Concurrent cerebral aspergillosis and abdominal mucormycosis during ibrutinib therapy for chronic lymphocytic leukaemia

Comment on Invasive aspergillosis with pulmonary and central nervous system involvement during ibrutinib therapy for relapsed chronic lymphocytic leukaemia: case report. [Clin Microbiol Infect. 2018]International audienceWe read with great interest the article from Peri et al. describing a case report of invasive aspergillosis (IA) with primary pulmonary involvement followed by central nervous system (CNS) involvement in a patient treated for chronic lymphocytic leukaemia (CLL) with ibrutinib [1]. The clinical outcome has been favourable with a combination of voriconazole and liposomal amphotericin B (L-AmB). This case highlights the need for systematic screening of CNS involvement in patients receiving ibrutinib therapy for CLL and concurrent invasive fungal infection, which was not performed during the initial course of pulmonary aspergillosis in the case reported by Peri et al. To complement Peri et al.'s work, we would like to report a case with primary CNS involvement that has benefited from a systematic screening for extra-neurological involvement and additional invasive tissue biopsies. As ibrutinib-associated fungal infections are an emerging syndrome, we would like to describe clinical issues in the management of these infections. A 52-year-old woman presented with a 5-year history of CLL. In 2015 she received a combination of rituximab, fludarabine and cyclophosphamide with complete remission. She relapsed in September 2017 when a treatment with ibrutinib was started. At that time, she experienced neutropenia (between 0.4 and 0.6 G/L). She presented to the hospital on 16 March 2018 with a 2-week history of confusion, behaviour disorders and aggression. The pa-tient's temperature was 38.3 C. Cerebral computed tomography (CT) demonstrated a well-defined rim-enhancing lesion with a hypodense centre surrounded by oedema in the left external capsule region complicated by a mass effect on the left ventricle and a subfalcine herniation (Fig. 1a). A stereotaxic biopsy was performed, and mycological cultures were positive for Aspergillus fumigatus with negative direct examination. Antifungal susceptibility tests showed the following MICs (EUCAST method): vor-iconazole 0.19 mg/L; isavuconazole 0.25 mg/L; posaconazole 0.094 mg/L; itraconazole 0.36 mg/L; caspofungin 0.094 mg/L. Bacterial cultures were also positive for Propionibacterium acnes. No tumour cell was detected on pathological examination. After the biopsy was performed, she subsequently received cefotaxime and metronidazole for 7 days and a single dose of prednisolone of 1 mg/kg. Intravenous voriconazole (400 mg/12 h at day one then 200 mg/12 h) was started after the result of fungal cultures. Serum galactomannan antigen was negative. (1,3)-b-D-glucan serum titres were 84 pg/mL. Aspergillus fumigatus PCR in serum was negative. Sinus and chest CT scans were normal. A systematic abdominal CT scan revealed a lesion of the upper pole of the left kidney and a lesion of the spleen both consistent with abscesses (Fig. 1c). A CT-guided biopsy was performed of the kidney lesion. The histopathological examination showed ischaemic ne-crosis associated with non-septate broad hyphae. Fungal culture