Psoriaris : what is the genetic link?

Psoriaris | Tebu Bio

Psoriasis is an inflammatory skin disease. It is generally characterized by the appearance of thick patches of peeling skin (which come off in the form of white “scales”).

The plaques appear in different places on the body, most commonly on the elbows, knees, and scalp. They leave areas of red skin. This chronic disease evolves in cycles, with periods of remission. It is not contagious and can be well controlled with treatment.

Psoriasis can be very unpleasant or even painful when it appears on the palms of the hands, the soles of the feet or in the folds of the skin. The extent of the disease varies from person to person. Depending on where the plaques are located and how extensive, psoriasis can be embarrassing and detrimental to social life. Indeed, the look of others on skin diseases is often a blessing.

It is due to an accelerated renewal of the skin cells and occurs in genetically predisposed subjects. Psoriasis can affect both children and adults, and men and women.

It is more common in people with white skin. It most often begins in adolescence or young adulthood. Familial forms tend to occur in adolescents between the ages of 10 and 20. After 40 years, rather isolated forms appear with very few family attacks.

Types of psoriasis

There are several types of psoriasis. The most common form is plaque psoriasis, also called psoriasis vulgaris (because it accounts for more than 80% of cases), generally marked by red patches with adherent white scales, with well-defined contours, affects bastion areas (elbows, knees, etc.). This is the most common form.

Guttate psoriasis

In less than one in 10 cases, mostly in children and adolescents, psoriasis takes the form of small plaques less than one centimeter in diameter. This is a form of psoriasis called “guttate psoriasis”.

This condition can follow a streptococcal infection. In the case of guttate psoriasis, it does not appear in patches, but in small droplets scattered all over the body, especially on the areas of friction with clothing (trousers waistband, bra, etc.) or no (forearm, scalp…). Guttate psoriasis does not leave large irritating patches but small areas that heal faster after the scales fall off.

Reverse psoriasis

Reverse psoriasis (also called fold psoriasis) is a form of psoriasis in which the red (and smooth) patches are restricted to the fold areas (armpits, groin, navel, etc.).

Reverse psoriasis owes its name to the location of the red and irritating plaques: these are on the areas spared in the common form of psoriasis (submammary, intergluteal and inguinal folds).

The genital areas can be affected as well as the popliteal and axillary hollows. It is also called fold psoriasis. Large folds are prone to the appearance of well-demarcated, red and smooth patches (without scaling).

Other more specific types of psoriasis exist but the most common forms are defined above.

What are the complications of psoriasis?

Certain diseases are more frequently observed in patients with psoriasis than in the general population. These psoriasis-associated diseases appear to share similar onset mechanisms: chronic inflammation and, possibly, genetic predisposition. Among the diseases that may precede, be associated with or follow psoriasis:

Inflammatory rheumatism (rheumatoid arthritis and spondyloarthritis, for example);
– Certain chronic inflammatory diseases of the digestive tract (Crohn’s disease, ulcerative colitis, for example),
Vitiligo, a skin disease that results in depigmented spots (white spots),
– Certain inflammations of the thyroid.

It also appears that more cardiovascular disorders (eg myocardial infarction) and cases of type 2 diabetes are being diagnosed in patients with psoriasis.

Where does it come from?

Many factors play an intricate role in the onset of psoriasis. It is now considered to be an autoimmune disease that develops in people with a predisposed condition and under the influence of certain so-called predisposing factors.

An autoimmune disease

The origin or psoriasis can be found in human genetics. Genes play a role in the development of psoriasis, within the immune system, gene mutations can be responsible for this disease.

American researchers have found genes which take part in the development of this disease on several chromosomes: some genes located on chromosomes 1, 3, 6, 8, 17 and 20 play a role in the genetic predisposition.

For example, it has been observed that patients with 5 or 6 copies of certain genes (coding for small antimicrobial and proinflammatory proteins which can be expressed on the skin) located on chromosome 8 are more likely to develop psoriasis than people with only 2 copies of them.

For not yet firmly established reasons, T lymphocytes (immune cells) migrate to the skin and produce cytokine (inflammatory molecule), then cytokine stimulates the production of keratinocyte (skin cells made up of keratin). The accumulation of these newly created skin cells cause the increased thickness of the external layer of the epidermis which is called hyperkeratosis.

Favorable or aggravating factors

Scratching, skin trauma, certain ENT infections, stress, taking certain medications, being overweight, excess alcohol or tobacco, environmental factors like the season change can trigger or aggravate psoriasis flare-ups.

A genetic predisposition

Psoriasis is a disease with a hereditary component but transmission from generation to generation is not systematic even if it often runs in families.

At most, we inherit genes that make us more likely to develop psoriasis. If a member of the family suffers from psoriasis, the other members of his family are likely to develop psoriasis too.

Nearly 40% of patients have one or more members of their family also affected. If one of the two parents is affected, the risk for the child of suffering from this affection varies from 5 to 10%.

Medical advice

Here are some general tips to reduce flare-ups:

– No long exposition to sun
– No Alcohol
– No smoking
– Losing a little weight
– Psychotherapy
– Reduce stress

Available treatments

Methotrexate

It is one of the reference treatments for severe psoriasis. It is an anti-inflammatory and immunosuppressive agent whose role is to halt tissue cell proliferation by interfering with the normal use of folic acid during cellular reproduction.

Because proliferation of malignant cells is higher than the one of healthy cells, methotrexate can slow their proliferation without inducing irreversible damage to healthy tissues.

Patients taking methotrexate should be regularly monitored to detect any potentially serious adverse effects on the liver, lungs or blood. It is contraindicated in pregnant women and in women of childbearing age without effective contraception.

Cyclosporine

Cyclosporine, an immunosuppressive drug, has an efficacy comparable to methotrexate. This substance has the property of blocking certain cells involved in immune reactions. This molecule sticks to T lymphocytes and halts their action. These main side effects are kidney toxicity, high blood pressure, liver problems, tremors, tingling hands and feet, excessive hair growth, digestive disorders, swelling of the gums.

Retinoids

Acitretin is part of the retinoid family. Retinoids are

  • A vitamin synthetic derivatives,
  • A vitamin intervenes in the development and differentiation of white cells such as T lymphocytes,
  • A vitamin also maintains the integrity of the skin.

Acitretin slows the renewing of skin by inhibiting the migration of inflammatory cells from blood to skin. Its effect on psoriasis plaques appears after six to eight weeks. It is more effective in children than in adults.

Its main adverse effect is the dryness of the skin and mucous membranes it causes. The initial prescription must be written by a dermatologist. Acitretin is contraindicated in case of alcohol consumption, pregnancy or in women of childbearing age without effective contraception.

Anti-TNF agents

Biotherapies in the treatment of psoriasis include anti-TNF agents (adalimumab, certolizumab, infliximab, etanercept). These substances act by blocking the action of a molecule produced by immune cells, the Tumor Necrosis Factor or TNF, involved in the body’s inflammatory processes.

TNF is a cytokine (inflammatory molecule) which plays a role in cells survival, proliferation, differentiation and death. It is secreted by inflammatory cells. It can activate anti-apoptotic pathways or death pathways. In regard to cancer, TNF is a double-dealer.

On one hand, TNF could be an endogenous tumor promoter, because TNF stimulates cancer cells’ growth, proliferation, invasion and metastasis, and tumor angiogenesis. On the other hand, TNF could be a cancer killer. The property of TNF in inducing cancer cell death renders it a potential cancer therapeutic, although much work is needed to reduce its toxicity for systematic TNF administration.

The proinflammatory activities link TNF-alpha with a wide variety of autoimmune diseases, including psoriasis. Systemic inhibitors of TNF such as anti-TNF antibodies have been approved for the treatment of inflammatory bowel disease, psoriasis and rheumatoid arthritis. These drugs, however, exhibit severe side effects and are expensive.

When receiving an anti-TNF drug, it is important to remain vigilant and to report to your doctor any sign that may suggest an infection: fever (even low) or weight loss (even moderate). Indeed, a neglected infection can have extremely serious consequences in people who receive anti-TNFs.

 

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