Kaposi Sarcoma

Kaposi sarcoma is a cancer of the cells lining blood vessels found in tissues beneath the skin, in mucous membranes, and in other organs of the body. The typical manifestation of the disease is the development of purple- or brown-colored spots on the skin or inside the mouth, nose, or anus. The disease was uncommon up until the early 1980s, when the acquired immunodeficiency syndrome (AIDS) made its appearance and when the occurrence of Kaposi sarcoma increased dramatically. The cause of Kaposi sarcoma was discovered in 1994 and found to be a new virus called human herpes virus 8 (HHV-8).



Types
There are four main types of Kaposi sarcoma. Although all have been associated with HHV-8, they differ in their symptoms, risk factors, how aggressively they grow, and which organs are affected.

Classic Kaposi sarcoma
Classic Kaposi sarcoma occurs more often in men with a ratio of about 10 or 15 men to 1 woman. Among immunocompetent people, Kaposi sarcoma usually occurs in people of Eastern European or Mediterranean descent with the age of onset between 50 and 70 years of age. Clinically, classic Kaposi sarcoma presents with one or more asymptomatic (no symptoms present) red, purple, or brown colored plaques or nodules on the skin. The plaques or nodules are typically localized to one or both lower extremities, especially the feet and soles of the feet.

The disease usually runs a benign, slow course for 10 to 15 years or more with slow enlargement of the original tumors and the gradual development of additional plaques. Edema (swelling) of the lower legs can occur due to involvement of the lymphatic system. Spread of the tumors internally is uncommon although the gastrointestinal tract and internal lymph nodes can be affected. As many as 33% of people with the classic form of Kaposi sarcoma can develop a second type of cancer, most often non-Hodgkins lymphoma.

African (endemic) Kaposi sarcoma
Kaposi sarcoma has been recognized as a relatively common tumor involving native populations in equatorial Africa since the 1950s. Kaposi sarcoma accounts for about 9% of all cancers seen in Ugandan men. African Kaposi sarcoma can present in either an indolent (slow growing) form, or it can appear as an aggressive illness involving deeper layers of the skin, muscles, and bones. People with this form of the disease tend to be younger than those with the classic form. A very aggressive type can occur in African children, with a male to female ratio of 3 to 1. This type involves spreading to the lymph nodes and internal organs. The outcome is usually very poor, with close to 100% mortality.

Immunosuppressive treatment-related Kaposi sarcoma
The first case of Kaposi sarcoma associated with immunosuppression (a weakened immune system) was seen in 1969 in a patient who had received a kidney transplant. Since then, a number of patients who have had an organ transplant and who received prednisone and azathioprine (medications that inhibit the immune system to prevent rejection), developed Kaposi sarcoma.

Kaposi sarcoma is 150 to 200 times more likely to develop in someone who has had an organ transplant compared with the general population. This is because of the immunosuppressive medications that transplant recipients take to prevent rejection of the new organ. The average time to develop Kaposi sarcoma after a transplant is 16 months. The tumors of Kaposi sarcoma can be localized to the skin, or can be widespread. They can sometimes shrink as a result of reduction or changes in the immunosuppressive therapy.

Epidemic Kaposi sarcoma
Epidemic (or AIDS-related) Kaposi sarcoma develops in people who are infected with the human immunodeficiency virus]] (HIV) and who are immunosuppressed as a result. Approximately 95% of cases of Kaposi sarcoma seen in AIDS has occurred in men who have sex with men compared with other HIV risk groups such as injection drug users. This is thought to be due to the fact that the causative agent of Kaposi sarcoma, HHV-8, is sexually transmitted in this population.

The plaques that develop in epidemic Kaposi sarcoma usually involve the skin, the mouth, lymph nodes, and internal organs such as the gastrointestinal tract, lung, and liver. The sites of involvement in the body are much more varied than in classic Kaposi sarcoma. Without therapy, the disease will spread to internal organs in most people with epidemic Kaposi sarcoma. Involvement of the lungs can be a serious, life-threatening complication and usually occurs in people who are severely immunosuppressed.

A form of non-epidemic Kaposi sarcoma occurring in men who have sex with men and who repeatedly test negative for HIV has been reported.

Signs and Symptoms
Kaposi sarcoma involving the skin appears as small, painless, flat areas (lesions) ranging in color from red to purple to dark brown. The lesions can take on a nodular form and can appear relatively quickly. It is not uncommon for a single lesion to appear first, then other lesions follow. Any part of the skin and the mucous membranes (lining of the mouth, nose, or anus) can be affected. The lesions of Kaposi sarcoma usually do not bleed spontaneously.

The disease can involve internal organs such as lymph nodes, gastrointestinal tract, and lungs. If lymph nodes are involved, they are usually enlarged, painless, and feel rubbery. There may also be swelling of the limbs as a result of decreased drainage through the lymph system. If Kaposi sarcoma involves the gastrointestinal tract, there can be abdominal pain, nausea, vomiting, and bleeding. Involvement of the lungs can lead to a harsh cough, wheezing, shortness of breath, and blood in the sputum (secretions coughed up from the lungs).

Causes
Kaposi sarcoma is caused by a virus called human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus. It was originally discovered in 1994, and has been found in all four types of Kaposi sarcoma. HHV-8 belongs to the genus (group) Rhadinovirus and is similar to the virus that causes mononucleosis, and to the herpes virus.

Diagnosis
The diagnosis of Kaposi sarcoma (KS) can often be made on clinical appearance alone, particularly in the epidemic (AIDS-related) form. In questionable cases a skin biopsy can be taken and the tissue examined under the microscope.

Kaposi sarcoma can spread to organs inside the body, in which case the diagnosis may require further procedures such as the following:
 * Chest X-ray
 * Bronchoscopy, insertion of a thin, flexible tube into the lungs to take a biopsy
 * Endoscopy, insertion of a thin, flexible tube into the stomach or lower intestines that allows the doctor to view inside and to take a biopsy

Sometimes AIDS-related KS affects other organs, such as the liver, spleen, heart, or bone marrow. In almost all cases the disease can be diagnosed from biopsies of other tissues, such as skin, lungs, or intestines.

Treatment
Treatment of Kaposi sarcoma is based on the type of tumor present, the location and size of the lesions, and whether other conditions exist such as AIDS or immunosuppression resulting from medications being taken after an organ transplant. Generally, four different types of treatment may be used:
 * Chemotherapy
 * Local therapy
 * Radiation therapy
 * Liquid nitrogen
 * Topical alitretinoin gel
 * Injection of vinblastine into lesions
 * Biological therapy with interferon-alpha
 * Surgery in cases where large tumors may be present

Other forms of treatment include improving the underlying immunodeficiency in AIDS-related Kaposi sarcoma using highly active antiretroviral therapy, or changing immunosuppressive treatment in the case of organ transplant recipients.

Prevention
In many countries, Kaposi sarcoma is found predominantly in people with HIV infection. Therefore, taking measures to avoid the spread of HIV could prevent most cases of Kaposi sarcoma.

Living with Kaposi Sarcoma
Some people will have Kaposi sarcoma that is slow-growing or that does not cause much of a problem in day-to-day living. Unfortunately for many, the appearance of Kaposi sarcoma lesions may be the first indication that they have AIDS. In this situation, Kaposi sarcoma can be emotionally overwhelming.

It often helps to talk to someone who understands the special needs and problems of people with cancer and with HIV infection. There are a large number of organizations that offer help and support for people with cancer or AIDS.

Kaposi sarcoma can also cause distress because of the physical appearance of the lesions. Some groups offer camouflage make-up which can help cover the skin lesions. Support groups are a great help in this area as well.

Risk factors
The risks of developing Kaposi sarcoma are increased based on the following factors:


 * Ethnic origin: People of Eastern European or Mediterranean descent, or Africans living in Africa have a higher rate of developing the classic form of Kaposi sarcoma.


 * Gender: Men are much more likely to develop Kaposi sarcoma than women, and it is more likely to develop in white men than in other racial groups.


 * Sexual activity: Men who have sex with men are at increased risk of becoming infected with HHV-8. Women who have sex with these men also have an increased risk of acquiring HHV-8 (and HIV).


 * Immune deficiency: People who are immunosuppressed, either because of diseases such as AIDS, or because of medications required to prevent rejection of an organ transplant, have an increased risk of developing Kaposi sarcoma. The risk can be reduced with improvement in the immunosuppression or, in the case of transplant recipients, changing to immunosuppressive drugs such as sirolimus.

How Kaposi Sarcoma is Spread
In many countries, the agent that causes Kaposi sarcoma, HHV-8, is believed to be spread through sexual contact. However, this route of transmission may not explain all cases of Kaposi sarcoma, and research is underway to better define how the virus is spread.

Clinical Trials
For a list of clinical research trials that are ongoing, please visit ClinicalTrials.gov.

Research
A great deal of research is ongoing to find more effective treatments for Kaposi sarcoma. Drugs such as angiogenesis inhibitors which block the formation of new blood vessels in tumors are being studied as possible Kaposi sarcoma treatments.

New combinations of chemotherapy drugs and new methods of delivering them are being explored for the treatment of this disease. Research into treatments for HIV will also benefit the treatment of Kaposi sarcoma.

Expected Outcome
The prognosis (chance of recovery) depends on the following:
 * The type of Kaposi sarcoma.
 * The general health of the patient, especially the immune system.
 * Whether the cancer has spread.
 * Whether the cancer has just been diagnosed or has recurred (come back).

Most cases of AIDS-related Kaposi sarcoma tend to follow the course of the immunosuppression caused by HIV. In cases where antiretroviral therapy has been effective in suppressing HIV and restoring immune function, Kaposi sarcoma often causes few problems and may even improve. In people with immunosuppression from HIV or other causes who do not receive adequate treatment, Kaposi sarcoma can spread to internal organs. If it spreads to the lungs, it can often be fatal.

History
Kaposi sarcoma was first described by Moritz Kaposi in 1872 in Hungary. Up until the appearance of the acquired immunodeficiency syndrome (AIDS), Kaposi sarcoma was a rare tumor primarily seen in men of Eastern European or Mediterranean ancestry. With the advent of AIDS and other forms of immunosuppression, Kaposi sarcoma has become a much more frequent clinical disease.

The virus now associated with Kaposi sarcoma, human herpes virus 8 (HHV-8) was discovered by Chang and co-workers in 1994.

Epidemiology
Several epidemiologic investigations suggested that Kaposi sarcoma was caused by an infectious agent and that it was likely to be transmitted sexually. With the discovery of the causative agent, further research has attempted to define the spread of HHV-8 throughout the world.

Seroprevalence studies that look for evidence of infection with HHV-8 have shown the following:



Epidemiologic data also shows that the incidence of Kaposi sarcoma in the United States has been declining. The likely reason for this is the use of highly active antiretroviral therapy (HAART) in the treatment of HIV-infection and AIDS. The use of HAART can lead to improvement in the immunosuppression seen in AIDS. This can prevent the development of Kaposi sarcoma in people who are infected with HIV and HHV-8.