Psoriasis as a systemic disease
Section snippets
Epidemiologic data
It has been observed epidemiologically that the frequency of some noncutaneous diseases and conditions is significantly increased in psoriasis.5 One report divides comorbidities into two groups.6 The first group includes diseases that are pathogenetically associated with psoriasis, such as psoriatic arthritis, CD, and pustular dermatoses. The second group includes diseases such as metabolic syndrome and cardiovascular diseases (CVD) that are associated with psoriasis through its severe chronic
Psoriasis and psoriatic arthritis
The prevalence rate of psoriatic arthritis in general population is estimated to 0.25%,8 although it is reported to be between 5% and 48% among patients with psoriasis.9., 10., 11. These results demonstrate that the prevalence rate of arthritis in patients with psoriasis may actually be higher than the previously accepted rate of 7%.12
Psoriasis and CD
Prevalence of psoriasis among patients with CD is higher than in the general population. Results from five independent case–control studies reveal that 9% of patients with CD have psoriasis versus 1.4% of the control subjects.13 In addition, families with psoriasis or CD have an increased risk for development of the other disease. Another study shows that 10% of patients with CD have a first-degree relative with psoriasis compared with 3% of the control subjects.14
Psoriasis and CD also have a
Psoriasis and metabolic syndrome
Metabolic syndrome has been identified as a clustering of metabolic abnormalities in individuals and is associated with an increased risk for type 2 diabetes and CVD.17 The most recent definition of metabolic syndrome requires central obesity (body mass index > 30 kg/m2) and any two of the following abnormalities: elevated plasma triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and raised fasting plasma glucose.18
In a study comparing 625 hospitalized
Psoriasis and CVD
It has been more than 35 years since McDonald et al.26 reported that rates of occlusive vascular diseases such as thrombophlebitis, myocardial infarction, pulmonary embolism, and cerebrovascular incidents were significantly higher in patients with psoriasis than in those without psoriasis. Since then, substantial data have been accumulating on the association between psoriasis and CVD.27., 28., 29. Psoriasis has been found to be an independent risk factor for myocardial infarction, stroke,
Impact of psoriasis onset and severity
A cohort study among 8991 hospitalized patients with psoriasis and 19,757 ambulatory patients with psoriasis was conducted.35 The authors found a 50% increased risk for CV mortality in hospitalized patients. The risk was positively associated with the number of hospitalizations and the earlier age of first hospitalization. In their large, population-based study among patients of the General Practice Research Database in the United Kingdom, investigators also demonstrated that young and severe
Psoriasis, alcohol, and smoking
Alcoholism and liver cirrhosis are reportedly more common in psoriasis, with a reported prevalence rate of alcoholism of 18% among patients with psoriasis compared with 2% in other dermatologic control patients.37 Alcohol consumption is positively correlated with psoriasis severity.38., 39. It is higher before psoriasis onset than it is before other skin disease onset and the increased alcohol consumption is sustained throughout the psoriasis course.40 Among hospitalized dermatologic patients,
Psoriasis and psychiatric/psychological diseases
The first reports on the impaired psychosomatic health of psoriasis patients date back to the 1960s of last century.44 The association between psoriasis and high depression scores, anxiety, obsessiveness, and difficulty in verbalizing emotions (especially anger) is well-known45; furthermore, an association has been reported between severe psoriasis and clinical depression and suicide ideation in 7.2% of hospitalized patients.46 This association was found in only 2.5% of outpatients, which is
Pathogenic mechanisms shared between psoriasis and comorbidities
Although epidemiologic studies have demonstrated an increased risk for adverse cardiac events among patients with psoriasis, they do not provide insight to the cause of this increased risk. The term march of psoriasis was first introduced by Boehncke et al.49 to describe the causal link that may exist between psoriasis and CVD (Figure 1).
The concept is that systemic inflammation associated with psoriasis enhances insulin resistance, causing endothelial dysfunction, subsequent atherosclerosis,
Common inflammatory molecules and pathways between psoriasis and CVD
T helper cells type 1 (Th1) and type 17 (Th17), and regulatory T cells (Tregs) play integral roles in psoriasis and atherosclerosis pathogenesis. In psoriasis, the disease cycle is perpetuated through Th1 cytokines (interferon [IFN]-γ, interleukin [IL]-2, and TNF-α), stimulated keratinocytes, as well as the production of more cytokines (TNF-α, IL-1, and IL-6) and chemokines.52., 53. The recruitment and localization of T cells to the dermis and epidermis are mediated through various adhesion
Common inflammatory molecules and pathways between psoriasis and obesity
Adipose tissue is an active endocrine organ with many secretory products. Leptin, an adipokine secreted by adipocytes, has been shown to participate in the pathogenesis of immune-mediated inflammatory diseases such as type 1 diabetes, RA, inflammatory bowel disease, and psoriasis.84 High levels of leptin in obese patients are associated with increased proinflammatory mediators that may lead to development of psoriasis.85
Adiponectin, another adipocyte-specific protein, was shown to inhibit TNF-α
Common inflammatory molecules and pathways between psoriasis and diabetes
Chronic inflammation in psoriasis leads to increased insulin-like growth factor II in the skin and blood of patients with psoriasis.89 Insulin-like growth factor II promotes epidermal proliferation and is also implicated in promoting atherosclerosis, in modulating body fat mass and lipid metabolism in mice, and is linked to diabetes and hyperlipidemia in animal and human models.90 Immunocytes and keratinocytes in psoriatic skin produce angiogenic factors, such as VEGF, which promote
Common inflammatory molecules and pathways between psoriasis and hypercoagulation
In psoriasis, thrombotic events could be triggered through established platelet activation.92 Activated platelets may exert a role in psoriasis pathogenesis by favoring leukocyte rolling in the skin microvasculature.93 In patients with psoriasis, there is a homeostatic misbalance toward a prothrombotic state, which might be sustained by platelet hyperactivity.94
Inflammatory markers in psoriasis, such as TNF-α, IL-1, and IL-6, can induce synthesis and release of acute-phase proteins, that is,
Common inflammatory molecules and pathways between psoriasis and hypertension
Angiotensinogen is the precursor of Angiotensin I, which, after conversion to Angiotensin II, has a major role in blood pressure regulation. It was shown that upon Angiotensin II stimulation, peripheral blood T cells are activated to produce TNF-α and IFN-γ, and to express tissue-homing receptors.96 Blocking TNF-α by etanercept normalized the blood pressure and vascular O2– production in Angiotensin II–infused animals.
Treatment data
Because there is strong evidence that psoriasis is an independent risk factor for the development of metabolic and CV comorbidities, the most important question is whether long-term control of psoriasis could prevent, reverse, or attenuate its comorbidities. An investigation into the effect of continuous systemic therapy found that patients who responded to therapy had significant correlations between psoriasis area severity index and high-sensitivity C-reactive protein, VEGF, and the
Cholesterol-lowering agents
A pilot study evaluated the effectiveness of simvastatin, which is a cholesterol-lowering statin, on serum lipoprotein levels and dermatitis in patients with severe psoriasis.98 The authors found increased high-density lipoprotein cholesterol levels and diminished psoriasis area severity index during the therapy, concluding that statins can correct lipid metabolism and reduce cutaneous lesions in psoriasis. A decreased risk for psoriasis associated with statin intake has been reported.99 Oral
Thiazolidinediones
Researchers studied the effect of pioglitazone in psoriasis.101 In 70 patients with moderate-to-severe disease, the psoriasis area severity index scores improved significantly in treated versus placebo patients with greater benefit being noted in those receiving higher doses of pioglitazone.101
Traditional systemic therapies for psoriasis
Traditional systemic therapies for psoriasis using methotrexate and cyclosporine may reduce the risk for CVD by decreasing inflammation.102 Treatment with methotrexate has been shown to be associated with decreased risk for CVD.103 The traditional treatments, however, are limited by the potential for adverse effects such as hypertension, dyslipidemia, hyperhomocysteinemia, and renal and hepatic toxicity.
Biologic agents
Novel investigations have focused on how biologics, used in psoriasis or RA, may affect patients’ CV risk factors and adverse cardiac outcomes. In a retrospective cohort, it was shown that the risk for diabetes was lower in patients with psoriasis starting a TNF-α blocker or hydroxychloroquine compared with those initiated on other disease-modifying antirheumatic drugs.104 Methotrexate initiation was not associated with any significant diabetes risk reduction. Compared with placebo, there was
Conclusions
Psoriasis is now considered a chronic, immune-mediated inflammatory disease presenting with skin lesions and development of comorbidities. Further investigation of the epidemiologic link between psoriasis and comorbidities should take into account various confounding factors. The proposed common pathways between psoriasis and comorbidities highlight the importance of treating psoriasis as a multifaceted disease and the need of regular screening of patients with psoriasis for CV risk factors.
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