Psoriatic arthritis (PsA) is considered a complex illness because doctors believe many different elements work together to cause its development. In addition to the presence of certain genes, one critical factor is a malfunctioning immune system. Certain environmental factors that trigger the immune system to malfunction are also critical elements.
The Immune System
Doctors first recognized a link between the immune system and psoriasis in the late 1970s. While using a drug called cyclosporine to suppress the immune system in patients who had undergone bone marrow transplantation, the doctors saw that a case of psoriasis abated at the same time. They realized the immune system was involved in what had been thought to be purely a skin disease.
In a healthy immune system, a type of white blood cell called a T-cell circulates throughout the body and protects it from infection and disease by destroying bacteria, viruses and other foreign substances collectively known as antigens. The presence of an antigen activates the T-cell, which then initiates an immune response to neutralize the cell. Autoimmune diseases, such as rheumatoid arthritis, psoriasis and psoriatic arthritis, cause the immune system to accelerate, and it begins attacking the very cells, organs and tissues in the body that it is designed to protect.
Part of this response involves the release of interleukins, which are any of a class of lymphokines. Lymphokines are also known as cytokines or non-antibody proteins that the immune system uses as intercellular mediators. In the overstimulated immune system associated with psoriasis, cytokines send messages to skin cells to reproduce and mature at a much faster rate than normal. In the case of psoriatic arthritis, cytokines draw white blood cells into the joints, which results in a painful swelling of the joints and of the hands and feet. This process can also lead to inflammation in body tissues, such as the tendons and cartilage, and in the eyes, heart, lungs and kidneys. The cytokines also cause the recruiting and activation of additional T-cells, and the release of more cytokines, which continues the vicious cycle.
Since the role of the immune system was identified, treatments that suppress its destructive behavior have been used with success. Cyclosporine, normally given to prevent the rejection of a transplanted organ, and methotrexate, which is commonly indicated for cancer patients, are two immunosuppressive drugs that have been used to suppress some of the inflammatory reactions that are associated with psoriatic arthritis. However, these medicines also impact the immune system's ability to fight infection, and they have other serious side effects.
As doctors have learned more about how the immune system functions, they have been able to target the actual mechanisms that cause specific immune responses, rather than targeting the entire immune system.
For example, a class of medications known as biologics has shown promise in their ability to isolate specific cytokines, such as the tumor necrosis factor-alpha (TNF-alpha), which has been found to carry inflammatory messages that help fuel the overall immune response and the overstimulation of T-cells. Biologic treatments aimed at blocking their migration are already on the market.
Health
Doctors surmise that psoriatic arthritis may also occur when the cytokines that normally suppress inflammation are missing or are present in low numbers. Scientists are working to develop biologic medications that will increase their numbers, thus rebalancing the immune system and restoring it to its normal purpose.
Environmental Factors Play a Role Too
Although the presence of genes and the function of the immune system are important to the development of psoriatic arthritis, doctors say that there is another factor that explains why some people with a family history of the disease never acquire it. They believe the cascade of events that results in psoriatic arthritis is set off by external events that affect the body or environmental triggers.
Some studies suggest that a physical trauma, such as an injury, may trigger the immune system's response. In fact, there have been cases reported where the symptoms of psoriatic arthritis developed in a joint after an injury. Also, it is possible for a viral, bacterial or fungal agent to trigger the chronic stimulation of the immune system in someone who is susceptible. For example, it has been suggested that there is a relationship between the bacterium streptococcus and psoriatic arthritis. It has also been noted that psoriatic arthritis seems to flare up in people whose immune systems are compromised by the HIV infection. However, this correlation remains under review.
Other environmental elements that may trigger psoriatic arthritis include reactions to certain medications or vaccines. As doctors continue to focus their efforts on understanding the disease, more environmental triggers may come to light. At the same time, researchers hope that by better understanding how genes, the immune system and environmental triggers work together, they may be able to eventually understand why psoriatic arthritis occurs.
In the meantime, learning to recognize the events which precipitate a flare-up of psoriatic arthritis is important to patients, who can then take the proper precautions to avoid them. In addition, these flare-ups should be viewed as important signals that require effective and immediate treatment.
