Psoriasis

Kim A. Papp, MD, PhD, FRCPC


What is Psoriasis?

Psoriasis is a life-long, non-contagious skin disease that causes dry, red, scaly patches (called lesions) on the skin.  These lesions can make the skin itch, burn, flake, or bleed. The most common form, plaque psoriasis, involves patches of raised, red skin covered with a silvery, white, flaky scale.

 

What Causes Psoriasis?

Psoriasis can appear at any age, can be unpredictable, and can vary in severity. This skin condition not only affects people physically, but emotionally as well. There is no known cure for psoriasis.

We now understand that psoriasis is a condition caused by a misdirection of the immune system. Like a combination lock, three things must occur in order to unlock the psoriasis lurking within our bodies. First, you must have the genes for psoriasis. Second, you must be exposed to a trigger and there are two possibilities: injury to the skin or an infection. Finally, the immune system must be in a particular way that permits the psoriasis to develop and to persist.

 

Genetics of Psoriasis

As yet, we do not know which genes are responsible for psoriasis. Though many candidate genes have been identified, none explain all causes of psoriasis. It is very likely that more than one gene is necessary to get psoriasis. In fact, psoriasis sometimes behaves as if each person had a "different" disease with huge variations in types and severity of psoriasis suggesting multiple genetic programs. The idea that multiple genes are involved is supported by the very different response to treatment seen between patients. One person's psoriasis may respond well to many different therapies while another person's psoriasis - appearing identical to the first, responds poorly to almost everything.

 

Psoriasis Triggers

Triggers are as important as genes in the development of psoriasis. Genes are from our biological parents - we cannot choose our genes. Similarly, psoriasis triggers are part of life and cannot be avoided. Accidental injuries, scrapes, cuts, burns, stitches, infection which may even include the common cold - can trigger psoriasis in some people. No one knows for sure but it is very possible that the psoriasis trigger is different for each person depending upon their genes.

 

Psoriasis and the Immune System

The ultimate player in the psoriasis game is the immune system. Think of the immune system as a community of individuals - cells. Each cell has a specific job such as detecting an infection, carrying debris for identification or destruction or killing abnormal cells. Cells communicate with one another by direct contact or by signals - cell cytokines. Cytokines are specializing substances which can flow through tissue and the blood stream. Cytokines relay messages to cells resulting in specific activation or deactivation of cell activity. Hormones and the nervous system can have some impact on the immune system. With such a complex system, multiple cells and multiple organs all interconnected, it is easy to see that the immune system is more like an ocean with different waves of activity in different parts of the body and with very different cells and signals moving about.

The immune system will determine whether a person gets psoriasis which persists for weeks, months, or years. The immune system will determine whether a person gets Crohn's disease, ulcerative colitis, and maybe diabetes, hypertension, and coronary arterial disease. The immune system is a big part of many of the diseases which can affect all of us, especially inflammatory diseases like psoriasis. The moment we appreciate that psoriasis is instigated and perpetuated by the immune system the causes, the treatments, and maybe possible cures are explained.

Our first case study involves a patient of Dr. Kim Papp's named Jane. As a child Jane fell off her bicycle while learning to ride. She scraped her knee, not a bad scrape but it hurt. Her body immediately activated the healing process to heal the skin and the immune system to ward off any potential infection.

Jane's immune system responded normally, just like everyone else but Jane has genes that redirect her immune response. In her case the immune system, activated by the injury, initiated psoriasis where she scraped her skin. Jane's psoriasis slowly spread to other areas of her body but it is now controlled by cream.

Paul, like Jane, developed psoriasis after an injury. In Paul's case, he was an adult who injured his arm at work. The psoriasis developed in the skin weeks after healing and spread rapidly. Creams were unable to control Paul's psoriasis; however, he is now taking a new injection which is controlling his psoriasis well.

 

How Did I Get Here?

What appears to happen is the immune system becomes confused. The immune system is programmed to react to something in or on the skin. The confusion occurs very early in the immune system's process. After the injury, antigen presenting cells (APC) take debris from the wound to a local lymph node. Once it is in the lymph node, the APC interacts with naive T-cells. If the signals are just right, the APC and naive T-cells make direct contact and transform the naive T-cells to be activated and proliferate, dividing rapidly to make many more, identical, activated T-cells.

Activated T-cells will make an extraordinary journey. They leave the lymph node and enter the blood circulatory system. Directed by cytokines, activated T-cells leave the circulatory system and enter the skin - but only when the cytokine signals tell them. Activated T-cells, in the skin, release new cytokines. These new cytokines direct the skin cells to grow faster and thicker. These new cytokines cause more blood to flow through the skin and new blood vessels to form.

Now you have psoriasis - red plaques because of the increased blood to the skin, thick and scaly because the skin is growing faster than normal.

It is because of genetics that the immune system engaged the APC to respond to the antigens. It is because of genetics that the naive T-cells were bombarded, proliferated, and surrounded. And it is because of genetics that the T-cells migrate to the skin, release the cytokine messengers that increase blood flow and cause the skin cells to increase the rate of growth.

The state of the immune system where the APC activates the T-cells will determine how and where psoriasis will occur. Psoriasis may be a few small spots on one area of skin or scattered over the whole body. Psoriasis might be a little patch on the skull or thick plaque with oyster like scale covering 80% of the body, or anything between.

 

What Happens if I Don't Do Anything?

Psoriasis can be uncomfortable and unsightly. Whether it does anything else to the body if untreated, we do not know.

About 1/3 of people with psoriasis develop psoriatic arthritis. We do not know if early treatment could prevent the arthritis.

We know that people with psoriasis are more likely to develop diabetes, high blood pressure, and elevated cholesterol. We also know that people with psoriasis are more likely to suffer heart attacks. We still do not know if treatment will prevent diabetes or reduce the risk of heart attacks.

 

What Are My Options?

Finally, we can understand why some treatments work and others do not. Any effective treatment must affect the immune response: interfere with T-cell activity, interfere with cell trafficking into skin, or interfere with cell activity in the skin. The treatment must affect cells directly or affect the signals. All effective treatments that we know of alter the immune response by stopping or eliminating the cells involved or by altering or blocking cytokine signals.

Knowing the process is only part of the solution. With each new treatment carries a better understanding, and with better understanding comes the hope of finding a new and better therapy; one that will provide more relief, largely more effective, and softer than the others. Research for us must continue. Each new therapy brings us a little closer to the ultimate goal - cure or prevention.


In 1992, Dr. Kim Papp, established a clinical research centre located in Kitchener-Waterloo, Ontario. To learn more about Dr. Papp's research and ongoing studies for psoriasis visit: ResearchTrials.org - K. Papp Clinical Research.

 

For more information on psoriasis please visit:

ResearchTrials.org: Psoriasis

National Psoriasis Foundation: www.psoriasis.org

 

Active Studies

 

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