Therapy for Severe Psoriasis E-Book

Expert Consult

Jashin J. Wu, Steven R Feldman, Mark G. Lebwohl

• Publisher: Elsevier
• Year: 2016
• ISBN:
  9780323447980
• Topic: Medizin
• Subtopic: Dermatologie

A brand-new title in the field of dermatology, Therapy for Severe Psoriasis provides the ultimate coverage of the treatment options available for today's most serious cases, including biologics and oral therapies. It features discussions of the newest drug therapies, recent FDA-approved biosimilars, and combination approaches to care, while an overview chapter was designed to aid those new to the field in understanding the nuances of difficult-to-treat subtypes of psoriasis. Comprehensive and focused, Therapy for Severe Psoriasis will be a welcome addition to the library of any dermatologist seeking in-depth information on the challenges of this condition.

• Each of the 16 chapters includes either an in-depth focus on a single therapy or an overview of a unique aspect of psoriasis, including: UVB therapy, methotrexate, acitretin, cyclosporine, apremilast, etanercept, infliximab, adalimumab, ustekinumab, secukinumab, and ixekizumab.
• Takes an evidence-based approach to hard-to-treat severe psoriasis.
• Discusses the newest drug therapies (such as ixekizumab), plus recent FDA-approved biosimilars, a topic unique to this particular psoriasis text.
• Presents combination approaches for instances when standard treatments are not successful.
• Includes an overview chapter to help beginners understand the nuances of the disorder.

Chapter 1

Overview of Psoriasis

Michael Kelly-Sell, MD, and Johann E. Gudjonsson, MD, PhD

Keywords

Psoriasis; Plaque psoriasis; Clinical subtypes; Pustular psoriasis; Nail psoriasis; Comorbidities

Key points

• Today, psoriasis is a global disease causing significant impairment in quality of life, disfiguring morbidity, and increased mortality.

• Psoriasis affects men and women equally. Two-thirds of patients are thought to have mild disease, and one-third of patients are thought to have more severe involvement.

• Psoriasis is found in practically all racial groups and is thought to affect approximately 2% of the world’s population.

• Psoriasis may appear at any age, but it most commonly presents between the ages of 15 and 30.

• Over the last 20 years, many of the immunologic drivers of psoriasis have been uncovered, and this research has been translated to the clinic with the development of increasingly powerful but selective biologic drugs targeting these immune pathways.

Psoriasis was first described by the ancient Greeks, Hippocrates and Galen, and grouped together with leprosy. The term psoriasis was derived from the Greek “psora” which means an, “itch, mange, scab.” In the early nineteenth century, Robert Wilan and Hebra refined the description of psoriasis and distinguished it from leprosy. In 1879, Koebner described the appearance of psoriatic lesions at sites of injury, called the “Koebner phenomenon.” Today, psoriasis a global disease affecting 125 million people across the world and causing significant impairment in quality of life, disfiguring morbidity, and even mortality. In the late twentieth century, basic science research demonstrated that psoriasis is an immune-mediated polygenic disorder that can be triggered by various environmental triggers. Over the last 20 years, many of the immunologic drivers of psoriasis have been uncovered, and this research has been translated to the clinic with the development of increasingly powerful but selective biologic drugs targeting these immune pathways. This increased understanding of the immunology of psoriasis has led to remarkable improvements in the treatment of psoriasis and makes it an exciting time to care for patients with psoriasis.

Epidemiology

Psoriasis affects male and female patients equally. Two-thirds of patients are thought to have mild disease, and one-third of patients are thought to have more severe involvement. Psoriasis is found in practically all racial groups and is thought to affect approximately 2% of the world’s population. Although psoriasis is a global disease, there are some regional variations in prevalence, with rates varying from 0.4% in Asians to 2.6% in the United States and 2.9% in Denmark. In Africa, there is a higher prevalence in East Africans as opposed to West Africans, which may help explain racial differences within the United States. Interestingly, a study of 26,000 South American Native Americans did not document a single case of psoriasis.

Age of onset

Psoriasis may appear at any age, but it most commonly presents between the ages of 15 and 30. An earlier age of onset and family history have been associated with particular HLA class I antigens, most notably HLA-Cw6. Based on this finding, Henseler and Christophers¹ proposed that 2 different forms of psoriasis exist: type I psoriasis, with onset before the age of 40; and type II psoriasis, with age of onset after the age of 40. Both types of psoriasis respond similarly to treatment.

Cause and Pathogenesis

The root cause of psoriasis remains unknown. However, research is beginning to link the complex genetic, biochemical, and immunologic abnormalities that underlie the disease. These changes can be seen in both psoriatic lesions and normal-appearing skin of psoriatic patients.

There is strong evidence suggesting at least a partial genetic basis in psoriasis. Genome linkage studies in the 1990s identified a locus termed psoriasis susceptibility 1 (PSORS1) in the major histocompatibility complex (chromosome 6p21.3), home of the HLA genes.² Many HLA markers have been associated with psoriasis, but HLA-Cw6 has constantly demonstrated the highest relative risk for psoriasis in Caucasian populations.³ HLA-Cw6 is also strongly associated with early onset, guttate psoriasis, and psoriatic arthritis. However, only about 10% of HLA-Cw6 carriers develop psoriasis and the PSORS1 may account for only one-third of the genetic liability to psoriasis.⁴ In recent years, additional genetic risk variants have been identified for psoriasis, with more than 60 genetic loci identified to date. These findings confirm the polygenic nature of psoriasis and also its heterogeneity because most patients carry different combinations of these risk variants, and this may influence clinical course of the disease as well as therapeutic responses.

Development of a lesion

Psoriasis is characterized clinically by red and scaly plaques sharply demarcated from normal skin. Histologically, it is characterized by marked proliferation of keratinocytes, altered epidermal differentiation, and proliferation of endothelial cells accompanied by an influx of a variety of inflammatory cells. The development of a psoriatic lesion is a complex and multicellular process that involves keratinocytes, T cells, dendritic cells, macrophages, mast cells, endothelial cells, and neutrophils. Cytokines and growth factors initiate and sustain inflammation in this process through pathways that involve cells of both the innate and the acquired immune systems. Initial pinhead-sized macular lesions show edema and mononuclear cell infiltrates within the upper dermis. The overlying epidermis becomes spongiotic, and there is a focal loss of the granular layer. As the plaque matures, the epidermis becomes thickened in the center with increasing parakeratosis, capillary elongation, and perivascular infiltration of various types of immune cells. Mature psoriatic lesions contain elongated and uniform rete ridges with thinning of the epidermis overlying the dermal papillae. The tips of the rete ridges may become clubbed with dilated, tortuous capillaries in the dermal papillae. There is typically confluent parakeratosis and hyperkeratosis.⁵ More inflammatory cells are present with CD4+ T cells and dendritic cells in the upper dermis and CD8+ T cells in the epidermis. Neutrophils are commonly seen in psoriatic lesions and form characteristic collections in the spinous layer (spongiform pustules of Kogoj) and in the stratum corneum (Munro microabscesses). Eosinophils are not seen in psoriasis, unless the disease is drug induced.

T cells

The role of T cells in psoriasis was first documented in the 1980s, and the last 30 years of scientific and clinical research...