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Immunotherapy

Immune responses in the human body play a major role during disease or abnormality. The immune system responds according to the stimulus it receives from the brain either to fight a pathogen or to eradicate an unwanted cell in the body. Immunotherapy enhances or suppresses the immune system to act on the respective disease. Immunotherapy varies in types depending upon its administration requirements. In case of allergic reactions or autoimmune diseases, immunotherapy is used to suppress the immune response to control the adverse reactions caused by allergens and abnormal proteins.


Types of Immunotherapeutic Agents

Immunotherapy is selective for each disease. There are many types of immunotherapeutic agents available. Some are used to enhance the immune system in facilitating the process of phagocytosis and some are used to block the allergic reactions and autoimmune responses of the body.


Monoclonal antibodies

Monoclonal antibodies which are prepared in the lab are used as anticancer agents. These antibodies are unique as they target specific locations of the cancer cells. Monoclonal antibodies can used in many ways depending upon the type of case. Some monoclonal antibodies can be used directly without any additives. Some are coated with a radioactive material or an additional anticancer drug to act on the cancer cells. These antibodies adhere to the target cell thus interfering with the cancer cell activity.

Many conditions such as Hodgkin’s Lymphoma, chronic lymphocytic leukemia have US FDA approved immunotherapy drugs. Rituxan and Campath are the first monoclonal immunotherapy FDA approved drugs in treatment of cancer. The common side effects noticed in the administration of monoclonal antibodies both as single and conjugated forms include fever, headaches, nausea, rash, low red blood cell count as it interferes with the marrow and also liver disorders. Monoclonal antibodies conjugated with radioactive material in case of radio immunotherapy may trigger severe allergic reactions.


Cytokines

Cytokines such as interferon and interleukin are generally used as immunotherapeutic agents because of their involvement with cell signaling pathways. They are naturally secreted by the body and they are also called nonspecific immunotherapeutic agents. They are predominantly used in treating infections, cancers and tumors. Alpha interferon is widely used in the treatment of cancers such as T-cell lymphoma, Chronic myelogenous leukemia and non-Hodgkin lymphomas. They inhibit the proliferation of cancer cells by interfering with the growth factors.

Interleukins are also used in the treatment of cancers such as lymphoma, leukemia and mylomas of various origins. Interleukin 2 (IL2) is a widely recommended agent for myelomas. Interleukin and interferon therapies have side effects such as extreme fluid accumulation, fever, chills and dizziness. Cytokine therapies based on lymphocyte infusion can cause graft versus host disease leading to the destruction of host cells by the induced lymphocyte cells.


Kaposi Sarcoma

Of the seven types of Sarcomas, the incidence of Kaposi Sarcoma, a type of skin cancer is found to be more prevalent in persons with immune deficiency disease like AIDS. The rate of Kaposi Sarcoma is reported to be 20 times more. It is estimated that 15% of HIV infected persons will develop Kaposi Sarcoma. The weakened immune system is unable to fight the Kaposi Sarcoma Herpes Virus. Thanks to HAART (highly active anti-retrovirus therapy), the incidence rate has decreased.


Sarcoma is a rare type of cancer. The malignant tumors occur in the body's connective tissues - the tissues that support, connect and bind various parts of the body. Muscles, fat, fibrous tissues, nerves, blood vessels, cartilage, bones and joint tissues are all connective tissues.

Sarcomas fall into three broad categories.

Soft tissue cancers

  • Benign (non cancerous)
  • Malignant (cancerous)

Primary bone cancer

Gastro-intestinal stromal tumors

Kaposi Sarcoma is a soft tissue sarcoma, malignant in nature.


Kaposi Sarcoma causes

Human herpes virus 8 (HHV8) also called Kaposi Sarcoma associated herpes virus (KSHV), a virus causes the infection. Though as many as 1 in 20 people may have this virus sans any symptom, certain groups of people are vulnerable to its effect and develop Kaposi Sarcoma. Mostly, people whose immune system isn't working properly either due to a medical condition or medication (immunosuppressive medications) can develop Kaposi sarcoma. The weakened immune system allows the HHV8 to multiply to high levels in the blood thus increasing the chance of developing Kaposi Sarcoma.


Kaposi Sarcoma symptoms

The first symptom is the lesion appearing on the skin. It can be bluish-red, or brown or purple spots or lesions on the skin, flat or as a slightly raised bump, linear or in a symmetrical distribution. In fact, the appearance of the lesion indicates the possibility of the person being infected with HIV or the condition it causes, namely, AIDS. Kaposi Sarcoma can also affect internal organs which can lead to a range of symptoms, depending on the organ that is affected.


Skin lesions

The lesions can appear anywhere on the body but in most cases the lesions appear on the face (ears, mouth and tip of the nose), legs and feet and the genital area. It could occur in a single area in the beginning. These can merge to form a large tumor.


Lymph nodes: Swollen lymph nodes are the symptoms of Kaposi Sarcoma affecting the lymph nodes.

Arms and legs: If Kaposi Sarcoma affects the lymph vessels, there is buildup of fluid in the arms and legs. This condition is called lymphoedema.

Lung problems: Kaposi Sarcoma affecting the lungs can lead to breathlessness and coughing up blood.

Digestive system: Nausea, vomiting, stomach pain and diarrhea are symptoms related to Kaposi Sarcoma affecting the digestive system.


HIV related Kaposi Sarcoma: Being HIV positive or having AIDS increases the risk factor of HIV-related Kaposi Sarcoma. Compared to women, men have higher chances as also gay and bisexual men who are HIV positive are at risk of HIV related Kaposi Sarcoma.


Classic Kaposi Sarcoma: A rare condition, classic Kaposi Sarcoma affects middle-aged and elderly men of Mediterranean or Ashkenzi Jewish descent. There is a high possibility of being born with a pre-existing genetic vulnerability to the HHV-8 virus.


Endemic African Kaposi sarcoma: This type is a common cancer in parts of Africa with high levels of HIV. In most cases, the reason is either undiagnosed HIV infection or a pre-existing genetic vulnerability to HHV-8 virus.


Transplant related Kaposi Sarcoma: After an organ transplant, a strong immune system can reject the new organ. In order to weaken the immune system thereby preventing the rejection of new organ, medications (immunosuppressant) are used. This makes the person vulnerable to HHV-8 virus infection.


Tests for diagnosis of Kaposi Sarcoma

For a definitive diagnosis, a small amount of tissue is removed for examination under the microscope. If the biopsy results confirm, further tests are required to know the spread to internal organs. X-ray, Endoscopy, Bronchoscopy, CT scan and photography are the diagnostic tests that reveal the spread of cancer - staging of the cancer.


Kaposi Sarcoma staging

For all cancer types, staging determines the treatment options and the patient's survival outlook. With regard to Kaposi Sarcoma, the staging is largely influenced by the person's weakened immune system and the presence of AIDS related infections. For Kaposi Sarcoma staging, doctors use the AIDS Clinical Trial Group system. Three factors are considered under the AIDS Clinical Trial Group system while categorizing patients in good risk group and poor risk group.


  • The extent of the tumor
  • The status of the immune system as measured by the number of certain immune cells (CD4 cells) present in the blood
  • Systemic illness

These factors have two subgroups. After assessing the features, the type of Kaposi Sarcoma, doctors discuss the most suitable treatment option.


Kaposi Sarcoma treatment

Kaposi Sarcoma is incurable but can be controlled with treatment. The stage, the type of Kaposi Sarcoma, the number of lesions, age and general health are considered by the doctors before determining the appropriate treatment option. It could be chemotherapy, immunotherapy, antiviral drugs or radiation therapy. There are possible side effects for each of these treatment options.


Chemotherapy: Chemo drugs can be given into a vein or by mouth to enter the blood stream to reach all areas of the body. Chemotherapy is a treatment option when the cancer has spread to many areas of the body. Chemo drugs cannot be given for long periods as it can weaken the immune system. Particularly for HIV infected patients, there is a need to strengthen the immune system. In such cases, combined antiretroviral therapy can be used along with chemo drugs. Drug interaction is taken into account before prescribing the combined therapy. After tests indicate control of Kaposi sarcoma, chemo drugs may be stopped and the treatment may continue with combined antiretroviral therapy alone.


Immunotherapy: Transplant related Kaposi Sarcoma is usually treated using immunosuppressant medications or immunotherapy. The aim is to strengthen the immune system so as to fight the HHV-8 while ensuring the body doesn't reject the transplanted organ. Alternatively, radiotherapy or chemotherapy may also be considered.


cART: Combination antiretroviral therapy (cART) involves the use of several different medications called antiretroviral therapy to lower HIV levels in the blood by slowing down the rate at which the virus can multiply.


Radiotherapy: If Kaposi Sarcoma spreads and affects the internal organs, symptoms such as breathlessness and swelling of the arms and legs cause immense distress. Radiotherapy is chosen as a treatment option as the high-energy rays destroy cancer cells cautiously without harming the healthy cells in the body.


Surgery: If the lesions are small, after injecting local anesthetic to numb the area, surgery is performed to remove the lesion.


Cryotherapy: Cryotherapy involves freezing small lesions with liquid nitrogen.


Retinoic acid gel: Retinoic acid is applied directly to the skin several times a day on the small lesions. After few weeks of application, significant improvement can be noticed.



Melanoma

Melanoma is a type of skin cancer that develops from abnormal moles, or the pigment skin present in the skin. Because of its nature to spread to other parts of the skin, melanoma is more serious that other forms of skin cancer. It can cause serious illness and death. Derived from Greek origin 'melas' which means 'dark', melanocytes are cells that produce dark pigment called melanin which is responsible for the color of the skin. Melanoma is a most common form of cancer and the risk can increase with age. However, melanoma affects people of all ages, races, and genders and ethnicity.


Signs and symptoms

As melanoma occurs in the skin and it can be seen, patients themselves are the first to detect many melanomas. If caught early, melanomas can be cured by relatively minor surgery. However, early diagnosis and detection are crucial as it may otherwise invade healthy tissues and spread to other parts of the body making it out of control. The ABCD of melanoma can be described as:

Asymmetry: that is the shape of one half does not match with the other half.
Border: the edges are blurred, irregular.
Color is uneven and includes shades of black, brown and tan.
Diameter: there is a change in size as it increases.


Causes of Melanoma

Researchers opine that a gene known as BRAF plays a lead role in causing melanoma. As BRAF is a switch gene, it allows other cells to divide and grow. Mutations in this gene can cause explosive growth and the resultant melanoma skin cancer.

  • Sunburns, especially slow daily sun exposure, even without burning.
  • White ancestry (Caucasian)
  • Fair skin, light hair and light colored eyes
  • Intense exposure to sun especially during childhood
  • Many moles in the body, to the tune of more than hundred
  • Large irregular funny looking moles
  • History of close relatives especially parents, siblings or children with melanoma- presence of close family melanoma is a high risk factor; although only 10% of cases run in families.

Melanoma can occur on any skin surface – it is common on the area between a man's shoulders and hips. For women, melanoma generally develops on the lower legs. People with darker skin develop melanoma on their palms and soles as well as under toe and fingernails.


Diagnosis of melanoma

Get the dermatologist to examine your body fully and find out whether the moles are odd. The medical term for such moles is 'atypical'. The dermatologist will perform a skin biopsy to evaluate if the mole is cancerous or not. The doctor will remove all or part of the skin under local anesthesia and send the specimen to a pathologist for analysis. The biopsy report will reveal:

  • A totally benign condition that requires no further treatment, as in the case of a regular mole.
  • An atypical mole which depends on the judgment of the pathologist to treat – either conservative removal by taking off a bit of the normal skin all around to make sure that the spot is completely out or
  • A melanoma requiring surgery
  • Some doctors may perform epiluminescence or dermatoscopy.

Melanoma treatment

Once melanoma is diagnosed as cancer and staged, then the doctor will discuss the treatment options with the patient. Treatment is based on the stage of cancer and other related factors. In case of normal moles, which are small brown spots or growths of skin that appear in the first few decades of life in almost everyone, no treatment is necessary.

People with classic atypical mole syndrome have more than 100 moles, with many moles over 8 mm diameter and one or more moles are atypical. Treatment options include Surgery, chemotherapy, and immunotherapy and radiation therapy. Sometime a combination of treatment is used. In general melanoma is treated by surgery alone. But surgery need not be extensive, as was some years ago. During early stages of melanoma, surgeons will remove only a centimeter or even less of normal tissue around the melanoma. Whereas, deeper and more advanced cancers would require extensive surgery. The removal of nearby lymph glands depend upon factors that include tumor thickness, body location, age etc. If the stage is pretty advanced, immunotherapy treatments are adopted.


Prevent melanoma

Reduce sun exposure. Perhaps avoidance of sun exposure is the best means to prevent melanoma. Wear hats and tightly woven clothing and apply sunscreens liberally when going out. Although there is a controversy among dermatologists about sunscreen protecting against melanoma, it is certainly preferred to unprotected sun exposure.

Early detection is the key to prevention. Get your skin checked at least once every few years. In the US, the American Academy of Dermatology sponsors free skin cancer screening clinics every year all over the country. Special pigmented lesion clinics have also been established in many medical centers to allow close clinical and photographic follow ups of patient with high risk. But a reference from a concerned dermatologist is essential to undergo the screening.

Any person with high risk and having a close relative who has/had melanoma should be screened by a doctor for cancer of the skin. As with any other cancer, early diagnosis and proper evaluation and treatment is the essence.


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Collection of Pages - Last revised Date: December 10, 2017