Psoriasis: Heterogeneity, Innate Immunity and Comorbidities
Psoriasis: Heterogeneity, Innate Immunity and Comorbidities
Psoriasis is a common inflammatory skin disease that presents with a variety of different subtypes and disease activities. There is evidence that various forms, including pustular psoriasis, represent different entities. Genome-wide association studies revealed more than 20 susceptibility loci on various chromosomes. These are mostly linked to immune regulation and barrier formation. Immune regulation in psoriasis is complex with an emphasis on Th1-directed autoimmunity. Recently Th17 cells have become a focus of interest and are shown to be pivotal in regulating cytokine overproduction, which stimulates growth and differentiation of keratinocytes. Circumstantial evidence shows bimodal immunopathology with adaptive, as well as innate, immune pathways. The inflammatory nature of psoriasis is associated with an increased risk of comorbidities, including myocardial infarction, metabolic syndrome and reduced life expectancy. Awareness of these complications is mandatory when treating patients with psoriasis.
Psoriasis is one of the most common inflammatory skin disorders affecting 2% of the Western population. During the last century, many aspects of psoriasis have been studied and new pathogenetic concepts have been propagated, reflecting the changing state of knowledge in medicine. In recent years, with the advancements in immunology, activated T cells have gained a key role, suggesting autoimmunity is a basic mechanism of the disease. However, close observation of different psoriasis phenotypes, the variable course of disease with periodic outbreaks, as well as results from immunotyping are reasons to extend the autoimmunity concept. There is now evidence (see below) that innate immunity and autoinflammation play a significant role.
Although psoriasis is primarily a skin disease, a significant proportion of patients suffer from associated disorders such as psoriatic arthritis (PsA), Crohn's disease and systemic comorbidities. These have become major determinants of disease severity. In this paper, three major features of psoriasis will be discussed. These include phenotype heterogeneity, role of innate and adaptive immunopathology, and the increasing importance of systemic comorbidities.
Abstract and Introduction
Abstract
Psoriasis is a common inflammatory skin disease that presents with a variety of different subtypes and disease activities. There is evidence that various forms, including pustular psoriasis, represent different entities. Genome-wide association studies revealed more than 20 susceptibility loci on various chromosomes. These are mostly linked to immune regulation and barrier formation. Immune regulation in psoriasis is complex with an emphasis on Th1-directed autoimmunity. Recently Th17 cells have become a focus of interest and are shown to be pivotal in regulating cytokine overproduction, which stimulates growth and differentiation of keratinocytes. Circumstantial evidence shows bimodal immunopathology with adaptive, as well as innate, immune pathways. The inflammatory nature of psoriasis is associated with an increased risk of comorbidities, including myocardial infarction, metabolic syndrome and reduced life expectancy. Awareness of these complications is mandatory when treating patients with psoriasis.
Introduction
Psoriasis is one of the most common inflammatory skin disorders affecting 2% of the Western population. During the last century, many aspects of psoriasis have been studied and new pathogenetic concepts have been propagated, reflecting the changing state of knowledge in medicine. In recent years, with the advancements in immunology, activated T cells have gained a key role, suggesting autoimmunity is a basic mechanism of the disease. However, close observation of different psoriasis phenotypes, the variable course of disease with periodic outbreaks, as well as results from immunotyping are reasons to extend the autoimmunity concept. There is now evidence (see below) that innate immunity and autoinflammation play a significant role.
Although psoriasis is primarily a skin disease, a significant proportion of patients suffer from associated disorders such as psoriatic arthritis (PsA), Crohn's disease and systemic comorbidities. These have become major determinants of disease severity. In this paper, three major features of psoriasis will be discussed. These include phenotype heterogeneity, role of innate and adaptive immunopathology, and the increasing importance of systemic comorbidities.
