Sudden Atelectasis and Respiratory Failure in a Neutropenic Patient: Atypical Presentation of Pseudomembranous Necrotizing Bronchial Aspergillosis
A 39-year-old female with a diagnosis of acute myeloid leukemia with multi-lineage dysplasia was treated with induction chemotherapy including idarubicin (12 mg/m2 for 3 days) and cytarabin (100 mg/m2 for 7 days). She failed to achieve complete remission, and was referred to our hospital for salvage chemotherapy, which was carried out with a FLAG-Ida regimen (fludarabine 30 mg/m2 for 5 days, cytarabin 2 g/m2 for 5 days, and idarubicin 12 mg/m2 for 3 days, with granulocyte colony-stimulating factor support).\nWhile the patient had neutropenia due to bone marrow suppression after chemotherapy, she had no episodes of febrile neutropenia. On the 21st day after chemotherapy, she complained of a mild cough. There was no fever and her breathing sounds were smooth on auscultation. Two days later the patient developed a fever of 38.3℃; however, her physical examination was unremarkable. We initiated empirical antibiotics, with cefepime 1 g q 12 hours and vancomycin 1 g q 12 hours for febrile neutropenia. Her chest X-ray showed a focal atelectasis (). The following morning, the patient complained of a sudden onset of dyspnea. Her vital signs were as follows: blood pressure 100/60 mmHg, heart rate 102 beats/min, respirations 32/min, and body temperature 37.0℃. By auscultation, breath sounds were nearly absent in the left-lung field. Laboratory findings, including arterial blood gas analysis, showed severe hypoxia and pancytopenia: pH 7.47, PaCO2 29.9 mmHg, PaO2 32.5 mmHg, HCO3 21.3 mmol/L, saturation 67.7%, hemoglobin 7.4 g/dL, white blood cell count 100/µL, absolute neutrophil count 0/µL, and platelet count 25,000/µL. Chest X-rays showed a diffuse radiopaque density with volume decrease of the entire left-lung field, suggesting the development of total left-lung atelectasis (). The patient was transferred to the intensive care unit and mechanical ventilator support was provided. Fiber-optic bronchoscopy revealed a large quantity of necrotic material at the distal trachea. The orifice of the left main bronchus was not visible because of a large quantity of grayish necrotic material covering the opening of the main bronchus (). Bronchoscopic biopsy, at the necrotic membrane, was performed. Due to suspicion of PNBA, we started intravenous administration of amphotericin B (0.5 mg/kg/day for the first day, 0.75 mg/kg/day on the subsequent day, and 1 mg/kg/day for the following 8 days). Serum galactomannan was also positive, with a level of 2.0 (normal range, 0 to 0.5). Biopsy of the necrotic membrane revealed the presence of fungus with hyphae suggestive of Aspergillus (). In spite of vigorous treatment in the intensive care unit for 5 days, the lung lesions rapidly progressed with worsening hypoxia. This infection was likely associated with the patient's persistent neutropenia, which was characterized by an absolute neutrophil count < 100/µL. We changed the antifungal agent to voriconazole due to the poor response to amphotericin B. Voriconazole was administered at 6 mg/kg q 12 hours for the loading dose and 4 mg/kg q 12 hours for the maintenance dose. However, respiratory distress progressed and the patient died 3 days later. Culture of the bronchial washing yielded Aspergillus nidulans.