Abstract
Jellyfish stings represent a significant global marine hazard, causing injuries from localized skin damage to fatal systemic complications. While skin reactions are the most common symptom, heart toxicity (cardiotoxicity) is the primary cause of death. A growing body of evidence shows that the immune system's response worsens this venom-induced heart damage. However, current research remains disproportionately focused on cutaneous inflammatory responses, leaving systemic immunopathological processes-especially those potentiating cardiotoxicity-poorly understood. Moreover, few jellyfish toxins (like those from the Chironex fleckeri) have been thoroughly studied, and the molecular mechanisms of heart injury remain largely unknown. This review introduces a novel pathophysiological classification of jellyfish envenomation into three distinct categories-immunotoxicity-dominant, cardiotoxicity-dominant, and dual-mechanism synergistic-based on clinical and mechanistic profiles. By synthesizing current knowledge on venom components and their multi-system interaction, we aim to identify actionable therapeutic targets and propose mechanism-driven treatment strategies. This refined classification offers a foundation for future clinical decision-making and the development of targeted therapies, potentially improving patient outcomes through more personalized envenomation management.