A 62-year-old man had been well until 2 weeks before he presented to our hospital with a high fever. Two years before this presentation, he had been diagnosed with myelodysplastic syndrome (MDS) and showed a chromosomal abnormality in 46XY,+1,der(1;7)(q10:p10). The patient had not previously received any immunosuppressive treatment and had not previously undergone bone marrow transplantation. Although a rapid influenza antigen test was negative, zanamivir and acetaminophen were prescribed due to an ongoing influenza epidemic. The patient revisited our hospital four days after his initial presentation due to a persistent fever. A chest X-ray showed consolidation in the right lower lung field and the patient was admitted to our hospital (Fig. 1A). His vital signs on admission were as follows: temperature, 40.1C; heart rate, 127/min; blood pressure, 198/119 mmHg; respiratory rate, 28/min; and oxygen saturation on room air, 97%. There were no remarkable physical or laboratory examination findings. No infectious agents were detected in the patient's blood or sputum cultures on admission. The patient was negative for serum autoantibodies, serum antigens against fungi, and urinary antigens against pneumococcus and legionella.
Piperacillin-tazobactem, azithromycin, and voriconazole were initiated from the first day of admission and switched to meropenem, levofloxacin, and amphotericine B on day 4. Peramivir and sulfamethoxazole-trimetoprim were added on days 2 and 3, respectively. In spite of the treatment, the patient's respiratory status worsened. On day 4 of hospitalization, his PaO2 level was 56 mmHg with the administration of 15 L O2 by a non-rebreather mask and his blood pressure was 68/41 mmHg. He was transferred to the intensive care unit (ICU) with mechanical ventilation (Fig. 1B). After noradrenaline therapy proved ineffective against the patient's persistent hypotension, hydrocortisone [200 mg/day (50 mg/day of prednisolone equivalent)] was administered to maintain circulation. His blood pressure subsequently increased to the normal range and his respiratory status showed improvement. The corticosteroid dosage was increased to prednisolone (60 mg/day) on day 9 of hospitalization, and he was successfully weaned from mechanical ventilation on day 11 without additional immunosuppressive agents (Fig. 2).
The first TBLB on day 15 of hospitalization revealed the cardinal features of AFOP, namely, abundant fibrin exudate, immature organization in the alveolar spaces, and lymphoplasmacytic infiltration in the alveolar septa (Fig. 3A). The consolidation in the right lower lobe persisted, despite prolonged corticosteroid treatment, possibly suggesting another complication such as a fungal infection. A second TBLB performed on day 42 revealed the replacement of these features by fibroblasts and evidence of organization, which are the histological features of OP (Fig. 3B). Neither TBLB revealed any typical fibrin balls, hyaline membranes, eosinophilic infiltration, bleeding, vasculitis or infection. The diagnosis of AFOP and OP was made based on the histological and clinical signs. The dosage of the prednisolone was tapered to 7 mg/day when the patient recovered and was discharged on day 52 of hospitalization (Fig. 4). In spite of four months of azacytidine treatment, which was initiated after hospital discharge, the patient's MDS progressed to leukemia. Thereafter, the patient refused to undergo any additional chemotherapies or hematopoietic stem cell allograft transplantation. The patient died five months after hospital discharge. During the course of the disease, his respiratory status remained good.