2017 Update: Etiology and Pathogenesis of Psoriasis

By Sara N. Fischer, PhD

Reviewed by Alice B. Gottlieb, MD, PhD

Take Note
 Psoriasis affects 1%-4% of the population worldwide, manifesting as chronic inflammation
of the skin and characterized by scaly, erythematous patches, papules, and plaques,
which are often pruritic.
 Immunopathogenesis involves interactions between the innate and adaptive immune
systems.
Advances in the understanding of the immunopathogenesis and genetics of psoriasis have
established psoriasis as a chronic, immune-mediated systemic disease associated with significant
morbidity and impaired quality of life.1Affecting 1% to 4% of the worldwide population, psoriasis is
also linked with serious comorbid conditions, such as diabetes/metabolic syndrome, cardiovascular
disease, and psoriatic arthritis (PsA).2,3 Increased understanding of the underlying
immunopathogenesis and genetics of psoriasis has led to the development of several systemic
therapies, many of which have been approved for the treatment of specific patient
populations.1Therefore, it is important for clinicians to understand current data and clinical evidence
regarding the pathogenesis of psoriasis and its related comorbidities.
Clinical features and etiology of psoriasis
Psoriasis is a multisystem disease predominately manifested as chronic inflammation of the skin and
characterized by scaly, erythematous patches, papules, and plaques, which are often pruritic.4 As a
chronic disease, psoriasis waxes and wanes throughout a patient's lifetime.4 The disease course is
modified with initiation and cessation of treatment, and spontaneous remission is rare.4 Historically,
psoriasis phenotypes have been based on morphologic classifications, but clinical findings may
show overlap of several different categories in individual patients .4 The severity of psoriasis is
defined by the extent of body surface involvement as well as the involvement of areas that
substantially affect daily life, such as the hands, feet, face, and genital region.5
Approximately 80% of patients have mild to moderate disease and 20% have moderate to severe
disease.5 Although the precise etiology of psoriasis remains unknown, a combination of
immunologic, genetic, and environmental factors contribute to its development and exacerbation.4
Immunopathogenesis of psoriasis
The immunopathogenesis of psoriasis involves interactions between the innate and adaptive
immune systems, which lead to alterations in the epidermis and vasculature.5-11 Following an initial
trigger, innate immunity danger signals activate plasmacytoid and CD11c+ dendritic cells, which
secrete cytokines such as interferon-alpha and tumor necrosis factor (TNF)-alpha,
respectively.6,7 Early clinical studies of TNF inhibitors demonstrated the important role of this cytokine
in driving psoriatic disease, prompting investigators to consider psoriasis to be primarily Th1-
response driven.6,12 However, recent reports indicate both Th17 cells and interferon-gamma-
producing Th1 cells play essential roles in the pathogenesis of psoriasis.5,9,13In addition to its well-
documented proinflammatory properties, TNF-alpha signaling also promotes the generation and
proliferation of Th17 cells.8 Th17 cell-mediated secretion of interleukin (IL)-17 and IL-22 results in
keratinocyte proliferation, cytokine and chemokine secretion, and altered antimicrobial peptide
production.5,7 In the skin, myeloid dendritic cells produce IL-12 and IL-23, which further induce the
activation of Th1 and Th17 cells, respectively.6,9
A study of a murine arthritis model showed IL-23 induced spondyloarthropathy via actions on a
specific population of entheseal T cells.10 These findings provide further evidence for the link
between skin and joint disease and suggest agents that target the IL-23 pathway may be effective
for the treatment of these conditions.10 Other studies highlight the potential role of another Th17-
related cytokine, IL-36, in the pathogenesis of psoriasis.11,14 Taken together, continuous activation of
the Th1 and Th17 pathways contribute to the chronic inflammatory phenotype observed in psoriasis
patients.6 These findings have led to the development of systemic biologic therapies that target these
pathways.7
Conclusion
Psoriasis is characterized by scaly, erythematous patches, papules, and plaques, which are often
pruritic. The pathogenesis of psoriasis involves the complex interplay of immunologic, genetic, and
environmental factors. Taken together, current understanding of the underlying pathogenesis of
psoriasis has given rise to the development of new therapeutic options for this complex disease.
Published: 01/06/2017
References:
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and Th17 T cells. J Invest Dermatol. 2008;128:1207-1211.
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