Pembrolizumab-Induced Simultaneous and Refractory Systemic Capillary Leak and Cytokine Release Syndromes: A Case Report

Systemic Capillary Leak Syndrome (SCLS) and Cytokine Release Syndrome (CRS) have both been described as rare but severe adverse reactions induced by Programmed cell death protein 1 (PD-1) inhibitors such as pembrolizumab. We report the case of a 40-year-old woman undergoing treatment with pembrolizumab for a stage 4 cervical squamous cell carcinoma who presented with anasarca, hypotension, hemoconcentration and signs of multisystemic inflammation. After elimination of alternative causes such as nephrotic syndrome, cardiac dysfunction and cirrhosis, she was diagnosed with both pembrolizumab-induced SCLS and CRS. She was successfully treated with a multimodal treatment approach including intravenous immunoglobulins, steroids, diuretics and axitinib for SCLS as well as ruxolitinib for CRS. After several months of hospitalization, her symptoms finally improved with this treatment regimen, and she was able to attain euvolemic state and be discharged from the hospital. This case highlights certain rare and severe adverse effects of treatment with PD-1 inhibitors. Furthermore, it proposes a novel therapeutic approach for similar cases based upon probable underlying physiopathological mechanisms in SCLS and CRS.