleural diseases (empyema, pus in the pleural space, was excluded). A MEDLINE search from 1966 to 1999 of the English-language literature was instituted, matching pleural effusion with each of the specific diseases most commonly associated with pleural effusions. The search included case reports and retrospective and prospective case series of pleural effusions that resolved spontaneously or with medical management, excluding pleural space manipulation. Of the 393 articles retrieved, only 110 specified a time course of resolution. With the available information, an estimated time course of resolution was determined for the specific pleural process (Table 1 ).

	Parapneumonic Pleural Effusions

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
The annual incidence of bacterial pneumonia in the United States is estimated at 4 million.¹ Parapneumonic effusions develop in 36 to 66% of hospitalized patients with bacterial pneumonia.^{2 3 4 5} When both ambulatory and hospitalized patients are studied, the incidence decreases to 9% (168 of 1,906).⁶ The vast majority of parapneumonic effusions resolve with antibiotic therapy alone, with only a small percentage of patients requiring operative intervention for resolution. The following paragraphs discuss the time course of resolution of parapneumonic effusions associated with specific etiologic agents (Table 2 ).

Despite the high incidence of pneumococcal pneumonia, few studies have delineated the time course of resolution of the associated effusion. Jay and coworkers⁷ reported that pleural disease occurred in 34% (27 of 80) of cases of S pneumoniae pneumonia, including nine sterile pleural effusions. Pleural changes on radiograph tended to resolve between 8 weeks and 14 weeks, but no time course is mentioned for pleural effusions. Macfarlane and colleagues⁹ also report complete clearing of infiltrates in bacteremic and nonbacteremic pneumococcal pneumonia at 16 to 20 weeks and 12 to 16 weeks, respectively. After resolution of pulmonary infiltrates, residual pleural thickening was present in 37% and 9%, respectively. More recently, Trejo and associates¹⁰ reported a 14% (9 of 65) incidence of pleural effusion in a non-HIV population with S pneumoniae pneumonia. These effusions tended to resolve in 2 to 4 weeks.

Mycoplasma pneumoniae
M pneumonia typically occurs in the 5- to 25-year age group, but can occur in adults of all ages.¹¹ The incidence of parapneumonic effusions is 4 to 20% with the use of lateral decubitus radiographs.^{9 12 13 14 15} The effusions are usually small and ipsilateral to the pulmonary infiltrate but may be massive and bilateral.^{13 15 16} It appears that patients with sickle cell disease have a higher incidence of effusions and larger volumes of PF.¹⁷

Macrolides or tetracyclines will help resolve the febrile course, reduce the duration of cough, and hasten the radiographic resolution of the pulmonary infiltrates¹⁸ and effusions. The resolution of the pleural effusions ranges from 5 days to 8 weeks, with the majority resolving in 2 to 3 weeks.^{9 12 13 14 15 19 20 21} Residual pleural thickening is unusual.^{15 20}

Legionella pneumophila
Community-acquired pneumonia (CAP) caused by Legionella has a varied severity without unique clinical features.²² The prevalence of this pathogen in CAP ranges from 2% (8 of 456) when ambulatory and hospitalized patients are studied,²³ to 12% (47 of 392)²⁴ and 16% (55 of 346)²⁵ when only hospitalized patients are included. Pleural effusions have been described in 12 to 35% of patients, and may precede the parenchymal infiltrate.^{9 25 26 27 28 29} Effusions are typically small and unilateral but may be large and bilateral. Once macrolide therapy is begun, resolution occurs in 5 days to 4 months, with the majority resolving within 4 weeks.^{25 26 27 28 29} The presence of pleural effusions tends not to affect outcome.³⁰ However, empyemas occur^{30 31} warranting a thoracentesis if clinically indicated.

Chlamydia Pneumonias
The prevalence of Chlamydia pneumoniae as an etiologic pathogen in CAP typically ranges from 3 to 22%,^{23 24 25 32} but can be as high as 43% during seasonal epidemics.³³ Pleural effusion has been reported in 20% to 55% of Chlamydia psittaci pneumonia,^{34 35 36} are extremely rare in Chlamydia trachomatis pneumonia,^{37 38 39} and have been found in 8 to 53% of pneumonias caused by C pneumoniae.^{40 41 42 43 44} Most effusions by any of the Chlamydia organisms are small to moderate in size, with large effusions being uncommon. The time of resolution of C psittaci or C pneumoniae pneumonic infiltrates has been reported, but the resolution of pleural effusions has not been commented on previously. The clearance of pneumonic infiltrates was observed in 75 to 100% by 6 to 9 weeks,^{34 35 42 45} with pleural adhesions or thickening observed in 4 to 20% after > 12 weeks.^{36 42}

Francisella tularensis
Although tularemia has declined in incidence since first described by Francis in 1925,⁴⁶ it continues to occur both sporadically and in epidemics in the United States. Pleuropulmonary disease has occurred in up to 80% of hospitalized patients.⁴⁷ Pleural involvement is more likely to occur when parenchymal abnormalities are present, and has been described in 13 to 64% of patients.^{47 48 49 50} The incidence of pleural effusions increases as untreated diseases progresses, although PF has been found as early as 3 days after the onset of symptoms.^{47 51} Streptomycin is the drug of choice, with resolution of the pleural effusion in 6 to 7 weeks.^{49 52}

	Fungal Infections

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Coccidioides immitis
C immitis is endemic in southwestern United States, northern Mexico, and certain areas of Central and South America. Pleural effusions may occur during either acute primary or chronic progressive disease,⁵³ with the reported incidence ranging from 7 to 19%.^{54 55 56} Effusions tend to develop within a week after the onset of symptoms. The effusions are usually small, but occasionally may be massive. The natural history of acute coccidioidal effusions is self-limited, with radiographic resolution in 1 to 8 weeks.^{56 57} No specific therapy is warranted unless there is evidence of dissemination. Therapeutic thoracentesis may be beneficial to relieve the dyspnea with large effusions.

Pleural effusion in the chronic form of coccidioidomycosis occurs with cavity rupture into the pleura space, with the development of a bronchopleural fistula and empyema. These patients require early drainage and systemic antifungal therapy.

Histoplasma capsulatum
Histoplasmosis is encountered worldwide, with the highest endemic area in the United States being along the Ohio-Mississippi River valleys. Pleural effusion with histoplasmosis is an unusual occurrence in HIV-negative patients.⁵⁸ In a severe epidemic, the incidence of pleural effusions was 5% (21 of 435),⁵⁹ while nonepidemic histoplasmosis has an incidence of < 1% (1 of 269).⁶⁰ Even with disseminated histoplasmosis in AIDS patients, pleural effusions are uncommon (0 of 72), despite abnormal radiographic findings in > 50% of cases.⁶¹

Based on the limited number of cases in the literature, the presence of a pleural effusion associated with histoplasmosis does not influence the prognosis. Specific therapy should be dictated by the underlying condition of the host. In a normal host, spontaneous resolution of the pleural effusion can be expected in 2 to 4 weeks.^{53 62} Amphotericin B should be initiated if the effusion persists > 4 weeks, the patient is immunosuppressed, or the chronic pulmonary form is present.⁵³ Residual pleural thickening and extensive pleural fibrosis requiring pleurectomy has been reported.⁶³

	Viral Infections

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Viral lower-respiratory-tract infections have been associated with pleural effusion. The incidence of pleural effusions in viral pneumonia is reported to be 2% (2 of 123)⁶⁴ to 9% (2 of 23)¹² of cases. When pleural effusions are specifically targeted with lateral decubitus chest views, 18% (2 of 11) with viral pneumonia revealed an effusion.¹³ A variety of viral infections, including influenza,^{13 64} parainfluenza,⁶⁴ respiratory syncytial virus,^{64 65 66} herpes simplex virus,⁶⁷ cytomegalovirus,^{68 69} and adenovirus^{12 13 66 70 71} have been associated with pleural effusions. Many of these patients were immunocompromised. In general, these effusions are small, transient, and asymptomatic. They tend to resolve within 2 weeks and require no pleural space drainage.^{12 13 72}

	Tuberculosis

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Eight million people developed tuberculosis in 1990 worldwide, with 95% occurring in underdeveloped countries.⁷³ The frequency of pleural effusion in tuberculosis varies from country to country. In the United States, tuberculous pleural effusions represent 4% (905 of 22,764) of all cases of tuberculosis⁷⁴ ; in Spain, it affects 23% (146 of 637).⁷⁵

Radiographs typically show small-to-moderate, unilateral effusions, although massive effusions are seen in 14 to 29% of those with primary disease.^{76 77 78 79} Bilateral effusions occur in approximately 10% of cases, and appear to be more common in HIV-positive patients.^{77 79 80}

Tuberculous effusions resolve spontaneously within 2 to 4 months in most healthy individuals; however, if untreated, 65% (92 of 141) of patients will develop pulmonary or extrapulmonary tuberculosis within 5 years.⁷⁶ Therefore, it is important to start antituberculous therapy in patients with tuberculous pleurisy. Therapy with isoniazid and rifampin for 6 months is effective; two studies in non-HIV patients documented a relapse rate of zero, with a mean follow-up of > 3 years.^{81 82} Complete resolution of the radiograph was seen at the end of 6 months, but no specific data are provided on the resolution rate of the pleural effusion.^{81 82} With a 9-month course of isoniazid and rifampin, resolution of pleural effusion occurred within 6 weeks; pleural thickening may persist for years.⁵³ Before the standardization of therapy, several studies^{83 84 85} administering different drug regimens reported resolution of effusions from 3 to 9 months, with the majority clearing at 3 to 6 months. The current recommendation for tuberculous effusions consists of isoniazid, rifampin, and pyrazinamide for 2 months, followed by isoniazid and rifampin for the next 4 months.⁸⁶ This standard regimen was administered without supervision to 65 patients, with complete resolution of effusion by 14 months; 75% had resolved by 6 months of therapy.⁸⁷ The relapse rate was 0% at 20 months. During the initial weeks of therapy, effusions may enlarge in a small minority; but this does not imply treatment failure.⁸⁸

Corticosteroids have been advocated as an adjunct to hasten the resolution of symptoms and absorption of PF and to prevent residual pleural thickening. Three randomized, double-blind, placebo-controlled trials^{89 90 91} have been completed, but all had important methodologic differences. Lee and coworkers⁸⁹ administered isoniazid, rifampin, and ethambutol for the initial 3 months, and isoniazid and rifampin for the subsequent 6 to 9 months and either prednisolone, 0.75 mg/kg/d, or placebo. Diagnostic thoracentesis (< 50 mL) was done on the first day of hospitalization. PF in the steroid group (21 patients) resolved in a mean of 55 days, and in the placebo group (19 patients) in 123 days (p < 0.01). No significant difference was observed in residual pleural thickening. Galarza and associates⁹⁰ administered isoniazid and rifampin for 6 months and either prednisone, 1 mg/kg/d, or placebo; all effusions were drained to equal amounts (a third the hemithorax). The reabsorption rate at 1 month was 93% (53 of 57) and 89% (53 of 60; p = 0.01) in the steroid and placebo groups, respectively. However, the difference between groups disappears thereafter. No difference was observed between groups with respect to residual pleural thickening. In contrast, Wyser and colleagues⁹¹ administered isoniazid, rifampin, and pyrazinamide for 6 months, prednisone (0.75 mg/kg/d; 34 patients) or placebo (36 patients), and complete drainage of effusion via thoracoscopy. No difference in symptoms, recurrence of effusion after drainage, or residual pleural thickening was observed in either treatment group.

Based on these data, routine use of corticosteroids cannot be recommended and should only be used if acute symptoms, such as fever, chest pain, or dyspnea, are disturbing to the patient.

A reasonable management strategy for tuberculous effusions would be to perform a diagnostic and therapeutic thoracentesis, especially in those with large effusions, attempting to evacuate as much fluid as possible and initiate antituberculous chemotherapy.

	AIDS

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
The incidence of pleural effusion in patients with AIDS varies in different populations and geographic areas. In a large series of 4,511 HIV-positive patients admitted to a New York hospital, pleural effusions were seen in only 1.7% of cases; however, the stage of these cases is not commented on in this abstract.⁹² In a series from South Carolina,⁹³ the prevalence of pleural effusion was 17% in 350 HIV-positive hospitalized patients, but there was a significant difference in CD4 counts in those with (72 ± 12 cells/L) and without (274 ± 26 cells/L) pleural effusion (p < 0.001).

The three most common causes of AIDS-related pleural effusions are parapneumonic effusions or empyemas, tuberculosis, and Kaposi’s sarcoma. The frequency of these conditions varies depending on regional variability, HIV risk factors (ie, IV drug use, homosexuality), and stage of the disease.^{92 93 94 95}

Parapneumonic Effusions
Bacterial pneumonia is more frequent in HIV-positive individuals than in seronegative control subjects. In a large multicenter, prospective study,⁹⁶ the prevalence of bacterial pneumonia was 5.5/100 person-years and 0.9/100 person-years in HIV-positive and HIV-negative patients, respectively. The course of CAP in AIDS is often complicated, as reflected by higher rates of bacteremia (58% [11 of 19] vs 18% [17 of 96]; p < 0.001), parapneumonic effusions (21% [21 of 99] vs 13% [116 of 884]; p < 0.05), and empyemas requiring chest tube drainage (71% [15 of 21] vs 44% [51 of 116]; p < 0.05) in HIV-positive patients compared to HIV-negative patients.⁹⁷

The management of HIV-positive patients with a parapneumonic effusion is similar to that of the immunocompetent patient. However, because of a higher incidence of infection with Staphylococcus aureus in HIV-positive patients, appropriate antibiotics must be chosen to cover this organism. Trejo and colleagues¹⁰ found no significant difference in morbidity or mortality between HIV-positive and HIV-negative patients with uncomplicated parapneumonic effusions. In their study,¹⁰ pleural effusions resolved in 17 ± 11 days and 24 ± 22 days (mean ± SD) in the HIV-positive patients and HIV-negative patients, respectively.

Tuberculous Pleural Effusions
The incidence of tuberculous pleurisy in HIV-positive patients has been reported as higher,^{98 99} lower,¹⁰ or the same^{100 101 102 103} as in HIV-negative patients. Among patients with AIDS, the percentage of tuberculous effusions is higher in patients with CD4+ counts > 200 cells than in those with CD4+ counts < 200 cells.¹⁰⁴

Therapy for tuberculous effusions in HIV-positive patients does not differ from the standard treatment but should be prolonged if there is evidence of a slow or suboptimal response.⁸⁶ No significant difference in morbidity and mortality was seen between the HIV-positive and HIV-negative patients.¹⁰ As shown by Trejo and coworkers¹⁰ tuberculous effusions resolved in 79 ± 81 days in the HIV-positive patients and 69 ± 61 days (mean ± SD) in HIV-negative patients.

	Congestive Heart Failure

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Congestive heart failure (CHF) is the most common cause of a transudative pleural effusion, and is probably the most common cause of all pleural effusions. Defining the precise incidence of pleural effusion with CHF is problematic, because there is variance between techniques used to detect the effusion and the stage and degree of heart failure at the time of the evaluation. Earlier literature reports an incidence of 38% (136 of 356) clinically and radiographically,¹⁰⁵ and as high as 72% (290 of 402) at autopsy.¹⁰⁶ More recently, a large epidemiologic study from Czechoslovakia demonstrated pleural effusions in 46% (65 of 142) of CHF patients.¹⁰⁷ Radiographically, these effusions are usually bilateral, right greater than left, with associated cardiomegaly; however, if unilateral, there is a right-sided predominance.^{106 108 109}

It is believed that PF accumulates in patients with CHF when they have left, but not right, ventricular failure.^{110 111} Therefore, treatment should consist of decreasing pulmonary venous hypertension and improving cardiac output. When heart failure is treated successfully, effusions tend to resolve in < 1 month.^{106 112 113} Occasionally, refractory cases may require repeated thoracentesis or chemical pleurodesis for symptomatic relief.¹¹⁴ Pleuroperitoneal shunt is also an option.¹¹⁵

	Postcardiac Injury Syndrome

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
The postcardiac injury syndrome (PCIS) occurs days, weeks, or months after a variety of myocardial or pericardial injuries. The syndrome has been described after cardiac surgery (postpericardiotomy syndrome),^{116 117 118 119 120 121} myocardial infarction (postmyocardial infarction or Dressler’s syndrome),^{122 123 124 125} blunt chest trauma,^{126 127} pacemaker implantation (postpericardial trauma syndrome),^{128 129 130 131} and angioplasty.^{132 133} This autoimmune syndrome is manifested by pericarditis, with variable features of fever, leukocytosis, high erythrocyte sedimentation rate, and pulmonary infiltrates and/or pleural effusion. The incidence of PCIS varies with the sustained injury. PCIS after myocardial infarction has been reported in 1 to 7%,^{122 123 125} with pleural effusion occurring in 40% (16 of 40)¹²³ to 68% (30 of 44) of patients.¹²² The PCIS occurs more frequently after cardiac surgery, with an incidence ranging from 17 to 31%,^{116 118 119 121} with the incidence of pleural effusion ranging from 47% (16 of 34)¹³⁴ to 68% (26 of 38).¹¹⁹

Pleural effusions resolve over a variable period, modulated by the response to anti-inflammatory drugs. For most postmyocardial infarction patients, the effusions resolved 1 to 5 weeks after nonsteroidal anti-inflammatory drugs (NSAIDS) or prednisone were initiated.^{122 123} After cardiac surgery, the effusions tend to resolve spontaneously by 2 months; some cases resolve in a few days to 3 weeks with anti-inflammatory drugs.¹¹⁹ Salicylates, other NSAIDS, or corticosteroids should be used for the symptomatic patient or those with large-to-moderate symptomatic pleural effusion.

	After Coronary Artery Bypass Surgery

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Pleural effusions are common after coronary artery bypass graft surgery. The reported incidence ranges from 40 to 90%, depending on the diagnostic modality used to detect the presence of PF.^{135 136 137 138 139} The majority of pleural effusions are small and usually left sided; however, large and bilateral effusions have been reported.

These effusions have multiple causes. They could be related to CHF, PCIS, atelectasis, chest tubes, pleural lymphatic injury from the pleurotomy, injury to the internal mammary artery bed, or pericardial inflammation.¹³⁷ Despite conflicting data, the incidence of pleural effusions in patients receiving internal mammary artery grafts appears to be higher (70 to 85%) than those receiving saphenous vein grafts (30 to 50%).^{135 136 138} There is no difference between bilateral mammary artery and left internal mammary artery grafting in the incidence or severity of postoperative pleural effusions.¹³⁹

Pleural effusions after coronary artery bypass graft surgery should be treated conservatively. Other causes for these effusions should be sought only if the patient is febrile, the effusion is large, or if it fails to resolve in the appropriate time frame. These effusions tend to resolve within 8 weeks,¹³⁶ but long-term effusions have persisted for 3 to 20 months.^{140 141 142} Some long-term effusions result from prolonged oozing of blood and serum into the pleural space at the site of harvest of the internal mammary artery,¹⁴⁰ while others are the result of trapped lung.¹⁴³

	Rheumatoid Pleurisy

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Pleural involvement appears to be the most common intrathoracic manifestation of rheumatoid arthritis (RA), occurring in approximately 5% of patients.^{144 145} However, based on autopsy findings, clinical presence of pleural effusion and pleurisy significantly underestimates pleural involvement in RA patients. Postmortem series¹⁴⁶ report a 40 to 70% incidence of pleuritis; this clinicopathology discrepancy suggests that many patients are asymptomatic or that anti-inflammatory drugs mask minimal symptoms. In two large series, the incidence of rheumatoid pleurisy with effusion was 4% (21 of 516)¹⁴⁷ and 5% (9 of 180),¹⁴⁴ with a striking predominance in men; other predisposing factors for the development of effusion in RA include age > 45 years and subcutaneous nodules.^{144 147 148} Pleural effusion may occur at any time during the course of RA, with 20% preceding or occurring at the onset of arthritis, and 50% developing within 5 years of onset of articular manifestations.¹⁴⁷

The clinical presentation may mimic bacterial pneumonia or be asymptomatic.¹⁴⁹ Radiographs usually reveal a small-to-moderate unilateral pleural effusion; however, large and occasionally massive pleural effusions have been documented.^{150 151} A rheumatoid pleural effusion can be transient, long-term, or relapsing.^{147 152} It is uncommon for the effusion to resolve in < 4 weeks; most effusions resolve in 3 to 4 months.^{144 147 148 149 153 154 155} Fifty percent of the patients have a protracted course that lasts from 7 months to 5 years,^{144 147 148 149 153 154 155 156} with occasional progression to marked pleural thickening and trapped lung requiring decortication.^{144 157 158 159 160}

There are no controlled studies evaluating the efficacy of corticosteroids or NSAIDS in the treatment of rheumatoid pleural effusion. Both systemic and intrapleural corticosteroids have been used, with variable results.^{144 147 148 153 154 155 156 161 162 163} If the main goal of therapy is the prevention of progressive pleural fibrosis, anti-inflammatory drugs should be considered. A reasonable strategy would be to institute therapy with aspirin, other NSAIDS,¹⁶⁴ ) or prednisone¹⁶⁵ early in the disease process. If at 8 to 12 weeks the effusion resolves, therapy could be discontinued. If the effusion does not resolve, therapeutic thoracentesis and intrapleural corticosteroids should be considered.

	Systemic Lupus Erythematosus

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Pleurisy (pleural inflammation), a common feature of systemic lupus erythematosus (SLE), is usually associated with chest pain with or without pleural effusion, and occurs in 45 to 56% of patients during the course of the disease.^{166 167} Radiographic evidence of pleural effusion is less common, with an incidence of 16 to 37%.^{166 167 168} Pleural effusions occur more frequently in female patients and usually are a late manifestation of the disease but may be the presenting feature in 5% of cases.^{166 168 169} The most common radiographic presentation of lupus pleuritis is small-to-moderate bilateral pleural effusions, although unilateral and massive effusions has been reported.^{168 170 171 172}

In contrast to rheumatoid pleuritis, the majority of lupus pleural effusions resolve rapidly with corticosteroid therapy. Hunder and associates¹⁵⁶ reported that in five of six patients, pleural effusions resolved "quickly" once corticosteroids were initiated; the sixth patient’s effusion gradually resolved after 6 months. In the series of Winslow and colleagues,¹⁶⁸ 11 patients received corticosteroid and the effusions cleared in < 2 weeks; in contrast, only 10 of 16 effusions cleared without corticosteroid therapy at 2 weeks. Other researchers^{173 174 175} have reported clearing of the effusion in 7 days to 6 weeks with prednisone, 20 to 30 mg/d.

Other causes for pleural effusion should be considered when patients with SLE develop effusions, such as nephrotic syndrome, CHF, pulmonary embolism, parapneumonic effusion, uremia, and drug-induced SLE pleuritis. In the latter, therapy consists of withdrawing the offending drug. Once other causes of the effusion have been excluded, therapy with prednisone, 60 to 80 mg/d, should be initiated and rapidly tapered once the acute pleurisy has subsided.¹⁶⁵ Rarely, lupus pleuritis can be massive and refractory to steroid therapy. Adding a second immunosuppressive drug, such as cyclophosphamide or azathioprine, may be successful. Alternative treatments for refractory cases include chemical pleurodesis with tetracyclines^{176 177} or talc,¹⁷⁸ IV immunoglobulins,¹⁷⁹ and pleurectomy.^{180 181}

	Sarcoidosis

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Although the lung is affected in > 90% of patients with sarcoidosis, pleural involvement is an uncommon manifestation. The incidence of pleural effusion with sarcoidosis ranges from 0 to 5%^{182 183 184} but has been reported to be as high as 7.5%.¹⁸⁵ Patients with sarcoid pleural effusion usually have extensive parenchymal disease (stage 2 or stage 3) and frequently have extrathoracic sarcoidosis.^{182 183 184 185} Chest radiographs usually show unilateral, small-to-moderate effusions, but bilateral and massive effusions have been noted.^{182 184 185 186 187 188 189 190} Pleural sarcoidosis is a diagnosis of exclusion in the proper clinical setting when tuberculosis and fungal disease have been excluded.

Sarcoid pleural effusions may resolve spontaneously or require corticosteroids for resolution. The time of spontaneous resolution is variable, but most resolve in 1 to 3 months.^{183 185 187 191 192} However, there are reports of resolution at 2 weeks with steroid therapy,^{188 193} and as long as 6 months with or without steroid administration.^{183 186} Therefore, the management of sarcoid pleural effusion should be guided by the clinical presentation. In the absence of symptoms, the effusion usually resolves spontaneously. If the effusion is symptomatic and recurrent, steroid therapy is recommended for symptomatic relief and to hasten the resolution of the effusion. Incomplete resolution of these effusions has been reported with eventual progression to chronic pleural thickening.¹⁸⁵

	Pulmonary Embolism

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Pulmonary embolism should be a diagnostic consideration in every patient with an acute, unilateral pleural effusion. Pleural effusion occurs in 10 to 50% of patients with pulmonary embolism^{194 195 196 197 198 199} ; an associated ipsilateral parenchymal infiltrate is seen on chest radiography in 50% of patients.¹⁹⁵ Effusions secondary to pulmonary embolism generally are small and occupy less than a third of the hemithorax.^{195 197 198 199} The effusion tends to be larger if an associated infiltrate is present.¹⁹⁵ In the absence of complications, pleural effusions tend to reach their maximal size early and should not enlarge after the third day after admission.¹⁹⁵ If effusions increase after the third day, recurrent pulmonary embolism, hemothorax from anticoagulation, secondary infection, or an alternate diagnosis should be suspected. On standard chest radiographs, most effusions are unilateral even if bilateral pulmonary emboli are present¹⁹⁵ ; however, using spiral chest CT, bilateral small effusions are present in 75% of cases.¹⁹⁹

The course of resolution of these effusions has not been extensively studied. To our knowledge, the study of Bynum and Wilson¹⁹⁵ is the only one that has addressed this issue. In their series, pleural effusion without parenchymal infiltrates (infarction) resolved in < 7 days in 72% (18 of 25) of cases, with five effusions resolving within 3 days. Among the 31 patients that completed follow-up at 10 days, all patients with an associated parenchymal infiltrate had a persistent effusion. No data are reported on the time of resolution for those cases that persisted > 7 days.¹⁹⁵

	Benign Asbestos Pleural Effusion

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
Pleural effusion resulting from asbestos exposure is the most common asbestos-related pleuropulmonary abnormality during the first 20 years after exposure; however, it may occur from 1 to 60 years from initial exposure.^{200 201 202} Benign asbestos pleural effusion (BAPE) is defined as an effusion that occurs in the setting of asbestos exposure, in the absence of other conditions, and is not followed by the development of a malignancy within 3 years. Using this definition, Epler and coworkers²⁰⁰ reported an incidence of 9.2 effusions, 3.9 effusions, and 0.7 effusions per 1,000 person-years after heavy, moderate, and mild asbestos exposures, respectively. Cookson and associates²⁰¹ reported an incidence of 8% (24 of 280) in patients with heavy asbestos exposure. Hillerdal and Özesmi²⁰² reported an incidence of 4% (60 of 1,500), but only 20% of the patients had moderate or heavy asbestos exposure.

Most patients (46 to 66%) are asymptomatic at the time the pleural effusion is discovered,^{200 202} usually by screening radiograph. Most effusions are small to moderate in size and unilateral; bilateral or massive effusions occur in approximately 10%.²⁰⁰ The natural history of BAPE is one of chronicity with frequent recurrences. Most effusions resolve in 3 to 4 months, with a range of 1 to 17 months.^{201 202 203 204} Resolution typically results in a blunted costophrenic angle (80 to 90%), with diffuse pleural thickening occurring in approximately 50% of patients.^{200 202} Recurrences are frequent (30 to 40%) and usually occur within 3 years of the initial presentation.^{200 204} A number of patients have developed malignant pleural mesothelioma years after an episode of BAPE,^{200 205} but large epidemiologic studies are needed to confirm a relationship.

	Pleural Effusion After Organ Transplantation

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Lung and Heart-Lung Transplantation
Pleural effusions are the rule in the early postoperative period. One series²⁰⁶ of heart-lung transplants reported a 100% (10 of 10) incidence of pleural effusions. More parapneumonic effusions have been noted in double-lung transplants than in single-lung transplants (16% [4 of 25] vs 0% [0 of 5]).²⁰⁷ The latter is possibly explained by the greater pretransplant incidence of pulmonary sepsis in double-lung recipients with cystic fibrosis and COPD.

Most of these pleural effusions are small to moderate in size, but rarely may be massive.²⁰⁸ In the vast majority of cases, pleural effusions resolve spontaneously within 9 to 14 days after transplantation,²⁰⁹ although a small percentage may increase in size over the first 3 postoperative weeks.²⁰⁶ This correlates with animal studies^{210 211 212} demonstrating that allograft lymphatics reconstitute and become functional 2 to 4 weeks after transplantation. Failure of resolution by 3 weeks suggests a pathologic process, such as the pulmonary reimplantation response, infection, or acute lung rejection. Therapy targeted to these complications usually is accompanied by clearing of the pleural effusion.

Liver Transplantation
Pleural effusions unrelated to primary cardiopulmonary disease usually develop after liver transplantation. The reported incidence of pleural effusions is between 48% and 100%,^{213 214 215 216 217} with most reporting a 100% incidence. Injury to the right hemidiaphragm from right-upper-quadrant abdominal dissection and retraction, perioperative infusion of blood products, hypoalbuminemia, and atelectasis all may contribute to the development of pleural effusions.²¹⁷ The most important factor probably is operative transection of hepatic lymphatics, in particular the pulmonary ligament that communicates with the visceral pleural lymphatics, as shown in a swine model.²¹⁸ These severed lymphatics may leak lymph and result in the immediate development of ascites and subsequent right pleural effusion via congenital or acquired diaphragmatic defects.²¹⁸

The pleural effusions are bilateral in about a third of patients, but the amount of fluid is always greater on the right.²¹⁷ These effusions typically develop and enlarge over the first 3 to 7 days after surgery.^{213 215 216} Most effusions resolve within 2 to 3 weeks,^{213 214 215} although there may be persistence for months.^{216 217} Thoracentesis or tube thoracostomy for symptomatic relief was required in 11 to 30% of cases,^{213 214 215 217 219} and the fluid had the characteristics of a transudate.²¹³ If accumulation of PF persists after 7 days, a subdiaphragmatic process or pleural infection should be suspected.^{216 220}

	Uremic Pleural Effusions

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis AIDS Congestive Heart Failure Postcardiac Injury Syndrome After Coronary Artery Bypass... Rheumatoid Pleurisy Systemic Lupus Erythematosus Sarcoidosis Pulmonary Embolism Benign Asbestos Pleural Effusion Pleural Effusion After Organ... Uremic Pleural Effusions Pleural Effusion in Pancreatitis Persistent Benign Pleural... Conclusion References

 
In 1836, Bright²²¹ reported that only 29% of patients with albuminous urine had healthy pleura at autopsy. Fibrinous pleuritis has been found in 20 to 58% of uremic patients at autopsy.^{222 223} There are several reasons why pleural disease may be common in patients with renal failure: (1) CHF because of tenuous fluid balance, ischemic heart disease, and dilated cardiomyopathy; (2) increased risk of infection^{224 225} ; (3) diseases associated with renal and pleural manifestations (ie, SLE); (4) uremic pericarditis^{226 227 228} ; (5) increased risk for certain malignancies^{229 230} ; (6) pulmonary embolism; and (7) uremic pleurisy from an unknown putative agent.^{231 232} Therefore, uremic pleuritis is a diagnosis of exclusion.

Two retrospective studies have studied the incidence of uremic pleurisy in hospitalized patients receiving long-term dialysis. Berger and coworkers²³³ reported a 4% (14 of 436) incidence of pleural effusion; however, the incidence could have been underestimated because patients who had a small effusion or resolved rapidly after detection were not included. Jarratt and Sahn²³⁴ reported a 16% (16 of 100) incidence of pleural effusions secondary to uremia. The chest radiograph usually shows a unilateral, moderate-sized pleural effusion, although massive and bilateral effusions have been described.^{233 235 236} Pleural effusions usually resolve (80%) with continued dialysis in 4 to 6 weeks,²³³ but recurrences may occur. Effusions may persist despite aggressive hemodialysis, and progress to fibrothorax requiring decortication.^{235 236 237} Toxins or immune complexes not removed with dialysis may be pathogenic, and possibly other modalities of therapy may be helpful in removal of the substances from the circulation (ie, plasmapheresis).^{231 232}

	Pleural Effusion in Pancreatitis

TOP Introduction Parapneumonic Pleural Effusions Fungal Infections Viral Infections Tuberculosis