Key Points
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Psoriasis is a common immune disorder whose major manifestation is in the skin. It most frequently begins in young adults, and is a lifelong condition.
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The most common form of psoriasis — psoriasis vulgaris or plaque-type psoriasis — is characterized by the presence of red, raised scaly plaques that can cover any body surface.
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Patients with limited disease can respond well to topical treatments, but established therapies for more severe disease, such as systemic immunosuppressive drugs and phototherapy, have several drawbacks, including inconvenience and/or toxicity, which means that treatments are used intermittently.
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So, patients experience cycles of clearance with normal quality of life that alternate with active disease and poor quality of life. There is therefore a need for therapies that result in safe and effective long-term maintenance of disease clearance for patients with moderate-to-severe psoriasis.
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Advances in the understanding of psoriasis in recent years have highlighted the importance of aberrant activation of and migration of T cells into the skin in the pathogenesis of the disease.
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Several agents that target the molecules involved, such as tumour-necrosis factor-α, have been recently approved for the treatment of psoriasis, or are in clinical trials. Such agents have also proved valuable in understanding disease pathogenesis.
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This article first reviews current knowledge on the pathogenesis of psoriasis, and then discusses clinical results with immunobiological agents that have been approved or that are in development. Finally, novel potential targets for the development of drugs to treat psoriasis are highlighted.
Abstract
Psoriasis is a chronic inflammatory skin disorder that is characterized by thickened, scaly plaques, and is estimated to affect ∼1–3% of the Caucasian population. Traditional treatments, although effective in patients with limited disease, have numerous shortcomings, including inconvenience and toxicity. These drawbacks mean that many patients experience cycles of disease clearance, in which normal quality of life alternates with active disease and poor quality of life. However, as this review discusses, recent advances have highlighted the key role of the immune system in the pathogenesis of psoriasis, and have provided new defined targets for therapeutic intervention, offering hope for safe and effective psoriasis treatment.
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Acknowledgements
This work was funded in part by grants from the David Ju Foundation and a Center of Excellence grant from the Federation of Clinical Immunology Societies (FOCIS).
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A.B.G. receives research funding from Amgen Inc.; Biogen Idec, Inc.; Centocor, Inc.; Genentech, Inc; WH Conzen Chair in Clinical Pharmacology; Abbott Labs; Ligand Pharmaceuticals Inc.; Beiersdorf, Inc.; Fujisawa Healthcare, Inc.; Merck, Inc.; Celgene Corp.; and Novartis AG.
A.B.G.'s Speakers' Bureau Memberships include Amgen Inc.; Biogen Idec, Inc.; Wyeth Pharmaceuticals; Centocor, Inc.; and Schering-Plough Corp.
A.B.G. currently has consulting agreements with Amgen Inc.; Biogen Idec, Inc; CellGate, Inc; Centocor, Inc.; Genentech, Inc; Novartis AG; QUATRx Pharmaceuticals Co.; Wyeth Pharmaceuticals, Schering-Plough Corp.; Eisai; Celgene Corp.; Bristol Myers Squibb Co.; Beiersdorf, Inc., Warner Chilcott, Abbott Labs., Kemia, Sankyo
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DATABASES
Entrez Gene
OMIM
Glossary
- TOPICAL THERAPY
-
Therapy applied to the skin.
- PHOTOTHERAPY
-
Ultraviolet light irradiation therapy.
- KERATINOCYTE
-
Keratinocytes are a type of cell found in the epidermis (the top layer of skin). Psoriasis is characterized by hyperproliferation of keratinocytes.
- NATURAL KILLER CELLS
-
(NK cells). Lymphocytes that confer innate immunity. They were originally defined on the basis of their cytolytic activity against tumour targets, but it is now recognized that they serve a broader role in host defence against invading pathogens.
- INTEGRIN
-
Integrins are a family of adhesion molecules that mediate cell–cell, cell–extracellular matrix and cell–pathogen interactions by binding to various ligands. Integrins are non-covalently associated α/β heterodimers.
- MAJOR HISTOCOMPATIBILITY COMPLEX
-
A genetic region encoding proteins that are involved in antigen presentation to T cells. MHC class I molecules bound to antigen are most often recognized by the T-cell receptors of CD8+ T cells.
- IMMUNOLOGICAL SYNAPSE
-
A large junctional structure that is formed at the cell surface between a T cell that is interacting with an antigen-presenting cell. Important molecules involved in T-cell activation — including the T-cell receptor, numerous signal-transduction molecules and molecular adaptors — accumulate in an orderly manner at this site.
- MEMORY EFFECTOR T CELLS
-
Antigen-experienced T cells that have immediate effector capabilities and can efficiently migrate to peripheral sites of inflammation.
- φX174
-
φX174 is an experimental immunogen (vaccine) used to assess immune integrity in humans
- MUNRO'S ABSCESSES
-
Collections of neutrophils in the stratum corneum in psoriatic plaques.
- SHARP SCORES
-
A radiographic score composite of joint-space narrowing and bone erosions in joints of the hand and wrist.
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Gottlieb, A. Psoriasis: emerging therapeutic strategies. Nat Rev Drug Discov 4, 19–34 (2005). https://doi.org/10.1038/nrd1607
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DOI: https://doi.org/10.1038/nrd1607
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