Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread immune dysregulation that affects multiple organ systems, including the skin and cardiovascular system. The crosstalk between different cell death pathways-such as apoptosis, necroptosis, and neutrophil extracellular trap (NETosis), plays a pivotal role in the pathogenesis of SLE, influencing both cutaneous and cardiac manifestations. Cutaneous lupus erythematosus (CLE) is one of the most common early signs of SLE, affecting up to 80% of patients. CLE presents in several forms, including acute, subacute, and chronic lesions, each with varying degrees of association with systemic disease. Cardiac involvement, although often underrecognized, significantly contributes to morbidity and mortality in SLE patients, manifesting as pericarditis, myocarditis, valvular disease, and accelerated atherosclerosis. Emerging research suggests that these cutaneous and cardiac manifestations may be connected through shared immune mechanisms, including immune complex deposition, endothelial dysfunction, and chronic inflammation driven by cytokines such as Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The severity of skin involvement may correlate with an increased risk of cardiovascular events, underscoring the importance of early diagnosis and a multidisciplinary approach to treatment. This review explores the crosstalk among cell death pathways in SLE and examines how these pathways contribute to both cutaneous and cardiac manifestations. Furthermore, it highlights the clinical implications of this crosstalk and discusses potential therapeutic strategies aimed at modulating these cell death pathways to improve patient outcomes. Challenges and gaps in current research are also addressed, emphasizing the need for further investigation into these complex interactions.