A Man on Ibrutinib Develops Cerebral Aspergillosis

Key TakeawaysCerebral aspergillosis can present without fever or systemic inflammation in patients receiving targeted hematologic therapies, with subtle cognitive, language, and gait deficits that may mimic those of stroke or encephalopathy. Although neuroimaging can identify multifocal enhancing lesions with extensive edema, it may not distinguish fungal, bacterial, or neoplastic diseases. Therefore, histopathologic examination of resected tissue may be necessary to establish a diagnosis.The case report by Konstantinos Iason Tompler, MD, internal medicine specialist and resident physician in the Gastroenterology Division, University Hospital of Bern (Inselspital) in Bern, Switzerland, and colleagues described cerebral aspergillosis in a patient receiving ibrutinib and highlighted the importance of considering opportunistic fungal infections in immunosuppressed patients and pursuing tissue diagnosis when neurologic findings and imaging are inconclusive.The Patient and His HistoryA 68-year-old man presented to the emergency department with neurologic and mental status changes, including sudden personality change, attention deficits, psychomotor retardation, speech difficulties with receptive aphasia, and worsening ataxia for approximately 3 days. His medical history was significant for chronic lymphocytic leukemia, for which he had been receiving ibrutinib 420 mg orally once daily.Findings and DiagnosisUpon admission, the patient’s vital signs were measured. The respiratory rate, heart rate, blood pressure, oxygen saturation on room air, and body temperature were all within their respective normal ranges.Inspection, auscultation, palpation, and percussion of the patient’s body revealed no significant findings.Neurologic examination revealed attention deficits, episodic Wernicke-type sensory aphasia, slurred speech, and left-sided ataxia. Laboratory tests revealed a mild elevation in the neutrophil count (10,800/μL) in the context of known leukocytosis. The C-reactive protein level was within the normal range.Brain CT revealed a circumscribed hypodense lesion with indistinct margins in the right frontopolar region, involving the gyrus rectus, olfactory structures, and orbital gyri. The lesion had an expansile appearance and caused a slight deviation of the rostral midline due to the mass effect and parietal edema. A second hypodense lesion was located subcentrally on the left side.MRI confirmed two distinct contrast-enhancing lesions, measuring approximately 15 mm and 5 mm, with extensive surrounding edema. Further sequences showed multiple bilateral parieto-occipital foci with extensive adjacent edema and atypical signal patterns, including central diffusion restriction, thickened peripheral capsules, and focal susceptibility artifacts suggestive of blood degradation products or paramagnetic elements.A PET-CT scan revealed multifocal, metabolically active nodular lesions in both the supra- and infradiaphragmatic regions. The differential diagnoses included lymphoma, pyogenic abscesses, metastases from other cancers, and fungal infection.Empirical antibiotic therapy with ceftriaxone, metronidazole, voriconazole, and dexamethasone was initiated to treat inflammatory edema.Craniotomy and resection of the right frontobasal intracerebral space-occupying lesion were performed, followed by histopathologic examination. Histopathology revealed granulomatous inflammation and necrotic tissue harboring branching, septate fungal hyphae, features consistent with Aspergillus species. On the basis of the overall findings, an infection with Aspergillus fumigatus was diagnosed.Discussion“Ibrutinib and other newer immunosuppressants can increase the risk of mycotic infections. Neurological symptoms in immunosuppressed patients have a broad differential diagnosis, including opportunistic infections. MRI can provide clues, but a biopsy is often necessary,” wrote the authors.This story was translated from Univadis Germany, part of the Medscape Professional Network.