Journal of Clinical and Aesthetic Dermatology

Psoriasis and Cutaneous Supplement 2016

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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S 1 2 S U P P L E M E N T T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y [ S E P T E M B E R 2 0 1 6 • V O L U M E 9 • N U M B E R 9 ] affected), and severe (>10% of BSA affected). 44 These three groups accounted for 51.8, 35.8, and 12.4 percent of the psoriasis patients, respectively. Using the Charlson Comorbidity Index (CCI), it was found that the CCI score was higher in patients with psoriasis than without (p<0.05), and trend analysis demonstrated that the severity of psoriasis was associated with an increasing number of serious comorbidities (p<0.05). Rheumatoid arthritis (RA) is widely recognized to be associated with cardiovascular morbidity, and is a chronic inflammatory disease that responds to similar treatments for psoriasis, such a methotrexate and TNF inhibitors. Therefore, it makes a useful comparison in contextualizing psoriasis comorbidities. In a longitudinal cohort study in the United Kingdom, patients with psoriatic arthritis (n=8,706), RA (n=41,752), and psoriasis (n=138,424) were compared to control patients (n=82,258) for a total of 1,442,357 person years. Psoriasis and RA were associated with an increased risk of mortality, but psoriatic arthritis was not associated with greater mortality. 64 In a population-based study (n=4,196 subjects with psoriatic arthritis, n=59,281 subjects with psoriasis, and n=11,158 subjects with RA), the incidence of diabetes was greater in patients with psoriasis, psoriatic arthritis, but not RA, compared to the general population. 65 The findings suggest that more severe psoriasis has similar rates of excess MACE events and mortality compared to RA treated with similar systemic drugs, but that psoriasis is more specifically associated with diabetes, whereas RA is not (Figure 1 64–66 ). New pediatric data suggest that metabolic problems associated with psoriasis emerge early. Among pediatric patients, metabolic syndrome occurs in 30 percent of psoriasis patients versus 7.4 percent of controls (p<0.05). 67 Pediatric psoriasis patients are more likely to be obese than similar control patients 68 and their lipoprotein profile is more atherogenic. 69 Metabolic and cardiovascular gene expression have been associated with inflammatory disease categories in lesional and nonlesional psoriasis biopsies, providing new mechanistic insights into psoriasis comorbid with cardiometabolic disorder. In a murine model, KC-Tie2 psoriasis-specific skin inflammation was associated with the development of aortic inflammation and thrombosis. 70,71 This raises the intriguing question as to whether or not the aggressive treatment of psoriasis might lower the patient's risk of cardiovascular disease. Observational data suggest that psoriasis patients treated with methotrexate and TNF inhibitors (similar data are not yet available for phototherapy, apremilast, ustekinumab, or secukinumab) have a lower rate of cardiovascular events. 72–76 This aligns with a meta-analysis in patients with RA, psoriatic arthritis (PsA), or psoriasis treated with TNF inhibitors or methotrexate, which found a relative risk for all cardiovascular adverse events was 0.70 for TNF inhibitors and 0.72 for methotrexate, indicating a cardioprotective effect. 77 In a five-year study of 6,902 patients with severe psoriasis, methotrexate and TNF inhibitors were associated with significantly lower rates of cardiovascular events (hazard ratio [HR] 0.52 and 0.46, respectively) than other anti-psoriasis treatments (HR 0.58, 1.06, 1.80, and 1.52 for biologics, cyclosporine, retinoids, and ustekinumab, respectively). 78 Two ongoing randomized clinical trials are further studying the potential impact of psoriasis treatment on cardiovascular risk. The Vascular Inflammation in Psoriasis Trial (VIP) and VIP-Ustekinumab are studying whether the treatment of moderate-to-severe psoriasis with adalimumab or phototherapy will lower vascular inflammation and improve lipid metabolism. The Cardiovascular Inflammation Reduction Trial (CIRT), TABLE 5. Adverse comorbid outcomes associated with mild and severe forms of psoriasis 45–47,61,63 OUTCOME RISK RATIO MILD PSORIASIS SEVERE PSORIASIS Myocardial i nfarction 1.05 1.5 Stroke 1.06 1.4 Cardiovascular death * 1.6 Major adverse cardiac event * 1.5 Diabetes 1.11 1.5 *These evaluations are not available. Figure 1. The risk for diabetes, cardiovascular death, or all-cause mortality in patients with psoriasis or rheumatoid arthritis taking a disease-modifying antirheumatic drug (DMARD) is shown. The use of a DMARD is thought to indicate patients with a more severe form of the disease. 64–66

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