Pembrolizumab-Induced Autoimmune Encephalitis: A Rare Case

Immune checkpoint inhibitor-induced encephalitis (ICIiE) is a rare but potentially life-threatening neurological immune-related adverse event associated with cancer immunotherapy. Pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, has demonstrated significant efficacy across multiple malignancies; however, its use can lead to dysregulated immune activation affecting the central nervous system. Clinical presentation is highly variable and often mimics infectious or paraneoplastic encephalitis, making diagnosis challenging, particularly in immunocompromised patients. We report the case of a 63-year-old woman with grade III breast carcinoma, status post mastectomy, receiving adjuvant chemotherapy with paclitaxel and carboplatin in combination with pembrolizumab, who presented with persistent high-grade fever one week after immunotherapy administration. She was initially managed as a case of neutropenic sepsis and treated with broad-spectrum antibacterial and antifungal therapy; however, she developed progressive neurocognitive deterioration characterized by confusion, disorientation, irritability, and intermittent dystonic posturing, prompting intensive care unit admission. Extensive infectious evaluation, including repeated cultures, viral studies, and imaging, was unrevealing. Cerebrospinal fluid (CSF) analysis demonstrated marked lymphocytic pleocytosis and significantly elevated protein levels, while bacterial and viral polymerase chain reaction panels were negative. Brain MRI showed no definitive acute abnormalities. Given the temporal relationship with pembrolizumab exposure and exclusion of alternative etiologies, a diagnosis of immune checkpoint inhibitor (ICI)-related encephalitis was made. High-dose intravenous methylprednisolone was initiated, resulting in rapid defervescence and complete neurological recovery, normalization of inflammatory markers, and a return to baseline mentation. This case highlights the importance of maintaining a high index of suspicion for immune checkpoint inhibitor-related encephalitis in patients receiving immunotherapy who present with unexplained fever and subacute neurological decline. Early multidisciplinary evaluation and prompt initiation of immunosuppressive therapy are critical to preventing morbidity and achieving favorable neurological outcomes.