Psoriasis is an inflammation of the skin. It is not contagious but heavy forms of it make sufferers' lives a misery. Over the years, the pharmaceutical industry has discovered many medicines to treat it. Current research is likely to result in even better therapies in the future.

What is psoriasis? Top

Psoriasis is a chronic inflammatory skin disorder, often with relapses and remissions, characterised by red disc-like raised lesions with dry, silvery scaling, most frequently on the elbows, knees or scalp. These build up because the rate of cell (keratinocyte) division of psoriasis skin is much higher than normal. Most cases are mild, but a few can be widespread and disfiguring. Psoriasis is not contagious. Its cause is still not known.

Until the 1980s, the disease was thought to be caused by cells dividing at an abnormally high rate. However, as scientists began to perceive psoriasis as an immunological condition, research has focused on the role of inflammatory messenger compounds (cytokines) in the condition’s progress, as well as on the role of T-lymphocytes (white blood cells), and on genetic factors.

In November 2003, research groups in Europe and the USA reported independently on the implication of three genes on human chromosome 17 and of the regulatory gene RUNX 1 in psoriasis. While the disease is not curable, treatment can bring periods of remission and improve both appearance and mood.

Who does psoriasis affect? Top

In Europe, it is estimated that plaque psoriasis has a prevalence of about 0.8 per cent. This means that the disease affects about 3.7 million Europeans, with about 2.4 million people considered to have moderate to severe disease. Psoriasis usually occurs in young adults (15-40 years, with mean age of onset of 33), with men and women equally likely to be affected.

Present treatments Top

Mild to moderate skin plaques are traditionally treated with topical formulations containing either dithranol or coal tar and colloidal sulphur. Ointments containing vitamin D derivatives or a vitamin A derivative are also used to treat chronic plaques. Steroids applied to the skin are also frequent first-line treatments, but inflammation may recur when they are stopped. A combination cream containing both a vitamin D derivative and a steroid is also available.

Antibacterial and antifungal solutions may be useful in preventing infection of the inflamed skin. Exposure to certain wavelengths of ultraviolet light while simultaneously taking psoralen and a vitamin A derivative can be beneficial in some cases. In severe psoriasis, immunosuppressive medicines are effective.

None of the former treatments for psoriasis has been really satisfactory. Many topical preparations are messy, slow acting (four to six weeks) and none get rid of the condition: relapse is inevitable. A retinoid given orally persists in the body for a long time and can cause birth defects, so women of child-bearing age are warned not to become pregnant for two years after a course of this type of treatment.

With new understanding of the disease’s action has come a new generation of medicines that offer the first new approaches in 40 years. One is a human fusion protein which is given by injection and consists of two different parts. Through its dual function, the fusion protein inhibits so-called memory-effector T-lymphocytes, which are thought to play a key role in psoriasis.

Effector T-lymphocytes are also targeted by an injectable anti-CD11a monoclonal antibody that has been available for a few years. Both medicines are intended for use in moderate to severe psoriasis and appear to have similar efficacy, with about 35 per cent of patients achieving a reduction in symptom score of 75 per cent or more.

Finally, several new compounds have been developed that are directed against the inflammatory mediator tumour necrosis factor alpha (TNF-α). In the US and the EU, TNF-α-inhibitors are approved for the treatment of moderate to severe plaque psoriasis in patients who have failed to respond to other systemic therapy, or have a contraindication against it or are intolerant of it.

The compounds have also been shown to have a positive influence on joint and skin components of the disease. They are used to reduce the signs and symptoms of psoriatic arthritis in adults with moderate to severe disease who have shown inadequate response to disease modifying anti-rheumatic medicines.

What’s in the development pipeline? Top

The range of biological treatments for psoriasis is set to expand. New treatments under development include an anti-interleukin (IL)-2-monoclonal antibody. Already approved for transplant rejection, this is being tested to see whether it can prolong the disease-free period after an initial response to immunosuppressive treatment with a calcineurin inhibitor. The cytokine IL-8, a potent keratinocyte growth factor and greatly raised in psoriasis, is the target of a specific monoclonal antibody in Phase 3 trials.

Another monoclonal antibody in Phase 3 trials is directed against the CD2 antigen found on activated T-lymphocytes in psoriasis. IL-18 binding protein, a human recombinant molecule directed against the mediator of inflammation IL-18, has recently moved into Phase 3 clinical investigation.

An analogue compound of the calcineurin inhibitor cyclosporine is also in Phase 3 trials. The strong correlation between the new compound’s concentrations and efficacy might allow for accurate dosing of patients compared with existing calcineurin inhibitors.

Since some patients with psoriatic arthritis do not respond to typical therapy, alternatives are needed. Findings suggest that IL-12 and IL-23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. A human monoclonal antibody that inhibits receptor-binding of these cytokines is being tested in Phase 2 to assess its efficacy and safety in psoriatic arthritis.

Research groups have linked up to develop a transdermal delivery system for the treatment of psoriasis. The needle-free injection device works by using high-pressure. It is already used by diabetics for the self-administration of insulin and is said to cause less pain and dermal damage than other devices.

Studying genetic variants in the genomes of patients with psoriasis and healthy controls has resulted in the detection of a genetic variant within what is known as the LCE gene cluster. One of the LCE genes’ functions is to code proteins that are part of cells located in the outermost layers of skin. These proteins are important for maintaining the skin’s barrier function.

The findings suggest that a compromised skin barrier function plays a role in the development of psoriasis. It represents another advancement in the general understanding of the genetic basis of psoriasis, which in turn is important for early diagnosis and prediction of an individual’s risk of having the disease.

A psoriatic plaque before and after 2, 4 and 8 weeks treatment with a topical retinoid, showing a good response.

The longer-term future Top

Although psoriasis is still not well understood, the new biological compounds under development all focus on molecules that are known to be involved in its progress and are more specific in their actions than older medicines such as steroids, immunosuppressants, vitamins and coal tar.

There is therefore good hope of treatments that give better control of symptoms with fewer troublesome side-effects and greater convenience in use.