Psoriasis is a chronic inflammatory disease of the skin that manifests as red, scaly patches. It is most often a mild disease, but there are severe forms (about 20% of cases), associated with generalized involvement and/or joint pain. At present, we do not know how to cure this disease, but treatments can reduce the symptoms and improve the quality of life of patients. Researchers are trying to describe the mechanisms that will eventually block its progression.
Understanding Psoriasis
Psoriasis is a multifactorial inflammatory disease of the skin (dermatosis) that affects approximately 2% of the French population. It occurs in people with a genetic predisposition and under the influence of contributing factors. The disease can appear at any age, but there is a peak of appearance between 20 and 40 years of age. About a third of cases occur before the age of 20, including in very young subjects. Early onsets are not more severe but are associated with more recurrences later.
Inflammatory mechanisms increasingly understood
Psoriasis is an immune disorder that leads to chronic and exaggerated skin inflammation and overproduction of keratinocytes, the keratin-producing cells that mainly make up the epidermis.
For unknown reasons, immune cells (activated T lymphocytes and neutrophils) are found in the skin and produce inflammatory molecules (cytokines Il-17, Il-22, TNF-alpha, and others). These stimulate the proliferation of keratinocytes. The renewal time of these cells, normally three weeks, then increases to three days. This results in an accumulation of immature keratinocytes on the surface of the skin, increasing the thickness of the outer layer (the cornea). We are talking about hyperkeratosis.
The immunological disorders at the origin of the disease are still poorly understood. However, they seem to be favored by different triggering factors such as stress, infection, or alcohol.
Symptomatic treatments
There is currently no treatment to cure psoriasis. However, some treatments significantly reduce symptoms and improve quality of life. They must be taken continuously to avoid relapses.
First-line drugs are anti-inflammatory ointments based on cortisone or vitamin D.
When psoriasis has spread beyond 20 to 30% of the body surface, treatment by the oral route (acitretin, methotrexate, ciclosporin, etc.) or by exposure to ultraviolet rays under dermatological control (puvatherapy) is indicated, with the effectiveness of approximately 50%.
If the psoriasis is resistant to at least two of these treatments, the last resort is biotherapy, which most often offers remarkable results for resistant psoriasis and psoriatic arthritis. It consists of the injection of monoclonal antibodies (etanercept, infliximab, adalimumab) that specifically target an inflammation mediator (TNF-alpha). With these treatments, more than two-thirds of patients achieve remission of more than 75% of their symptoms.
Spa treatments can be prescribed in certain situations and are covered by health insurance. However, their therapeutic benefit remains controversial.
Research challenges
Available treatments can be improved, particularly in their efficacy in certain patients and their safety. Thus, biotherapies are not devoid of adverse effects, with a particular risk of infection due to the depression of the immune system that they induce. In addition, in the case of discontinuation, psoriasis usually returns after a few weeks. New drugs are therefore being developed, in particular an immunosuppressant (apremilast), which inhibits the phosphodiesterase-4 enzyme necessary for the proper functioning of T lymphocytes. 17 (secukinumab).
To develop new, more specific, and better-tolerated drugs, laboratories are also trying to better understand pathological mechanisms such as the interactions between inflammatory cells and skin cells, or the nature and role of the different molecules present in inflammation. They are thus studying the contributions of several T lymphocyte populations, such as CD4+ Treg, TH17, and cytotoxic CD160+. At Inserm, a team is working on TREM molecules. These are receptors present on the surface of activated T lymphocytes in the skin that are found in abnormally high quantities in the case of psoriasis. The team is trying to block this receptor in an animal model of the disease (mouse) to assess the therapeutic effect.
Researchers are also trying to clarify the observed link between psoriasis and cardiovascular disorders. Several hypotheses are formulated: could psoriasis be the consequence of a disturbed metabolism? On the contrary, would it lead to a metabolic disorder? Could there be an immune and inflammatory factor common to both types of disease? Researchers are comparing the metabolism and the cutaneous and immune phenotypes in psoriatic patients and healthy individuals to provide some answers to these Questions.
Psoriasis: the causes
The precise cause of psoriasis is not known. Several factors are thought to be involved in the onset of the disease, in particular genetic and environmental factors.
Thus, there is a family history of psoriasis in about 40% of cases. Physical stress (infections, injuries, surgery, medications, etc.) or psychological stress (nervous fatigue, anxiety, etc.) can contribute to the onset of the disease.
Psoriasis could also be caused by autoimmune reactions occurring in the skin. These reactions would stimulate the multiplication of cells in the epidermis.
In people with psoriasis, these cells renew themselves at a much too fast rate: every 3 to 6 days rather than every 28 or 30 days. Since the lifespan of skin cells remains the same, they accumulate and form thick scabs.
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