Autoimmune GFAP astrocytopathy associated with sintilimab immunotherapy in a patient with esophageal squamous cell carcinoma: a case report and literature review.

Esophageal squamous cell carcinoma (ESCC) is a highly lethal malignant tumor. Immune checkpoint inhibitors (ICIs), represented by sintilimab, have become an important treatment option for advanced ESCC, but they may induce immune-related adverse events (irAEs) involving multiple systems, among which neurological irAEs, though rare, can be severe. Autoimmune glial fibrillary acidic protein (GFAP) Astrocytopathy is a novel autoimmune disorder of the central nervous system (CNS). Its occurrence in ESCC patients receiving sintilimab immunotherapy has not been previously documented in detail. This report presents a rare case of Autoimmune GFAP Astrocytopathy in a 55-year-old male patient with advanced ESCC following sintilimab (200 mg) combined with paclitaxel and cisplatin chemotherapy. Additionally, a systematic literature review identified 17 cases of immune-associated encephalitis induced by PD-1 inhibitors, whose clinical features were similar to those in this case. This case provides detailed clinical, laboratory and imaging data of sintilimab-related autoimmune GFAP astrocytopathy in a patient with advanced esophageal squamous cell carcinoma, supplementing real-world clinical evidence of CNS immune-associated adverse events induced by sintilimab. We explore the potential pathogenesis, diagnostic criteria, and treatment strategies for this condition. The patient achieved complete remission after early high-dose glucocorticoid pulse therapy combined with intravenous immunoglobulin (IVIG), with sustained neurological remission observed during a 3-month outpatient observation window (partial completion of the planned 6-month steroid tapering regimen).This study emphasizes the need for clinical vigilance regarding Autoimmune GFAP Astrocytopathy in ESCC patients presenting with neurological manifestations during PD-1/PD-L1 inhibitor therapy, and highlights that early detection, prompt discontinuation of ICI, and aggressive immunosuppressive therapy are critical for improving patient outcomes. These findings provide valuable clinical insights for the early diagnosis and individualized management of CNS irAEs associated with PD-1 inhibitor therapy in ESCC patients. Notably, only a temporal association between sintilimab therapy and disease onset can be confirmed; direct causal evidence remains unproven.