Management of Psoriasis as a Systemic Disease: What Is the Evidence?

N.J. Korman


The British Journal of Dermatology. 2020;182(4):840-848. 

In This Article

Abstract and Introduction


Background: Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques. Psoriasis pathogenesis is driven by proinflammatory cytokines and psoriasis is associated with increased risk for comorbidities, including, but not limited to, psoriatic arthritis, cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease compared with the general population.

Objectives: To explore the pathophysiological relationship between psoriasis and its common comorbidities and discuss the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis.

Methods: This narrative review summarizes the published evidence related to the ability of biological therapies to ameliorate the consequences of systemic inflammation in patients with psoriasis.

Results: Current evidence suggests that preventing damage associated with inflammation, and preventing development of future inflammatory damage and comorbidities, may be a potentially achievable treatment goal for many patients with moderate-to-severe plaque psoriasis when biological therapies are utilized early in the disease. Encouraging data from recent studies suggest that the loftier goal of reversing existing inflammatory damage and improving signs and symptoms of inflammatory comorbidities could also possibly be attainable.

Conclusions: Results from ongoing prospective studies regarding the effects of biologics on markers of systemic inflammation in patients with psoriasis will strengthen the clinical evidence base that can be used to inform treatment decisions for patients with moderate-to-severe psoriasis.


Psoriasis is an immune-mediated, chronic inflammatory condition affecting approximately 3% of adults and 0·1% of children and adolescents in the U.S.A.[1,2] It is characterized by well-demarcated, erythematous plaques covered by silvery-white scales, typically occurring in a symmetrical distribution involving the elbows, knees, trunk and scalp.[3] Psoriasis onset is triggered when genetic and/or environmental factors activate plasmacytoid dendritic cells, resulting in the production of numerous proinflammatory cytokines, including tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, IL-22, IL-23 and IL-1β.[4] Many of these cytokines stimulate keratinocyte hyperproliferation, which perpetuates a cycle of chronic inflammation.[5]

In moderate-to-severe psoriasis, elevated levels of multiple proinflammatory cytokines are found not only in skin lesions, but also in the blood.[6–9] Systemic elevations in these cytokines promote chronic subclinical inflammation (asymptomatic inflammation that can cause tissue damage over time) associated with comorbidities that disproportionately affect patients with psoriasis, including psoriatic arthritis (PsA), cardiovascular disease (CVD), diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease (NAFLD) (Table 1).[10–14]

It is hypothesized that early systemic treatment targeting proinflammatory cytokines associated with psoriasis pathogenesis will not only improve cutaneous symptoms but also reduce systemic inflammation, hence improving long-term outcomes through mitigation of comorbidity progression.[15] This review explores the pathophysiological relationship between psoriasis and its common comorbidities, and discusses the need for new treatment paradigms that include strategies to reduce the effects of systemic inflammation in moderate-to-severe plaque psoriasis.