# Generalized Pustular Psoriasis and Systemic Organ Dysfunctions
## 5 Cardiovascular Events in GPP  
While the connection between psoriasis and the initiation of cardiovascular events is well-established in the medical literature, emerging studies have begun to explore the reciprocal relationship, particularly how cardiovascular events might influence the progression and severity of GPP. Notably, comparing baseline comorbidities, a significant disparity was found between individuals diagnosed with GPP and those with severe psoriasis [72]. Using the French national database (SNDS), three psoriasis cohorts were identified: a prevalent cohort from 2010 to 2018, an incident cohort from 2012 to 2015, and a severe psoriasis cohort. The severe psoriasis cohort was compared with the GPP incident cohort using propensity score matching [72]. For instance, ischemic heart disease was considerably more common in the GPP incident cohort, appearing in 26% of cases, as opposed to in 18% for those with severe psoriasis. This suggests a unique cardiovascular risk profile in GPP patients [72]. Moreover, existing cardiovascular diseases have emerged as critical factors in predicting the clinical outcomes of GPP. A nationwide, population-based retrospective cohort study was conducted to assess adult inpatients with GPP from January 2007 to December 2020 [73]. Research indicates that patients with a history of myocardial infarction are significantly more likely to develop GPP, with an odds ratio of 4.29 after adjusting for age and sex [73]. This correlation becomes even more pronounced in fatal cases of GPP, where the history of myocardial infarction carries an odds ratio of 5.10 after adjusting for age and sex, highlighting a strong link between severe cardiovascular conditions and lethal outcomes in GPP [73]. Despite these findings, the impact of GPP on the occurrence of cerebrovascular diseases remains poorly defined, with few studies directly addressing this aspect. This gap in understanding points to the need for further research into how GPP may affect or be affected by cerebrovascular conditions. Lastly, the biological mechanisms through which GPP may regulate or be influenced by cardiovascular events are still not fully understood. This area of study is crucial, as unraveling these mechanisms could lead to better targeted therapies and preventive strategies for patients suffering from both GPP and cardiovascular diseases. Interleukin-36 (IL-36) is increasingly recognized as a pivotal trigger in the production of interleukin-17A (IL-17A) within the skin [70; 74; 75], which in turn plays a crucial role in the development of atherosclerosis, a major contributor to cardiovascular disease [76; 77]. This pathway underscores a significant link between inflammatory processes in dermatological conditions and broader vascular health issues. The mechanism through which IL-36 prompts the release of IL-17A involves a complex cascade of immune responses, which ultimately lead to inflammation and subsequent changes in the vascular walls, facilitating atherosclerotic developments. In light of this, therapies targeting IL-17A have garnered attention for their potential to not only manage psoriasis, but also to mitigate associated vascular inflammation that can lead to serious cardiovascular events. One such therapy, secukinumab, which functions as an IL-17A inhibitor, has shown promising results in reducing vascular inflammatory markers in patients with psoriasis [78; 79]. This effect suggests that IL-17A blockage could serve as a strategic intervention to decrease the future risk of cardiovascular events in these patients. The implications of such treatments are profound, as they offer a dual benefit: alleviating the skin symptoms of psoriasis, while simultaneously addressing the heightened risk of cardiovascular diseases linked to systemic inflammation. Ongoing research and clinical trials are crucial to further elucidate the efficacy and safety of IL-17A inhibitors, potentially paving the way for novel therapeutic strategies that integrate the management of psoriasis and cardiovascular risk.