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Comorbidities


liver to induce production of acute-phase reactants, including prothrombotic cytokines such as fibrinogen, and dyslipidaemia. These processes promote endothelial dysfunction and atherosclerosis, and together with the prothrombotic state, lead to an increased risk of cardio- or cerebrovasculatory events.17


The presence of a chronic


inflammatory state may also contribute to an increased rate of malignancy in patients with psoriasis, in addition to other factors such as the effects of


diseases in psoriatic patients.19 TNF-a antagonists might also, by decreasing levels of proinflammatory cytokines, have a beneficial impact on fatigue and symptoms of depression associated with psoriasis.2


5. Armstrong AW, Harskamp CT, Armstrong EJ. Psoriasis and metabolic syndrome: a systematic review and meta-analysis of observational studies. J Am Acad Dermatol 2013;68(4):654–62.


In a double-


blind treatment study on 618 patients with moderate to severe psoriasis receiving either placebo or 50mg etanercept twice a week, a greater proportion of patients receiving etanercept had at least a 50% improvement in depression at week 12 compared with the placebo group.


“Systemic anti-inflammatory therapies can also have a beneficial effect on comorbidities, especially on cardiovascular diseases”


immunosuppressive therapies and lifestyle factors (increased rate of smoking and alcohol misuse). This, together with the induced vascular changes, leads to an increased rate of mortality.2


14


Clinical studies have demonstrated that treatment with methotrexate and especially with TNF-a antagonists can have a beneficial impact on cardiovascular diseases. For example, in a cohort study of 2400 patients with severe psoriasis, age- and sex-adjusted HRs for cardiovascular disease event rates were 0.28 (95% CI: 0.12–0.64) and 0.65 (95% CI: 0.42–1.00) for patients treated with biological agents (>80% received TNF-a blockers) and methotrexate, respectively, using other therapies (retinoids, cyclosporin and phototherapy) as the reference cohort.18 In their review examining the impact of common psoriasis therapies on cardiovascular outcomes, Hugh et al19 concluded that, although there is not enough evidence to recommend therapies for psoriasis solely based on cardiovascular impact, methotrexate and TNF-a-inhibitors offer the best evidence of beneficial effects on cardiovascular


Effects of therapy on inflammation and associated comorbidities Given that psoriasis and its associated comorbidities share common inflammatory mechanisms, it could be suggested that therapies targeting the underlying inflammation may be effective in treating both psoriasis and these comorbidities. There is some evidence that this hypothesis could be true.2


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Patients receiving etanercept also showed significant improvements in fatigue (5.0 versus 1.9; p<0.0001, 95% CI: 1.6–4.5).20


evidence in this regard might become available in future for the newer immunomodulatory biologics.


Conclusions


The chronic systemic inflammatory state underlying psoriasis seems to be the central causal factor for most of the associated comorbidities. Some clinical studies were able to demonstrate that a systemic anti-inflammatory therapy, for example, anti-TNF-a blockers, can also have a beneficial impact on these comorbidities, especially on cardiovascular diseases. As


cardiovascular risk factors appear to be more strongly associated with severe psoriasis than with mild psoriasis, it could be recommended to develop a more differentiated view on the psoriatic patient group in order to choose the most beneficial therapeutic option. l


References 1. Gladman DD. Psoriatic arthritis. Dermatol Ther 2009;22(1):40–55.


2. Gottlieb AB, Chao C, Dann F. Psoriasis comorbidities. J Dermatolog Treat 2008;19(1): 5–21.


3. Neimann AL et al. Prevalence of cardiovascular risk factors in patients with psoriasis.J Am Acad Dermatol 2006;55(5):829–35.


4. Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes 2012;3;2:e54.


It remains to be seen what


6. Xu T, Zhang YH. Association of psoriasis with stroke and myocardial infarction: meta-analysis of cohort studies. Br J Dermatol 2012;167(6):1345–50.


7. Gelfand JM et al. Risk of myocardial infarction in patients with psoriasis. JAMA 2006;296(14):1 735–41.


8. Xiao J et al. Prevalence of myocardial infarction in patients with psoriasis in central China. J Eur Acad Dermatol Venereol 2009;23(11):1311–15.


9. Samarasekera EJ et al. Incidence of cardiovascular disease in individuals with psoriasis: a systematic review and meta- analysis. J Invest Dermatol 2013;133(10): 2340–6.


10. Gulliver W. Long-term prognosis in patients with psoriasis. Br J Dermatol 2008;159(Suppl 2):2–9.


11. Abuabara K et al. Cause-specific mortality in patients with severe psoriasis: a population- based cohort study in the U.K. Br J Dermatol 2010;163(3):586–92.


12. Schmitt J, Ford DE. Psoriasis is independently associated with psychiatric morbidity and adverse cardiovascular risk factors, but not with cardiovascular events in a population-based sample. J Eur Acad Dermatol Venereol 2010;24(8):885–92.


13. Esposito M et al. An Italian study on psoriasis and depression. Dermatology 2006;212(2): 123–7.


14. Frentz G, Olsen JH. Malignant tumours and psoriasis: a follow-up study. Br J Dermatol 1999;140(2):237–42.


15. Brauchli YB et al. Psoriasis and risk of incident cancer: an inception cohort study with a nested case-control analysis. J Invest Dermatol 2009; 129(11):2604–12.


16. Gelfand JM et al. The risk of lymphoma in patients with psoriasis. J Invest Dermatol 2006;126(10):2194–201.


17. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005;352(16):1685–95.


18. Ahlehoff O et al. Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti-inflammatory drugs: a Danish real-world cohort study. J Intern Med 2013;273(2):197–204.


19. Hugh J et al. From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies. J Am Acad Dermatol 2014;70(1): 168–77.


20. Tyring S et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double- blind placebo-controlled randomised phase III trial. Lancet 2006;367(9504):29–35.


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