Psoriasis is a chronic inflammatory disease that targets principally the skin and one that is possibly of autoimmune aetiology. Skin in many patients becomes reddened and scaly (psoriatic plaques) due to inflammatory reactions and excessive production of skin in these localised areas. There is no general pattern to the distribution of plaques and several forms have been identified. Plaques may occur, among other regions, on the legs and arms, at the joints, on the genital organs or on the scalp.
These are the most prevalent forms and are termed ‘psoriasis vulgaris’ or ‘plaque psoriasis’. In some patients inflammation is confined to finger- and toenails, when the term ‘psoriatic nail dystrophy’ is used. A form of arthritis (psoriatic arthritis) is diagnosed when the inflammation occurs at the joints. Other forms of psoriasis include flexural psoriasis, which manifests itself in the folds of the skin, e.g. under the arms or on genital folds.
The most severe and potentially fatal form is erythrodermic psoriasis, when most of the skin peels off with consequent loss of temperature regulation and the loss of barriers to the external environment. In addition to physical stress, many patients with this (and other disfiguring skin conditions) become acutely self-conscious and may even become reclusive.
Causes of Psoriasis
The cause or causes of psoriasis are unknown with certainty, and theories are based on the degree of success of different treatments, e.g. the success of immune-suppressants in temporarily clearing plaques lends weight to the idea that psoriasis may be an autoimmune disease. Alternatively, the lesion may be confined to the skin itself, in which there is abnormal and unregulated overproduction of skin in certain areas of the body. Dry as opposed to oily skin appears more vulnerable.
Stress, infection or seasonal factors may contribute. Putative chemical irritants include alcohol, cigarette smoking and drugs, e.g. b blockers and chloroquine, an antimalarial drug. Precipitation of the disease has been reported following, for example, antimalarial drugs, antibiotics such as streptomycin, b blockers and lithium salts.
The genetic aetiology of psoriasis (and of course those of several other inflammatory diseases) is currently the subject of much research because this knowledge provides direction for the design of biological drugs. In the case of psoriasis, linkage analysis, which attempts to establish links between different genes in families in order to study disease-producing mutations, has produced evidence for at least nine loci on different chromosomes that are linked to the occurrence of psoriasis.
The genes identified are called psoriasis susceptibility genes 1–9 (PSORS1–9). Several of these mutated genes have been implicated in the occurrence of psoriasis. An interesting finding is that gene PSORS1, on chromosome 9, which is the most commonly occurring linkage gene, controls the production of certain proteins that occur in abnormally high amounts in the skin of people with psoriasis, and also the production of components of the immune system. Of particular interest are genes that direct the up-regulation of TNF-α and interferon-α.
Treatment of psoriasis
Traditional treatment may be topical, when soothing and emollient creams, lotions and ointments are applied directly to affected areas. Drugs used are relatively traditional preparations, including coal tar and mineral oil, and topical corticosteroids. These are of limited value, and corticosteroids are associated with skin thinning and rebound flares when withdrawn from use. Traditional systemic treatments include corticosteroids, which have severe adverse effects with prolonged use. Other immune-suppressants used include anti-metabolites and cytotoxic drugs, e.g. methotrexate, azathioprine and ciclosporin.
Treatment of psoriasis with biological drugs
The biological drugs used target specific inflammatory mediators or cells. Drugs used include adalimumab, etanercept, infliximab and ustekinumab, which binds to IL-12 and IL-23 and blocks their action.