Introduction

    Nilanjita Chanda, final BHMS student, Metropolitan Homoeopathic Medical College, Kolkata explores the immuno pathology of psoriasis.


Definition:

    Psoriasis is a non-infectious, inflammatory disease of the skin, characterized by well-defined erythematous plaques with large, adherent, silvery scales.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.

Histopatholgy

    The primary disease activity leading to psoriasis occurs in the epidermis, the top of the five layers of the skin. The main abnormality in it is increased epidermal proliferation due to excessive division of cells in the basal layers.

• The process starts in the basal layer of the epidermis, where keratinocytes are manufactured.
  
• Keratinocytes are immature skin cells that produce keratin, a tough protein that helps to form hair and nails as well as skin. In normal cell growth, keratinocytes mature and migrate from the bottom (basal) layer to the surface and are shed unobtrusively. This process takes about a month.
  
• In psoriasis, however, the keratinocytes proliferate very rapidly and travel from the basal layer to the surface in about four days. The skin cannot shed these cells quickly enough so they accumulate as thick, dry patches, or plaques.
  
• Silvery, flaky areas of dead skin build up on the surface of the plaques and are shed. The underlying skin layer, the dermis , is red and inflamed.
  
• The dermis contains nerves, blood and lymphatic vessels, which supply the abnormally multiplying keratinocytes with their blood supply and also transport potent immune factors that cause the underlying inflammation and redness.

Normal Skin

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 white blood cells: especially lymphocytes and neutrophils. Lymphocytes include two subtypes known as T-cell s and B-cells. Both types of cells are designed to recognize foreign substances (antigens) and to launch a protective 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 also the joints in the case of psoriatic arthritis, (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.

                                                                                                        Psoriasis

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 interleukins 8 (IL-8), 11 (IL-11), and 12 (IL-12), which appear to play strong roles in the destructive psoriatic process, and in IL-10, which may be protective and block cell growth leading to psoriasis.

Neutrophils: Cytokines attract to the scene large numbers of 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:

l Leukotrienes, which attract even more white blood cells to the area, and

l 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 disease 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. It should be noted, however, that 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 others trigger

    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 Köbner Response :

    The Köbner 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.