Exploring new concepts in the successful management of psoriasis

Historically, psoriasis has been perceived as a disease primarily of the skin with few associated diseases or co-morbidities. As research enhances our knowledge of the pathological processes involved, and with renewed efforts in epidemiological research, the perceptions and understanding of psoriasis are now changing from that of a skin manifestation with the occasional co-morbid condition to a complex, systemic disease. Traditional perceptions of psoriasis as primarily a skin disease have, in part, led to the widespread use of topical therapies with little regard for specifically targeting the systemic inflammatory processes involved. Therapy has habitually taken a step-wise approach from topical therapy to the introduction of phototherapy and moving towards intermittent systemic therapy. Co-morbidities were generally not considered when assessing treatment options as these were thought to occur at a low incidence rate. Psoriasis has long been considered a disease of the keratinocytes, with deregulation of these skin cells leading to the plaques and manifestations characteristic of psoriasis. As research has enhanced our understanding, our perception has shifted to consider psoriasis as an immune-mediated disease in which the immunological circuits continue to be defined with a complex orchestra of cells and cytokines that drive inflammation which may also lead to systemic disease. The involvement of both the innate and adaptive immune systems reflects the intricacies of psoriatic pathogenesis. The mounting evidence for extensive roles of the innate and adaptive immune systems in psoriasis disease pathogenesis have not only revealed its intricate nature, but also identified mechanistic features it shares with its co-morbid conditions, and an increasing recognition that these co-morbidities are more common than had previously been anticipated. The new concept of psoriasis as a systemic disease has changed the way this condition is viewed, in terms of both its pathophysiology and associated co-morbidities. This has led to the development of new, advanced treatment options, giving dermatologists an enhanced armamentarium to counter the disease. In turn, alteration of this fundamental concept is now leading to increasingly efficacious patient outcomes. In particular, therapeutics targeting tumour necrosis factor (TNF)-α, and the p40 subunit common to interleukin (IL)-12 and IL-23, have proven beneficial in the treatment of psoriasis as clinical trials have clearly indicated the efficacy and safety of these drugs. In addition, new trials targeting other cytokines (such as IL-17 and IL-23) and small molecules (such as JAK kinase and apremilast) will add to our basic understanding of the disease and may offer new therapeutic alternatives. The enhanced understanding we now have regarding psoriasis and its pathological processes puts dermatologists in a sentinel-like position to identify risk factors and the early-stage development of co-morbidities. For example, the joint symptoms of psoriatic arthritis are often preceded by psoriasis skin symptoms by up to 10 years. Timely and appropriate responses may improve patient outcomes. This supplement reports the proceedings of the symposium, ‘Exploring new concepts in the successful management of psoriasis’, held during the 20th European Academy of Dermatology and Venereology congress on 22 October 2011 in Lisbon, Portugal. Here, we aim to review current understanding of psoriasis as a multifaceted, systemic disease driven by inflammation with a high occurrence of co-morbid conditions. Professor Reich explores the complex interplay between psoriasis, obesity and associated cardiovascular morbidities and the implications for treatment decisions.1 Professor Mrowietz continues by exploring how these developments alter treatment guidelines and the crucial role of therapeutic goals in facilitating the decisions required to ensure that optimal patient outcomes are reached.2 The final article addresses the issue of treatment optimization with systemic and biologic therapies.3 This is illustrated through the classic example of methotrexate, a drug that is well established in the treatment of psoriasis but whose route and dose relies on undocumented dermatologist experience. The benefit–risk profiles of biologic therapies are also examined here. This is a concept that can help the dermatology community to understand the benefit–risks of individual treatments and communicate these with patients. Our new perspective of psoriasis as an inflammatory disorder with several genetic and environmental risk factors is revealing the multifaceted nature of psoriasis and its associated diseases. Changes in disease management are now leading to early, more appropriate treatment with specific endpoints, or goals, which guide dermatologists in their decisions. R.G.L. has served as consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis including Abbott, Amgen, Astellas, Boehringer Ingelheim, Celgene, Centocor, Genentech, Merck, Novartis and Pfizer.

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