Postcardiac Injury Syndrome

REFERENCES

1 Quillin SP, Shackelford GD. Postpneumonectomy syndrome after left lung resection. Radiology 1991; 179:100-02 2 Powell RW, Luck SR, Raffensperger JG. Pneumonectomy in infants and children: the use of a prosthesis to prevent mediastinal shift and its complications. J Pediatr Surg 1979; 14:231-37 3 Audry G, Balquet P, Vazquez MP, et al. Expandable prosthesis in right postpneumonectomy syndrome in childhood and adolescence. Ann Thorac Surg 1993; 56:323-27 4 Szamicki R, Maurseth K, de Leva! M, et al. Tracheal compression by the aortic arch following right pneumonectomy in infancy. Ann Thorac Surg 1978; 25:231-35 5 Wasserman K, Jamplis RW, Lash H, et al. Postpneumonectomy syndrome-surgical correction using Silastic implant. Chest 1979; 75:78-81 6 Downey RJ, Trastek VF, Clay RP. Right pneumonectomy syndrome: surgical correction with expandable implants. J Thorae Cardiovasc Surg 1994; 107:953-55 7 Grillo HC, Shepard JO, Mathisen DJ, et al. Postpneumonectomy syndrome: diagnosis, management, and results. Ann Thorac Surg 1992; 54:638-51 8 Rousseau H, Dahan M, Lauque D, et al. Self-expandable prosthesis in the tracheobronchial tree. Radiology 1993; 188:199-203 9 Sawada S, Tanigawa N, Kobayashi M, et al. Malignant tracheobronchial obstructive lesions: treatment with Gianturco expandable metallic stents. Radiology 1993; 188:205-08 10 Dumon J. A dedicated tracheobronchial stent. Chest 1990; 97:328-32

Postcardiac Injury Syndrome* An Immunologic Pleural Fluid Analysis Sola Kim, MD; and Steven A. Sahn, MD, FCCP

The postcardiac injury syndrome (PCIS) is characterized by inflammation of the pericardium, pleura, and pulmonary parenchyma following a variety of cardiac injuries. Although it has been clinically recognized for decades, confirmation of the syndrome has been problematic owing to lack of a sufficiently diagnostic test. Previously, we have reported pleural fluid characteristics which help to exclude other diagnoses that may mimic the syndrome. We describe the first immunologic assessment, including antimyocardial antibody testing, of pleural fluid from a patient with PCIS which supports a local immunologic mechanism in the pathogenesis of the syndrome. These results support the important role of pleural fluid analysis in the diagnosis of PCIS. (CHEST 1996; 109:570-72) AMA=antimyocardial antibody; PCIS=postcardiac injury syndrome

*From the Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston. Reprint requests: Dr. Sahn, Division of Pulmonary and Critical Care Medicine, 812 Clinical Science Building, 171 Ashley Avenue, Charleston, SC 29425

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Key words: anti myocardial antibody; pleural effusion; postcardiac injury syndrome

T

he postcardiac injury syndrome (PCIS) is characterized by fever, pericardia! inflammation, and pleuropulmonary manifestations days to weeks following a variety of injuries to the myocardium or pericardium. It has been described following myocardial infarction, 1 cardiac surgery, 2 blunt chest trauma, 3 percutaneous left ventricle puncture,4 and implantation of a pacemaker.5 Although PCIS has been a clinically recognized entity for several decades, the lack of a confirmatory diagnostic test renders the diagnosis one of exclusion. Previously, we have identified several pleural fluid characteristics which help to differentiate the diagnosis of the syndrome from other clinical conditions that may appear following cardiac injury. 6 Now we describe the first report of antimyocardial antibody (AMA), reduced complement levels, and immune complexes identified in the pleural effusion of a patient with PCIS following coronary artery bypass grafting. We suggest a new utilization of pleural fluid analysis to aid in the diagnosis of PCIS. CASE REPORT

A 37-year-old man was hospitalized 11 days after coronary artery bypass surgery with several days of dyspnea, low-grade fever, and pleuritic chest pain. His symptoms progressed despite outpatient treatment with a diuretic and a nonsteroidal anti-inflammatory agent. The bypass operation utilized bilateral internal mammary artery grafting during which both pleural spaces were entered. He had no history of preexisting autoimmune disease. Physical examination showed a temperature of 38.0°C and a respiratory rate of 30 breaths per minute. Jugular venous pressure was not elevated. An S3 gallop was absent. A trace amount of pedal edema was noted. The chest radiograph showed bilateral, moderate, free-flowing pleural effusions. With the patient breathing room air, arterial blood gas values were as follows: pH, 7.45; PaC02, 41 mm Hg, Pa02, and 72 mm Hg. Other laboratory findings included a WBC count of 16,400/JIL and an erythrocyte sedimentation rate of 41 mmlh. Thirteen days postoperatively, thoracentesis was performed on the right effusion, which revealed a serosanguineous fluid with a total protein level of 3.7 gldL (serum, 5.4 gldL); lactate dehydrogenase level, 999 lUlL (serum, 218 lUlL); WBC count, 1,092/pL (64% lymphocytes, 24% macrophages, 8% polymorphonuclear leukocytes, 3% eosinophils, 1% basophils); RBC count, 21,306/JIL; glucose value, 105 mgldL (serum, 103 mgldL); and pH, 7.37. Routine bacteriologic studies were negative for organisms. Ventilation-perfusion lung scan disclosed a low probability for a pulmonary embolus. The echocardiogram showed an ejection fraction greater than 60% and a small pericardia! effusion. AMA was detected in pleural fluid and serum by indirect immunofluorescence staining against monkey heart tissue substrate and striated muscle control specimens 7 The pleural fluid AMA titer was positive at 1:80 dilution, while the serum AMA titer was positive at 1:40 dilution (Table 1). Pleural fluid complement levels were low: C3, 44.7 mgldL, and C4, less than 8 mgldL. Serum complement levels were within normal range: C3, 116 mgldL (normal, 83 to 177 mgldL), and C4, 21 mgldL (normal, 15 to 45 mgldL). When complement levels were adjusted for total protein concentrations (pleural-to-serum C3 ratio divided by pleural-toserum total protein ratio8), the C3 index was 0.56 and the C4 index, less than 0.56. The Clq binding assay detected the presence of immune complexes in the pleural fluid but not in the serum. Despite treatment with ibuprofen, the patient experienced Selected Reports

Table l-Immunologic Analysis of Pleural Fluid and Serum in PCIS

Pleural fluid Serum

AMA Titer

Total Protein Level, (gldL)

Total Protein PIS Ratio*

1:80 1:40

3.7 5.4

0.69

C3, mgldL 44.7

116

C3 PIS Ratio*

C3 Index 1

C4, mgldL

C4 PIS Ratio*

C4 Index 1

C1q Binding

0.39

0.56

<8 21

<0.38

<0.56

Present Absent

* . Pleural Fluid PIS ratio= Serum .

tc

C I d =Pleural Fluid Complement/Serum Complement 3 or 4 n ex Pleural Fluid Total Protein/Serum Total Protein ·

recurrent symptomatic pleural effusions requiring repeated therapeutic drainage by thoracentesis. He was subsequently treated with corticosteroid therapy with resolution of his symptoms and pleural effusions. DISCUSSION

For decades, the diagnosis of PCIS has been based primarily on the clinical recognition of the manifestations of the syndrome. The development of pericardia!, pleural, and pulmonary parenchymal inflammation following cardiac injury may be suggested by pleurisy, fever, dyspnea, rubs, rales, elevated erythrocyte sedimentation rate, leukocytosis, pleural effusion, and pulmonary parenchymal inHltrates.6 Nonetheless, these common clinical manifestations and laboratory features of PCIS are nonspecific. The finding of a bloody, exudative pleural effusion with a pH greater than 7.30 also may help to confirm a clinical suspicion of PCIS, but these pleural fluid characteristics also are not pathognomonic.6 Thus, arriving at a presumptive diagnosis of PCIS currently requires both clinical pattern recognition and exclusion of other diagnoses that may arise in this setting, namely, pulmonary embolism, congestive heart failure, atelectasis, and pneumonia. This difficulty in securing a diagnosis unfortunately spawns extensive diagnostic evaluations and has been known to precipitate iatrogenic complications of erroneous therapy, including cardiac tamponade due to anticoagulation for presumed pulmonary emboli, hypotension and electrolyte disturbance due to diuretic therapy for suspected heart failure, and side effects of antibacterial therapy for presumed pneumonia. 6 The absence of a definitive diagnostic test reflects the lack of understanding of the precise pathogenesis of PCIS. Immunologic mechanisms have been most widely postulated and are supported by a clinical course that is characterized by a latent period, rapid response to corticosteroid or nonsteroidal therapy, and a tendency for relapses, sometimes related to steroid withdrawal. 9 Furthermore, several studies have found an association between antiheart antibodies in the serum and the development of PCISJ0- 15 Although antibodies against myocardium may be a nonspecific finding after cardiac injury, 16-18 the medical literature suggests that patients with PCIS tend to have higher titers of serum AMA. Unfortunately, a comparison of these studies is problematic because of varying methods, measuring techniques, and reporting of titers. While a correlation between PCIS and serum AMA appears to have been suggested, the strength of such a relationship has not been adequately established. Thus, a more sensitive and specific test in the diagnosis of

PCIS is clearly needed. The evidence of AMA in the serum of our patient supports the previously mentioned immunopathogenic etiology for PCIS, but to our knowledge, this is the first report of the finding of AMA in pleural fluid of a patient with PCIS, especially in a titer greater than that in serum. Although the pericardia! and pleural space was entered during the bypass operation, we believe that the AMA titer in pleural fluid greater than that in serum suggests a local immunologic injury and cannot be satisfactorily explained by only a contribution from the systemic circulation. The present case not only serves to reemphasize a common pleuropulmonary manifestation of the syndrome, namely, a bloody, exudative, lymphocytic pleural effusion with normal pH,6 .19 but also for the first time strengthens the role for an immune mechanism of pleural inflammation that characterizes the syndrome. We also are the first to demonstrate the presence of both immune complexes as well as reduced complement levels in the pleural fluid of a patient with PCIS. The C3 and C4 indexes which adjust for total protein concentrations indicate significant consumption of complement in the pleural fluid. As with systemic lupus erythematosus and rheumatoid arthritis, 20 the low complement levels and presence of soluble immune complexes in the pleural fluid of this patient suggest a local immunologic mechanism in the pathogenesis of pleuritis in PCIS. We believe that, in concert with preexisting clinical and laboratory criteria, these pleural fluid findings have the potential to become confirmatory tests that serve to secure the diagnosis of PCIS. A reduced complement ratio or pleuralto-serum AMA ratio greater than 1.0 could serve to support a presumptive diagnosis which relies heavily on clinical pattern recognition. Since the syndrome at times provides a difficult therapeutic challenge, marked by a prolonged course and repeated relapse on treatment withdrawal, the aforementioned findings could provide more diagnostic certainty. Further studies are clearly needed to define the role of pleural fluid testing in the detection of PCIS. REFERENCES

1 Dressler W. The post-myocardial-infarction syndrome: a report on 44 cases. Arch Intern Med 1959; 103:28-42 2 Ito T, Engle MA, Goldberg HP. Postpericardiotomy syndrome following surgery for nonrheumatic heart disease. Circulation 1958; 17:549-56 3 Tabatznik B, Isaacs JP. Postpericardiotomy syndrome following traumatic hemopericardium. Am J Cardiol 1961; 7:83-96 4 Peters RH, Whalen RE, Orgain ES, et al. Postpericardiotomy CHEST /109/2/ FEBRUARY, 1996

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syndrome as a complication of percutaneous left ventricular puncture. Am J Cardiol 1966; 17:86-90 Kaye D, Frankl W, Arditi LI. Probable postcardiotomy syndrome following implantation of a transvenous pacemaker: a report of the first case. Am Heart J 1975; 90:627-30 Stelzner TJ, King TE Jr, Antony VB, et al. The pleuropulmonary manifestations of the postcardiac injury syndrome. Chest 1983; 84:383-87 Twomey SL, Bernett GE. Immunofluorescence method for detecting anti-myocardial antibodies, and its use in diagnosing heart disease. Clin Chern 1975; 21:1903-06 Link H, Tibbling G. Principles of albumin and IgG analyses in neurological disorders: II. Relation of the concentration of the proteins in serum and cerebrospinal fluid. Scand J Clin Lab Invest 1977; 37:391-96 Khan AH. The postcardiac injury syndromes. Clin Cardiol1992; 15:67-72 De Scheerder I, Vandekerckhove J, Robbrecht J, et al. Post-cardiac injury syndrome and an increased humoral immune response against the major contractile proteins (actin and myosin). Am J Cardiol1985; 56:631-33 De Scheerder I, De Buyzere M, Robbrecht J, et al. Postoperative immunological response against contractile proteins after coronary bypass surgery. Br Heart J 1986; 56:440-44 Engle MA, McCabe JC, Ebert PA, et al. The postpericardiotomy syndrome and antiheart antibodies. Circulation 1974; 49:401-06 Engle MA, Zabriskie JB, Senterfit LB, eta!. Immunologic an virologic studies in the postpericardiotomy syndrome. J Pediatr 1975; 87:1103-08 Engle MA, Gay WA, McCabe J, et al. Postpericardiotomy syndrome in adults: incidence, autoimmunity and virology. Circulation 1981; 64(suppl 11):58-60 Maisch B, Berg PA, Kochsiek K. Clinical significance of immunopathological findings in patients with post-pericardiotomy syndrome: I. Relevance of antibody pattern. Clin Exp Immunol 1979; 38:189-97 Liem KL, Ten Veen JH, Lie KI, et al. Incidence and significance of heartmuscle antibodies in patients with acute myocardial infarction and unstable angina. Acta Med Scand 1979; 206:473-75 Vander Geld H. Anti-heart antibodies in the postpericardiotomy and the postmyocardial-infarction syndromes. Lancet 1964; 2:617-21 Webber SA, Wilson NJ, Fung MY, et al. Autoantibody production after cardiopulmonary bypass with special reference to postpericardiotomy syndrome. J Pediatr 1992; 121:744-47 Kim YK, Mohsenifar Z, Koerner SK. Lymphocytic pleural effusion in postpericardiotomy syndrome. Am Heart J 1988; 115:1077-79 Pettersson T, Klockars M, Hellstrom PE. Chemical and immunological features of pleural effusions: a comparison between rheumatoid arthritis and other diseases. Thorax 1982; 37:354-61

Similar Pleural Fluid Findings in Pleuropulmonary Tularemia and Tuberculous Pleurisy* Tom Pettersson, MD; Peter Nyberg, MD; Dan Nordstrom, MD; and Henrik Riska, MD, FCCP

Biochemical and cellular characteristics of pleural fluid from two patients with pleuropulmonary tulare, *From the Mjolbolsta Hospital, Mjolbolsta, Finland, and the Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.

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mia and 39 patients with tuberculous pleurisy were compared. High pleural fluid concentrations of adenosine deaminase, lysozyme, and ~ 2 -microglobulin occurred in both diseases. As is the case with tuberculous pleural effusions, pleural fluid in tularemia showed an abundance of lymphocytes, predominantly CD4-positive T lymphocytes. The similar pleural fluid findings suggest analogous local pathogenetic mechanisms in tularemia and tuberculosis. In the diagnostic evaluation of a lymphocyte-rich exudative pleural effusion with a high adenosine deaminase concentration, a possible cause to consider is tularemia.

(CHEST 1996; 109:572-75)

ACE=angiotensin-converting enzyme; ADA=adenosine deaEninase; ~M=lysozyme

Key words: adenosine deaminase; pleural effusion; T lymphocytes; tuberculosis; tularemia ,llthough tularemia is regarded as a rare cause of pleural

f t effusion, tularemic pneumonia often is complicated by

pleural involvement and effusion.l· 2 Pleurisy and pleural effusion without pneumonia is another, more uncommon presentation of tularemia. 3 Pleuropulmonary tularemia often causes differential diagnostic difficulties and may, in particular, be confused with tuberculous pleurisy. 4•5 The pleural effusion in pleuropulmonary tularemia has been described as a turbid or serosanguineous exudate with a predominance of either lymphocytes or neutrophils. 4•6•7 The effusion is not a low-glucose one, and there is no pleural fluid acidosis. 8 The biochemical composition of pleural fluid in tularemia, however, has not been described in detail. We analyzed lymphocyte subpopulations and several biochemical variables in the pleural fluid of two patients with tularemia and compared the results with those obtained in patients with tuberculous pleurisy. CASE REPORTS CASE

1

A 66-year-old previously healthy gardener was admitted to the hospital because of a 2-month history of breathlessness on exertion, mild right-sided chest pain, upper abdominal discomfort, and lowgrade fever. Physical examination revealed dullness with decreased breath sounds at the right lung base. He had no cutaneous symptoms and no lymphadenopathy or splenomegaly, but the liver appeared slightly enlarged. A chest x-ray film revealed a right-sided pleural effusion but no pulmonary parenchymal infiltrates or hilar adenopathy. He had a moderate leukocytosis with 65% lymphocytes and among them reactive forms. A tuberculin skin test (2 tuberculin unit [TU]) was positive. The pleural effusion was a sanguinolent exudate with a lymphocytic predominance (Table 1). A diagnosis of tuberculous pleurisy was considered likely, but an incidental serologic investigation revealed a diagnostic agglutination titer against Francisella tularensis of 1:160. He was treated with streptomycin, 1 ggiven IM each day for 2 weeks. Symptoms of pleurisy gradually disappeared. A chest x-ray film 2 months afterdiscontinuation of the medication showed clearing of the effusion, but pleural adhesions remained. AsubseSelected Reports