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You made it—if you’ve been following our herpes series, this is the eighth and final virus in the herpesvirus family that affects human beings. Human herpesvirus-8 (HHV-8) is also known as Kaposi sarcoma-associated herpesvirus (KSHV), which hints at perhaps the most important disease process that HHV-8 causes. Let’s learn more about the signs, symptoms, and treatment of this virus.
- Human herpesvirus-8 (HHV-8) is a member of the herpesvirus family
- Most healthy people that get HHV-8 don’t get any symptoms
- In people who have weakened immune systems, such as those with human immunodeficiency virus (HIV) or transplant patients, HHV-8 can cause more serious complications such as Kaposi sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman’s disease
- HHV-8 is likely spread through sexual contact as well as saliva
What is human herpesvirus 8 (HHV-8)?
HHV-8 was discovered in 1994 by Drs. Yuan Chang and Patrick S. Moore, two virology and infectious disease researchers at Columbia University who were looking for a virus causing Kaposi sarcoma, a rare cancer that was getting more and more common due to the HIV/AIDS (acquired immunodeficiency syndrome) epidemic (Chang, 1994). Later, it was discovered to be the cause of primary effusion lymphoma (PEL) and multicentric Castleman’s disease.
HHV-8 is a member of the herpesvirus family, which includes cytomegalovirus (CMV), Epstein-Barr virus (EBV), and the viruses that cause genital herpes, chickenpox, and shingles. Like other human herpesviruses, it has the ability to go into latency, where it hides out in cells of the human body after the primary infection and waits for times when your immune system is weak to strike again through reactivation.
HHV-8 is relatively rare in the United States, with studies showing a prevalence of around 1–5% (Pellett, 2003). It’s much more common around the world with rates of infection reportedly as high as 35% in parts of some Mediterranean countries and 50% in Uganda (Rohner. 2014). In the United States, HHV-8 infections are more common in men who have sex with men (MSM) and people who are HIV positive (Rohner, 2016).
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What are the signs and symptoms of human herpesvirus-8 infection?
In most people with healthy immune systems, HHV-8 infections are asymptomatic (Casper, 2007). Children that get infected with HHV-8 might have a brief illness with fever, rash, and lymph node swelling that lasts up to two weeks (Andreoni, 2002). These infections usually get better on their own and are treated with supportive measures like fluids, anti-inflammatories to reduce fever, and rest.
Unfortunately, this isn’t the full story. HHV-8 also causes a cancer called Kaposi sarcoma. This rare cancer grows from the cells that line blood vessels and lymphatic vessels. Lymphatic vessels are important for moving fluid around your body and act as the highway for the white blood cells of your immune system to get where they’re needed.
There are 4 major types of Kaposi sarcoma:
- The first is called Classic Kaposi sarcoma. It affects older Mediterranean and Jewish men. This was the type of cancer that Dr. Moritz Kaposi, Kaposi sarcoma’s namesake, first described in 1872. Classic Kaposi sarcoma is usually slow growing and chronic. It usually appears as red, blue, black, or purple patches on the legs and feet.
- The second major category is AIDS-related or epidemic Kaposi sarcoma. At the height of the HIV/AIDS epidemic in the 1980’s, Kaposi sarcoma afflicted 40% of those with AIDS in San Francisco (Martin, 1998). A study in the journal Lancet found that Kaposi sarcoma was 20,000 times more likely to develop in AIDS patients than in the general population in the USA (Beral, 1990). AIDS-related Kaposi sarcoma is much more aggressive than the classic type. It can grow rapidly and cover large areas of the skin. It is also more likely to affect other areas of the body, including the mouth, lymph nodes, stomach, intestines, lungs, chest, liver, and spleen. AIDS-related Kaposi sarcoma can be serious and life-threatening, though the prognosis is now much better with treatment. The Centers for Disease Control and Prevention (CDC) has named Kaposi sarcoma as an AIDS-defining illness. This means that once someone is diagnosed with Kaposi sarcoma, their HIV infection has progressed to AIDS.
- The third category is called endemic or African Kaposi sarcoma. Like AIDS-related Kaposi sarcoma, it can be aggressive and often affects people under 40 (Stefan, 2011). Compared with the other types, endemic Kaposi sarcoma more commonly causes lymph node enlargement and less commonly causes skin lesions.
- The last category is the organ-transplant associated or immunosuppression-associated Kaposi sarcoma. These patients develop Kaposi sarcoma after organ transplantation likely due to the drugs that transplant recipients have to take stop their immune systems from attacking the donated organ (Farge, 1993). These transplant patients get a version of Kaposi sarcoma that’s most similar to the classic type, where the cancer is slow-growing and mostly affects the skin.
According to the National Cancer Institute, the five year survival rate after diagnosis of Kaposi sarcoma is 74% (ACS, 2020).
HHV-8 can also cause a disorder called Castleman’s disease. Named after Dr. Benjamin Castleman, the pathologist that first described the disease in 1956, it has multiple subtypes whose commonality is the enlargement of lymph nodes—glands that act as part of the immune system where white blood cells are housed. The subtype that HHV-8 causes is called HHV-8-associated multicentric Castleman disease (MCD). That mouthful of a name describes the way this subtype is different from others—it has markers that are associated with HHV-8 infections, and it affects multiple regions of lymph nodes across the body. This disease causes lymph node swelling, fevers, night sweats, weight loss, weakness, and fatigue. In some patients, there’s swelling of the liver and spleen, rashes, and a drop in white blood cell numbers because the bone marrow is affected. Castleman’s disease is rare, with only around 7,000 new cases every year in the United States, and the majority of these cases aren’t associated with HHV-8 (Munshi, 2014). Improvements in treatment for HHV-8-associated Castleman’s disease has improved the prognosis—in one study, 92% of patients were alive 5 years after diagnosis (Pria, 2017).
The third major disease that HHV-8 can cause is called primary effusion lymphoma (PEL). It’s a type of cancer that comes from B-cells, which are a type of white blood cells in your immune system. PEL characteristically affects the body cavities and cause the build up of fluid within them. The first symptoms of PEL develop based on where the cancer is residing in their body—if it’s on the surfaces surrounding the lung (also called the pleura) or heart (also called the pericardium), the person will first experience shortness of breath (Narkhede, 2018). PEL can also affect spaces in the abdomen and joints, causing swelling and discomfort. In rare cases, PEL can cause fluid buildup in the space around the brain and spinal cord. Like Kaposi sarcoma, PEL is associated with HIV (Chen, 2007). However, PEL is rare, accounting for 4% of lymphomas in HIV patients (Chen, 2007). Once diagnosed with PEL, prognosis is generally very poor with median survival of only 6 months (Chen, 2007).
How is HHV-8 transmitted?
Researchers are still trying to figure out exactly how HHV-8 spreads from one person to another. Some studies have suggested that HHV-8 is spread through sexual contact. Among men who have sex with men, researchers have found that a major risk factor for HHV-8 infections is the number of sexual partners (Martin, 1998). Rates of infection are high in sex workers (Lavreys, 2003) and in people that go to sexually transmitted disease (STD) clinics (Eltom, 2002). HHV-8 has also been detected in the semen of infected men (Bobroski, 1998).
Other research shows that saliva can be the way HHV-8 spreads. Many children in sub-Saharan Africa are infected with HHV-8 prior to puberty (Mayama, 1998). HHV-8 has also been detected in the saliva—one study showed that 60% of people with known HHV-8 had the virus in their saliva (Pauk, 2000). The quantity of HHV-8 in saliva may be higher than in semen (LaDuca, 1998).
How is HHV-8 diagnosed?
If one of the diseases that HHV-8 causes is suspected, a sample of tissue is needed for the diagnosis. This sample is obtained from a part of the body affected by either Kaposi sarcoma, HHV-8-associated multicentric Castleman disease, or primary effusion lymphoma. The sample will then be sent to the laboratory where it will be stained with antibodies that look for the HHV-8-encoded latency-associated nuclear antigen (LANA), which confirms the diagnosis. There are polymerase chain reaction (PCR) tests that look for the HHV-8 DNA directly in the blood, as well as serological tests that look for antibodies which are present when your body reacts against HHV-8. However, neither of these tests are very reliable and are rarely used. And because of this, screening for HHV-8 is not recommended (AIDSinfo, 2019).
How is HHV-8 treated? Can it be prevented?
The way HHV-8 is treated depends on what disease process it is causing. In healthy adults, most HHV-8 infections are asymptomatic and don’t require treatment. Healthy children that are newly infected with HHV-8 that get a mild illness with fevers, rashes, and lymph node swelling usually don’t require treatment either, other than making sure they get the fluids, nutrition, and rest that they need.
In Kaposi sarcoma, surgery or cryotherapy (where skin lesions are frozen off) are used in disease limited to the skin in small areas (Schneider, 2017). If Kaposi sarcoma is more extensive or affects other organs in the body, chemotherapy becomes the treatment of choice. In HIV-positive patients, helping the immune system recover with antiretroviral therapy is also very important.
In multicentric Castleman’s disease, the treatment of choice is usually antiviral medications, which may be paired with antiretroviral medications in HIV-positive patients and immunotherapy targeted against B-cells. In primary effusion lymphoma, chemotherapy and antiretroviral medications are used as well.
Preventing HHV-8 infections is difficult because there’s no vaccine against the virus. The best advice is to practice safe sex including the use of condoms. This also prevents HIV infections which are associated with the development of many of the diseases that HHV-8 causes. If you do become HIV-positive, consistently taking highly active antiretroviral therapy (HAART), a combination of medications that protect your immune system against HIV, will reduce the chance that you develop a disease associated with HHV-8 (Cannon, 2003).