Mechanism of Action: IL-17 and IL-23 Axis

Overview / Definition The IL-17 and IL-23 axis is a critical pathway involved in the immune response and inflammation, particularly in dermatological conditions like psoriasis and hidradenitis suppurativa. IL-23 promotes the differentiation of naïve T cells into Th17 cells, which in turn secrete IL-17, a pro-inflammatory cytokine that plays a central role in the pathogenesis of several skin disorders. Epidemiology Psoriasis affects approximately 2-3% of the population worldwide, with variations in prevalence based on ethnic background and geographic location. Hidradenitis suppurativa, while less common, has an estimated prevalence of 1-4% in the general population. Both conditions exhibit a higher incidence in individuals with a family history of autoimmune diseases. Pathophysiology / Mechanism The IL-17 and IL-23 axis is pivotal in the inflammatory cascade. Here’s how it works: IL-23 is secreted by antigen-presenting cells. It activates naïve T cells, promoting their differentiation into Th17 cells. Th17 cells produce a variety of cytokines, including IL-17A, IL-17F, and IL-22. IL-17A stimulates keratinocytes to release pro-inflammatory cytokines, chemokines, and antimicrobial peptides. This leads to a cycle of inflammation, further recruiting immune cells and perpetuating the inflammatory response. This pathway not only contributes to the inflammatory milieu seen in psoriasis but also plays a role in other skin diseases with an autoimmune component. Clinical Presentation Patients with conditions driven by the IL-17 and IL-23 axis often present with: Psoriasis: Characterized by well-defined, erythematous plaques with silvery scales, typically located on extensor surfaces. Hidradenitis suppurativa: Presents with painful nodules, abscesses, and sinus tracts in intertriginous areas. Other manifestations: Psoriatic arthritis may occur, affecting joints and leading to significant morbidity. Diagnosis / Workup The diagnosis of psoriasis and hidradenitis suppurativa prima