Snapshot A 23-year-old woman presents to the emergency department with fever, headache, vomiting, rash, and confusion. She was in her usual state of health approximately two days prior to presentation. She is currently in menses and uses tampons. Her temperature of 38.9°C (102.0°F), blood pressure is 88/58 mmHg, pulse is 110/min, and respirations are 22/min. On physical exam, there is diffuse macular erythroderma and vaginal hyperemia. Introduction Superantigens activate T-cells to result in massive cytokine production Pathogenesis under normal conditions an antigen is taken up, processed, and expressed on MHC class II of antigen-presenting cells (APCs) T-cells recognize this via its T-cell receptor superantigens interact directly with the MHC class II molecule on APCs forming superantigen-MHC complex that interacts with the many T cell receptor to release excessive amounts of IL-1, 2, TNF-alpha and beta, and IFN-gamma leading to systemic toxicity Clinical correlate toxin shock syndrome toxin-1 (TSST-1) from Staphylococcus aureus leading to toxic shock syndrome exotoxin A from Streptococcus pyogenes leading to toxic shock-like syndrome