Causes and Risk Factors of Kaposi's Sarcoma

Immunosuppression (the partial or complete lack of an immune response) and an infection with a human herpesvirus 8 (HHV8) virus is the ultimate cause of Kaposi's sarcoma (KS). It is most commonly associated with advanced human immunodeficiency virus (HIV) but has other forms that affect different populations.

This article looks at the causes of the different types of Kaposi's sarcoma and which factors place you at an increased risk of this rare form of cancer.

Common Causes

Kaposi's sarcoma can only occur in people with HHV8 (also known as Kaposi's sarcoma-associated herpesvirus, or KSHV). The virus, which is closely related to the Epstein-Barr virus (EBV), is mainly passed from person to person through saliva. But unlike EBV, repeated exposure is generally needed.

HHV8 is relatively rare in the United States, affecting between 1% and 3% of the general population. By contrast, between 10% and 20% of people living in certain Mediterranean countries and 30%–80% of those living in parts of sub-Saharan Africa have HHV8.

There are six major subtypes of HHV8—subtypes A, B, C, D, E, and F—some of which are confined to specific geographic regions. It is thought that some of these subtypes may be more aggressive than others, but the evidence of this is limited. There is also no clear association between an HHV8 subtype and any specific type of KS.

Having HHV8 does not mean that you will get KS. This is because HHV8 is opportunistic, meaning that it can only cause disease when the immune system has been weakened. When this happens, the dormant virus will suddenly activate, causing tumors on the skin and mucous membranes that appear as purplish lesions or nodules.

The underlying cause of immunosuppression differs by the type of KS a person has.

HIV-Associated Kaposi's Sarcoma

HIV-associated Kaposi's sarcoma, sometimes referred to as epidemic KS or AIDS-related KS, typically occurs when HIV is advanced and a person's immune system is compromised. Unlike certain forms of KS, it tends to be quite aggressive.

HIV causes disease by targeting and killing immune cells known as CD4 T cell lymphocytes. As more and more of these cells are destroyed, the immune system becomes less and less able to defend itself against otherwise harmless infections.

KS tends to affect people with AIDS (acquired immune deficiency syndrome), the most advanced stage of HIV infection. AIDS is defined in part by a blood test known as a CD4 count. A normal CD4 count is between 500 and 1,500 cells per cubic milliliter of blood (cells/mm3). A person is said to have AIDS when the CD4 count drops below 200.

Even so, KS can and does occur at CD4 counts above 200.

Men who have sex with men (MSM) with HIV are 3 times more likely to have KS than other people living with the disease. This is due in part to the high rate of HIV among MSM—not only in the United States but globally.

Classic Kaposi's Sarcoma

Classic Kaposi's sarcoma is a slowly progressing form of KS that mainly affects older men of Mediterranean or Eastern European descent. Jewish, Greek, and Italian men are most predominantly affected.

Unlike KS in people with HIV, which can spread to internal organs, classic KS is rarely aggressive and tends to be limited to the lower legs and hands. Even oral lesions in the mouth and gums are uncommon.

Beyond sex and ethnicity, the overriding risk factor for classic KS is age. Studies suggest that the average age of diagnosis of people with classic KS is 69 years (although some only develop the disease in their 90s).

Transplant-Related Kaposi's Sarcoma

Transplant-related Kaposi's sarcoma, sometimes called immunosuppression-associated KS or iatrogenic KS, affects organ transplant recipients on immunosuppressant drugs. Immunosuppressants are drugs used to prevent organ transplant rejection (in which the body regards donated organs as foreign and launches an immune assault).

The rate of transplant-related KS varies by how common HHV8 is in a geographic population. In some cases, a person may have HHV8 before undergoing a transplant, while others may get HHV8 from the donor organ.

More often than not, having HHV8 before a transplant increases the risk of developing KS.

As with classic KS, transplant-related KS tends to affect the lower limbs and will typically clear once the immunosuppressant drug is stopped. While it is uncommon for transplant-related KS to spread to internal organs, the prognosis (expected outcome) is generally poor if it does.

Endemic Kaposi's Sarcoma

Endemic Kaposi's sarcoma is mainly confined to sub-Saharan Africa. The two types that differ not only by how aggressive they are but also by the population they affect are:

• African lymphadenopathic Kaposi;s sarcoma is an aggressive form of KS that mainly affects children under age 10. It typically causes tumors on the lymph nodes that may or may not be accompanied by skin lesions. When both the skin and internal organs are involved, the risk of death is high, usually occurring within two months.
• African cutaneous Kaposi's sarcoma mostly affects men between the ages of 20 and 50. It causes large nodules on the lower extremities that can progress rapidly, clear spontaneously, or remain stable for many years. Although it is less likely to affect internal organs, the lesions can sometimes bleed or form ulcers.

For reasons unknown, people of sub-Saharan African descent appear to be more susceptible to KS if they have HHV8. Unlike the other forms of KS, endemic KS can affect people whose immune function is impaired but is still largely intact.

It is thought that malnutrition and multiple chronic illnesses are risk factors for endemic KS. Certainly compared with other parts of the world, Africa faces more serious health concerns and a heavier burden of diseases, which may account for the increased susceptibility and lower immune response.

Genetics

To date, it is unclear how much or little genetics contributes to the risk of Kaposi's sarcoma. With that said, there is some evidence that classic KS may be passed down in families.

Although the condition—referred to as familial KS—is rare, a 2014 study published in Case Reports in Dermatological Medicine identified five such cases in Greece.

In each of the five cases, two family members developed KS, none of whom had HIV. Interestingly, not only were male family members affected but also female family members in some cases. Most cases developed after the age of 50.

While this is by no means proof of a genetic link, it does suggest that genetics and environment may play a part in the risk of KS in tandem with immune suppression and HHV8 infection.

Lifestyle Risk Factors

It is hard to suggest that there are any lifestyle factors that can reduce a person's risk of KS given that the risk factors—age, sex, ethnicity, etc.—are largely unmodifiable.

The one exception is the use of antiretroviral therapy in people with HIV. Antiretroviral drugs work by preventing the virus from making copies of itself. By doing so, the virus is suppressed to levels at which it can do the body little harm, allowing the immune system to gradually rebuild itself.

Given that KS is more common in people with AIDS, the early diagnosis and treatment of HIV are essential to preserving a person's immune function. Delaying treatment until the CD4 count is very low makes it all the more difficult to restore the CD4 count to normal or near-normal levels.

Summary

Kaposi's sarcoma (KS) is an uncommon form of cancer that affects the skin and mucous membranes of the gastrointestinal tract and, in rare cases, the lymph nodes and lungs. KS is due to the combination of immune suppression and infection with the human herpesvirus 8 (HHV8).

While KS is most commonly associated with HIV infection (HIV-associated KS), it can also affect organ transplant recipients (transplant-related KS), older men of Mediterranean or Eastern Europe descent (classic KS), and vulnerable children and younger men in Africa (endemic KS).

There are different risk factors for each of the four different KS types. Genetics and environmental factors may also play a part, although further research is needed.

A Word From Verywell

Kaposi's sarcoma is of serious concern as it is most often associated with advanced HIV infection. In some cases, it may even be the first sign of HIV. This is especially true given that 13% of 1.2 million people living with HIV in the United States are undiagnosed.

Antiretroviral therapy not only shrinks KS tumors but prevents them from spreading to internal organs. By getting diagnosed and treated early, you are not only less likely to experience serious HIV-associated illnesses like KS but more likely to live a normal, healthy life span.