Is psoriasis an autoimmune disease?

Psoriasis as an Immune-Mediated Inflammatory Disease

Psoriasis is an immune-mediated inflammatory disease rather than a true autoimmune disease, as it lacks specific autoantibodies, well-defined autoantigens, and classical autoimmune genetic risk factors. 1

Pathophysiology and Classification

• Psoriasis is characterized by dysregulated inflammation with inappropriate activation of cutaneous T cells and dendritic cells, leading to the release of cytokines that cause hyperproliferation of keratinocytes 2
• The disease involves both innate and adaptive immune mechanisms, with genetic susceptibility linked to at least 8 chromosomal loci (PSORS I-VIII), with HLA-Cw6 (PSORS1) being the major susceptibility gene 2
• Environmental triggers play an important role in pathogenesis, including drugs, skin trauma (Koebner's phenomenon), infection, and stress 2

Evidence Against Autoimmune Classification

• Unlike true autoimmune diseases, psoriasis lacks:
  • Specific autoantibodies directed against self-antigens 1, 3
  • Well-defined autoantigens 1, 3
  • Classical autoimmune genetic risk factors 1, 3
• Recent genetic findings show that the majority of psoriasis susceptibility loci are associated with innate immunity rather than adaptive autoimmunity 3
• The presence of neutrophils in skin lesions and activation of the innate immune system suggests psoriasis may better fit within the category of autoinflammatory disorders 1

Evidence Supporting Immune-Mediated Classification

• The efficacy of immunosuppressive drugs (methotrexate, cyclosporine) and immune-targeting biologics (TNF-blockers) in treating psoriasis strongly supports an immune-mediated pathogenesis 2
• Resolution of psoriasis is associated with decreased lesional infiltration of T cells, dermal dendritic cells, Langerhans cells, and neutrophils 2
• Psoriasis shows decreased expression of TNF-α, interferon-γ, and IL-12/23-dependent genes with successful treatment 2
• Inflammasome complexes, which are involved in innate immunity, play significant roles in psoriasis pathophysiology 1

Relationship with Other Immune-Mediated Diseases

• Psoriasis is associated with several other immune-mediated inflammatory diseases (IMIDs):
  • Psoriatic arthritis occurs in 25-30% of patients with psoriasis 2
  • Crohn's disease is 3.8-7.5 times more common in patients with psoriasis than in the general population 2
  • Multiple sclerosis appears more common in families with psoriasis 2
• These associations suggest shared genetic susceptibility and pathophysiological mechanisms rather than classical autoimmunity 2

Clinical Implications

• Understanding psoriasis as an immune-mediated inflammatory disease rather than an autoimmune disease has important implications for treatment approaches 3
• Current therapeutic strategies successfully target T cells or their products regardless of whether the disease is classified as autoimmune or autoinflammatory 4
• Patients with psoriasis should be monitored for associated comorbidities including cardiovascular disease, obesity, depression, and other immune-mediated conditions 2

Common Pitfalls in Classification

• Misclassifying psoriasis as purely autoimmune may lead to inappropriate therapeutic approaches or misunderstanding of disease mechanisms 3
• The presence of some autoantibodies in psoriasis patients has contributed to confusion about its classification, but these may be secondary phenomena rather than primary drivers of the disease 5
• UV light treatment of psoriasis may induce autoantibodies in some individuals, further complicating the classification 5

In conclusion, while psoriasis shares some features with autoimmune diseases and is certainly immune-mediated, the current evidence suggests it is better classified as an immune-mediated inflammatory disease with both autoinflammatory and autoimmune features, rather than a primary autoimmune disease 1, 3.