Dermatology Express Report

Satellite Symposium at the 68th Annual Meeting of The Society for Investigative Dermatology

Publication date: 2007-07-01

Regulation of Inflammation in Psoriasis—A New Understanding

This report was reviewed for medical and scientific accuracy by Amy S. Paller, MD, Professor and Chair of Dermatology, Professor of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Expert Commentary

Brian J. Nickoloff, MD, PhD, Professor and Associate Chairman of Pathology, Director, Oncology Institute, Deputy Director, Cardinal Bernardin Cancer Center, Director, Skin Disease Research Program, Loyola University of Chicago Medical Center, Maywood, Illinois

Psoriasis is a chronic inflammatory, immune-mediated disease characterized by periods of spontaneous remissions and exacerbations afflicting approximately 2-3% of the population worldwide. ¹ Although psoriasis can begin at any age, epidemiological studies demonstrate that psoriasis most commonly appears for the first time between the ages of 15 and 25 years. ² Not only can psoriatic lesions be intensely pruritic and disfiguring, but the clinical manifestations of psoriasis can so disrupt a patient's quality of life that patients with psoriasis contemplate suicide. ³

Although simplistic, the pathogenesis of psoriasis can be considered in the context of 3 phases: phase I is an interaction between genetic and environmental factors; phase II is an interaction between innate/adaptive immunity and the resident skin cells; and phase III consists of epidermal and dermal remodeling (characterized by the “psoriatic plaque”) with subsequent reversibility to healthy appearing skin with little, if any, evidence of the epidermal and dermal changes that led to the development of the psoriatic plaque. ⁴ Another way to consider these 3 components of the disease is that phase I resembles the “seed”, whereas phase II resembles the “fertilizer/soil”; and when both the seed and the soil come together, a psoriatic plaque is created as depicted in phase III (Figure 1).

Many theories and models have been proposed to explain psoriatic plaque development and the “tissue remodeling” associated with psoriatic plaque. However, one unifying hypothesis of psoriasis pathophysiology, which assimilates cell types and soluble mediators, is the cytokine network model, ⁵ which has been portrayed as a plexus of cellular events incited by a cascade of cytokines. This complex network of cytokines, chemokines, and growth factors ultimately results in a psoriatic plaque characterized by intraepidermal CD8+ T cells and neutrophils, accompanied by epidermal thickening, scale production, and an angiogenic tissue reaction completely remodeling the lesional site. ¹

While research has provided considerable progress in the understanding of the immunopathogenesis and genetics of psoriasis, the cause of psoriasis remains unknown and there is no cure. A more thorough understanding of the underlying inflammatory nature of psoriasis is critically important in providing further insights to the prevention and treatment of this devastating disease.

This Dermatology Express Report^TM reviews exciting and promising data presented during a satellite symposium at the 68^th Annual Meeting of The Society for Investigative Dermatology on recent advances in the understanding of the underlying molecular, cellular, and signaling events that mediate the inflammatory response associated with the psoriatic process. In understanding these complex events, potential targets for therapeutic intervention can be identified which may lead to safer and more efficacious treatment options for psoriasis.

Cutaneous Inflammation and Psoriasis

“Inflammation may be derived from innate immunity which mediates inflammation to microbial targets or from adaptive immunity which focuses inflammation on specific molecular targets and thus modifies inflammation based on T-cell cytokines,” advised Thomas S. Kupper, MD, Professor, Harvard Medical School, and Chairmen, Department of Dermatology, Brigham a