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Kaposi’s Sarcoma (KS)

Definition:
Kaposi’s sarcoma (KS) is a type of cancer. It causes growths under the skin, although they can grow in the lining of the mouth, nose, throat and other organs. It is different from other cancers as it starts in several areas of the body at once. Most cancers start in one place and then spread.

KS causes abrasions or tumors (growths). They most commonly appear on the skin as small, flat, colored lesions that can be brown, blue, red or deep purple. Lesions can also develop on the internal organs, such as the lymph nodes (part of the immune system), the lungs, and the digestive system, including the bowel, liver and spleen.

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It was originally described by Moritz Kaposi, a Hungarian dermatologist practicing at the University of Vienna in 1872. It became more broadly known as one of the AIDS defining illnesses in the 1980s. The viral cause for this cancer was discovered in 1994.

According to Medilexicon’s medical dictionary:
Kaposi’s sarcoma is: “A multifocal malignant neoplasm of primitive vasoformative tissue, occurring in the skin and sometimes in the lymph nodes or viscera, consisting of spindle cells and irregular small vascular spaces frequently infiltrated by hemosiderin-pigmented macrophages and extravasated red blood cells. Clinically manifested by cutaneous lesions consisting of reddish-purple to dark-blue macules, plaques, or nodules; seen most commonly in men older than 60 years of age and in AIDS patients, as an opportunistic disease associated with human herpes virus-8 infection.”

There are four types of Kaposi’s sarcoma (KS):

1.HIV– or AIDS-related KS…….>AIDS-related KS
2.Classic KS…………………………
3.Endemic or African KS………..>Endemic or African KS
4.Transplant-related KS…………>ks_1

1.HIV- or AIDS-related KS: KS can develop in people whose immune system has been severely weakened by HIV or AIDS. Gay men with HIV or AIDS are mostly affected. It is thought that the virus that causes KS is spread during unprotected anal sex.

In the past, HIV- or AIDS-related KS used to be the most common complication affecting gay men living with HIV and was a leading cause of death. This is no longer the case due to anti-HIV medications that were developed in the 1990s, known as highly active antiretroviral therapy (HAART).

The outlook for HIV- or AIDS-related KS is variable and depends on a person’s age and the state of their immune system. In an older person with a weakened immune system, the cancer often spreads aggressively to other parts of the body (metastasis).

The estimated survival rate for HIV- or AIDS-related KS is five years, although many people live a lot longer. The improvement of survival rate is directly linked to the improvement in medication for treating HIV.

2.Classic KS: It is a rare condition, usually only affecting men between 50 and 70 years of age who are of Mediterranean or eastern European descent. It is thought that people who develop classic KS were born with a pre-existing genetic vulnerability to the virus that causes it.

The outlook for classic KS is good. The cancer tends to spread slowly and does not usually spread to other parts of the body. Classic KS primarily affects older people.

3.Endemic or African KS: It is common in parts of Africa. It is one of the most widespread types of cancer in that region. As with classic KS, endemic KS is thought to develop due to a pre-existing genetic vulnerability to the virus that causes it.

Many people may now be more vulnerable to the virus because of the HIV epidemic in Africa and a weakened immune system due to HIV or AIDS.

The outlook for endemic KS is poor. In addition, access to treatment such as chemotherapy is often limited in parts of the world where endemic KS is widespread.

4.Transplant-related KS: It is an uncommon complication of organ transplants. People who have had an organ transplant usually take medication to weaken their immune system (immunosuppressant) to prevent their body rejecting the new organ. The weakening of their immune system makes them more vulnerable to the virus that causes KS.

The outlook for transplant-related KS is generally good because the condition can usually be successfully treated by reducing or stopping a person’s course of immunosuppressant. However, there is a higher risk of rejection of the donated organ.
Symptoms:
A symptom is something the patient feels and reports, while a sign is something other people, such as the doctor detect. For example, pain may be a symptom while a rash may be a sign.

The symptoms of KS depend on where the lesions or growths develop.

Skin

Any part of the skin, including the inside of the mouth, can be affected. KS usually appears as small, painless flat lesions or lumps. They can be of different colors (brown, red, blue and purple). They often look like bruises but do not lose their color when pressed like a bruise does.

…….images……images-1…..KS

KS growths may start in one place and then can develop in more than one area. The growths often eventually merge into each other to form a larger tumor.

Internal organs :

The lymph nodes, lungs and organs of the digestive system are most commonly affected. The symptoms of KS depend on which organs are affected.
*Lymph nodes: There may be swelling in the arms and legs. It can be very painful and uncomfortable. This is known as lymphedema and is caused by the KS cells blocking the flow of fluid through the lymph nodes. As a result, the tissue fluid backs up. This causes swelling in the body’s tissues.

LUMPS..lymph

*Lungs: symptoms may include breathlessness.

lymph-nodes-of-pulmonary-system

*Organs in the digestive system: symptoms include nausea, vomiting and bleeding.

..stomach cancer stages

Causes :-

Cancer

Cancer initiates with a change in the structure of DNA, which is found in all human cells. DNA provides our cells with a basic set of instructions such as when to grow and reproduce. A change in its structure, called a genetic mutation, can cause the cells to reproduce uncontrollably. This produces a lump of tissue known as a tumor.

Left untreated, cancer can quickly grow and spread to other parts of the body. It usually spreads through the lymphatic system. Once the cancer reaches the lymphatic system, it can spread to any other part of the body, including the bones, blood and organs.

The human herpes virus 8 (HHV-8)

Kaposi’s sarcoma (KS) is caused by a virus called the human herpes virus 8 (HHV-8). It is also known as the Kaposi’s sarcoma-associated herpes virus (KSHV).

It is thought that HHV-8 contains genetic material that interferes with the normal working of cells. This causes them to reproduce in an uncontrollable manner.

However, HHV-8 does not cause Kaposi’s sarcoma in everyone who contracts the virus. It only seems to cause Kaposi’s sarcoma in:
*people who have an inherited (genetic) vulnerability to HHV-8
*people with a weakened immune system
*HHV-8 was first identified in 1994. There is no firm evidence as to how the virus is spread.

However, there is indication that HHV-8 can be spread during unprotected anal sex. The rates of HHV-8 in specific countries reveal that the virus is almost always more widespread in the gay community. There is circumstantial evidence that HHV-8 can be passed on through saliva. This means the virus could also be spread by kissing.

Diagnosis:
Before diagnosing Kaposi’s sarcoma (KS), the patient´s general health is reviewed and there is a careful examination of the skin.

If KS is suspected, further testing may be required. People with HIV or AIDS, will usually have their tests carried out at a specialist centre where staff are experienced in treating complications of HIV and AIDS.

*Biopsy: It is the most effective way to confirm a diagnosis of KS. This involves taking a small sample of cells from an affected area of skin. The sample is then checked at a laboratory for the presence of KS cells.

*Endoscopy: It may be carried out if KS is suspected in the digestive system. The procedure involves inserting a thin, flexible tube called an endoscope down the throat. It allows looking inside parts of the digestive system, such as the bowel, liver and spleen, for any abnormalities or signs that KS is present. A biopsy may be taken.

A mild sedative may be given. A local anesthetic will be sprayed on to the throat to prevent discomfort as the tube is passed down.

A similar method can be used to look at the lungs (bronchoscopy) if KS in the lungs is suspected.

*Computerized tomography scan (CT): In the case it is suspected that KS has spread to the lymph nodes or other parts of the body.

A CT scan works by taking a series of X-rays which build up a three-dimensional picture of the inside of the body. A radioactive dye may be given to drink before the CT scan, to allow particular areas of the body to been seen in greater detail.

Treatment :-
The treatment of KS depends on:
*the severity of the symptoms
*the size and location of the lesions
*the type of KS
*the patient´s general health
Treatment plans can vary from person to person, but the usual plan for each type of KS is outlined below.

HIV- or AIDS-related KS

Patients with HIV- or AIDS-related KS will usually be given a course of highly active antiretroviral therapy (HAART) to help strengthen their immune system. HAART may be followed by courses of radiotherapy and/or chemotherapy.

Classic KS

As classic KS spreads slowly, immediate treatment is not usually required. Doctors may recommend waiting and closely monitor the evolution. Treatment will be delayed to see if any symptoms of progressive cancer develop. This is often recommended for older people when it is unlikely that the cancer will affect their natural life span. If treatment is required, radiotherapy is normally used to treat classic KS.

Endemic KS

Usually, endemic KS is treated using a combination of radiotherapy and chemotherapy.

Transplant-related KS

Transplant-related KS is usually treated by reducing or stopping the immunosuppressants. The goal is to strengthen the immune system in order to fight off the humanherpes virus 8 (HHV-8) while ensuring that the body does not reject the transplanted organ. It may be difficult to find the best balance between these two treatment goals.

HAART

It involves using a combination of medicines that interrupt the reproductive cycle of the HIV virus. This helps to prevent the virus from spreading quickly. It also protects and strengthens the immune system.

HIV can quickly adapt and become resistant to a single medicine, therefore a combination of medicines is required. In some people, the medicines used to treat HIV will cause side effects. Usually, there is improvement after a few weeks as the body gets used to the medicines.

Common side effects of HIV medication include:
*diarrhea
*mood changes
*nausea
*skin rashes
*tiredness
*gaining fat on one part of your body while losing it on another (lipodystrophy)

Surgery:-

If the lesion is small, surgery may be used to remove KS from the skin. Cryotherapy may also be given. This freezes the lesions using liquid nitrogen.

Chemotherapy

Chemotherapy uses medicines to treat cancer. The medicines destroy rapidly growing cancer cells. The medicines can either be given intravenously or as a tablet that is taken orally. If the lesion is small, chemotherapy may be injected directly into it. This is called intralesional chemotherapy.

Chemotherapy can cause side effects including vomiting, hair loss, tiredness, and increased vulnerability to infection.

Often, liposomal chemotherapy is used to treat KS. The medicines used in chemotherapy are covered in a fat-based coating called liposome. The extra coating means reduces the side effects and the medication works more efficiently.

Radiotherapy

Radiotherapy uses high-energy rays to locate and destroy the KS cells. It can be very effective in reducing symptoms of internal KS, such as swelling, pain and bleeding.

Possible side effects of radiotherapy include: tiredness, sore skin (particularly for people with HIV or AIDS), stiff joints and muscles, nausea, temporary hair loss, loss of appetite, loss of libido (interest in sex), early menopause, and temporary impotence in men. Once the course of treatment is over, most side effects gradually disappear.

Immunotherapy

Immunotherapy is also known as biological therapy. It is often used in combination with other treatments such as HAART. Immunotherapy uses special proteins that have been genetically developed in a laboratory.

Generally, the body does not consider the cancerous cells as foreign objects. As a result, the immune system does not attack them. In immunotherapy, special antibodies are created in a laboratory. They change the composition of cancerous cells so that the immune system regards them as foreign objects. The immune system then starts to attack the cells in the same way that it would normally attack an infection.

Interferon is one of the most common types of medicines used in immunotherapy. It is usually given by daily injections into the skin over a number of weeks.

Side effects of immunotherapy include:
*back ache
*aching joints and muscles
*chills
*headaches
*high temperature (fever) of 38°C (100.4°F) or above
*loss of appetite
*nausea
*tiredness

Prevention:-
It is not clear how HHV-8 spreads. It might be spread through sexual activity and deep kissing. As with other opportunistic infections, a healthy immune system can control HHV-8 infection. The best way to prevent KS is by using strong anti-HIV medications to keep your immune system strong.

The following are being studed for KS :-

Anti-cytokine approaches: There is a lot of research on cytokines, proteins that the immune system uses to sti mulate cells to grow. Researchers think that substances that can inhibit these (and similar) growth factors can also slow down the growth of KS.

Monoclonal antibodies: These drugs are produced through genetic engineering. Their names end in “-mab,” such as bevacizumab.

Other drugs: Scientists are studying several drugs that slow down the development of new blood vessels (angiogenesis.)

The bottom line is :-
KS is a disease that affects up to 20% of people with AIDS who are not taking ART. It is partly caused by a herpes virus called HHV-8.

The best treatment for KS is strong antiretroviral therapy (ART.) KS in the skin can be treated in several ways and is not a serious problem. KS in internal organs can be life threatening. Internal KS is usually treated with anti-cancer drugs.

If you notice new dark spots on your skin, have your health care provider look at them to see if you might have KS.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:

http://www.aids.org/factSheets/511-Kaposis-Sarcoma-KS.html
http://www.medicalnewstoday.com/articles/173259.php
http://www.dentistry.leeds.ac.uk/oralpath/viruses/viral%20infections/HHV8.htm

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Waking up Dormant HIV

World HIV/AIDS Awareness Day
Image by reflexblue via Flickr

HAART (highly active anti-retroviral therapy) has emerged as an extremely effective HIV treatment that keeps virus levels almost undetectable; however, HAART can never truly eradicate the virus as some HIV always remains dormant in cells. But, a chemical called suberoylanilide hydroxamic acid (SAHA), recently approved as a leukemia drug, has now been shown to ‘turn on’ latent HIV, making it an attractive candidate to weed out the hidden virus that HAART misses.
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Matija Peterlin at UCSF and colleagues had previously identified another chemical called HMBA that could activate latent HIV, but the risk of several toxic side effects made HMBA clinically non-viable. However, the chemically similar SAHA had received FDA approval, making it a potentially safer alternate.

So, the researchers examined whether SAHA had any effect on HIV latency. They found that SAHA could indeed stimulate latent HIV to begin replicating, which exposes the infected cell to HAART drugs. SAHA could activate HIV in both laboratory cells as well as from blood samples taken from HIV patients on antiretroviral therapy. Importantly, this successful activation was achieved using clinical doses of SAHA, suggesting toxicity will not be a problem.

Sources
:http://www.asbmb.org/News.aspx?id=2286

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