Kaposi's Sarcoma Health Article

Definition

Kaposi's sarcoma is a form of skin cancer that can involve internal organs. It is most often found in patients with acquired immunodeficiency syndrome (AIDS), and can be fatal.

Description

Kaposi's sarcoma (KS) was once a very rare form of cancer, primarily affecting elderly men of Mediterranean and eastern European background, until the 1980s, when it began to appear among AIDS patients. It manifests in four distinct forms. The first form, called classic KS, was described by the Austrian dermatologist Moricz Kaposi more than a century ago. Classic KS usually affects older men of Mediterranean or eastern European backgrounds by producing tumors on the lower legs. Though at times painful and disfiguring, they are not generally life-threatening. The second form of the disease, African endemic KS, primarily affects boys and men. It can appear as classic KS, or in a more deadly form that quickly spreads to tissues below the skin, the bones and lymph system, leading to death within a few years of diagnosis. Another form of KS, iatrogenic KS, is observed in kidney and liver transplant patients who take immunosuppressive drugs to prevent rejection of their organ transplant. Iatrogenic KS usually reverses after the immunosuppressive drug is stopped. The fourth form of KS, AIDS-related KS, emerged as one of the first illnesses observed among those with AIDS. Unlike classic KS, AIDS-related KS, tumors generally appear on the upper body, including the head, neck, and back. The tumors also can appear on the soft palate and gum areas of the mouth, and in more advanced cases, they can be found in the stomach and intestines, the lymph nodes, and the lungs,

Kaposi's sarcoma is reported to be found in 20% of homosexual men who have HIV, 3% in heterosexual intravenous drug users, 3% in women and children, 3% in transfusion recipients, and 1% in hemophiliacs. Once regarded as only a defining illness for AIDS, KS has proven to be a progressive, fatal disease on its own, especially when the disease becomes systemic. Yet, involvement throughout the body is not the only factor in patient mortality. Research in 2000 found that patients with KS in oral mucosa had a higher risk of death than those with KS appearing only on the skin.

Causes

A variety of factors appear to contribute to the development of KS. One of the first avenues offered as causal agents was genetic predisposition. People with classic KS, and those who develop the tumors after transplantation, are more likely than others to possess a genetically determined immune factor called HLA-DR. Cases of KS that run in families, however, are rare.

The fact that the disease is more likely to afflict men than women suggests sex hormones, such as testosterone in men, may stimulate the growth of KS tumors, and that estrogen in women may retard their growth.

Immune suppression was the next likely cause since liver, kidney, and bone marrow patients who take immunosuppressive drugs to prevent transplant rejection frequently develop KS lesions. Similarly, KS has been observed in patients receiving systemic treatment with high-dose corticosteroids, which also suppresses the immune system. Immune suppression is the hallmark of AIDS.

The current theory is the discovery of an infectious agent. A number of viruses have been proposed as possible causes, including cytomegalovirus and human papilloma virus, fragments of which have been found in KS

tumor specimens. A more likely candidate, however, is a new herpes virus that has been called human herpes virus 8 (HHV-8) or KS-associated herpes virus (KSHV). Since fragments of the virus were first disclosed in KS samples in 1994, they have since been found in KS samples taken from patients with classic KS, African endemic KS, and KS in transplant patients. Fragments of HHV-8, however, have also been found in patients who have other skin diseases but who do not have KS,

Studies in 2000 showed that HHV-8 was indeed the culprit behind KS. Nevertheless, it does not work alone. In combination with a patient's altered response to cytokines (regulatory proteins that are produced by the immune system) and the HIV-1 transactivating protein Tat which promotes the growth of endothelial cells, HHV-8 can then encode interleukin 6 viral proteins, specific cytokines that stimulate cell growth in the skin. This becomes KS.

HHV-8 destroys the immune system further by directing a cell to remove the major histocompatibility complex (MHC-1) proteins that protect it from invasion. These proteins are then transferred to the interior of the cell and are destroyed. This leaves the cell unguarded and vulnerable to invaders which would normally be targeted for attack by the immune system.

Research in early 2001 showed that transmission of HHV-8 virus can be more casual than was once thought, giving rise to incidence among women and children. Women who are intravenous drug users and who also have had a sexually transmitted disease have been found to harbor HHV-8. This evidence shows that women can contract HHV-8 through blood. In addition, researchers in 2000 found that HHV-8 could be transmitted orally though kissing. This study found more HHV-8 virus in oral samples than in genital secretions. In fact, HHV-8 was difficult to find in genital samples. This may indicate why children and women who were not intravenous drug users have had KS.