Pathophysiology, Clinical Presentation, and Treatment of Psoriasis

Abstract

ImportanceApproximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders.ObservationsPlaque psoriasis is the most common variant of psoriasis. The most rapid advancements addressing plaque psoriasis have been in its pathogenesis, genetics, comorbidities, and biologic treatments. Plaque psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic diseases, and depression. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles. Specifically, inhibitors to tumor necrosis factor α (TNF-α) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL-12 and IL-13 (ustekinumab), IL-17 (secukinumab, ixekizumab, bimekizumab, and brodalumab), and the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab). Biologics that inhibit TNF-α, p40IL-12/23, and IL-17 are also approved for the treatment of psoriatic arthritis. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. The most commonly prescribed light therapy used to treat plaque psoriasis is narrowband UV-B phototherapy.Conclusions and RelevancePsoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients’ quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF-α, p40IL-12/23, IL-17, and p19IL-23, as well as an oral phosphodiesterase 4 inhibitor.

Potential for Targeting Myeloid Cells in Controlling CNS Inflammation

“…Some of the current MS disease-modifying therapies may act on myeloid cells even if these cells were not the original intended targets ( 18 ). However, interfering directly with myeloid cell has proven to be efficacious in other diseases including psoriasis with multiple drugs targeting IL-23 (Guselkumab, Risankizumab, and Tildrakizumab) or IL-12 and IL-23 (Ustekinumab) ( 19 ), Crohn's disease and ulcerative colitis targeting IL-12 and IL-23 (Ustekinumab) ( 20 ), rheumatoid arthritis targeting IL-1 (Anakinra) ( 21 ), systemic juvenile idiopathic arthritis targeting IL-1β (Canakinumab) ( 22 ), and many others. There are ongoing clinical trials in rheumatoid arthritis, stroke, atherosclerosis, and cancer using agents that target myeloid cells and their products.…”

Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

“…Numerous studies point that interleukin (IL)-23/IL-17 axis plays a central role in psoriasis pathogenesis [3] . It has been validated by the therapeutic e cacy of blocking IL-23 and IL-17 pathway in moderate-to-severe psoriasis, such as ustekinumab and brodalumab [4] . However, these clinical methods have limitations, and symptoms are likely to reappear upon cessation of therapy.…”

Dysbiosis of gut microbiota and its correlation with dysregulation of cytokines in psoriasis patients

“…The viewpoint that the immune system is involved in the pathogenesis of psoriasis also has been widely accepted (3), especially Th17 cells play a crucial role in the pathogenesis and development of psoriasis (4). Th17 cells as well as Th1 cells and keratinocytes secrete TNF-α,IFNγ IL-1β IL-6,IL-12,IL-17A IL-22,IL-23 participating in pathophysiologic processes of psoriasis (5) and current biological therapies as T cell-directed agents have demonstrated excellent e cacy in psoriasis.…”