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

Psoriasis: A Systemic Inflammatory Disease

Historically, psoriasis was considered a disease that was limited to the skin and was typically treated with topical agents or phototherapy. Although such therapies can provide effective relief of localized skin symptoms, they do little to affect underlying disease causes.[16] With recent advances in understanding the inflammatory nature of psoriasis, research efforts have focused on elucidating the roles of specific proinflammatory cytokines that contribute to disease pathogenesis, with the goal of developing new targeted therapies.[4,17,18]

Psoriasis develops when activated plasmacytoid dendritic cells produce the proinflammatory cytokine IFN-α, which activates myeloid dendritic cells in conjunction with IFN-γ, TNF-α, IL-1β and IL-6.[19] These activated myeloid dendritic cells produce IL-12 and IL-23, which correspondingly activate T helper (Th)1 and Th17 cells.[19] Once initiated, this cycle of inflammation continues chronically, as activated Th1 cells produce TNF-α and Th17 cells produce IL-17A, IL-17F and IL-22.[19] These cytokines further activate keratinocytes that produce a variety of cytokines, chemokines and antimicrobial peptides that promote an ongoing proinflammatory response (Figure 1).[19]

Figure 1.

Psoriasis. Systemic inflammation. DDC, dermal dendritic cell; IFN, interferon; IL, interleukin; KC, keratinocyte; KGF, keratinocyte growth factor; LC, lymphocyte; PDC, plasmacytoid dendritic cell; Tc, cytotoxic T cell; Th, T helper cell; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor; VLA, very late antigen. Adapted from Di Cesare et al.,76 with permission from Elsevier.

As psoriasis progresses, its systemic nature is evidenced by increased serum levels of multiple proinflammatory cytokines, including TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17A and IL-18, in patients with psoriasis compared with healthy controls.[6–9] Observations from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) studies also validate the hypothesis that psoriasis is a systemic inflammatory disease. In these studies, patients with moderate-to-severe psoriasis demonstrate subclinical inflammation in the liver, joints and tendons, in addition to significantly increased global arterial and subcutaneous inflammation, and patients with mild psoriasis had subclinical inflammation in the aorta.[20–22] Also, ultrasound of femoral arteries can improve detection of subclinical atherosclerosis in patients with moderate-to-severe psoriasis and insulin resistance helps to provide a better prediction of subclinical atherosclerosis than traditional CVD risk factors.[23] Such observations have led to a better understanding of how a subset of inflammatory molecules diffuse into the systemic circulation and then to various organ systems; this may contribute to the pathology of common inflammatory comorbidities in psoriasis (Figure 2).[24] Table 2 highlights findings from recent studies showing that shared systemic inflammatory pathways contribute to the pathogenesis of both psoriasis and its comorbidities. Increased understanding of the roles of these pathogenic molecular pathways has enabled an appreciation of the systemic nature of psoriasis and given rise to the development of multiple biological agents that target key cytokines involved in the disease.[17,18,25]

Figure 2.

Psoriasis. Comorbidities and key inflammatory cytokines. IFN, interferon; IL, interleukin; TNF, tumour necrosis factor.