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Comorbidities


Predisposition – Heredity


– Antigen-presenting cell/T-cell defect Obesity


Adipose tissue produces: – TNF-a, IL-6, IL-1b, PGE2 – Leptin Adiponectin => Modulation of immune cell function


+ Free fatty acids


Plasminogen activator inhibitor


– Serum amyloid A – CRP


– Fibrinogen Liver


=> acute phase reactants


Fibinogen Prothrombic state


Atherosclerotic vascular disease


All-cause mortality


Figure 1: Potential mechanisms for the association between psoriasis and comorbidities. CRP: C-reactive protein; IFN: interferon; IL: interleukin; TNF-a: tumour necrosis factor-a; PGE2: prostaglandin E2. Readapted and modified from Gottlieb et al 20082


a severe manifestation of psoriasis has been shown to shorten lifespan, according to studies.


Depression and quality of life In a case-control study of 3147 patients with psoriasis, who were matched for age and gender, and 3147 controls without psoriasis, psoriasis was associated with increased rates of depression (OR: 1.49; 95% CI: 1.20–1.86), stress-related disorders (OR: 1.41; 95% CI: 1.22–1.62), and behavioural disorders (OR: 1.58; 95% CI: 1.05–2.39).12


Consistently, in a


large questionnaire-based study of 2391 patients with psoriasis, symptoms of depression were reported by 62%.13 Studies were able to show that psoriasis is associated with profound psychiatric morbidity.


Malignancy


Studies have found a greater overall incidence of cancer among patients with psoriasis.2


For example, in a study of


6905 patients with psoriasis, the standardised incidence ratio for all malignancies was 1.4-times higher (95% CI: 1.21–1.51; p<0.05) than the general population, mainly due to cancer of the skin, lung, pharynx and larynx.14


to be more prevalent among psoriasis patients. In a large population-based cohort study that compared 153,197 patients with psoriasis to 765,950 corresponding subjects without psoriasis, an increased risk for all lymphomas (HR: 1.35; 95% CI: 1.17– 1.55), Hodgkin’s lymphoma (HR: 1.48; 95% CI: 1.05–2.08), and a substantial increased risk for cutaneous T-cell lymphoma (HR: 4.34; 95% CI: 2.89– 6.52) was observed in the patients with


“Studies have found a greater overall incidence of cancer among patients with psoriasis”


psoriasis.16 Other studies were also able


to find an increased risk for oral cavity, pharynx and neck malignancies, which could, however, be related to the higher rate of alcohol consumption and smoking in patients with psoriasis.2 Longer-term psoriasis and more severe disease may increase the risk of some cancers.2


Another


population-based study found a slightly greater overall incidence of cancer among patients with psoriasis (incidence ratio 1.13, 95% CI: 1.02–1.24).15 Lymphomas have also been recognised


Taken together, patients with psoriasis seem to have a higher risk of cancer: especially skin cancer, cancer along the airway (lung, pharynx and larynx), and lymphomas. This could be due to either the effects of therapies, the


lifestyle factors (higher rate of smoking and alcohol consumption), or because of the psoriasis itself as a chronic inflammatory disease.


Lifestyle factors In some studies, patients with psoriasis showed approximately twice the risk of smoking cigarettes or alcohol misuse compared with the general population.2,10 There is evidence that smoking and alcohol misuse is more prevalent in psoriatic patients.


Potential mechanisms for comorbidities


The chronic systemic inflammatory state associated with psoriasis generates elevated proinflammatory cytokines and acts likely in concert in predisposing patients with psoriasis to increased risk of cardiometabolic diseases, cancer and probably also reduced life quality (depression, fatigue) (Figure 1). It is well known that excess adipose tissue produces proinflammatory cytokines and hormones, such as IL-1, IL-6, TNF-a, leptin, and free fatty acids. This plays a central role in the development of metabolic syndrome, by inducing metabolic changes including dyslipidaemia, and insulin resistance, which might also promote the chronic systemic inflammatory state associated with psoriasis. The proinflammatory cytokines and free fatty acids act on the


www.hospitalpharmacyeurope.com HDL LDL TGI VLDL


Depression Fatigue


Quality of life


Chronic systemic inflammation (CRP, TNF-a, IL-6 leptin, adipoectin, etc)


Local and systemic proinflammatory state IFN-a, TNF-a and other type 1-cytokines in skin, joints and blood


Manifestation


– Immune factors – Environmental factors


Psoriasis


Metabolic syndrome – Dyslipidaemia – Insulin resistant – Hypertension


Cancer Smoking, alcohol abuse


13


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