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Psoriasis: from Pathogenesis to Targeted Therapies

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Abstract

Over the last decade, the management of psoriasis has witnessed a paradigm shift. Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted treatments with monoclonal antibodies have been developed. These antibodies, which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and efficacious in the management of most patients with moderate to severe chronic plaque psoriasis. Recently, molecular and genetic studies in pustular and erythrodermic psoriasis have identified additional inflammatory pathways, providing evidence that psoriasis is a heterogeneous disease and highlighting the requirement for personalized disease characterization for treatment optimization. In this article, we will review these advances and provide an update on the currently available treatment arsenal. We discuss the efficacy and safety profile of these individual therapeutic agents and describe their use in special indications. We will also describe the current understanding of psoriasis as a systemic disease associated with multiple comorbidities and illustrate its impact in the management of psoriatic patients. Finally, we discuss ongoing therapeutic developments as well as unmet needs and future perspectives in the field of psoriasis.

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Abbreviations

TNF:

Tumor necrosis factor

IL:

Interleukin

CD:

Cluster of differentiation

Th:

T helper cell

Tc:

T cytotoxic

ADAMTSL5:

A disintegrin and metalloproteinase with thrombospondin motifs like 5

TNFAIP3:

Tumor necrosis factor alpha-induced protein 3

NFKBIA:

Nuclear factor kappa B

HLA-Cw6:

Human histocompatibility antigen Cw6

ERAP1:

Endoplasmic reticulum aminopeptidase 1

ETS1:

E26 Transformation-specific transcription factor 1

SOCS1:

Suppressor of cytokine signaling 1

TNFRSF9:

Tumor necrosis factor receptor superfamily member 9

SNP:

Single nucleotide polymorphism

PPPP:

Palmoplantar pustular psoriasis

GPP:

Generalized pustular psoriasis

ACH:

Acrodermatitis continua of Hallopeau

IL-36RN:

Interleukin-36 receptor antagonist

type I IFN:

Type 1 interferon

pDC:

Plasmaytoid dendritic cells

PASI:

Psoriasis area and severity index

IFNAR:

Interferon alpha receptor

TLR:

Toll-like receptors

PDE-4:

Phosphodiesterase-4

NAPSI:

Nail Psoriasis Severity Index

JAK:

Janus kinase

PSOLAR:

Psoriasis Longitudinal Assessment and Registry

NMSC:

Non-melanoma skin cancer

MACE:

Major adverse cardiac events

BMI:

Body mass index

CVD:

Cardiovascular disease

RA:

Rheumatoid arthritis

HIV:

Human immunodeficiency virus

UVB:

Ultraviolet B rays

LCE3B:

Late cornified envelope 3B

siRNA:

Small interfering ribonucleic acids

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Conrad, C., Gilliet, M. Psoriasis: from Pathogenesis to Targeted Therapies. Clinic Rev Allerg Immunol 54, 102–113 (2018). https://doi.org/10.1007/s12016-018-8668-1

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