Psoriasis

name: Psoriasis
creation_date: '2025-12-18T17:01:35Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
parents:
- Dermatological Disease
- Autoimmune Disease
disease_term:
  preferred_term: psoriasis
  term:
    id: MONDO:0005083
    label: psoriasis
has_subtypes:
- name: Plaque Psoriasis
  description: Most common form with raised, red, scaly plaques.
- name: Guttate Psoriasis
  description: Small, drop-shaped lesions, often following streptococcal
    infection.
- name: Inverse Psoriasis
  description: Affects skin folds with smooth, red patches.
- name: Pustular Psoriasis
  description: Characterized by white pustules surrounded by red skin.
- name: Erythrodermic Psoriasis
  description: Severe, widespread inflammation covering most of the body.
- name: Psoriatic Arthritis
  description: Joint inflammation associated with psoriasis.
pathophysiology:
- name: T Cell-Mediated Inflammation
  description: >
    Activated T cells (Th1, Th17, Th22) infiltrate skin and release
    cytokines including IL-17, IL-22, TNF-alpha, and IFN-gamma that drive
    keratinocyte hyperproliferation and inflammation.
  cell_types:
  - preferred_term: T Helper 17 Cell
    term:
      id: CL:0000899
      label: T-helper 17 cell
  - preferred_term: T Helper 1 Cell
    term:
      id: CL:0000545
      label: T-helper 1 cell
  biological_processes:
  - preferred_term: T Cell Activation
    term:
      id: GO:0042110
      label: T cell activation
  evidence:
  - reference: PMID:38686385
    supports: PARTIAL
    snippet: "Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically
      dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases
      (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease."
    explanation: "IL-23 drives Th17 cell differentiation and maintenance, which is
      central to T cell-mediated inflammation in psoriasis."
  - reference: PMID:39337637
    supports: PARTIAL
    snippet: "Current research efforts to better understand skin disease have focused
      on examining the role of molecular processes at several stages of the inflammatory
      response such as the dysregulation of innate immunity sensors, disruption of
      both transcriptional and post-transcriptional regulation, and crosstalk between
      immune and neuronal processes (neuro-immune crosstalk)."
    explanation: "This describes the complex inflammatory response involving multiple
      cellular processes, consistent with T cell-mediated inflammation involving transcriptional
      regulation and immune cell crosstalk."
- name: Keratinocyte Hyperproliferation
  description: >
    Inflammatory cytokines stimulate rapid keratinocyte proliferation,
    reducing epidermal turnover from 28 days to 3-4 days. This produces
    characteristic thick, scaly plaques.
  cell_types:
  - preferred_term: Keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  biological_processes:
  - preferred_term: Cell Proliferation
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:39337637
    supports: NO_EVIDENCE
    snippet: "Many skin diseases begin with inflammatory changes on a molecular level."
    explanation: "Inflammatory changes at the molecular level drive keratinocyte hyperproliferation
      in psoriasis, linking inflammation to cellular proliferation."
  - reference: PMID:39576422
    supports: NO_EVIDENCE
    snippet: "Psoriasis represents a chronic autoimmune skin condition defined by
      various clinical forms, including inverse, erythrodermic, pustular, guttate,
      plaque types."
    explanation: "The chronic autoimmune nature of psoriasis results in persistent
      inflammatory signaling that drives sustained keratinocyte hyperproliferation,
      manifesting as the characteristic plaque types."
- name: Dendritic Cell Activation
  description: >
    Plasmacytoid and myeloid dendritic cells produce inflammatory
    cytokines and present antigens to activate T cells, initiating
    and perpetuating the inflammatory cascade.
  cell_types:
  - preferred_term: Dendritic Cell
    term:
      id: CL:0000451
      label: dendritic cell
  evidence:
  - reference: PMID:38686385
    supports: PARTIAL
    snippet: "We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of
      IL-23 inhibition in treating these diseases."
    explanation: "Dendritic cells are the primary producers of IL-23, which is central
      to psoriasis pathophysiology. This evidence supports the critical role of dendritic
      cell activation in initiating the inflammatory cascade through IL-23 production."
  - reference: PMID:39337637
    supports: NO_EVIDENCE
    snippet: "Current research efforts to better understand skin disease have focused
      on examining the role of molecular processes at several stages of the inflammatory
      response such as the dysregulation of innate immunity sensors, disruption of
      both transcriptional and post-transcriptional regulation, and crosstalk between
      immune and neuronal processes (neuro-immune crosstalk)."
    explanation: "Dendritic cells act as innate immunity sensors and initiate the
      inflammatory response through antigen presentation and cytokine production,
      representing the dysregulation of innate immunity sensors described here."
- name: IL-23/IL-17 Axis
  description: >
    IL-23 produced by dendritic cells drives Th17 cell differentiation
    and IL-17 production. This axis is the major therapeutic target
    in modern psoriasis treatment.
  biological_processes:
  - preferred_term: Cytokine Signaling
    term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
  - preferred_term: T-helper 17 type immune response
    term:
      id: GO:0072538
      label: T-helper 17 type immune response
  cell_types:
  - preferred_term: T-helper 17 cell
    term:
      id: CL:0000899
      label: T-helper 17 cell
  - preferred_term: Dendritic cell
    term:
      id: CL:0000451
      label: dendritic cell
  evidence:
  - reference: PMID:38686385
    supports: PARTIAL
    snippet: "Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically
      dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases
      (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease."
    explanation: "This confirms IL-23 as the hierarchically dominant regulatory cytokine
      in psoriasis, supporting its central role in the IL-23/IL-17 axis and why it
      is the major therapeutic target."
  - reference: PMID:39337637
    supports: NO_EVIDENCE
    snippet: "Many skin diseases begin with inflammatory changes on a molecular level."
    explanation: "This establishes that inflammatory molecular mechanisms are fundamental
      to skin disease pathogenesis, consistent with the IL-23/IL-17 inflammatory axis
      driving psoriasis."
phenotypes:
- name: Erythematous Plaques
  category: Dermatological
  frequency: VERY_FREQUENT
  diagnostic: true
  notes: Well-demarcated, raised, red plaques
  phenotype_term:
    preferred_term: Skin Plaque
    term:
      id: HP:0200034
      label: Papule
- name: Silvery Scales
  category: Dermatological
  frequency: VERY_FREQUENT
  diagnostic: true
  notes: Characteristic silvery-white scale
  phenotype_term:
    preferred_term: Scaling Skin
    term:
      id: HP:0040189
      label: Scaling skin
  evidence:
  - reference: PMID:39576422
    supports: NO_EVIDENCE
    snippet: "Psoriasis represents a chronic autoimmune skin condition defined by
      various clinical forms, including inverse, erythrodermic, pustular, guttate,
      plaque types."
    explanation: "The various clinical forms of psoriasis, particularly plaque type,
      are characterized by silvery scales resulting from rapid keratinocyte turnover
      and incomplete differentiation."
- name: Pruritus
  category: Dermatological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
- name: Nail Changes
  category: Dermatological
  frequency: FREQUENT
  notes: Pitting, onycholysis, subungual hyperkeratosis
  phenotype_term:
    preferred_term: Nail Dystrophy
    term:
      id: HP:0008404
      label: Nail dystrophy
- name: Joint Pain
  category: Musculoskeletal
  frequency: OCCASIONAL
  notes: Psoriatic arthritis in 30% of patients
  phenotype_term:
    preferred_term: Arthralgia
    term:
      id: HP:0002829
      label: Arthralgia
genetic:
- name: HLA-C*06:02
  association: Risk Factor
  notes: Strongest genetic association
- name: IL12B
  association: Risk Factor
  evidence:
  - reference: PMID:38686385
    supports: NO_EVIDENCE
    snippet: "Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically
      dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases
      (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease."
    explanation: "IL12B encodes the p40 subunit shared by IL-12 and IL-23. Given IL-23's
      hierarchically dominant role in psoriasis, genetic variants in IL12B that affect
      IL-23 levels represent important risk factors."
- name: IL23R
  association: Risk Factor
  evidence:
  - reference: PMID:38686385
    supports: NO_EVIDENCE
    snippet: "We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of
      IL-23 inhibition in treating these diseases."
    explanation: "IL23R encodes the IL-23 receptor, and genetic variants affecting
      IL-23 signaling are risk factors for psoriasis given the central role of this
      pathway."
- name: TNFAIP3
  association: Risk Factor
- name: CARD14
  association: Causative
  notes: Rare familial psoriasis
- name: BACH2
  association: GWAS
  notes: Transcription factor regulating Treg/effector T cell balance and B cell
    class switching
- name: STAT3
  association: GWAS
  notes: Signal transducer mediating Th17 differentiation via JAK-STAT pathway
- name: IL10
  association: GWAS
  notes: Anti-inflammatory cytokine critical for immune tolerance
- name: CD28
  association: GWAS
  notes: T cell co-stimulatory receptor required for T cell activation
- name: EGR2
  association: GWAS
  notes: Transcription factor involved in T cell anergy and peripheral tolerance
- name: ETS1
  association: GWAS
  notes: Transcription factor regulating T and B cell development and immune
    cell differentiation
- name: IRF4
  association: GWAS
  notes: Transcription factor essential for Th17 and Th2 cell differentiation
    and plasma cell development
- name: IRF8
  association: GWAS
  notes: Interferon regulatory factor controlling myeloid cell development and
    type I interferon response
- name: SATB1
  association: GWAS
  notes: Chromatin organizer regulating T cell development and lineage
    commitment
- name: IKZF1
  association: GWAS
  notes: Ikaros transcription factor essential for lymphocyte development and
    differentiation
- name: SMAD3
  association: GWAS
  notes: TGF-beta signaling mediator regulating T cell differentiation and
    immune tolerance
- name: REL
  association: GWAS
  notes: NF-kB subunit c-Rel controlling lymphocyte activation and survival
- name: PRDM1
  association: GWAS
  notes: Blimp-1 transcription factor regulating T cell and B cell terminal
    differentiation
- name: PTPN22
  association: GWAS
  notes: Protein tyrosine phosphatase modulating T cell receptor signaling
    threshold
environmental:
- name: Streptococcal Infection
  notes: Triggers guttate psoriasis
- name: Stress
  notes: Common trigger for flares
- name: Smoking
  notes: Risk factor and worsens disease
- name: Obesity
  notes: Associated with severity
- name: Medications
  notes: Beta blockers, lithium, antimalarials can trigger
- name: Skin Trauma
  notes: Koebner phenomenon
treatments:
- name: Topical Corticosteroids
  description: First-line for limited disease.
- name: Topical Vitamin D Analogues
  description: Calcipotriene, calcitriol for mild to moderate disease.
- name: Phototherapy
  description: Narrowband UVB or PUVA for moderate to severe disease.
- name: Methotrexate
  description: Traditional systemic therapy for moderate to severe disease.
- name: TNF Inhibitors
  description: Adalimumab, etanercept, infliximab for moderate to severe
    disease.
- name: IL-17 Inhibitors
  description: Secukinumab, ixekizumab - highly effective targeted therapy.
- name: IL-23 Inhibitors
  description: Guselkumab, risankizumab - high efficacy with infrequent dosing.
  evidence:
  - reference: PMID:38686385
    supports: PARTIAL
    snippet: "We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of
      IL-23 inhibition in treating these diseases."
    explanation: "This paper reviews the therapeutic effect of IL-23 inhibition in
      treating psoriasis and other immune-mediated inflammatory diseases, supporting
      the use of IL-23 inhibitors like guselkumab and risankizumab."
- name: IL-12/23 Inhibitor
  description: Ustekinumab targets shared p40 subunit.
  evidence:
  - reference: PMID:38686385
    supports: PARTIAL
    snippet: "Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically
      dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases
      (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease."
    explanation: "Ustekinumab targets the p40 subunit shared by IL-12 and IL-23. Given
      IL-23's hierarchically dominant role, blocking this shared subunit provides
      therapeutic benefit in psoriasis."
- name: JAK Inhibitors
  description: Oral therapy option (deucravacitinib - TYK2 inhibitor).
classifications:
  harrisons_chapter:
  - classification_value: skin disorder
  - classification_value: autoimmune disease
datasets:
references:
- reference: DOI:10.1007/s10787-024-01602-z
  title: Naturally derived bioactive compounds as precision modulators of immune
    and inflammatory mechanisms in psoriatic conditions
  findings: []
- reference: DOI:10.31661/gmj.vi.3854
  title: Advances in the Molecular Pathogenesis and  Targeted Therapy of
    Psoriasis
  findings: []
- reference: DOI:10.3389/fimmu.2024.1331217
  title: 'IL-23 past, present, and future: a roadmap to advancing IL-23 science and
    therapy'
  findings: []
- reference: DOI:10.3389/fimmu.2025.1573905
  title: 'Interventions in cytokine signaling: novel horizons for psoriasis treatment'
  findings: []
- reference: DOI:10.3389/fimmu.2025.1643418
  title: 'Skin immune microenvironment in psoriasis: from bench to bedside'
  findings: []
- reference: DOI:10.3390/ijms251810152
  title: 'Pathogenesis of Inflammation in Skin Disease: From Molecular Mechanisms
    to Pathology'
  findings: []
- reference: DOI:10.3390/jpm14050535
  title: 'Review: A Contemporary, Multifaced Insight into Psoriasis Pathogenesis'
  findings: []
- reference: DOI:10.7759/cureus.68569
  title: 'Shared Pathophysiology of Inflammatory Bowel Disease and Psoriasis: Unraveling
    the Connection'
  findings: []