Psoriasis

Description

Alternative Names

Causes

The precise causes of psoriasis are unknown. It is generally believed that psoriasis is a disorder in which factors in the immune system, enzymes, and other biochemical substances that regulate skin cell division become impaired. This abnormal immune response causes rapid proliferation of keratinocytes (immature skin cells) and inflammation. Such events are likely to be triggered by environmental factors, such as weather or stress, in people with genetic factors that make them susceptible.

Inflammatory Response and Autoimmunity

The Normal Immune System Response. The inflammatory process is a byproduct of the body's immune system, which fights infection and heals wounds and injuries:

• When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign invaders, such as bacteria or viruses.
• The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight any infective agents.
• In the process, the surrounding area becomes inflamed and some healthy tissue is injured.
• Under normal conditions, the immune system has other factors that control and limit this inflammatory process.

The Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T-cells and B-cells. Both types of cells are designed to recognize foreign substances (antigens) and to launch an offensive or defensive action against them:

• B-cells produce antibodies, which are designed to attack the antigens. Antibodies can either ride along with a B-cell or travel on their own.
• T-cells have special receptors attached to their surface that recognize the specific antigen.

T-cells are further categorized as killer T-cells or helper T-cells (TH cells).

• Killer T-cells directly attack antigens found on bacteria or other cells.
• Helper T-cells also recognize antigens, but their role is two fold. They stimulate B-cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T-Cells, Cytokines, and the Inflammatory Response. The actions of the helper T-cells (TH cells) are of special interest. Researchers have observed high numbers of TH cells in psoriatic plaques:

• The activated TH cells infiltrate the skin cells in psoriasis and, in the case of psoriatic arthritis, also the joints. (There has been some debate over whether psoriatic arthritis is a unique disorder, but evidence now suggests that both psoriatic arthritis and psoriasis are caused by the same faulty immune process.)
• TH cells normally stimulate B-cells to produce antibodies. In the case of psoriasis, however, they appear to direct the B-cells to produce autoantibodies (self antibodies), which are directed against the body's own cells. In the case of psoriasis, they target self antigens in skin cells; in psoriatic arthritis, cells in the joints also come under attack.
• In the resulting autoimmune process, autoantibodies remain in circulation and continue to mount an immune attack against these cells.

Helper-T-Cells and Cytokines. TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and injury during the psoriasis disease process. In psoriasis, researchers are particularly interested in cytokines known as GRO-alpha, tumor necrosis factor, and certain interleukins.

Neutrophils. Cytokines attract to the scene large numbers of other large white blood cells known as neutrophils. Neutrophils stimulate the production of arachidonic acid, which triggers about 30 different chemicals, including two key players in the inflammatory process:

• Leukotrienes, which attract even more white blood cells to the area.
• Prostaglandins, which open blood vessels and increase blood flow.

Genetic Factors

A combination of genes is involved with increasing a person's susceptibility to the conditions leading to psoriasis.

HLA Molecules. The processes leading to all autoimmune diseases involve the human leukocyte antigen (HLA) system, which is genetically regulated. HLA molecules are designed to pick off parts of antigens and present them on the surface of a cell so that the various infection-fighting factors in the immune system can recognize and destroy them. Malfunction of this system is at the root of most immune disorders, including psoriatic arthritis. For example, psoriasis patients with a specific HLA genetic factor called HLA-CW6 tend to develop psoriasis at an earlier than average age. However, only 10% of people who harbor these genes develop psoriasis. Other genetic and environmental factors, then, are required to actually trigger the disease.

PSORs. Researchers have now identified four key genes (named PSORs 1-4) that are involved with psoriasis. Of particular interest are the genes located in regions on specific chromosomes that are linked to HLA and tumor necrosis factor, an immune component strongly associated with psoriasis.

Environmental and Other Triggers

Outside factors, including weather, stress, injury, and infection, while not direct causes, are often important in triggering the disease process leading to onset and worsening of psoriasis.

Weather. Weather is a strong factor in psoriasis:

• Cold, dry weather is a common precipitant of psoriasis flare-ups.
• Hot, damp, sunny weather helps relieve the problem in most patients.
• To confuse matters, some people have photosensitive psoriasis, which actually improves in winter and worsens in summer when skin is exposed to sunlight.

Stress and Strong Emotions. Stress, unexpressed anger, and emotional disorders, including depression and anxiety, are strongly associated with psoriasis flare-ups. In one study, nearly 40% of patients remembered a specific stressful event that occurred within a month of a psoriasis flare. A 2001 study suggested that stress can trigger specific immune factors associated with psoriasis flares. Some evidence indicated that people with psoriasis may respond to stress differently from those without the skin disease. In one study, psoriasis patients had fewer aggressive verbal responses than others did when confronted with hostile situations.

Infection. Infections caused by viruses or bacteria can trigger some cases of psoriasis. Some examples include the following:

• Streptococcal infections in the upper respiratory tract, such as tonsillitis, sinusitis, and so-called "strep" throat, are known to trigger guttate psoriasis in children and young adults. The infections may also worsen ordinary plaque psoriasis.
• The human immunodeficiency virus (HIV) is also associated with psoriasis.
• An uncommon form of human papillomaviruses (HPV) called EV-HPV has been associated with psoriasis. Although EV-HPV is probably not a direct cause, it may play an indirect role in the perpetuation of psoriasis. (This HPV form is not the virus associated with cervical cancer and genital warts.)
• Helicobacter pylori (H. pylori) infection, a major cause of peptic ulcers, has been proposed as a possible cause of psoriasis. Research in 2001 indicated that this is highly unlikely, at least in children.

It seems reasonable to assume that pustular psoriasis, which resembles an infection, is caused by some organism, but none to date have been identified.

Skin Injuries and the Kbner Response. The Kbner response is a delayed response to skin injuries, in which psoriasis develops later on at the site. In some cases, even mild abrasions can cause an eruption, which may be a factor in the frequency of psoriasis on the elbows or knees. (It should be noted that psoriasis can develop in areas with no history of skin disruption.)

Drugs. A number of drugs can worsen or induce pre-existing latent psoriasis, including the following:

• The anti-malarial drug chloroquine.
• Certain drugs used for hypertension and heart problems, including angiotensin-converting enzyme (ACE) inhibitors. Beta-blockers may actually trigger the onset of psoriasis and produce flare-ups in people who already have it.
• Progesterone used in female hormone therapies.
• Lithium, which is used in bipolar disorder. (It may trigger the onset of the disease and cause severe flare-ups in people who already have psoriasis.)
• Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), can cause or worsen psoriasis. (Other NSAIDs, such as meclofenamate, may actually improve the condition.)
• Withdrawing from oral steroids or high-potency steroid ointments that cover wide skin areas can cause flare-ups of severe psoriasis, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.
• Agents that cause rashes, a side effect of many drugs, can trigger psoriasis as part of the Kbner response.