Psoriasis (L40)

Causes

Psoriatic disease—including psoriasis and psoriatic arthritis—arises from a multifactorial interplay between genetic susceptibility, immune dysregulation, and environmental triggers. Individuals often carry risk alleles in immune-regulatory genes, particularly within the HLA-C locus (notably HLA-C*06:02) and genes involved in the IL-23/Th17 signaling axis such as IL23R, IL12B, and TYK2. These genetic factors predispose the immune system to exaggerated inflammatory responses. Environmental triggers—including skin trauma (Koebner phenomenon), infections such as streptococcal pharyngitis, obesity, smoking, certain medications (e.g., lithium or beta-blockers), and psychological stress—can initiate disease in susceptible individuals. Mechanistically, these triggers activate innate immune cells in the skin, including dendritic cells and macrophages, which release cytokines such as IL-23 and TNF-α. This drives expansion and stabilization of Th17 and Th1 lymphocytes, leading to sustained production of inflammatory mediators such as IL-17, IL-22, and TNF-α, which ultimately promote keratinocyte hyperproliferation, vascular remodeling, and chronic tissue inflammation in both skin and joints. In essence, psoriatic disease reflects a genetically primed immune system that becomes locked into a self-amplifying inflammatory circuit following environmental provocation.

Pathophysiology

The pathophysiology of psoriatic disease is driven by a self-amplifying immune–keratinocyte inflammatory circuit centered on the IL-23/Th17 signaling axis. Activation of dendritic cells in the skin leads to production of IL-23, IL-12, and TNF-α, which promote differentiation and expansion of Th17 and Th1 T-cells. These activated lymphocytes release key effector cytokines—including IL-17A, IL-17F, IL-22, and TNF-α—that act directly on keratinocytes. In response, keratinocytes dramatically increase proliferation and produce additional inflammatory mediators such as IL-6, IL-8, antimicrobial peptides, and chemokines, which recruit neutrophils and additional immune cells into the epidermis. This creates the characteristic epidermal hyperplasia, parakeratosis, and neutrophilic microabscesses seen in psoriatic plaques. Parallel inflammatory signaling also affects the entheses, synovium, and bone, where cytokines such as IL-17 and TNF stimulate osteoclast activity and synovial inflammation, contributing to psoriatic arthritis. The disease therefore reflects a feed-forward inflammatory loop between immune cells and structural tissue cells, sustained by cytokine networks and intracellular signaling pathways such as JAK-STAT and NF-κB, which maintain chronic inflammation in skin and joints.

Clinical features

Psoriatic disease manifests through cutaneous, nail, and musculoskeletal features that reflect the underlying inflammatory process. The most recognizable presentation is plaque psoriasis, characterized by well-demarcated erythematous plaques covered with silvery scale, commonly affecting the extensor surfaces of the elbows and knees, scalp, and lower back. Lesions may itch, burn, or crack, and they often appear at sites of skin injury in a phenomenon known as the Koebner response. Nail involvement is frequent and includes pitting, onycholysis, subungual hyperkeratosis, and nail plate discoloration. In approximately 20–30% of patients, systemic inflammation extends to the joints, producing psoriatic arthritis, which can present with asymmetric oligoarthritis, distal interphalangeal joint involvement, dactylitis (“sausage digits”), enthesitis, and inflammatory back pain when the axial skeleton is involved. Beyond the skin and joints, psoriatic disease is increasingly recognized as a systemic inflammatory condition associated with higher rates of metabolic syndrome, obesity, cardiovascular disease, and depression, reflecting the broader impact of chronic immune activation.

Diagnosis

The diagnosis of psoriatic disease is primarily clinical, based on characteristic skin, nail, and musculoskeletal findings, supported by history and selective testing to exclude alternative conditions. Plaque psoriasis is recognized by well-demarcated erythematous plaques with silvery scale on typical sites such as the scalp, elbows, knees, and sacral region, while nail pitting, onycholysis, and subungual hyperkeratosis provide additional diagnostic clues. When joint symptoms are present, clinicians evaluate for psoriatic arthritis using features such as asymmetric joint inflammation, dactylitis, enthesitis, and distal interphalangeal joint involvement; the CASPAR (Classification Criteria for Psoriatic Arthritis) criteria are commonly used to support diagnosis in research and clinical settings. Laboratory tests are generally nonspecific, though inflammatory markers such as ESR or CRP may be elevated, and rheumatoid factor is typically negative, helping distinguish the condition from rheumatoid arthritis. Imaging—including X-ray, ultrasound, or MRI—may reveal joint erosions, new bone formation, or enthesitis in patients with suspected psoriatic arthritis. Skin biopsy is rarely required but can confirm the diagnosis when clinical findings are atypical by demonstrating epidermal hyperplasia, parakeratosis, and neutrophilic collections within the epidermis.

Mechanism of action videos

• The Biology of Psoriatic Disease
• Psoriasis Therapeutics- a 2026 Market Overview
• IL-23- Keeping the Alarm On
• IL-17A and IL-17F: Sisters in Inflammation
• What is IL-17?

Biological pathways

• Inhibition of nitric oxide production
• Inactivation of CSF3 (G-CSF) signaling
• TRAF6 mediated NF-kB activation
• Signaling by Retinoic Acid
• Interleukin-36 pathway
• RAC1 GTPase cycle
• Psoriasis mechanism and therapies
• Drug-induced formation of DNA interstrand crosslinks
• Signaling by Interleukins
• Nuclear Receptor transcription pathway
• Interleukin-4 and Interleukin-13 signaling
• Interleukin-23 signaling
• Interleukin-12 family signaling
• RUNX3 Regulates Immune Response and Cell Migration
• Generic Transcription Pathway
• DARPP-32 events
• SUMOylation of intracellular receptors
• Ovarian tumor domain proteases
• RNA Polymerase II Transcription
• SARS-CoV-2 activates/modulates innate and adaptive immune responses
• Differentiation of naive CD+ T cells to T helper 1 cells (Th1 cells)
• Differentiation of T cells
• Gene expression (Transcription)
• Signaling by CSF3 (G-CSF)
• Negative regulators of DDX58/IFIH1 signaling
• Evasion by RSV of host interferon responses
• SARS-CoV-2-host interactions
• NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake
• NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose
• NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis
• SARS-CoV Infections
• DDX58/IFIH1-mediated induction of interferon-alpha/beta
• SUMO E3 ligases SUMOylate target proteins
• NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
• SUMOylation
• Opioid Signalling
• Activation of anterior HOX genes in hindbrain development during early embryogenesis
• Activation of HOX genes during differentiation
• NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis
• Regulation of IFNG signaling

Clinical trials

• A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study With Open-Label Extension to Evaluate the Efficacy and Safety of Bimekizumab in Study Participants With Palmoplantar Pustulosis
• Phase 1b, Open-Label, Exploratory Biomarker Basket Study of S-4321 in Participants With an Autoimmune or Immune-Mediated Disease
• A Phase Ib Study of Nivolumab in Patients With Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)
• An Open-label Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of ORKA-001 in Participants With Moderate-to-Severe Plaque Psoriasis
• An Open-Label Extension Study to Evaluate Long Term Safety and Efficacy of Tildrakizumab in Patients With Psoriatic Arthritis.
• A Phase 3b Exploratory Multicenter Open-Label Study to Evaluate the Effect of Bimekizumab on Gene Expression Biomarkers in Study Participants With Moderate to Severe Plaque Psoriasis
• Proactive Therapeutic Drug Monitoring Versus Routine Care With the Novel Biologics in Psoriasis : a Pragmatic, Multicentric, Randomised, Controlled Study
• Effisayil® REP:An Open-label, Multicenter, Single-arm, Post-marketing Trial (in Select Countries) to Evaluate Efficacy and Safety and the Impact of Immunogenicity on Efficacy, Safety, and Pharmacokinetics of Spesolimab i.v. in Treatment of Patients With Generalized Pustular Psoriasis (GPP) Presenting With a Recurrent Flare Following Their Initial GPP Flare Treatment With Spesolimab i.v.
• Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine (Butantan-DV) in Patients With Autoimmune Rheumatic Diseases Living in Dengue-Endemic Areas
• A Multicenter, Randomized, Double-blinded, Placebo-controlled, Dose-range Finding Study of ORKA-001 in Participants With Moderate-to-Severe Plaque Psoriasis
• A Phase 3b/4 Multi-center, Randomized, Open-label, Long-term Safety Study of Deucravacitinib in Comparison to Ustekinumab in Participants With Moderate-to-Severe Plaque Psoriasis
• A Multicenter, Randomized, Parallel-Group, Double-Blind, Active-Controlled Study to Evaluate the Efficacy and Safety of Bimekizumab Compared to Ustekinumab in Children and Adolescents From 6 Years to Less Than 18 Years of Age With Moderate to Severe Plaque Psoriasis
• An Open-label, Randomized, Parallel-group, Noninferiority Study to Evaluate the Pharmacokinetics of Bimekizumab Administered Intravenously or as a Subcutaneous Injection in Participants With Active Psoriatic Arthritis and/or Active Axial Spondyloarthritis
• A Multicenter, Open-Label Extension Study to Assess the Long-Term Safety, Tolerability, and Efficacy of Bimekizumab in the Treatment of Subjects With Active Psoriatic Arthritis
• Multicenter, Open Label or Double-Blind, Placebo-Controlled Study to Evaluate the Pharmacokinetics, Safety, and Effectiveness of Certolizumab Pegol in Pediatric Study Participants With Moderate to Severe Chronic Plaque Psoriasis
• An Extension Study in Patients With Moderate to Severe Plaque Psoriasis to Evaluate the Long-term Safety, Efficacy, and Durability of Response to ESK-001
• Treatment of Psoriasis With Depression and/or Anxiety With Methotrexate vs Combined Methotrexate and Antidepressant, A Randomized Controlled Trial
• A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase Ⅱ/Ⅲ Clinical Study to Evaluate the Efficacy and Safety of CMS-D001 Tablets in Adult Patients With Moderate to Severe Plaque Psoriasis
• A Randomized, Active-Controlled, Double-Blind, Phase 3 Study to Compare Efficacy and Safety of CT-P55 With Cosentyx in Patients With Moderate to Severe Plaque Psoriasis
• Comparison of Efficacy of Methotrexate Versus Apremilast in the Treatment of Pruritus in Psoriasis: A Randomized Controlled Trial
• A Phase 4 Multicenter, Randomized, Double-Blind Study of Risankizumab for the Treatment of Adult Subjects With Moderate to Severe Genital Psoriasis or Moderate to Severe Scalp Psoriasis
• A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Deucravacitinib in Adolescent Participants (12 Years to Less Than 18 Years) With Moderate to Severe Plaque Psoriasis
• A Phase 3, Parallel-group, Randomized, Double-blind, 3-arm, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Subcutaneous Sonelokimab in Male and Female Participants Aged 18 Years and Over With Active Psoriatic Arthritis Who Are Naive to Biologic DMARDs
• A Phase 4 Multicenter, Randomized, Open-label, Efficacy Assessor Blinded Study of Risankizumab Compared to Deucravacitinib for the Treatment of Adult Subjects With Moderate Plaque Psoriasis Who Are Candidates for Systemic Therapy
• A Double-blind, Randomized, Placebo-controlled, Parallel-controlled, Multi-center Phase III Clinical Trial to Evaluate the Efficacy and Safety of a Botanical Total Coumarin Cream (TC Cream) in Treating Patients With Psoriasis Vulgaris
• A Phase 3, Randomized, Double-blind, Placebo Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Subcutaneous Tildrakizumab in Subjects With Moderate to Severe Genital Psoriasis
• Deucravacitinib-TNF Combination Therapy for Difficult-to-Control Psoriatic Disease
• A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Bimekizumab in Chinese Adult Study Participants With Moderate to Severe Plaque Psoriasis
• A Phase 1, Randomized, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Single Subcutaneous/Intravenous Administered SHR-1139 in Healthy Participants
• Triamcinolone With Vitamin D Synergistic Efficacy in Psoriasis
• Open-label, Randomized, Assessor-blinded, Efficacy, Safety, Tolerability, and Pharmacokinetics Study of Subcutaneous Risankizumab With an Adalimumab Reference Arm in Children With Active Juvenile Psoriatic Arthritis
• A Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Subcutaneously Administered Guselkumab in Improving the Signs and Symptoms and Inhibiting Radiographic Progression in Participants With Active Psoriatic Arthritis
• A Multi-Center, Randomized, Double-Blind, Placebo- and Active-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Zasocitinib (TAK-279) in Subjects With Active Psoriatic Arthritis Who Are Naïve to Biologic Disease-Modifying Antirheumatic Drugs (LATITUDE-PsA-3001)
• A Multi-Center, Randomized, Double-Blind, and Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Zasocitinib (TAK-279) in Subjects With Active Psoriatic Arthritis Stratified by Prior Biologic Use (LATITUDE-PsA-3002)
• A Phase 3, Multicenter, Open-label, Basket, LTE Study to Evaluate the Safety of Guselkumab in Pediatric Participants With Crohn's Disease, Ulcerative Colitis, or Juvenile Psoriatic Arthritis
• A Phase 3, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Participants With Generalized Pustular Psoriasis or Erythrodermic Psoriasis
• A Multicenter, Randomized, Double-Blind, Risankizumab-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Bimekizumab in Adult Study Participants With Active Psoriatic Arthritis
• A Proof-of-concept Phase 2a, Double-blind, 2-arm Trial to Investigate the Efficacy and Safety of Twice Daily Delgocitinib Cream 20 mg/g Compared With Cream Vehicle During a 16-week Treatment Period in Adult Subjects With Mild to Severe Palmoplantar Pustulosis
• A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of JNJ-77242113 for the Treatment of Biologic-naïve Participants With Active Psoriatic Arthritis
• A Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Who Had an Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor Alpha Agent