Acute lymphocytic leukemia with superimposed invasive aspergillosis and pneumopericardium successfully treated with voriconazole

Abstract

We present a 47-year-old man with acute lymphocytic leukemia with a pericardial friction rub heralding pericardial aspergillosis. The clinical course was complicated by pneumopericardium, likely secondary to a direct connection between the lung parenchyma and the pericardial space. Bronchoalveolar lavage cultures returned positive for methicillin-resistant Staphylococcus aureus and Aspergillus niger. Combination voriconazole and vancomycin resulted in symptomatic improvement within 2 weeks of hospitalization.

Aspergillus pericarditis is a rare clinical entity but is associated with potentially life-threatening complications that pose significant medical and surgical challenges to effective management (1–5). This case describes a case of Aspergillus pericarditis in a patient with leukemia.

CASE DESCRIPTION

A 47-year-old white man with acute lymphocytic leukemia (ALL) who had completed chemotherapy (Linker regimen) presented to the oncology clinic with mild left-sided pleuritic chest pain of a week's duration, associated with anorexia, occasional minimal hemoptysis, and shortness of breath with exertion. His course of chemotherapy was discontinued 3 weeks earlier due to neutropenic fever of unknown origin, which was treated empirically with vancomycin and piperacillin/tazobactam with subsequent resolution of symptoms. The patient's social history was notable for active smoking (45 pack-years total) with prior alcohol and intravenous drug use. He was cachectic-appearing and tachypneic, but hemodynamically stable. Diffuse fine crackles were audible at both lung bases, and a prominent pericardial rub was detected throughout the precordium and was accentuated during systole. No Kussmaul's sign or pulsus paradoxus was evident. He had a stable hemoglobin of 8.9 mg/dL, a serum sodium of 128 mEq/dL, and an albumin of 1.6 g/dL. Serial troponin and creatine kinase (total and MB fraction) measurements were negative. The chest x-ray revealed bilateral perihilar infiltrates suggestive of an infectious process. The electrocardiogram revealed concave ST segment elevation in V3 and V4 of 4.5 mm with concomitant PR segment depression. A transthoracic echocardiogram revealed a moderate-sized circumferential pericardial effusion that was not hemodynamically significant. A computed tomography (CT) image of the chest showed bilateral pulmonary cavities with a “halo formation” concerning for a necrotizing fungal pneumonia. The CT also showed that one of the cavities was in direct contact with the pericardium, creating a communication between the pulmonary parenchyma and the pericardial space (Figure). Blood cultures remained negative throughout the hospital course. A bronchoscopy revealed necrotizing pneumonia, which was neutrophil predominant and had concomitant vascular involvement. Cultures from the bronchoalveolar lavage isolated methicillin-resistant Staphylococcus aureus and Aspergillus niger.

Figure.

CT chest imaging demonstrating direct communication between the pulmonary parenchyma and the pericardial space associated with pneumopericardium.

Cardiothoracic surgery elected not to perform pericardial biopsy or undertake more invasive evaluation in this high-risk patient given his poor baseline functional status and his significant underlying comorbidities. The patient was started on amphotericin B, which was ultimately transitioned to voriconazole. Combination voriconazole and vancomycin was continued and resulted in symptomatic improvement within 2 weeks of hospital admission. The patient was discharged home in stable clinical condition on oral voriconazole for a total antifungal course of 12 weeks.

DISCUSSION

This report describes an unusual case of invasive aspergillosis presenting as fungal pericarditis in a patient with baseline immunosuppression complicated by pneumopericardium. To date, only 36 other cases of Aspergillus pericarditis have been reported since 1955. Among these, Aspergillus-related pericarditis was diagnosed before death in 13 of 36 patients, all of whom had established premortem diagnoses of invasive aspergillosis at other sites and had received antifungal therapy. A. fumigatus was the most common species, isolated in 28 cases (77%). A. niger, the species identified in our case, was found in only 4 cases (11%). In postmortem series, less than 5% of all patients with invasive aspergillosis had evidence of pericardial infiltration (6–8). This condition occurs primarily in severely immunocompromised patients and is generally a result of contiguous dissemination of Aspergillus from the lung or myocardium (9, 10). Aspergillus inoculation into the pericardium after invasive cardiac surgery has been previously documented (11). Leukemia was the most common predisposing condition, with a frequency of 47% (17 cases) (9).

The introduction of air into the pericardial space secondary to a fungal infection is extremely rare. The Table summarizes the five known cases (including the present report) of invasive aspergillosis complicated by pneumopericardium (2–5). All cases involved men with prior histories of leukemia, with similar clinical presentations of chest pain and dyspnea. Based on the CT findings, a necrotizing pulmonary parenchymal process likely promoted the formation of a direct communication with the airway system. Only one other case had identified A. niger in the pericardial fluid (3).

Table.

Summary of reported patients (all men) with leukemia, invasive aspergillosis, and pneumopericardium

First author	Year of study	Age (years)	Type of leukemia	ECG ST elevation	Drug Rx	SD	Duration of Rx prior to recovery (weeks)
Müller (2)	1987	40	CML	N/A	A	+	N/A
Owens (3)	1990	14	ALL	+	A	+	8
van Ede (4)	1994	29	AML	+	A+I	–	N/A
Merino (5)	1995	7	ALL	N/A	A+I	–	4
Alviar	2014	47	ALL	+	A+V	–	2

+, indicates present; −, absent; N/A, not available or applicable; A, amphotericin; ALL, acute lymphocytic leukemia; AML, acute myelogenous leukemia; CML, chronic myelogenous leukemia; ECG, electrocardiogram; I, itraconazole; Rx, treatment; SD, surgical decompression; V, voriconazole.

The prognosis of patients infected with Aspergillus with pericardial involvement is generally very poor (2, 4). Despite the increased morbidity and mortality, treatment regimens are similar to those for other forms of invasive aspergillosis. All other previous cases of Aspergillus-associated pneumopericardium were treated with conventional amphotericin B therapy with mixed outcomes and prolonged hospital courses (2–5). Based on the limited available data, however, voriconazole appears to have superior pericardial penetration compared with other agents, and current treatment guidelines favor this agent in the treatment of invasive aspergillosis (12–15). Medical management with voriconazole in our case resulted in early symptomatic recovery in a high-risk cachectic patient.