From the Guidelines
Psoriasis is primarily caused by an inflammatory, immune-mediated condition stemming from inappropriate activation of cutaneous T cells and dendritic cells with subsequent release of inflammatory cytokines. This condition leads to keratinocyte hyperproliferation, the influx of neutrophils, and further propagation of inflammation, as noted in the joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients 1. The key mechanisms involved include:
- Inappropriate activation of cutaneous T cells and dendritic cells
- Release of inflammatory cytokines such as interleukin (IL) 1, IL-6, IL-12, IL-17, IL-23, and tumor necrosis factor alpha
- Keratinocyte hyperproliferation
- Influx of neutrophils
- Propagation of inflammation These mechanisms contribute to the development of psoriasis and its various forms, including plaque, guttate, palmoplantar, inverse, and pustular psoriasis, as discussed in the guidelines 1. The inflammation associated with psoriasis also contributes to systemic disease associations, such as metabolic syndrome and arthritis. Understanding these mechanisms is crucial for the management and treatment of psoriasis, particularly in pediatric patients, as outlined in the guidelines 1.
From the Research
Mechanisms Leading to Psoriasis
The mechanisms leading to psoriasis are complex and involve multiple factors, including:
- Genetic susceptibility and environmental triggers 2
- Inflammatory pathways marked by excessive production of cytokines IL-12 and IL-23, driving differentiation of pathogenic T cell responses resulting in TNF and IL-17 production 2
- The TNF/IL-23/IL-17 axis, which is responsible for maintaining inflammation in psoriatic skin 2, 3
- A pathological network of interactions between immune cells and other types of cells, including dendritic cells, TH17 cells, and keratinocytes 3
- The role of innate immunity, including the presence of innate immune cells and their products in psoriatic skin plaques 4
- The dynamic interplay between multiple genetic risk foci, environmental risk factors, and excessive immunological abnormalities 5
Key Cells and Cytokines Involved
Key cells and cytokines involved in the pathogenesis of psoriasis include:
- Dendritic cells, which produce TNF-α and IL-23 to promote T cell differentiation toward TH17 cells 3
- TH17 cells, which produce key psoriatic cytokines IL-17, IFN-γ, and IL-22 3, 6
- Keratinocytes, which play a crucial role in the initiation and maintenance of psoriatic inflammation 3, 5
- TNF-α, IL-23, and IL-17, which are central to the pathogenesis of psoriasis 2, 3, 5
- Innate lymphoid cells (ILCs), particularly ILC3, which induces psoriasis rashes directly without T-cell/antigen interaction 5
Immunological Abnormalities
Immunological abnormalities in psoriasis include:
- Decreased Tregs function 6
- Increased production of inflammatory cytokines, such as TNF-α, IL-17, and IL-22 2, 3, 6
- Modulation of the activation of CD4+ T cells by immunomodulator or methotrexate treatment 6
- A significant decrease in the activated CD4+ T cells in patients on methotrexate or anti-TNF therapy 6