Stroke is the second leading cause of death and disability worldwide (1). In 2020, nearly 12 million people worldwide suffered a stroke, and acute ischemic stroke (AIS) is considered the most common subtype of stroke, accounting for approximately 65% of the total stroke incidence (2). Cheng et al. estimate that the global incidence of stroke will have exceeded 21 million cases by the year 2050 (3). Therefore, primary prevention, which includes not only the management and control of traditional cardiovascular risk factors such as hypertension, diabetes mellitus, dyslipidemia or atrial fibrillation but also lifestyle modifications, should be prioritized in public health (4). Inflammatory and infectious diseases have also long been considered potential risk factors for AIS, but the exact causal relationship remains uncertain (5). Recent studies indicate that autoimmune conditions associated with chronic systemic inflammation are often linked to AIS. Among these, rheumatoid arthritis appears to have the strongest association, yet there is also emerging evidence for the involvement of psoriasis in AIS pathophysiology (6).

Psoriasis is a chronic autoimmune erythematous-squamous disorder defined by proliferative changes predominantly affecting the skin, nails, and joints (psoriatic arthritis) (7–10). The prevalence of psoriasis varies from country to country, e.g., it affects only 0.05% of the general population in Taiwan, which makes it the country with the lowest psoriasis prevalence in the world (11). On the other hand, the prevalence of psoriasis in the United States has been estimated to be as high as 3%, making it one of the most common immune-mediated disorders there (12). Nonetheless, it is a common condition worldwide, affecting people of all ages (7) with a higher prevalence in adults, although it can also occur in children (11). Psoriasis affects both women and men, but in women, the onset typically occurs approximately 10 years earlier than in men, and is more common in patients with a positive family history of the disease (9). The pathophysiology of psoriasis has been linked to genetic susceptibility, in particular the presence of the HLA-C*06:02 risk allele, but also to environmental factors such as tobacco smoking, alcohol consumption, diet, obesity, low physical activity, streptococcal infections or stressful life events (7, 13). However, the exact etiology of psoriasis is complex and remains unclear (14).

For many years, psoriasis was considered a skin disease primarily treated with topical medications and, if necessary, phototherapy. It is now well known that psoriasis is a systemic inflammatory condition with multi-organ involvement (15). This state of chronic low-grade inflammation, usually subclinical, may be associated with comorbidities such as obesity, diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular disorders (15–17). For instance, according to a systematic review conducted by Correa et al., five out of eight studies included in their analysis indicated that psoriasis increased the risk of myocardial infarction (18). In addition to atherosclerotic diseases, psoriasis might be associated with increased risk of heart failure (19), also in in younger populations (20). According to a cross-sectional study conducted by Eckembrecher et al., among 2,485 hospitalizations of psoriasis patients, 13.7% had comorbid cardiovascular disease (21). Moreover, these individuals tended to have significantly longer hospital stays and generated higher medical costs compared to those without cardiovascular disease (21). Additionally, the risk of developing cardiovascular disorders in psoriatic patients increases with the severity of the underlying disease (17). Notably, the treatment of psoriasis can also modulate the cardiovascular risk profile, with tumor necrosis factor (TNF)-α inhibitors and methotrexate demonstrating beneficial effects (22).

Also, patients with psoriasis are at a higher risk of stroke than the general population, and a more severe course of the disease may increase this risk by 44% (23). A large Danish cohort study based on nationwide registries found that psoriasis is linked to an increased risk of atrial fibrillation (AF), one of the major AIS risk factors in the elderly, as well as to a severity-dependent increase in AIS risk (24). This relationship is complex and not fully understood. Nonetheless, psoriasis is associated with AIS not only through risk factors that are more common in patients with psoriasis but also through shared inflammatory pathways (16, 23). Moreover, endothelial dysfunction might represent a key mechanistic link between chronic systemic inflammation and the elevated cardiovascular risk in patients with psoriasis (25). Finally, in a study by Gelfand et al., the increased risk of stroke was present regardless of the treatment used, whether it potentially increased it, like oral retinoids, or theoretically reduced it, such as methotrexate (26). Figure 1 summarizes the multifaceted connection between psoriasis and AIS.

This narrative review aims to summarize the scientific literature and provide a comprehensive overview of the current understanding of the link between psoriasis and AIS, highlighting the potential role of the inflammatory pathomechanism underlying psoriasis in contributing to AIS incidence. It also explores psoriasis connection to traditional AIS risk factors.

A comprehensive literature search was conducted using the PubMed and Google Scholar databases, covering studies from their inception to 5 February 2025. Both experimental and clinical studies were analyzed. A review of the current literature on the relationship between psoriasis and AIS identified key areas to be explored in this review. The pathophysiology of psoriasis and its role in systemic inflammation is discussed, as is the contribution of inflammation as a risk factor for AIS. Also, the analysis extends beyond inflammatory pathways to examine the role of psoriasis-associated comorbidities in stroke development. Titles and abstracts were searched for key terms such as ‘psoriasis’, ‘systemic inflammation’, and ‘acute ischemic stroke’. However, the major limitation of this review is the predominance of observational and cross-sectional studies, which by design, are unable to establish temporal relationships or causality. These studies are prone to a variety of biases, including selection bias. Moreover, the lack of randomized or longitudinal data limits causal inference and underscores the need for more rigorous prospective studies to validate the associations described in this paper. To ensure comprehensive coverage, relevant references from identified articles were also manually reviewed. However, articles written in languages other than English and papers not published as full scientific papers, such as conference abstracts, were excluded from our search to ensure the relevance of the review. The literature search was conducted independently by three authors (PO, KK, RPP) in January and February 2025.

Psoriasis is a chronic systemic inflammatory disease that primarily affects the skin and involves uncontrolled epidermal hyperproliferation and differentiation of keratinocytes (27). Its pathogenesis involves dysregulation of the immune system. The pathogenesis of plaque psoriasis can be divided into an initial phase, which can occur spontaneously or might be potentially caused by trauma, drugs or infection, and a maintenance phase driven by the immune response via different T cell subsets (27, 28). The interleukin (IL)-23/IL-17 axis has been identified as the central cytokine network that drives disease (27). IL-17 binds to its receptor on keratinocytes and induces the production of keratinocyte antimicrobial peptides (AMPs). The most studied psoriasis-associated AMPs include LL-37, β-defensins, and S100 proteins (29). AMPs are typically overexpressed in psoriatic skin (28, 30), and they play a key role in the activation of plasmacytoid dendritic cells (pDCs), which promotes myeloid dendritic cells (mDCs) maturation (28, 30). Activated mDCs migrate to draining lymph nodes and secrete TNF-α, IL-12, and IL-23, leading to the proliferation of Th1 and Th17 cell subsets and secretion of inflammatory cytokines such as TNF-α, IL-17, IL-21, and IL-22 (28, 30). Th17 cytokines, namely IL-17, IL-21, and IL-22, activate keratinocyte proliferation in the epidermis; activated keratinocytes produce antimicrobial peptides, cytokines, and chemokines, thereby strengthening the IL-23/IL-17(A) axis (28, 30).

TNF-α, IL-17 and IL-23, are the key cytokines driving psoriasis, contributing to epidermal hyperproliferation and inappropriate keratinocytes differentiation, vascular angiogenesis and inflammatory cell infiltration (31–34). Epidermal hyperproliferation leads to acanthosis (thickening of other epidermal layers), hyperkeratosis (thickening of the stratum corneum), and accelerated cell turnover: keratinocytes retain their nuclei in the stratum corneum (parakeratosis) whereas normally they lose their nuclei in the stratum granulosum (35). This disruption of programmed keratinocyte differentiation results in a markedly thin or absent stratum granulosum (35). Cytokines (TNF-α, IL-17) stimulate the production of vascular endothelial growth factor (VEGF) and endothelial cells, leading to the proliferation of new capillaries (36, 37). VEGF levels are elevated in psoriatic plaques (36, 37). Inflammation results from the infiltration of neutrophils into the epidermis and superficial dermis and an infiltration of T lymphocytes into the dermis, with a predominance of CD8⁺ cells (29). IL-17A and IL-17F are two of several cytokines, capable of attracting neutrophils to the site of inflammation. LL-37, an AMP, is one of two well-studied T cell autoantigens in psoriasis (29). CD8⁺ T cells activated by LL-37 exhibit epidermotropism, recognize autoantigens, and secrete Th17 cytokines (38). Different pathomechanisms are associated with different psoriasis subtypes (38). While the TNFα–IL23–Th17 axis plays a central role in T cell-mediated plaque psoriasis, the innate immune system appears to play a more prominent role in the pustular variants of psoriasis (38). In guttate psoriasis, streptococcal superantigens are thought to stimulate the T cells expansion in the skin (39).

It is now well established that psoriasis is not merely a disease of a single organ; rather, inflammatory cytokines generated during its development and progression contribute to systemic inflammation affecting the entire body (15). Although reported results vary, it is generally assumed that serum levels of proinflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17A, IL-18 and IL-22, are elevated in patients with psoriasis and correlate with disease severity (40–43). Interestingly, Arican et al. reported no statistical difference in IL-17A levels between controls and patients with psoriasis (40), although this is a Th1- and Th17-mediated disease (44). In psoriasis, T cells are primarily stimulated by DCs, which are abundant in the skin. Activated T cells are responsible for the production of such cytokines as TNF-α, IFN-γ, IL-17, and IL-22 (44–46). Moreover, DCs themselves produce other cytokines, such as TNF-α and IL-20, as well as inducible nitric oxide synthase (iNOS), which is responsible for subsequent innate immune responses (44–46). All inflammatory mediators are produced locally in the skin lesions, but they are also released into the bloodstream, resulting in chronic systemic inflammation that may affect the entire body (illustrated in Figure 2) (44). Dowlatshahi et al. investigated serum levels of inflammatory markers in patients with psoriasis. The meta-analysis revealed that five out of the six investigated pro-inflammatory markers studied were elevated compared to healthy controls (IL-6, C-reactive protein (CRP), intracellular adhesion molecule (ICAM)-1, E-selectin, TNF-α). No differences were found for the pro-inflammatory IL-1β and the anti-inflammatory IL-10 (47).

Many comorbidities have been identified in patients with psoriasis, resulting from systemic inflammation, which, may, in turn, impact psoriasis progression (44). Hypertension, cardiovascular disease, metabolic syndrome, fatty liver disease, diabetes mellitus, inflammatory bowel disease, psoriatic arthritis and others, most of which are Th17 and/or TNF-α dependent, have been reported in patients with psoriasis (15, 48, 49). Pro-inflammatory cytokines are known to be involved in the pathophysiological mechanism of the above diseases, indicating the contribution of systemic inflammation to the dysfunction of many organs (15, 49, 50).

Arterial inflammation is a recognized feature of psoriasis (49). The formation of initial non-calcifying atherosclerotic plaque and endothelial inflammation has been observed, with the involvement of IL-6, IL-17 and TNF-α, whose levels are elevated in psoriasis, being postulated (49, 50). Cellular contribution involves T cells (Th1 and Th17) and neutrophils, and the influence of platelets has been observed (51). There is growing evidence highlighting the importance of Th17-dependent responses. Th17 cells present in atherosclerotic coronary arteries isolated from human patients produce IL-17 and IFN-γ, both of which are responsible for inducing the immune response in the vessel smooth muscles and further neutrophil infiltration (51). The involvement of Th17 cells in atherosclerotic plaque development has also been confirmed in ApoE−/− mice (52). Moreover, the number of Th17 cells was even increased in late-stage plaques. The effect was suppressed by the administration of IL-17 neutralizing antibodies to the mice (52). IL-17 neutralizing antibodies also increased plaque stability in ApoE−/− mice (53). Innate immune cells such as neutrophils, monocytes and macrophages are also found both in psoriatic and atherosclerotic plaques, leading to overall disease exacerbation (54). Similarly, platelet engagement as a source of immune mediators is observed in both diseases (54). Moreover, increased platelet aggregation has been observed in psoriasis patients, which may contribute to cardiovascular disorders (55). Proinflammatory cytokines, IL-6 and TNF-α, which are elevated in patients with psoriasis, are also involved in the stimulation of prothrombotic factors that may result in thrombosis (44).

As elevated levels of proinflammatory cytokines in systemic inflammation lead to blood–brain barrier (BBB) opening and subsequent immune infiltration into the central nervous system (CNS) (56, 57), this mechanism may also occur in CNS vasculature.

Chronic infections as well as systemic autoimmune inflammatory conditions have been linked to AIS (5, 58). Low-grade systemic inflammation, which is one of the characteristic features of psoriasis (15), is widely recognized as a triggering factor for atherosclerosis progression and plaque destabilization (59). Patients with psoriasis exhibit elevated levels of CRP compared to healthy individuals (47, 60). Moreover, patients with severe disease course, as indicated by the Psoriasis Area Severity Index (PASI) > 10, showed significantly higher levels of CRP than those with mild disease (60). Finally, CRP levels were significantly higher in patients with psoriasis and metabolic syndrome compared to those without (60). CRP is known to be associated with an increased risk of stroke incidence (61), which highlights the link between systemic inflammation and stroke. Moreover, IL-17A, the key pathophysiological driver of psoriasis (62), also contributes to the pathological process of AIS (63). Although the role of Th17 cells and IL-17 in the pathogenesis of AIS is not fully understood, research suggests that they may be involved in the development of atherosclerosis (63, 64). Psoriasis-related inflammation is also associated with endothelial activation, as evidenced by significantly increased levels of sICAM-1 in patients with psoriasis compared to controls (65). Additionally, there is evidence of platelet activation in these patients, as demonstrated by significantly elevated concentrations of sP-selectin (following adjustments for age and gender) compared to controls (65). Ultimately, all of the above link psoriasis to an altered coagulation profile, characterized by an increased likelihood of blood clot formation, as proven by thromboelastography (65). In a study by Zhao et al. over 55% of 267 patients with psoriasis had elevated fibrinogen levels (66). However, Marongiu et al. found no significant differences in fibrinogen levels between psoriasis patients and controls (67). Nonetheless, scanning electron microscopy shows fibrin clots in psoriasis patients to be denser than in healthy controls, with a larger fibrin fiber diameter associated with the disease (65). Additionally, elevated fibrinogen levels are linked to an increased risk of AIS (68).

Patients with psoriasis might face complications directly related to both chronic systemic inflammation and those associated with elevated higher prevalence of metabolic syndrome (69). Metabolic syndrome is an umbrella term that can be described as a concomitance of traditional cardiovascular risk factors, including obesity, insulin resistance, atherogenic dyslipidemia and hypertension (70). According to a recent study by Almenara-Blasco et al., obesity, dyslipidemia, and diabetes mellitus are among the most common comorbidities in patients with psoriasis (71). These are major risk factors for AIS, which are also interrelated. For instance, central obesity, which is common in AIS patients, is significantly associated with diabetes mellitus (72). Thus, the metabolic syndrome is a self-perpetuating group of pathologies in which insulin resistance and chronic low-grade inflammation create a vicious cycle that exacerbates disease progression and increases the risk of developing diabetes mellitus and cardiovascular complications (73).

The research consistently emphasizes the association between psoriasis and AIS (24). A more severe psoriasis course also correlates with a higher risk of stroke (24, 26, 122). Therefore, effective disease management seems to be crucial in mitigating these risks. On the other hand, it is important to note that some psoriasis treatments may also increase the risk of AIS (123). According to a large, nationwide population-based case–control study in Taiwan, treatment of psoriasis and/or psoriatic arthritis with cyclosporine, non-steroidal anti-inflammatory drugs (NSAIDs), or glucocorticoids was associated with an increased risk of hypertension (124). NSAIDs, including both cyclooxygenase 2-selective and nonselective medications, are known to be related to increased risk of cardiovascular events (125), whereas current glucocorticoids usage elevated the risk of 30-days mortality following AIS (126). Also, cyclosporine might increase the risk of AIS due to its hypertensive effects, though, to date evidence is insufficient to establish direct link between cyclosporine and AIS risk (127). Interestingly, cyclosporine was analyzed in AIS as an additional therapy to intravenous thrombolysis, however it did not significantly affect 30-day infarct volume compared with thrombolysis alone (128). Moreover, retinoids, including acitretin, one of the most commonly used drugs for the treatment of generalized pustular psoriasis (123), are typically associated with dyslipidemia (123, 129). Additionally, over 30% of patients treated with retinoids may experience abnormalities in their triglyceride levels (129), which elevates the risk of AIS by triggering atherosclerosis, thrombosis and increasing blood thickness (130). Ahlehoff et al. conducted a large study using a Danish nationwide cohort to assess the influence of systemic anti-inflammatory agents on the risk of cardiovascular events in patients with severe psoriasis. Interestingly, over a five-year follow-up period, methotrexate was associated with a reduced risk of cardiovascular death composite outcomes, myocardial infarction, and stroke compared with other therapies (131). Furthermore, treatment with TNF-α inhibitors was associated with a significant reduction in cardiovascular risk compared with other therapies, including the interleukin-12/23 inhibitor (i.e., ustekinumab) (131). A study by Wu et al. compared 9,148 patients with psoriasis treated with TNF-α inhibitors and 8,581 patients treated with methotrexate (132). The findings indicate that treatment with TNF-α inhibitors (i.e., adalimumab, etanercept, infliximab) reduced the risk of stroke and transient ischemic attack by almost 50%, compared to treatment with methotrexate (132). Furthermore, the treatment of psoriasis with TNF-α inhibitors may also have beneficial effects on the development of atherosclerosis and components of the metabolic syndrome, such as improving endothelial function, reducing the risk of diabetes mellitus, and improving insulin sensitivity (132). However, some studies have shown that TNF-α inhibitors are associated with an increase in body weight and body mass index in patients with psoriasis (123). In addition to TNF-α inhibitors, biological treatments for psoriasis include anti-IL-17 agents such as secukinumab, and no increased incidence of major cardiovascular events has been reported with these treatments (123). Moreover, given the association of IL-17 with AIS risk factors (115, 116), anti-IL-17 medications represent an interesting therapeutic option for the prevention of cardiovascular events. Thus, further research is needed to investigate this association (133).

In conclusion, when initializing systemic psoriasis treatment, it is crucial to consider cardiovascular safety, including baseline risk factors. Treatment with methotrexate and TNF-α inhibitors appears to be the most effective in reducing cardiovascular events in patients with psoriasis (134). Additionally, effective control and management of concomitant risk factors are crucial for optimal outcomes (23). Finally, newly developed treatments need to be carefully analyzed for their cardiovascular risk profile to ensure that they do not inadvertently increase the risk of these events, including AIS.

Psoriasis is a common disease worldwide and has been recognized as a systemic inflammatory condition rather than solely a cutaneous disorder. Psoriasis shares pathophysiological pathways with AIS, including inflammatory mechanisms and a higher incidence of traditional cardiovascular risk factors in patients with psoriasis. As a result, both mild and severe psoriasis are recognized as independent risk factors for stroke (26). Moreover, the risk of stroke is influenced not only by the disease itself and its pathological processes but also by the medications used to treat psoriasis, which may increase AIS incidence in this population. Thus, psoriasis is increasingly acknowledged as an emerging risk factor for AIS alongside other systemic inflammatory diseases. Nevertheless, longitudinal studies are warranted to establish causal relationships between these conditions. As foregoing studies based on observational and cross-sectional data, can overestimate the strength of the association between psoriasis and AIS. Finally, studies reporting positive or statistically significant links are more susceptible to be published than those with negative results.