A 35-year-old man with Crohn's disease was referred to our respiratory department due to a high fever and the presence of an infiltrated pulmonary nodule after eight infusions of infliximab (IFX). Pulmonary cryptococcosis was diagnosed in this patient according to positive cryptococcal antigen test results (x16 and x32) of the bronchoalveolar lavage fluid (BALF). He was subsequently treated with 400 mg/day oral FLCZ. The infiltration of the left lower lobe of the lung gradually improved and was nearly eliminated after 3 months of FLCZ treatment. IFX treatment was resumed 1 month after the initial FLCZ treatment to control the patient's Crohn's disease. He received FLCZ for 6 months, as we previously described. IFX therapy was continued once every 8 weeks, and prednisolone was adjusted to approximately 10 mg/day.
The patient, however, developed a high fever, resistance to beta-lactam and levofloxacin antibiotics, general fatigue, and night sweats at 16 months after the completion of FLCZ treatment and 22 months after restarting IFX treatment. Chest radiography and computed tomography (CT) revealed a 3x2 cm mass-like region and a small nodule in the left and right upper lobes of the lung (Fig. 1). He had no symptoms indicating any type of central nervous system infection, such as a headache or consciousness disturbance. He also had no history of significant exposure to birds, including pigeons, or travel abroad around the time of the clinical progression or the onset of the first episode. Laboratory tests revealed a normal leukocyte count (4,300/mm3) and a slightly elevated C-reactive protein level (1.76 mg/dL). The test for serum cryptococcal antigen (Eiken, Tokyo, Japan) was negative, and the beta-D-glucan assay level (Wako, Osaka, Japan) was below the cut-off value (3.2 pg/mL). Bronchoscopy with BALF was performed, and a transbronchial lung biopsy (TBLB) was obtained from the left upper lobe region for further examination. The culture and microscopic examinations of the BALF were also negative. BALF cytology revealed periodic acid-Schiff stain-positive bodies, phagocytized by macrophages, which was indicative of Cryptococcus spp. (Fig. 2). The cryptococcal antigen test of the BALF was positive (x2). A histological examination of the TBLB showed granulomatous regions in the lung parenchyma. These findings confirmed the diagnosis of pulmonary cryptococcosis, and retreatment with 300 mg/day oral FLCZ at our outpatient clinic was started. Discontinuation of IFX treatment followed. The mass-like region found in the left upper lobe of the lung, however, deteriorated 2 months after restarting FLCZ. A change to antifungal treatment of 200 mg/day itraconazole (ITCZ) combined with 3 g/day flucytosine was initiated. After the initiation of this treatment, the region of the left upper lobe gradually decreased in size, and finally diminished in size on chest CT performed 10 months after the relapse (Fig. 3). The patient is presently continuing ITCZ treatment, although at a reduced dose of 100 mg/day due to the development of mild liver dysfunction.