PSORIASIS: IMMUNOPATHOGENESIS, CLINICAL CLASSIFICATION, COMORBIDITY BURDEN, AND EVIDENCE-BASED THERAPEUTIC STRATEGIES IN CONTEMPORARY DERMATOLOGY

Abstract

Background: Psoriasis is a chronic, immune-mediated, inflammatory skin disease affecting approximately 2–3% of the global population, with an estimated 125 million people living with the condition worldwide. Characterized by well-demarcated, erythematous, scaly plaques resulting from keratinocyte hyperproliferation and dysregulated immune activation, psoriasis carries a profound burden beyond the skin—including psoriatic arthritis in 30% of patients, and significantly elevated risks of cardiovascular disease, metabolic syndrome, inflammatory bowel disease, depression, and suicidality. The discovery of the IL-23/Th17 immunological axis as the central pathogenic pathway has transformed the therapeutic landscape, enabling a generation of highly targeted biologic agents with unprecedented efficacy.

Objective: To provide a comprehensive, evidence-based review of the immunopathogenesis, clinical classification, comorbidity spectrum, and pharmacological management of psoriasis within the framework of contemporary dermatological practice, synthesizing evidence from eight primary peer-reviewed sources.

Methods: A systematic review of eight primary sources was conducted, including original research articles, randomized controlled trials, meta-analyses, and authoritative clinical guidelines published between 2003 and 2024.

Results: Psoriasis pathogenesis is driven by dendritic cell activation triggering the IL-23/IL-17A axis, with Th17 cells producing IL-17A, IL-17F, and IL-22 that stimulate keratinocyte hyperproliferation, neutrophil recruitment, and antimicrobial peptide overexpression. Clinical forms include plaque psoriasis (90% of cases), guttate, inverse, pustular, and erythrodermic variants. The Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) provide validated disease quantification. Biologic therapies targeting TNF-α (adalimumab, etanercept), IL-12/23 (ustekinumab), IL-17A (secukinumab, ixekizumab), and IL-23p19 (guselkumab, risankizumab) achieve PASI 90 responses in 60–88% of patients, vastly superior to conventional systemic therapies (methotrexate, cyclosporine).

Conclusion: The paradigm shift from broad immunosuppression to cytokine-specific targeted therapy has fundamentally transformed psoriasis outcomes. Individualized treatment algorithms integrating disease severity, comorbidity profile, and patient preference, guided by treat-to-target strategies, offer the prospect of clear or almost-clear skin as a realistic treatment goal for most patients with moderate-to-severe psoriasis.