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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Page 18 of 35

U pdates on Psoriasis and Cutaneous Oncology: Proceedings from the 2016 MauiDerm Meeting [ 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 ] 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 1 5 90mmHg) was more likely in patients with moderate-to- severe psoriasis than those with milder forms of psoriasis. 80 The severity of psoriasis also associated with aortic vascular inflammation beyond cardiovascular risk factors in an observational study of 50 psoriasis patients, mean age 47 years, low cardiovascular risk factors. 98 A 500,000 person-year study found that the risk of herpes zoster infection increased with combination systemic psoriasis therapy with a biologic, but did not increase when psoriasis was treated with phototherapy, methotrexate, cyclosporine, or a biologic alone. By the same token, systemic psoriasis treatment with acitretin decreased the risk of herpes zoster infection. 99 The risk of serious infection with biologic and systemic treatment of psoriasis was published with results from the PSOLAR registry. 100 Immunology. The association of genetic variants in the IL-23- and NF-κB-mediated inflammatory pathways appears to be different in mild versus severe psoriasis skin disease, such that the IL-23 genes (p19, p40, IL- 23R) and TNF genes (NFKB1, TNIP1) are associated with the more severe forms of psoriasis. 101 This suggests the value of phenotyping patients for long-term genetic studies. In a study of transgenic mice engineered to produce continuous low levels of IL-17A, the mice eventually developed psoriasis-like skin lesions in a process that could be accelerated with skin trauma. 102 An intriguing murine study was published in 2015 that is based on the observation that conventional αb T-cells can form long-lasting resident memory T-cells (TRM), related to a concept called "innate memory," where nonadaptive branches of the immune system can deliver rapid, intensified immune response upon re-infection or re-challenge. 103 This study identified a subset of gδ cells in mice capable of establishing long-lived memory in the skin. This finding may explain psoriasis recurrences in the same areas, namely areas where there are long-lived IL-17 producing cells. Small-molecule-mediated inhibition of the retinoic receptor-related orphan nuclear receptor g (RORg) t- dependent gene expression and autoimmune disease pathology was evaluated in vivo. RORgt is a transcription factor that regulates both IL-17A and IL- 17F production. An RORgt inhibitor selectively blocked IL-17A/F production and improved psoriasis-like disease in mice, 104 making it a potentially relevant target for future drug development. This novel drug is in early phase development for potential application in psoriasis treatment. In another in vitro (human and murine cells) and in vivo study, cells were genetically engineered to detect high levels of pro-psoriatic cytokines, TNF and IL- 22, and respond to them by turning on the production of TABLE 7. A selection of some of the most important reviews from 2015 relating to psoriasis and its treatment REVIEW FINDINGS OF NOTE European League Against Rheumatism, Gossec et al 106 New treatment guidelines issued for psoriatic arthritis: (1) NSAIDs, (2) methotrexate, (3) TNF blockers, (4) ustekinumab/secukinumab/apremilast Updated pharmacological recommendations Effects of TNF inhibitors, methotrexate, NSAIDs, and corticosteroids on CV events in R A, psoriasis, and psoriatic arthritis, Roubille et al 77 In RA patients, TNF blockers and methotrexate are associated with decreased MACE risk, but not in psoriasis o r psoriatic arthritis patients Emerging information in CV comorbidities; systematic review and meta-analysis Rationale for using biologics in moderate-to-severe psoriasis 107 The role of biologics as "gold standard" in moderate-to- severe psoriasis Addressed to non-biologic users IL-23/IL-17A dysfunction phenotypes 108 These phenotypes may inform possible clinical effects of IL-17A therapies Offers insight into the biologic basis of possible side effects of anti-IL-17 therapy Ixekizumab 109 Comprehensive review of the newest biologic for treating psoriasis FDA approval imminent at time of publication CV=cardiovascular

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