Ann Thorac Surg 1997;63:1200-1204
© 1997 The Society of Thoracic Surgeons
Current Review
Candida Pericarditis: Clinical Profile and Treatment
Reuven Rabinovici, MD,
Damian Szewczyk, MD,
Philip Ovadia,
Jeffrey R. Greenspan, MD,
Jocelyn J. Sivalingam, MD
Department of Surgery and Division of Infectious Diseases, Jefferson Medical College; and Division of Gastroenterology, John F. Kennedy Hospital, Philadelphia, Pennsylvania
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Abstract
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Background. Candida pericarditis is a rare medical and surgical emergency which, unless treated, leads to impaired cardiac function and death. To facilitate early diagnosis, the clinical features of this condition should be identified.
Methods. Twenty-five cases of Candida pericarditis reported in the last 30 years along with 1 new case were reviewed with regard to demographics, precipitating factors, diagnosis, treatment, and outcome.
Results. The syndrome occurred in immunocompromised (73%), antibiotic-treated (62%), or postpericardiotomy (54%) patients. The clinical presentation was frequently subtle and nonspecific. Nevertheless, unexplained fever, an increasing cardiac shadow on chest roentgenogram, or the development of cardiac tamponade may be suggestive. Positive culture for Candida in pericardial fluid or histologic evidence of yeast forms in pericardial tissue establishes the diagnosis. A combination of pericardiocentesis followed by operative drainage and antifungal agents is the usual treatment. Untreated, Candida pericarditis is 100% lethal, whereas prompt diagnosis and treatment lead to cure (mean follow-up, 19 months).
Conclusions. Fever and evolving cardiac tamponade in immunocompromised or postpericardiotomy patients may be suggestive of Candida pericarditis; the presence of organisms in pericardial fluid is diagnostic. Pericardiocentesis followed by operative drainage and antifungal agents appears to be the treatment that is most likely to be curative.
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Introduction
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Candida pericarditis, first described in 1967 [1], is an uncommon medical and surgical emergency caused by Candida infection of the pericardium. This syndrome has been reported in postpericardiotomy or immunocompromised patients as a manifestation of severe conditions such as disseminated malignancy or burns.
As in purulent pericarditis, the clinicopathologic features of Candida pericarditis result from compromised cardiac performance and progressive inflammation. Thus, unless it is recognized early, Candida pericarditis has been shown to cause severe systemic sepsis, cardiac tamponade, and death. To prevent delays in treatment, there is a need to characterize the clinical presentation of this rare disease and to examine therapeutic modalities and results. To that end, we reviewed 25 reported cases along with 1 new case.
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Material and Methods
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Twenty-five cases of Candida1 pericarditis identified by MEDLINE between 1967 and 1994 [1–17] along with 1 new case were reviewed with regard to the clinical profile, precipitating factors, diagnostic workup, treatment, and outcome.
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Reviewed Cases
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The median age was 46 years (range, 6 weeks to 77 years), and there was a male predominance (male to female ratio 2.4:1). Predisposing factors included immunosuppression in 19 (73%) (malignancy/chemotherapy in 8 [27%], steroid treatment in 4 [15%], sepsis in 4 [15%], burns in 2 [8%], and chronic renal failure in 1 [4%]); antibiotic treatment in 16 (62%); and pericardiotomy in 14 (54%) (cardiac operations in 10 [38%] and esophageal operations in 4 [15%]). The most common associated medical conditions were infections in 16 (62%) (pneumonia/upper respiratory infection in 7 [27%], wound infection in 4 [15%], mediastinitis in 3 [12%], and not specified in 2 [8%]); malignancy in 8 (31%) (leukemia/lymphoma in 4 [15%], esophageal cancer in 1 [4%], gastric cancer in 1 [4%], and not specified in 2 [8%]); endocrine/immunologic in 6 (23%) (diabetes mellitus in 4 [15%], systemic lupus erythematosus in 1 [4%], and thymic hypoplasia in 1 [4%]); trauma/burns in 5 (20%) (burns in 2 [8%], esophageal perforation in 2 [8%], and cardiac laceration in 1 [4%]); and renal failure in 1 (4%). The clinical presentation was often nonspecific, but fever, increasing cardiac shadow on chest roentgenogram, pleural effusion, and the development of cardiac tamponade were the more suggestive signs of Candida pericarditis (Table 1
). In the early series [1–3, 5–7], all patients were diagnosed postmortem. However, in the more recent reports [8, 9, 11, 13, 15–17], Candida pericarditis was diagnosed by analysis of pericardial fluid obtained by ultrasound-guided pericardiocentesis (10 patients).
The isolation of Candida species in cultures from pericardial tissue or fluid and histologic evidence of yeast forms in pericardial tissue were the major diagnostic criteria of Candida infection (Table 2). Species included Candida albicans (14 patients) or C tropicalis (4 patients), whereas in 9 patients, no species identification was provided. Candida cultures from other body fluids were positive in at least 42% of patients (Table 3). Unfortunately, the exact incidence of positive body fluid cultures for Candida in these patients is unknown because many of the reports were not detailed. Thus, it is conceivable that the percentage of patients with positive Candida cultures from extrapericardial fluids is higher.
All 10 patients who were diagnosed while alive were treated initially with pericardiocentesis. Definitive improvement occurred in only 1 patient (10%), who was alive and free of disease at 20 months' follow-up (Table 4). The remaining 9 patients (90%) required operative drainage of the pericardial sac because of reaccumulation of pericardial fluid. Of this latter group, 5 patients were alive without evidence of Candida infection at a mean follow-up of 19 months (see Table 4). Two patients died perioperatively of unrelated causes, 1 patient died after operation of an undisclosed cause, and 1 patient was lost to follow-up (see Table 4).
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Case Report
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A 51-year-old woman presented with a 6-month history of dysphagia, substantial weight loss, and fever. Diagnostic workup revealed an obstructing tumor of the distal esophagus. Shortly after admission, group F streptococcal sepsis and diffuse abdominal tenderness developed. Computed tomography of the abdomen showed marked enlargement of the tumor, which contained extensive necrotic areas with perforation. The patient was brought to the operating room. The distal esophageal tumor, diagnosed as adenocarcinoma, extended to the left lobe of the liver. To establish the tumor's relation to the inferior vena cava, it was necessary to open the pericardial sac. Indeed, encasement of the vena cava was noted, and the tumor was determined to be unresectable. An excisional wedge biopsy of a pulmonary lesion found during operation also was performed. The tumor-bearing areas of the distal esophagus and proximal stomach were excluded, and esophagogastrostomy was performed.
Postoperatively, the patient had continued fevers despite broad-spectrum antibiotic therapy. All cultures from sterile sites, including the blood, remained negative. However, yeast was isolated from a superficial culture of the thoracoabdominal incision. An upper gastrointestinal series showed no extravasation of contrast material. Meanwhile, antituberculous medications were instituted for caseating granulomas found in the lung biopsy specimen obtained during operation. Nine days after operation, a new cardiac murmur and a pericardial friction rub were noted. On the 15th postoperative day, the patient demonstrated hypotension, jugular venous distention, increased cardiac silhouette on chest roentgenogram, and low voltage in all electrocardiographic leads. A transthoracic echocardiogram confirmed the diagnosis of cardiac tamponade. Ultrasound-guided pericardiocentesis was used to drain 250 mL of serosanguinous fluid, with a dramatic improvement in the shock state. The aspirated fluid had a few white blood cells, but no organisms were seen on routine and fungal stains. Repeat echocardiogram performed 12 hours later demonstrated a large recurrent pericardial effusion. Because of deteriorating hemodynamic status, a subxiphoid pericardial window was performed. Four hundred milliliters of serous fluid was obtained, with an instant elevation of blood pressure and clinical improvement. The postoperative course was unremarkable. Culture of both the aspirated and surgically drained pericardial fluid grew C albicans and the patient was started on amphotericin 0.5 mg•kg-1•day-1. Histologic examination of the pericardial fluid was negative for fungal elements. The patient was discharged from the hospital in good condition and finished her course of amphotericin, which was continued for a total of 1 g.
Eight months later, the patient died of fulminant non-yeast sepsis secondary to a newly developed tracheobronchial fistula. Autopsy was not performed.
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Comment
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This retrospective review clearly identifies several factors that predispose patients to Candida pericarditis. The most common associated factor is immunosuppression induced by malignancy, chronic steroid therapy, and sepsis. The use of broad-spectrum antibiotics is also a major predisposing factor. Such a history was documented in 16 patients, but it is conceivable, in light of their severe illness, that other patients in this series also received courses of antibiotics. Another identified risk factor is pericardiotomy performed during both cardiac and esophageal operations.
The pathogenesis of Candida pericarditis is still obscure. Nevertheless, several considerations support the possibility that pericardial Candida infection is a form of hematogenously disseminated disease. First, antibiotic therapy, a major predisposing factor for Candida pericarditis, has been shown to promote fungal colonization of various organs, such as the skin [18], airways [18, 19], and urinary tract [20, 21], probably by facilitating superinfection [21, 22]. Second, immunosuppressed conditions such as malignancy [23–25] or chronic steroid therapy [26] have been identified to render patients susceptible to Candida infections. Third, nearly half of the patients reviewed in this study had positive Candida cultures in various body fluids (see Table 3
). On the other hand, it is possible that pericardial fungal infection is primarily a local event. This observation is supported by the high percentage of infected patients who had undergone pericardiotomy. Furthermore, most of these patients had additional complicating local factors that could promote pericardial inflammation, such as repeat thoracotomy, pericardial or mediastinal drainage tubes, and open cardiac resuscitation.
Cardiac tamponade, reported in 8 patients (see Table 1), is probably the only clinical manifestation that can be directly related to Candida pericarditis. Because ultrasound, which has greatly facilitated the diagnosis of cardiac tamponade [27], was not available in the earlier series, it is possible that the incidence of cardiac tamponade in patients with Candida pericarditis was actually higher. The presence of pericardial fluid in 11 patients and of progressively enlarging cardiac silhouette in 10 cases (see Table 1) strongly supports this assumption.
Most of the patients in the present series had multiple complex medical conditions such as sepsis, major operations, and an extended stay in the intensive care unit (data not shown). Therefore, it is extremely difficult to characterize accurately other clinical manifestations of Candida pericarditis per se. It is impossible, for example, to determine whether the fungal pericardial infection itself can produce a full-blown septic shock. Nevertheless, fever and a newly developed pericardial rub or cardiac murmur seem to be other prominent features of Candida pericarditis (see Table 1). Although electrocardiographic data were not available in the majority of cases, the most common findings were nonspecific changes with diffuse low voltage. A rapid increase in cardiac silhouette, especially without pulmonary vascular congestion, was the most prominent finding on the chest roentgenogram (reported in 10 patients).
Because the clinical presentation of Candida pericarditis is often nonspecific, prompt diagnosis of this syndrome can be difficult. Indeed, the majority of patients in this review were diagnosed on postmortem examination. In all other patients, ultrasound-guided pericardiocentesis facilitated the diagnosis by yielding a sample of pericardial fluid for microbiologic and histologic analysis (see Table 2). Isolation of Candida species in cultures from pericardial tissue or fluid and the demonstration of fungal elements on histologic sections, along with evidence of acute inflammation, establish a definitive diagnosis (see Table 2). Although blood cultures [28] and serologic tests [29] may facilitate the diagnosis of a systemic Candida infection, they do not indicate pericardial involvement.
Treatment of most patients diagnosed while having active disease included a combination of antifungal agents, pericardiocentesis, and operative drainage. Amphotericin B at 0.5 to 1.0 mg•kg-1•day-1 with a cumulative dose of 1.5 to 2.5 g has been the recommended antifungal agent [30]. The combined administration of amphotericin B with flucytosine has been reported as well [16]. However, none of the patients so far described were treated with the newer antifungal agent fluconazole. Based on its low toxicity, high tissue penetration, and demonstrated efficacy in various candidal infections [31], it may be an option in future cases of Candida pericarditis.
Pericardiocentesis has been shown to produce variable results. In most patients, this procedure provided only temporary relief of both infection and cardiac tamponade, with a rapid recurrence of effusion. Recurrence may be more prominent in patients with thick, loculated effusions, and multiple attempts at aspiration may lead to severe complications. Operative drainage of the pericardial sac is the definitive treatment and can be performed by either a transthoracic or a subxiphoid approach. The latter has the advantage of being performed through a small epigastric incision, as compared with a median sternotomy or a thoracotomy incision. On the other hand, some reports advocate the transthoracic approach when the pericardium is very thickened and tenacious [9]. Unfortunately, because of the limited available data, no definitive conclusion can be drawn regarding the optimal approach for operative drainage of the Candida-infected pericardial sac. Thoracoscopic evacuation can be considered as well.
All patients whose diagnosis was overlooked died of their disease, whereas patients who were diagnosed and treated survived for a mean follow-up of 19 months, with no signs of infection (see Table 4). Two patients died of unrelated complications after major surgical procedures, and 1 patient died postoperatively of unspecified cause.
To summarize, Candida pericarditis is a rare syndrome that should be suspected in immunocompromised patients in whom fever and cardiac tamponade develop after antibiotic treatments or pericardiotomy. The diagnosis should be esablished by microbiologic or histologic identification of Candida in pericardial fluid or tissue. Treatment includes antifungal agents in combination with pericardiocentesis and operative drainage. Unless it is treated, Candida pericarditis is highly lethal, but prompt diagnosis and treatment result in a favorable outcome.
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Footnotes
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Address reprint requests to Dr Rabinovici, Department of Surgery, Jefferson Medical College, 1025 Walnut Street, Philadelphia, PA 19107. (e-mail: rabinov1{at}jeflin.tju.edu).
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Abstract
Introduction
