Psoriasis is defined as a chronic, relapsing, inflammatory skin disease. However, it is not limited only to the skin, considering there is a wide range of comorbid conditions associated with psoriasis, including cardiovascular disease, obesity, diabetes, arterial hypertension, dyslipidemia, and metabolic syndrome, which have been found at a higher prevalence in patients with psoriasis compared to the general population. The aim of this review is to present the most significant cardiovascular and metabolic disorders in this subset of patients, as well as to present the role of cardiac medications, especially beta-blockers, in development and aggravation of psoriasis.

Multiple epidemiological studies have found psoriasis to be associated with comorbidities that increase the risk of cardiovascular disease, including hypertension, diabetes, dyslipidemia, and obesity (1-13). The concept of the so-called “psoriatic march” has been suggested in order to describe these relationships. These conditions occur as a result of accelerated atherogenesis and endothelial dysfunction (9, 14-17). Although the underlying pathophysiological mechanism has still not been fully elucidated, it seems that increased cardiovascular disease risk may be linked to the common pathogenic mechanisms in psoriasis and atherosclerosis (7, 8, 14, 18). Chronic inflammation plays a major role in both of these conditions, mainly through increased levels of proinflammatory cytokines and immunological mediators that cause oxidative stress and free radical production (2, 11, 14, 19-27). Furthermore, systemic inflammation causes insulin resistance, which results in reduced release of vasodilating factors such as nitric oxide and triggers endothelial cell dysfunction, which along with the accelerated atherosclerosis subsequently lead to complications such as myocardial infarction or stroke (26, 28, 29). In addition, elevated activity of the renin-angiotensin system in patients with psoriasis also contributes to the development of hypertension (25, 30). Other than the possible pathophysiological mechanisms mentioned above, due to the high psychological burden and substantial impairment of quality of life, patients with psoriasis tend to lead an unhealthy lifestyle including poor dietary habits, smoking, physical inactivity, and excessive alcohol consumption, which can also partly explain a higher prevalence of cardiovascular disease and metabolic syndrome in these patients (2, 21, 22, 31).

Metabolic syndrome (MS), which is comprised of several cardiovascular disease risk factors such as hypertension, abdominal obesity, glucose intolerance, and dyslipidemia, shows high association with psoriasis (2, 4, 21-23, 25, 32-36). This relationship seems to be particularly pronounced after the age of 40 (2). As opposed to a strong correlation between severity of skin lesions and cardiovascular risk, the relation between disease severity and MS is not so signficant (2, 21, 24, 35). However, there seems to be a strong relationship between greater duration of psoriasis and early onset of the disease (21, 35).

Considering numerous cardiovascular risk factors which are present in psoriasis, epidemiological reports and studies show that this group of patients have increased prevalence of ischemic heart disease, peripheral vascular disease, cerebrovascular disease, type II diabetes, hypertension, and hyperlipidemia compared with the general population, indicating an increased risk of cardiovascular morbidity as well as mortality related to cardiovascular events (2, 34, 36-40). A large amount of evidence shows that psoriasis is an independent risk factor for myocardial infarction and cardiovascular mortality, particularly at a younger age (5, 29, 37, 38, 41). In addition, the severity of clinical symptoms is associated with increased mortality in patients with psoriasis, suggesting that occurrence of cardiovascular complications may be restricted to the severe form of psoriasis (6, 19, 29, 37, 38, 41, 42).Longer duration of the disease is also associated with higher cardiovascular risk (5, 15, 40). Therefore, early suppression of disease activity as well as annual evaluation of cardiovascular risk and regular follow-up are recommended for all patients with psoriasis, particularly those with severe clinical forms (7, 8, 15, 24, 36, 40, 43, 44). Some research suggests that systemic treatment of psoriasis using biologic drugs or methotrexate may affect cardiovascular outcomes, reducing long-term cardiovascular risk (5, 29, 42, 45-49). Furthermore, educating patients on healthy lifestyle habits including weight loss, healthy diet, regular physical activity, and smoking cessation are vital to reduce cardiovascular risk factors (50).

Studies evaluating adverse drug reactions associated with antihypertensive drugs indicate that psoriasiform eruptions are among the most common reactions associated with this group of agents. Beta-blockers are cardiac drugs most frequently associated with the induction/exacerbation of psoriasis, although calcium-channel blockers and angiotensin-converting-enzyme inhibitors (ACE inhibitors) have been described as triggering drugs as well (51-64). Beta blockers are drugs that have been widely used in the management of angina pectoris, arrhythmia, heart failure, and hypertension. Although these agents have a good safety profile, beta-blockers are commonly identified as possible triggering factors for psoriasis. The underlying pathophysiological mechanism of this association is still unknown, although a possible explanation could be blockage of epidermal beta(2) receptors, leading to a decrease in intraepidermal cAMP (3'-5'-cyclic adenosine monophosphate), which is important for cellular differentiation and inhibition of proliferation, consequently causing accelerated proliferation of keratinocytes (51, 62, 63). Depending on the duration of beta-blocker therapy, onset of symptoms can vary greatly, from several days to up to 16 months after initiation of beta-blocker therapy (52, 63). This long latency period can cause difficulties in identifying psoriasiform eruption as a possible drug adverse event, since the majority of drug induced reactions tend to occur soon after drug exposure.

Although clinical presentation includes a broad spectrum of symptoms and almost all clinical types of psoriasis, psoriasis provoked or aggravated by beta-blockers tends to be clinically different from chronic psoriasis vulgaris (the most common type): skin lesions are less red and scaly and erythematosquamous plaques are not so thick. Moreover, these skin lesions rarely affect typical localizations, such as knees, elbows, and low back, which are typically affected in psoriasis (56) (Figure 1). Rare clinical types and more severe forms of psoriasis are more frequently seen, including pustular psoriasis (presence of pustules on erythematous and scaly plaque), palmoplantar psoriasis (erythematosquamous lesions localized on the palms of hands and soles of feet), erythroderma, or generalized psoriasis (63) (Figure 2). It should be noted that all of these clinical manifestations are dose independent.

In patients using beta-blocker therapy presenting with sudden onset of psoriasis or aggravation of preexisting psoriasis, these medications should always be taken into consideration as possible triggers, particularly in cases when there is simultaneously inadequate therapeutic response to conventional therapy for psoriasis. In these cases, beta-blocker therapy should be discontinued, at least for a short period of time, since the consequent regression of skin lesions will have not only therapeutic but a diagnostic value as well, suggesting that psoriasiform eruption had developed due to beta blocker therapy (56). Patients should be advised to avoid excessive sun exposure, alcohol, smoking, trauma, and stress, as these factors can worsen the clinical course of psoriasis. In terms of identifying this adverse reaction and offending drug, diagnosis can be truly challenging, especially for the subset of patients with a positive personal or family history of psoriasis, in whom progression of skin lesions can be observed even after cessation of the drug (51, 53, 63). However, for the majority of cases, discontinuation of beta blocker therapy will contribute to clinical improvement, and rapid resolution of the skin lesions can be observed within a few days to weeks after stopping the offending drug (51, 63, 64).

Patients with psoriasis exhibit numerous comorbidities, including metabolic syndrome and cardiovascular disease, which substantially reduce patient life expectancy and significantly contribute to morbidity and mortality. Numerous studies suggest that patients with psoriasis, particularly those with moderate to severe psoriasis, should be monitored for cardiovascular risks in order to prevent or to slow cardiovascular disease progression and improve health outcomes.

In conclusion, to fully address the medical needs of patients with psoriasis, their comorbidities must be acknowledged and recognized, and patients need to be routinely screened for cardiovascular risks and managed appropriately. Furthermore, clinicians must be aware that antihyprtensive medications, particularly beta-blocker agents, might induce or aggravate psoriasis. Considering these medications may be necessary for managing the patient's cardiovascular function, it is difficult to give general algorithms of management in terms of cessation of therapy. Therefore, the decision on the withdrawal of beta-blocker therapy and converting to an alternative antihypertensive agent must be based upon an individual benefit-risk ratio.