Advancements in understanding and treating psoriasis: a comprehensive review of pathophysiology, diagnosis, and therapeutic approaches

Abstract

Psoriasis is a chronic autoimmune disease affecting millions worldwide. This condition is characterized by scaly, red patches of skin that can be painful, itchy, and disfiguring. This non-contagious illness forms plaques and accelerates the dermal cell's life cycle. This review provides a comprehensive overview of the current knowledge on psoriasis, covering its definition, prevalence, causes, pathogenesis, clinical features, diagnosis, and treatment options. The psychosocial impact of psoriasis on patients and their coping mechanisms is also explored. Biologic agents, which target specific cytokines involved in psoriasis pathogenesis, have revolutionized psoriasis treatment and have significantly improved patient outcomes. However, effective and safe treatments for moderate to severe psoriasis are still needed. Future research directions include the development of biomarkers for predicting disease severity and treatment response, investigating new therapeutic targets like the microbiome and epigenetics, and leveraging advancements in technology and genomics for deeper insights into psoriasis pathogenesis and treatment. This study summarizes the key aspects of psoriasis, including its epidemiology, pathophysiology, clinical traits, disease burden, and management. However, further research is needed to improve treatment outcomes and enhance the quality of life for patients affected by this complex condition.

Keywords: Autoimmunity; Cytokines; Interleukin; Keratinocytes; NF-κB signaling pathway; Psoriasis; STAT signaling pathways; TNF.

Figure 1. Types of psoriatic skin conditions.

(A) Plaque psoriasis; (B) guttate psoriasis; (C) pustular psoriasis; (D) inverse psoriasis; (E) erythrodermic psoriasis and (F) nail psoriasis.

Figure 2. Pathogenesis of psoriasis.

The pathogenic axis of IL-23 and IL-17 is what causes psoriasis. The maturation of myeloid dendritic cells (mDCs) and their production of TNF-, IL-12, and IL-23 are encouraged by the activation of plasmacytoid dendritic (pDCs), which in turn triggers the activation of Th (T helper) 1 and Th17 and the release of inflammatory cytokines including TNF-, IL-17, IL-21, and IL-22. When these cytokines, particularly IL-17, activate keratinocytes, they create antimicrobial peptides, cytokines, and chemokines that increase inflammation.

Figure 3. The pathogenic process of psoriasis.

The pathogenic process of psoriasis is mostly shown in this image from the viewpoint of keratinocytes. Initial stimuli can excite keratinocytesand stressed keratinocytes produce self-nucleotides and antimicrobial peptides, activate pDCs and later DCs, and participate in psoriasis beginning phase. Activated keratinocytes impact the pathogenesis of psoriasis after being stimulated by cytokines in ways such as inflammatory infiltration, epidermal hyperplasia, innate immunity, tissue reorganization, etc.

Figure 4. NF-κB activation via the IκB degradation route is a common mechanism.

TRAF2, TRAF6, RIP, MALT1, and NEMO are all K63 polyubiquitinated in response to ligand interaction of certain membrane receptors. Through their interaction with TAB2 and TAB3, the polyubiquitin chains attract the TAK kinase complex. Activated TAK1 may phosphorylate and activate IKKβ, which in turn phosphorylates IκB bound to cytosolic NF-κB, causing its destruction by the proteasome and the βTrCP E3 ubiquitin ligase. The target genes are subsequently transactivated when free NF-κB moves to the nucleus. By removing K63 ubiquitinated chains from active TRAFs, RIP, and NEMO, deubiquitinating enzymes CYLD and A20 may prevent NF-κB activation. A20 may also stop NF-κB activation brought on by TNF-α by catalyzing the K48 ubiquitination of RIP, which results in its proteasomal destruction. The TNF receptor (TNFR1) not only encourages survival by activating NF-κB target genes, but it also increases antagonistic apoptotic pathways.

Figure 5. JAK/STAT signaling pathway activation.

(1) Cytokines and growth factors bind to the appropriate receptors, which causes the receptor to dimerize and draw in associated JAKs; (2) Tyrosine phosphorylation of the receptors and the creation of STAT docking sites occur as a result of JAK activation; (3) Tyrosine phosphorylates STATs; (4) The receptor and STATs separate, forming homodimers or heterodimers; (5) STAT dimers attach to DNA inside the nucleus and control transcription.