Biology of psoriasis

At a simple level, psoriasis is characterised by an over proliferation of keratinocytes, i.e. skin cells replicating too quickly. The number of proliferative cells in the basal layer doubles and the normal cell cycle (which is around 28 days) is speeded up by seven times, the transit time becoming around 4 days (although this will vary depending on disease severity). Not only does over proliferation occur but incomplete cell development, that is abnormal keratinocyte differentiation, is also seen. The granular layer is either absent or reduced and hyperkeratosis and parakeratosis develop. This hyperproliferation is accompanied by inflammation and vascular changes. Skin cells heap up into plaques and are then shed in noticeable clumps.

Clinically, a typical psoriatic plaque is salmon pink in Caucasian skin and a slightly darker shade of normal skin tone for skin types 4–6. The actual colour of the plaque may be masked by a covering of silvery, white skin scales. Because of the high level of vascular activity within the psoriatic plaques, there is a proliferation of blood vessels near the surface of the plaque. This accounts for the change in colour of the skin and also explains a unique symptom of psoriasis known as Auspitz sign. This describes the symptom of pin-prick bleeding when the skin is scratched or knocked by the slightest trauma. The hyperkeratosis leads to induration or skin thickening so that a plaque is raised from the rest of the skin surface.

The simple description of psoriasis being a hyperproliferative disorder with significant inflammatory components belies a complex cascade of immune stimulated reactions that occur in the skin. Understanding of these processes is increasing, but the picture is still somewhat incomplete. However, it is reasonable to describe psoriasis as an immune-mediated condition in which T-cells play a significant role; indeed, psoriasis is recognised as the most prevalent T-cell-mediated inflammatory condition seen in humans (Kreuger, 2002).

T-cells are a type of lymphocyte (other lymphocytes being B-cells and natural killer cells) and they play an important role in cell-mediated immunity. It is well recognised that T-lymphocytes infiltrate the skin where psoriatic plaques occur and more recently it has been possible to identify the sub-types of these T-cells as CD4⁺ and CD8⁺ T-lymphocytes. It is not entirely clear what causes this initial activation of the T-cells; however, once activated they move into the bloodstream and from there into the dermis by ‘squeezing’ through the blood vessel walls. Here they are reactivated; CD4⁺ cells into Type 1 helper cells (TH1) and CD8⁺ cells into Type 1 cytotoxic cells. Reactivation occurs through contact with antigen presenting cells. Together these two types of cells initiate an inflammatory cascade as inflammatory cytokines, whereby interferon gamma (IFN-γ) and tumour necrotising factor alpha (TNF-α) are produced. These cytokines incorporate with proinflammatory chemicals which in turn cause the keratino cytes to hyperproliferate. In patients without psoriasis, this inflammatory process is a response to a physical, biological or chemical trigger which threatens (or causes) injury. Once the injury is resolved, the inflammatory process is switched off. In patients with psoriasis, it is thought that the immune system mistakenly recognises the body’s cells as foreign, triggering the repair response causing inflammation. This response is not ‘switched off’ in the way that it is following an actual injury and skin cells continue to proliferate.