Teaching Case

Persistent fever for 2 weeks and severe right chest pain after bone marrow transplantation (BMT) for acute lymphoblastic leukaemia (ALL).

The patient, with acute lymphoblastic leukaemia (ALL), received an allogeneic bone marrow transplantation (BMT) from a matched unrelated donor. Immediately after the transplant the patient developed profound pancytopaenia and fever, and empirical treatment with broad-spectrum antibiotics and amphotericin B was started.

Three weeks later the patient was referred for chest radiography because of severe right chest pain and persistent fever. Chest films demonstrated an enlarged cardiac silhouette, pneumopericardium, and a pulmonary cavitated lesion with characteristic "air crescent" formation, located adjacent to the left side of the pericardium (Fig. 1). Based on clinical data and imaging findings, a provisional diagnosis of invasive pulmonary aspergillosis complicated with a bronchopericardial fistula was suggested.

A control chest film one week later revealed progression of the pneumopericardium with an air-fluid level (hydropneumopericardium) (Fig. 2). On the same day, a computed tomography (CT) scan of the thorax was performed (Fig. 3). The patient underwent an emergency pericardiocentesis, and Aspergillus fumigatus was cultured from the pericardial fluid. Bronchoalveolar lavage (BAL) was performed, also revealing Aspergillus on culture.

The patient had progressive respiratory distress and died a few days later. The suspected diagnosis of invasive pulmonary aspergillosis complicated with a bronchopericardial fistula and pericarditis was confirmed by autopsy.

Invasive pulmonary aspergillosis (IPA) is a serious infection that requires severe impairment of host defence mechanisms, usually due to acute leukaemia and granulocytopenia from chemotherapy. Pathologically IPA is characterised by the invasion and thrombosis of small- to medium-sized pulmonary arteries by fungal hyphae, which leads to haemorrhagic infarction with necrosis and cavitation. The diagnosis is difficult and should be suspected when airspace consolidation does not improve with broad spectrum antibacterial therapy. The prognosis is poor (mortality rate as high as 30-90%) and early recognition is imperative to improve survival.

CT plays an important role in early diagnosis (1). Characteristic findings correspond to haemorrhagic infarcts and consist of nodules or pleura-based, wedge-shaped areas of consolidation, surrounded by a halo of ground-glass attenuation. Histologically the "halo sign" represents haemorrhage around a focal area of lung infarction; it is best seen with high-resolution CT. This sign is non-specific; similar appearances are seen in tuberculosis, mucormycosis, candidiasis, herpes simplex, cytomegalovirus, Wegener's granulomatosis, Kaposi's sarcoma and haemorrhagic metastases. However, in the appropriate clinical setting, the CT halo sign is highly suggestive of IPA. Cavitation in the nodules or masses is a late finding that occurs with recovery from neutropenia, and it is associated with a better prognosis than consolidation without cavitation. It typically results in a distinctive radiographic appearance, the "air crescent" sign. This finding, also described as the "meniscus" sign, is an air crescent near the periphery of a lung nodule formed by contraction of infarcted tissue, trapping the air between the necrotic lung and the healthy surrounding parenchyma.

Pleural effusion is uncommon in IPA, and chest wall or mediastinal invasion and systemic dissemination can occur. The presence of adenopathy is rare. Pericardial involvement by Aspergillus is also uncommon (2,3). This case illustrates a patient who developed pericarditis and a pneumopericardium as a result of a bronchopericardial fistula following IPA. The pericardium was directly invaded by a necrotic mass with the characteristic "air crescent" appearance, creating an abnormal connection (fistula) between the pericardium and the lung. To our knowledge, the literature in English contains only four documented reports of pneumopericardium complicating IPA (2-5). Pneumopericardium is a very rare life-threatening complication, with important therapeutic significance since a large intrapericardial collection producing cardiac tamponade requires emergency pericardiocentesis. The diagnosis is made when air is located in the pericardial space surrounding the heart. The air is sharply defined and, in contrast with pneumomediastinum, is superiorly limited by the lower border of the aortic arch. Aspergillus pericarditis is also an unusual condition with high morbidity and mortality, reflecting the dificulty of diagnosis and treatment and the severity of the underlying disease.