Up to the beginning of the eighties, psoriasis was thought to be caused by a hyperproliferation of epidermal keratinocytes (cells of the surface of the skin which produce keratin, a molecule essential to its consistence), and to a loss of their differentiation. The skin inflammation was considered to be a side effect of the illness. Today, it has been demonstrated the psoriasis is an illness mediated by T cells (cells of the immune system) : it is an activation of the immune system that leads to a too rapid proliferation of the keratinocytes.
This better knowledge of the mechanism involved in psoriasis has led to new treatment strategies. Some are already available on the market. Here is an overview of two of these strategies : biotherapy treatments, and photodynamic treatments.
Biotherapy consists of using molecules to target actors (mainly T cells or inflammatory cytokines, small proteins involved in inter-cell communication) which are involved in the activation of the immune response which leads to the hyperproliferation of cells. This targeting works on the principle of the recognition of a molecule by an antibody.
Some of these treatments are already available, others are in a clinical or preclinical trial phase.
The main targets of biotherapies are:
- TNF-α (Tumor Necrosis Factor–α): a very pro-inflammatory cytokine which increases the recruitment of cells of the immune system. The anti-TNF-α act to decrease the interactions between the immune cells and the keratinocytes. The main molecules using this strategy are Etanercept, Adalimumab, Infliximab and Certolizumab.
- Interleukine-17 or IL-17: IL-17 plays an important role in the inflammatory response. Several treatments are being developed or evaluated, and the results published for one of the molecules (Secukinumab) have received very good press, especially with authorities which are very much involved in the treatment of psoriasis. Indeed, this molecule, thanks to its very specific targeting, seems to minimize side effects which are often associated to biotherapy treatments (mostly an immunosuppressive effect of the treatments, which facilitates infections). Other molecules like Ixekizumab or Brodalumab target the IL-17.
- IL13/IL12: the strategy of biotherapies targeting these classes of molecules is to block the differentiation of naive T cells in Th17 or Th1 (auxilliary T cells which help to recruit other cells of the immune system). The most accomplished molecules in this path are Ustekinumab and Apilimod.
- T cells: a molecule, Alefacept, targets the activation of T cells and in this way acts on two mechanisms: it decreases in the blood the number of memory T cell, CD8+ and CD4+ and it decreases the expression of several interleukins and TNF-alpha.
Biotherapies are very promising for the treatment of psoriasis. For certain patients, the use of these molecules have led to a spectacular improvement of their illness. However, the lack of an overall picture, the side effects that have been recorded and the cost of these treatments limit their use to moderate or severe cases of psoriasis. They require a strong medical surveillance.
Photodynamic therapy or PDT
Another promising treatment for psoriasis, less known, is photodynamic therapy or PDT. For a PDT treatment to be functional, 3 conditions must be met: the presence of a photosensitizer in the treated tissue, a visible light excitation and the presence of oxygen in the treated cells. Indeed, it is the liberation of singlet oxygen, which is very reactive, after the excitation of a photosensitizer by light which leads to cellular death in the treated zone. Studies are still being led to improve the side effects associated with these treatments (pain and burning sensation on the treated tissue).
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