Elsevier

The Lancet

Volume 386, Issue 9997, 5–11 September 2015, Pages 983-994
The Lancet

Seminar
Psoriasis

https://doi.org/10.1016/S0140-6736(14)61909-7Get rights and content

Summary

Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both. A diverse team of clinicians with a range of expertise is often needed to treat the disease. Psoriasis provides many challenges including high prevalence, chronicity, disfiguration, disability, and associated comorbidity. Understanding the role of immune function in psoriasis and the interplay between the innate and adaptive immune system has helped to manage this complex disease, which affects patients far beyond the skin. In this Seminar, we highlight the clinical diversity of psoriasis and associated comorbid diseases. We describe recent developments in psoriasis epidemiology, pathogenesis, and genetics to better understand present trends in psoriasis management. Our key objective is to raise awareness of the complexity of this multifaceted disease, the potential of state-of-the-art therapeutic approaches, and the need for early diagnosis and comprehensive management of patients with psoriasis.

Section snippets

Disease burden and epidemiology

Psoriasis is a common skin disorder that is associated with both a physical and psychological burden. As with other dermatoses, visible disfiguration can trigger a negative reaction in others, which can cause much of the readily measurable psychological burden of the disease. In a comparison with a selection of other chronic disorders including cancer, myocardial infarction, and congestive heart failure, only depression and chronic lung disease impaired psychological quality of life more than

Clinical manifestations of psoriasis

Psoriasis is a multifarious disease that is equally prevalent in both sexes, although results from a recent study have shown that on average men have more severe forms of the disease than do women.11 Five types of psoriasis have been reported: plaque psoriasis (also known as psoriasis vulgaris); guttate (droplet) or eruptive psoriasis, which is characterised by scaly teardrop-shaped spots; inverse psoriasis, also called intertriginous or flexural psoriasis that is usually found in folds of

Diagnosis and differential diagnosis

Diagnosis is usually made on clinical findings; skin biopsy is rarely used to diagnose psoriasis. The Psoriasis Area and Severity Index (PASI) score has been used to quantify disease severity of erythema, infiltration or thickness, scaling and the extent of lesions in patients with widespread disease.28 More recently, easier-to-use scores, such as the psoriasis global assessment (PGA) or lattice system-physician's global assessment (LS-PGA)have been developed for routine clinical practice.29

Pathogenesis

Involvement of the immune system in psoriasis is now widely accepted.33, 34 Genome-wide scans for psoriasis-associated genes have identified predominantly immune-related genes,35, 36 providing a mechanistic link between genetics and immunity. Psoriatic skin lesions originate as a result of dysregulated interactions of innate and adaptive components of the immune system with resident cutaneous cell types.

Research into the immunopathogenesis of psoriasis has resulted in several highly specific

Genetics and pharmacogenetics

Results from population studies suggest a higher incidence of psoriasis in first-degree and second-degree relatives of patients than in the general population.63 Furthermore, concordance rates in monozygotic twins are up to three times higher than in dizygotic twins.63 Genetic factors are also likely to have an effect on disease severity because, on average, patients with an early onset of the disease (type I psoriasis) have a more severe course and a positive family history, whereas patients

Comorbid disease

Several important diseases occur more often in patients with psoriasis than expected based on their respective prevalence in the general population. Comorbid diseases of psoriasis include psoriatic arthritis, Crohn's disease, cancer, depression, non-alcoholic fatty liver disease, metabolic syndrome (or components of it), and cardiovascular disorders,9, 79 all of which contribute substantially to morbidity and mortality in patients with psoriasis. Comorbid disease needs to be treated, therefore

Management and prevention

In recent years, several high-quality evidence-based guidelines have been developed for the treatment of psoriasis such as the German S3 guidelines,99 North American guidelines,100 and International European guidelines.101 The German S3 guidelines were the first to include topical therapies, phototherapy, and conventional and biological systemic therapies.

Unresolved questions, new developments, and unmet medical needs

Substantial progress has been made to understand the complex pathogenesis of psoriasis and to facilitate the development of more effective, targeted therapies. However, despite these advances more research is needed in several areas.123

Psoriasis has no known cure but many therapies can reduce or nearly stop symptoms. A treatment to which all patients respond adequately, and a reliable test that predicts individual responses before starting treatments, is not yet available.124 The identification

Conclusion

Psoriasis is a systemic inflammatory disorder that involves complex pathogenic interactions between the innate and adaptive immune system that can be targeted by innovative biological therapies. The treatment framework is changing from short-term intervention of acute rashes toward long-term management, taking into consideration both the skin symptoms and comorbid diseases. The quest to reduce medical risks of patients with psoriasis through comprehensive treatment and early identification of

Search strategy and selection criteria

We searched PubMed using the terms “psoriasis”, “epidemiology”, “pathogenesis”, “genetics”, “psoriasis susceptibility loci”, “therapy”, “guidelines”, and “comorbidity”. Our search covered articles published in English, German, and French published between 1974 and May 13, 2015. We identified additional reports from the reference list of seminal reviews.

References (137)

  • MA Lowes et al.

    Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells

    J Invest Dermatol

    (2008)
  • RR Keijsers et al.

    In vivo induction of cutaneous inflammation results in the accumulation of extracellular trap-forming neutrophils expressing RORγt and IL-17

    J Invest Dermatol

    (2014)
  • AS Büchau et al.

    Innate immunity and antimicrobial defense systems in psoriasis

    Clin Dermatol

    (2007)
  • C Rosenberger et al.

    Upregulation of hypoxia-inducible factors in normal and psoriatic skin

    J Invest Dermatol

    (2007)
  • I Teige et al.

    Regulatory T cells control VEGF-dependent skin inflammation

    J Invest Dermatol

    (2009)
  • PM Elias et al.

    Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis

    Am J Pathol

    (2008)
  • HS Young et al.

    Single-nucleotide polymorphisms of vascular endothelial growth factor in psoriasis of early onset

    J Invest Dermatol

    (2004)
  • MP Schön et al.

    The molecular basis of lymphocyte recruitment to the skin: clues for pathogenesis and selective therapies of inflammatory disorders

    J Invest Dermatol

    (2003)
  • EN Madva et al.

    Nerve-derived transmitters including peptides influence cutaneous immunology

    Brain Behav Immun

    (2013)
  • T Henseler et al.

    Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris

    J Am Acad Dermatol

    (1985)
  • RP Nair et al.

    Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene

    Am J Hum Genet

    (2006)
  • F Capon et al.

    Psoriasis and other complex trait dermatoses: from Loci to functional pathways

    J Invest Dermatol

    (2012)
  • M Cargill et al.

    A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes

    Am J Hum Genet

    (2007)
  • AS Haider et al.

    Cellular genomic maps help dissect pathology in human skin disease

    J Invest Dermatol

    (2008)
  • K Asumalahti et al.

    Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis

    J Invest Dermatol

    (2003)
  • T Tejasvi et al.

    TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis

    J Invest Dermatol

    (2012)
  • T Henseler et al.

    Disease concomitance in psoriasis

    J Am Acad Dermatol

    (1995)
  • JM Gelfand et al.

    The risk of lymphoma in patients with psoriasis

    J Invest Dermatol

    (2006)
  • EJ Samarasekera et al.

    Incidence of cardiovascular disease in individuals with psoriasis: a systematic review and meta-analysis

    J Invest Dermatol

    (2013)
  • EA Dowlatshahi et al.

    Psoriasis is not associated with atherosclerosis and incident cardiovascular events: the Rotterdam Study

    J Invest Dermatol

    (2013)
  • T Nijsten et al.

    Complexity of the association between psoriasis and comorbidities

    J Invest Dermatol

    (2009)
  • L Dubertret et al.

    European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey

    Br J Dermatol

    (2006)
  • World psoriasis day—document EB133.R2, agenda item 6.2. May 30, 2013

  • E Christophers

    Psoriasis—epidemiology and clinical spectrum

    Clin Exp Dermatol

    (2001)
  • M Augustin et al.

    Epidemiology and comorbidity of psoriasis in children

    Br J Dermatol

    (2010)
  • MP Schön et al.

    Psoriasis

    N Engl J Med

    (2005)
  • N Balato et al.

    Effect of weather and environmental factors on the clinical course of psoriasis

    Occup Environ Med

    (2013)
  • FO Nestle et al.

    Psoriasis

    N Engl J Med

    (2009)
  • D Hägg et al.

    The higher proportion of men with psoriasis treated with biologics may be explained by more severe disease in men

    PLoS One

    (2013)
  • J Ortonne et al.

    Scalp psoriasis: European consensus on grading and treatment algorithm

    J Eur Acad Dermatol Venereol

    (2009)
  • U Runne

    Alopecia psoriatica. Charakteristika eines bisher negierten Krankheitsbildes

    Hautarzt

    (1993)
  • K Reich

    Approach to managing patients with nail psoriasis

    J Eur Acad Dermatol Venereol

    (2009)
  • R Baran

    The burden of nail psoriasis: an introduction

    Dermatology

    (2010)
  • ES Tan et al.

    Nail psoriasis: a review

    Am J Clin Dermatol

    (2012)
  • S Marrakchi et al.

    Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis

    N Engl J Med

    (2011)
  • C Joyau et al.

    Anti-tumour necrosis factor alpha therapy and increased risk of de novo psoriasis: is it really a paradoxical side effect?

    Clin Exp Rheumatol

    (2012)
  • P Besgen et al.

    Ezrin, maspin, peroxiredoxin 2, and heat shock protein 27: potential targets of a streptococcal-induced autoimmune response in psoriasis

    J Immunol

    (2010)
  • BA Martin et al.

    How great is the risk of further psoriasis following a single episode of acute guttate psoriasis?

    Arch Dermatol

    (1996)
  • C Fotiadou et al.

    Management of psoriasis in adolescence

    Adolesc Health Med Ther

    (2014)
  • M Ståhle et al.

    Juvenile psoriasis and its clinical management: a European expert group consensus

    J Dtsch Dermatol Ges

    (2010)
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