Kaposi's sarcoma

Definition

Kaposi's sarcoma (KS) is a cancer of the skin, mucous membranes, and blood vessels; it is the most common form of cancer in AIDS patients. It was named for Dr. Moritz Kaposi (1837-1902), a Hungarian dermatologist who first described it in 1872. As of 2001, researchers disagree as to whether KS is a true cancer or a disorder of the skin that develops as a reaction to infection by a herpesvirus.

Description

The formal medical term for Kaposi's sarcoma is multiple idiopathic hemorrhagic sarcoma. This term means that KS develops in many different sites on the patient's skin or internal organs; that its cause is unknown; and that it is characterized by bleeding. The lesions (areas of diseased or damaged skin), which are usually round or elliptical in shape and a quarter of an inch to an inch in size, derive their characteristic purple or brownish color from blood leaking out of capillaries (small blood vessels) in the skin. In KS, the capillaries begin to grow too rapidly and irregularly, which causes them to become leaky and eventually break. The lesions themselves may become enlarged and bleed, or cause the mucous membranes of the patient's internal organs to bleed.

There are three types of KS lesions, defined by their appearance:

• Nodular. These are reddish-purple, but are sometimes surrounded by a border of yellowish or brown pigment. Nodular lesions may appear to be dark brown rather than purple in patients with dark skin.
• Infiltrating. Infiltrating lesions may be large or have a raised surface. They typically grow downward under the skin.
• Lymphatic. These lesions are found in the lymph nodes and may be confused with other causes of swollen lymph nodes.

As of 2001, KS is classified into five types:

• Classic KS. This form of KS is sometimes called indolent KS because it is slow to develop. Classical KS is most commonly found in males between 50 and 70 years of age, of Italian or Eastern European Jewish descent.
• African KS. This form of the disease appears in both an indolent and an aggressive form in native populations in equatorial Africa. It accounts for almost 10% of all cancers in central Africa.
• Immunosuppressive treatment-related KS. The third form of KS occurs in kidney transplant patients who have been given drugs to suppress their immune systems-usually prednisone and azathioprine . This form of KS is sometimes called iatrogenic KS, which means that it is caused unintentionally by medical treatment.
• Epidemic KS. Epidemic KS was first reported in 1981 as part of the AIDS epidemic. Most cases of epidemic KS in the United States have been diagnosed in homosexual or bisexual men.
• Non-epidemic gay-related KS. This form of KS occurs in homosexual men who do not develop HIV infection. Non-epidemic gay-related KS is an indolent form of the disease that primarily affects the patient's skin.

Demographics

The demographic distribution of KS varies considerably across its five types:

• Classic KS. Classic KS is considered a rare disease, with a male/female ratio of 10:1 or 15:1. In North America and Europe, most patients are between 50 and 70 years old. Classic KS is more common in men from Mediterranean countries and in Ashkenazic Jews.
• African KS. African KS has the same male/female ratio as classic KS, although most patients with African KS are younger. A form of African KS that attacks the lymphatic system primarily affects children, with a male/female ratio of 3:1.
• Immunosuppresive treatment-related KS. This form of KS occurs mostly in kidney-transplant patients, at a rate of 150 to 200 times as often as in the general population. It represents 3% of all tumors that occur in kidney-transplant patients. The male/female ratio is 2:1.
• Epidemic KS. Epidemic KS is overwhelmingly a disease of adult homosexual or bisexual males. It is 20,000 times more common in people with AIDS than in those without HIV infection. According to the National Institutes of Health (NIH), 95% of all the cases of epidemic KS in the United States have been diagnosed in homosexual or bisexual males. Epidemic KS is far more prevalent among homosexual or bisexual males with AIDS than among hemophiliacs or intravenous drug users with AIDS. Prior to 1995, about 26% of all homosexual males with AIDS had KS as their first symptom or eventually developed KS, as compared with fewer than 3% of heterosexual intravenous drug users with AIDS. This clustering of KS cases among a subpopulation of AIDS patients led to the hypothesis that a blood factor transmitted by sexual contact is a partial cause of KS. The number of new cases of AIDS-related KS has declined in recent years, for reasons that are not yet clear. Some researchers think that the introduction of highly active antiretroviral therapy, or HAART, is related to the decline in the number of cases of epidemic KS. As of 2001, only about 12% of AIDS patients develop KS.
• Non-epidemic gay-related KS. This small group of KS patients is entirely male.

Causes and symptoms

Causes

GENETIC FACTORS.

The role of genetic factors in KS varies across its five types. Classic KS is the only form associated with specific ethnic groups. In addition, patients with classic KS and immunosuppressive treatment-related KS have a higher incidence of a genetically determined immune factor called HLA-DR.

MALE HORMONES.

The fact that all forms of KS affect men more often than women may indicate that androgens (male sex hormones) may be a factor in the development of KS.

IMMUNOSUPPRESSION.

In addition to organ transplant patients receiving immunosuppressive drugs, patients who are taking high-dose corticosteroids are also at increased risk of developing KS.

INFECTIOUS AGENTS.

Some researchers think that cytomegalovirus (CMV) and human papilloma virus (HPV) may be involved in the development of KS because fragments of these two types of virus have been found in KS tumor samples. The most likely candidate for an infectious agent, however, is human herpesvirus 8 (HHV-8), which is sometimes called KS-associated herpesvirus (KSHV). Fragments of the HHV-8 genome were first detected in 1994 by using a technique based on polymerase chain reaction (PCR) analysis. HHV-8 belongs to a group of herpesviruses called rhadinoviruses, and is the first herpesvirus of this subtype to be found in humans. HHV-8 is, however, closely related to the human herpesvirus called Epstein-Barr virus (EBV). EBV is known to cause infectious mononucleosis as well as tumors of the lymphatic system, and may be involved in other malignancies, including the African form of Burkitt's lymphoma , Hodgkin's disease , and nasopharyngeal cancer . HHV-8 has been found in tissue samples from patients with African KS, classic KS, and immunosuppression treatment-related KS as well as epidemic KS. HHV-8 is also associated with a rare non-cancerous disease called Castleman's disease, which affects the lymph nodes. Some KS patients have been found to have KS and Castleman's disease occurring together in the same lymph node.

OTHER CAUSES.

Some practitioners of alternative medicine regard environmental toxins, psychological distress, and constitutional weaknesses as probable or partial causes of KS. These theories are discussed in more detail under the heading of alternative treatments.

Symptoms

CLASSIC KS.

The symptoms of classic KS include one or more reddish or purplish patches or nodules on one or both legs, often on the ankles or soles of the feet. The lesions slowly enlarge over a period of 10-15 years, with additional lesions sometimes developing. It is rare for classic KS to involve the patient's internal organs, although bleeding from the digestive tract sometimes occurs. About 34% of patients with classic KS eventually develop non-Hodgkin's lymphoma or another primary cancer.

AFRICAN KS.

The symptoms of the indolent form of African KS resemble those of classic KS. The aggressive form, however, produces tumors that may penetrate the tissue underneath the patient's skin, and even the underlying bone.

EPIDEMIC KS.

Epidemic KS has more varied presentations than the four other types of KS. Its onset is usually, though not always, marked by the appearance of widespread lesions at many different points on the patient's skin and in the mouth. Most HIV-infected patients who develop KS skin and mouth lesions feel healthy and have no systemic symptoms. On the other hand, KS may affect the patient's lymph nodes or gastrointestinal tract prior to causing skin lesions.

Patients with epidemic KS almost always develop disseminated (widely spread) disease. The illness progesses from a few localized lesions to lymph node involvement and further spread to other organs. Disseminated KS is defined by the appearance of one or more of the following: a count of 25 or more external lesions; the appearance of 10 or more new lesions per month; and the appearance of visible lesions in the patient's lungs or stomach lining.

In some cases, disseminated KS causes painful swelling (edema) of the patient's feet and lower legs. The lesions may also cause the surrounding skin to ulcerate or develop secondary infections. The spread of KS to the lungs, called pleuropulmonary KS, usually occurs at a late stage of the disease. KS involvement of the lungs causes bleeding, coughing, shortness of breath, and eventual respiratory failure. Most patients who die directly of KS die from its pleuropulmonary form.

Diagnosis

Physical examination and patient history

The diagnosis of any form of KS requires a careful examination of all areas of the patient's skin. Even though the characteristic lesions of classic KS appear most frequently on the legs, all forms of KS can produce lesions on any area of the skin. An experienced doctor, who may be a dermatologist, an internist, or a primary care physician, can make a tentative diagnosis of KS on the basis of the external appearance of the skin lesions (size, shape, color, and location on the face or body), particularly when they are accompanied by evidence of lymph node involvement, internal bleeding, and other symptoms associated with disseminated KS. The doctor may touch or press on the lesions to find out whether they turn pale (blanch); KS plaques and nodules do not blanch under fingertip pressure. In addition, KS lesions are not painful when they first appear.

Other signs of KS may appear on the soft palate or the membrane covering the eye (conjunctiva). In addition, the doctor will press on the patient's abdomen in order to detect any masses in the liver or spleen.

A thorough history is necessary in order to determine whether the patient's ethnic background, lifestyle, or medical history places him or her in a high-risk category for KS.

Biopsy

A definitive diagnosis of KS requires a skin biopsy in order to rule out bacillary angiomatosis, a bacterial infection resembling cat-scratch disease. It is caused by a bacillus, Bartonella henselae. Collecting a tissue sample for a biopsy is not difficult if the patient has skin lesions, but can be complicated if the nodules are primarily internal. An endoscopy of the upper end of the digestive tract may be performed in order to obtain a tissue sample from an internal KS lesion.

Under the microscope, an AIDS-related KS lesion will show an unusually large number of spindle-shaped cells mixed together with small capillaries. The origin of the spindle-shaped cells is still unknown. The tumor cells in a KS lesion resemble smooth muscle cells or fibrob-lasts, which are cells that help to form the fibers in normal connective tissue.

If the patient's lymph nodes are enlarged, a biopsy may be done in order to rule out other causes of swollen lymph nodes.

Other tests

Other diagnostic tests may be performed if the patient appears to have disseminated KS. These tests include:

• Chest x rays. A radiograph of the patient's lungs will show patchy areas of involved tissue.
• Gallium scan . The results will be negative in KS.
• Bronchoscopy . This procedure allows the doctor to examine the patient's bronchial pathways for visible KS lesions. It is not, however, useful for obtaining tissue samples for biopsy.
• Upper gastrointestinal endoscopy . Examination of the patient's stomach allows the doctor to examine the mucous lining for KS lesions as well as to obtain a tissue sample.

Treatment team

KS patients may receive treatment for skin lesions from a dermatologist or radiologist as well as treatment for lung or lymphatic involvement from internists or primary care practitioners. A surgeon may be called in to remove lesions in the digestive tract if they are bleeding or blocking the passage of food. Children with KS may be treated by pediatricians or by primary care physicians who specialize in treating AIDS patients.

Clinical staging, treatments, and prognosis

Staging

The NIH recommends individualized staging of patients with classic KS, due to the age of most patients, the localized nature of the lesions, the slow progression of the disease, and the low risk of spread to the internal organs.

The criteria for staging epidemic KS have evolved over the past decade in response to changes in the treatment of HIV infection and to the recognition that KS does not fit well into standard categories of tumor assessment. Several different systems have been used to stage epidemic KS, but none is completely satisfactory.

NYU STAGING SYSTEM.

One staging system that originated at New York University divides KS patients into four groups according to the following symptom clusters:

• Skin lesions that are indolent (slow-growing) and limited to relatively small areas of the body.
• Skin lesions limited to specific regions of the body but aggressive in growth. There may or may not be involvement of lymph nodes.
• General involvement of the skin and mucous membranes, with or without lymph node involvement.
• Involvement of the internal organs.

AIDS CLINICAL TRIALS GROUP (ACTG) STAGING SYSTEM.

The ACTG Oncology Committee published a staging system for epidemic KS in 1989. This system was reevaluated in 1995 and is undergoing continued assessment. It is based on three criteria: extent of tumor; condition of the patient's immune system; and presence of systemic illness:

• Tumor (T): Good risk (0) is a tumor limited to the skin and/or lymph nodes and/or minimal oral disease (limited to the palate). Poor risk (1) is any of the following: edema associated with the tumor; widespread KS in the mouth; KS in the digestive tract; KS in other viscera.
• Immune system (I): Good risk (0) is a CD4 cell count greater than 200 per cubic millmeter. Poor risk (1) is a CD4 cell count lower than 200 per cubic millimeter.
• Systemic illness (S): Good risk (0) is no history of opportunistic infections (OI) or thrush ; no "B" symptoms (unexplained fever , night sweats , diarrhea lasting more than 2 weeks, weight loss greater than 10%); performance status above 70 on the Karnofsky scale. Poor risk (1) is any of the following: history of OI or thrush; presence of "B" symptoms; Karnofsky score lower than 70; and other HIV-related illnesses.

Treatment

Treatment of KS depends on the form of the disease.

CLASSIC KS.

Radiation therapy is usually quite effective if the patient has small lesions or lesions limited to a small area of skin. Low-voltage photon radiation or electron beam therapy give good results. Surgical removal of small lesions is sometimes done, but the lesions are likely to recur. The best results are obtained from surgical treatment when many small lesions are removed over a period of years.

For widespread skin disease, radiation treatment with electron beam therapy is recommended. Classic KS has not often been treated with chemotherapy in the United States, but some researchers report that treatment with vinblastine or vincristine has been effective. Disease that has spread to the lymph nodes or digestive tract is treated with a combination of chemotherapy and radiation treatment.

IMMUNOSUPPRESSIVE TREATMENT-RELATED KS.

The standard pattern of therapy for this form of KS begins with discontinuing the immunosuppressive medications if they are not essential to the patient's care. Treatment of the KS itself may include radiation therapy if the disease is limited to the skin, or single-or multiple-drug chemotherapy.

EPIDEMIC KS.

As of 2001, there is no cure for epidemic KS. Treatment is aimed at reducing the size of skin lesions and alleviating the discomfort of open ulcers or swollen tissue in the legs. There are no data that indicate that treatment prolongs the survival of patients with epidemic KS. In addition to treatment of the KS itself, these patients also need ongoing retroviral therapy and treatment of any opportunistic infections that may develop. An additional complication in treating epidemic KS is that highly active antiretroviral therapy, or HAART, is not the "magic bullet" that some had hoped when it was introduced in 1998. HAART uses three-or four-drug combinations to treat HIV infection. Problems with HAART include severe psychiatric as well as physical side effects, in addition to the patient's risk of developing a drug-resistant form of HIV if even one dose of medication is missed. The complex dosing schedules as well as the medication side effects make it difficult to assess the effectiveness of treatments aimed at the KS by itself.

Small KS lesions respond very well to radiation treatment. They can also be removed surgically or treated with cryotherapy , a technique that uses liquid nitrogen to freeze the lesion. Lesions inside the mouth (on the palate) can be treated with injections of vinblastine. In addition, the patient may be given topical alitretinoin (Panretin gel), which is applied directly to the lesions. Alitretinoin received FDA approval for treating KS in 1999.

Systemic treatments for epidemic KS consist of various combinations of anti-cancer drugs, including vincristine (Oncovin), vinblastine (Velban), bleomycin (Blenoxane), doxorubicin (Adriamycin), daunorubicin (DaunoXome), interferon-alpha (Intron A, Roferon-A), etoposide (VePesid), or paclitaxel (Taxol). The effectiveness of systemic treatments ranges from 50% for high-dose therapy with interferon-alpha to 80% for combinations of vincristine, vinblastine, bleomycin, doxorubicin, and etoposide. The drawbacks of systemic treatment include the toxicity of these drugs and their many side effects. Interferon-alpha can be given only to adult patients with relatively intact immune systems and no signs of lymphatic involvement. The side effects of systemic chemotherapy include hair loss (alopecia ), nausea and vomiting , fatigue , diarrhea, headaches, loss of appetite (anorexia ), allergic reactions, back pain, abdominal pain, and increased sweating.

As of 2001, the standard for first-line treatment of epidemic KS is one of the FDA-approved anthracyclines such as liposomal doxorubicin (Doxil) or liposomal daunorubicin (DaunoXome), rather than a combination drug regimen. Liposomes are small sacs consisting of an outer layer of fatty substances used to coat an inner core of another medication. In addition to concentrating the drug's effects on the tumor, liposomes moderate the side effects.

In 1997 the FDA approved paclitaxel (Taxol) for epidemic KS resistant to treatment. Paclitaxel is a drug derived from the bark of the Pacific yew tree that prevents the growth of cancer cells by preventing the breakdown of normal cell structures called microtubules. After paclitaxel treatment, cancer cells become so clogged with microtubules that they cannot grow and divide. The drug has serious side effects, most notably suppression of the patient's bone marrow.

Experimental treatments for AIDS-related KS include retinoic acid, which is derived from vitamin A; and other drugs that inhibit the formation of new blood vessels (angiogenesis) in tumors. The reason for inhibiting angio-genesis is that new blood vessels keep a cancer supplied with oxygen and nutrients, which help the cancer grow and spread to other parts of the body. Antiangiogenic agents that have been proposed for treating KS include Fumagillin, SP-PG, and Platelet 4 factor. As of 2001, the effectiveness of these substances in humans is not yet known. Approval by the Food and Drug Administration will require several years after the test results are known.

Prognosis

The prognosis of KS varies depending on its form. Patients with classic KS often survive for many years after diagnosis; death is often caused by another cancer, such as non-Hodgkin's lymphoma, rather than the KS itself. The aggressive form of African KS has the poorest prognosis, with a fatality rate of 100% within three years of diagnosis. Patients with immunosuppressive treatment-related KS have variable prognoses; in many cases, however, the KS goes into remission once the immune-suppressing drug is discontinued. The prognosis of patients with epidemic KS also varies, depending on the patient's general level of health. As a rule, patients whose KS has spread to the lungs have the poorest prognosis.

Alternative and complementary therapies

SHARK CARTILAGE.

The only alternative treatment for epidemic KS that has been evaluated by the NIH is shark cartilage. Shark cartilage products are widely available in the United States as over-the-counter (OTC) preparations that do not require FDA approval. A 1995 review of alternative therapies found more than 40 brand names of shark cartilage products for sale in the United States to treat arthritis and psoriasis as well as KS. The cartilage can be taken by mouth or by injection.

The use of shark cartilage to treat KS derives from a popular belief that sharks and other cartilaginous fish (skates and rays) do not get cancer. This belief is countered by findings from samples of captured sharks that they do in fact develop various kinds of tumors. There are three explanations of the role of shark cartilage in preventing KS. Some researchers have proposed that it kills cancer cells directly. A second explanation is that cartilage stimulates the human immune system. The third theory, which has more evidence in its favor than the first two, is that the cartilage slows down or prevents angiogenesis. Two complex proteins in shark cartilage, identified as U-995 and SCF2, have been shown to inhibit angiogenesis in laboratory studies. As of December 2000, only three studies using human subjects have been published; the results are inconclusive. The complete results of three other studies using shark cartilage in human subjects have not yet been published in complete form. Preliminary reports of NIH-sponsored clinical trials are also not yet available; however, all three studies being currently conducted have received the lowest rating (3iii) for the statistical strength of the study's design.

The side effects of treatment with shark cartilage include mild to moderate nausea, vomiting, abdominal cramps, constipation, low blood pressure, abnormally high levels of blood calcium (hypercalcemia ), and general feelings of weakness.

OTHER ALTERNATIVE THERAPIES.

Other alternative treatments for KS are aimed almost completely at epidemic KS. Most are based on assumptions that AIDS victims have had their immune systems weakened by such environmental toxins as lead and radioactive materials, or by psychological stress generated by societal disapproval of homosexuality. Naturopaths would add such life-style stresses as the use of tobacco and alcohol, as well as poor sleep patterns and nutritional deficiencies. Homeopaths believe that AIDS is the product of hereditary predispositions to disease called miasms, specifically two miasms related to syphilis and gonorrhea respectively.

Alternative topical treatments for the skin lesions of AIDS-related KS include homeopathic preparations made from periwinkle, mistletoe, or phytolacca (poke root). Other alternative skin preparations include a selenium solution made from aloe gels, selenium, and tincture of silica; a mixture of aloe vera and dried kelp (sea-weed); and a mixture of aloe vera, tea tree oil, and tincture of St. John's wort. Alternative treatments for KS lesions on the internal organs include a mixture of warm wine and Yunnan Paiyao powder, a Chinese patent medicine made from ginseng; castor oil packs; or a three-to seven-day grape fast repeated every 120 days.

Alternative systemic treatments for AIDS-related KS include:

• Naturopathic remedies: High doses of vitamin C, zinc, echinacea, or goldenseal to improve immune function; or preparations of astragalis, osha root, or licorice to suppress the HIV virus.
• Homeopathic remedies: These include a homeopathic preparation of cyclosporine and another made from a dilution of killed typhoid virus.
• Ozone therapy: There are isolated reports from Europe and the United States of AIDS-related KS going into several months of remission after treatment with ozone given via rectal insufflation.

Alternative treatments aimed at improving the quality of life for KS patients include Reiki, reflexology, meditation, and chromatherapy.

Coping with cancer treatment

Studies of treatment side effects in patients with epidemic KS are complicated by the difficulty of distinguishing between side effects caused by treatment aimed at the HIV retrovirus itself and those caused by treatment for KS. Common problems related to KS treatment include damage to the bone marrow, hair loss, and nerve damage from medications.

Other treatment-related problems include weight loss due to poor appetite, and swelling of body tissues due to fluid retention. Patients may be given nutritional counseling, medications to stimulate the appetite, and radiation treatment or diuretics to reduce the level of fluid in the tissues.

Clinical trials

As of March 2001, there are thirteen open and active clinical trials being conducted for treatments for KS, twelve for epidemic KS and one for unspecified KS. Some of these are comparing the relative effectiveness of doxorubicin, daunorubicin, and paclitaxel. Others are studies of other agents, including interleukin-11, inter-leukin-12, cidofovir, and filgrastim . One is a study of the effects of HAART on AIDS-related KS. As of July 2000, the National Cancer Institute (NCI) reported that clinical trials of thalidomide indicated that the drug has some activity against epidemic KS. Updated information about the content of and patient participation in clinical trials can be obtained at the web site of the National Cancer Institute: http://cancertrials.nci.nih.gov.

Prevention

As of 2001, the only known preventive strategy for reducing one's risk for epidemic KS is abstinence from intercourse or modification of sexual habits. Homosexual or bisexual males can reduce their risk of developing KS by avoiding passive anal intercourse. Women can reduce their risk by avoiding vaginal or anal intercourse with bisexual males.

Kidney transplant patients who are at increased risk of developing KS as a result of taking prednisone or other immunosuppressive drugs should consult their primary physician about possible changes in dosage.

Special concerns

The two special concerns most likely to arise with epidemic KS are social isolation due to the disfigurement caused by KS lesions on the patient's face, and spiritual or psychological concerns related to the tumor's connection to AIDS and homosexuality. There are many local and regional support groups for cancer patients that can help patients deal with concerns about appearance. With regard to religious/spiritual issues, most major Christian and Jewish bodies in the United States and Canada have task forces or working groups dealing with AIDS-related concerns. The National Catholic AIDS Network (NCAN) maintains an information database and web site (http://www.ncan.org) and accepts call-in referrals at (707) 874-3031.

Resources

BOOKS

The Burton Goldberg Group. Alternative Medicine: The Definitive Guide. Fife, WA: Future Medicine Publishing, Inc., 1995.

"Hematology and Oncology." Section 11 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

James, Nicholas D., and Karol Sikora. "Immunotherapy of Tumors, " in Encyclopedia of Immunology, v. 3, 2nd ed., edited by Peter J. Delves and Ivan M. Roitt. San Diego and London: Academic Press, 1998.

Kubota, Marshall K., MD. "Human Immunodeficiency Virus Infection and Its Complications, " in Conn's Current Therapy, edited by Robert E. Rakel, MD. Philadelphia: W. B. Saunders Company, 2000.

Schulz, Thomas F. "Herpesvirus-8, Infection and Immunity, " in Encyclopedia of Immunology, v. 2, 2nd ed., edited by Peter J. Delves and Ivan M. Roitt. San Diego and London: Academic Press, 1998.

Silverberg, Ivan J., MD. "Kaposi's Sarcoma." In Dollinger, Malin, MD, Ernest H. Rosenbaum, MD, and Greg Cable. Cancer Therapy. Kansas City, MO: Andrews and McMeel, 1994.

PERIODICALS

Correspondence: Kaposi's Sarcoma. New England Journal of Medicine 343(8) (August 24, 2000).

San Francisco AIDS Foundation. Bulletin of Experimental Treatments for AIDS.

ORGANIZATIONS

AIDS Clinical Trials Group (ACTG). c/o William Duncan, Ph.D., National Institutes of Health. 6003 Executive Boulevard, Room 2A07, Bethesda, MD 20892.

American Cancer Society (ACS). 1599 Clifton Road, NE, Atlanta, GA 30329. (404) 320-3333 or (800) ACS-2345. Fax: (404) 329-7530. Web site: <http://www.cancer.org>

National Cancer Institute, Office of Cancer Communications.31 Center Drive, MSC 2580, Bethesda, MD 20892-2580.(800) 4-CANCER (1-800-422-6237). TTY: (800) 332-8615. Web site: <http://www.nci.nih.gov>.

NIH National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P. O. Box 8218, Silver Spring, MD 20907-8218. TTY/TDY: (888) 644-6226. Fax: (301) 495-4957.

San Francisco AIDS Foundation (SFAF). 995 Market Street, #200, San Francisco, CA 94103. (415) 487-3000 or (800) 367-AIDS. Fax: (415) 487-3009. Web site: http://www.sfaf.org.

Rebecca J. Frey, Ph.D.

KEY TERMS

Angiogenesis

—The formation of blood vessels. Some complex proteins found in shark cartilage appear to prevent angiogenesis in tumor cells in laboratory tests.

Cryotherapy

—A form of treating KS lesions that involves freezing them with liquid nitrogen.

Disseminated

—Widely distributed or spread. Epidemic KS almost always develops into a disseminated form, in which the disease spreads throughout the patient's body.

Highly active antiretroviral therapy (HAART)

—A form of drug-combination treatment for HIV infection introduced in 1998. Most HAART regimens are combinations of three or four drugs, usually nucleoside analogs and protease inhibitors.

Iatrogenic

—Caused unintentionally by medical treatment. Immunosuppressive treatment-related KS is sometimes called iatrogenic KS.

Immunosuppressive

—Any form of treatment that inhibits the body's normal immune response.

Indolent

—Relatively inactive or slow-spreading. Classic KS is usually an indolent disease.

Liposomes

—Artificial sacs composed of fatty substances that are used to coat or encapsulate an inner core containing another drug. Some drugs used to treat epidemic KS are given in the form of liposomes.

Opportunistic infections (OI)

—Diseases caused by organisms that multiply to the point of producing symptoms only when the body's immune system is impaired.

Kaposi's Sarcoma

Definition

Kaposi's sarcoma is a form of skin cancer that can involve internal organs. It most often is found in patients with acquired immunodeficiency syndrome (AIDS ), and can be fatal.

Description

Kaposi's sarcoma (KS) was once a very rare form of cancer, primarily affecting elderly men of Mediterranean and eastern European background, until the 1980s, when it began to appear among AIDS patients. It manifests in four distinct forms. The first form, called classic KS, was described by the Austrian dermatologist Moricz Kaposi more than a century ago. Classic KS usually affects older men of Mediterranean or eastern European backgrounds by producing tumors on the lower legs. Though at times painful and disfiguring, they generally are not life-threatening. The second form of the disease, African endemic KS, primarily affects boys and men. It can appear as classic KS, or in a more deadly form that quickly spreads to tissues below the skin, the bones and lymph system, leading to death within a few years of diagnosis. Another form of KS, iatrogenic KS, is observed in kidney and liver transplant patients who take immunosuppressive drugs to prevent rejection of their organ transplant. Iatrogenic KS usually reverses after the immunosuppressive drug is stopped. The fourth form of KS, AIDS-related KS, emerged as one of the first illnesses observed among those with AIDS. Unlike classic KS, AIDS-related KS tumors generally appear on the upper body, including the head, neck, and back. The tumors also can appear on the soft palate and gum areas of the mouth. In more advanced cases, they can be found in the stomach and intestines, the lymph nodes, and the lungs.

Incidence of Kaposi's sarcoma has been reported as high as 20% in homosexual men who have HIV, 3% in heterosexual intravenous drug users, 3% in women and children, 3% in transfusion recipients, and 1% in hemophiliacs. Once regarded as only a defining illness for AIDS, KS has proven to be a progressive, fatal disease on its own, especially when the disease becomes systemic. Yet involvement throughout the body is not the only factor in patient mortality. Research in 2000 found that patients with KS in oral mucosa had a higher risk of death than those with KS appearing only on the skin.

Causes and symptoms

A variety of factors appear to contribute to the development of KS. One of the first avenues offered as causal agents was genetic predisposition. People with classic KS, and those who develop the tumors after transplantation, are more likely than others to possess a genetically determined immune factor called HLA-DR. Cases of KS that run in families, however, are rare.

The fact that the disease is more likely to afflict men than women suggests sex hormones, such as testosterone in men, may stimulate the growth of KS tumors, and that estrogen in women may retard their growth.

Immune suppression was the next likely cause since liver, kidney, and bone marrow patients who take immunosuppressive drugs to prevent transplant rejection frequently develop KS lesions. Similarly, KS has been observed in patients receiving systemic treatment with high-dose corticosteroids, which also suppresses the immune system. Immune suppression is the hallmark of AIDS.

The current theory is the discovery of an infectious agent. A number of viruses have been proposed as possible causes, including cytomegalovirus and human papilloma virus, fragments of which have been found in KS tumor specimens. A more likely candidate, however, is a new herpes virus that has been called human herpes virus 8 (HHV-8) or KS-associated herpes virus (KSHV). Since fragments of the virus were first disclosed in KS samples in 1994, they have since been found in KS samples taken from patients with classic KS, African endemic KS, and KS in transplant patients. Fragments of HHV-8, however, also have been found in patients who have other skin diseases but who do not have KS.

Studies in 2000 showed that HHV-8 was indeed the culprit behind KS. Nevertheless, it does not work alone. In combination with a patient's altered response to cytokines (regulatory proteins produced by the immune system) and the HIV-1 transactivating protein Tat which promotes the growth of endothelial cells, HHV-8 can then encode interleukin 6 viral proteins. These specific cytokines stimulate cell growth in the skin, becoming KS.

HHV-8 destroys the immune system further by directing a cell to remove the major histocompatibility complex (MHC-1) proteins that protect it from invasion. These proteins then are transferred to the interior of the cell and are destroyed. This leaves the cell unguarded and vulnerable to invaders which normally would be targeted for attack by the immune system.

Research in early 2001 showed that transmission of HHV-8 virus can be more casual than once was thought, giving rise to incidence among women and children. Women who are intravenous drug users and who also have had a sexually transmitted disease have been found to harbor HHV-8. This evidence shows that women can contract HHV-8 through blood. In addition, researchers in 2000 found that HHV-8 could be transmitted orally though kissing. This study found more HHV-8 virus in oral samples than in genital secretions. In fact, HHV-8 was difficult to find in genital samples. This may indicate why children and women who were not intravenous drug users have had KS.

MORIZ KAPOSI, (1837–1902)

Moriz Kohn Kaposi was born in 1837 to very poor Hungarian parents. He studied dermatology under Ferdinand von Hebra at the University of Vienna, earning his medical degree in 1861. Kaposi took a position in Hebra's clinic and ultimately became a lecturer where he was responsible for educating numerous dermatologists. Kaposi and Hebra coauthored The Handbook of Diseases of the Skin which had great success. Kaposi married Hebra's daughter and the couple had one son, Hermann (1872). When Hebra died, Kaposi filled the vacant spot as director of the skin clinic and as Vienna's most renowned dermatologist.

Between 1872 and 1887, Kaposi discovered nine skin diseases that had not been previously documented. His discovery of a malignant disease that strikes the lymph nodes and skin (Kaposi's sarcoma 1872) has been documented as the most noteworthy. This disease was seen relatively rarely in the United States until the 1980s when it was tied to AIDS. This sarcoma has been the most common tumor found in AIDS patients. In 1872, Kaposi also studied cases of lupus erythematosus, which had no previous documentation. Kaposi was a prolific writer who published Pathology and Treatment of Diseases of the Skin in addition to numerous other publications, which he completed individually and with other authors. Kaposi died in 1902.

Kaposi's sarcoma produces pink, purple, or brown tumors on the skin, mucous membranes, or internal organs.

Diagnosis

Many physicians will diagnose KS based on the appearance of the skin tumors and the patient's medical history. Unexplained cough or chest pain, as well as unexplained stomach or intestinal pain or bleeding, could suggest that the disease has moved beyond the skin. The most certain diagnosis can be achieved by taking a biopsy sample of a suspected KS lesion and examining it under high-power magnification. For suspected involvement of internal organs, physicians will use a bronchoscope to examine the lungs or an endoscope to view the stomach and intestinal tract.

Treatment

Treatment goals for KS are simple: to reduce the severity of symptoms, shrink tumors, and prevent disease progression. Unfortunately, there is no single best treatment plan that can achieve all of these goals. Treatments range from topical agents for mild disease with few tumors to more aggressive systemic chemotherapy for more serious KS that has spread to large areas of skin or the internal organs. Physicians will frequently combine topical, radiation, and various systemic chemotherapy drugs, depending on the sites of the body affected, the speed at which it is progressing, and the patient's overall health, among other considerations.

Local therapy

When the number of KS tumors is small and the disease appears to be progressing slowly, physicians have had great success with the application, by the patient, of a topical gel containing alitretinoin. This product is a naturally occurring retinoid (a derivative of vitamin A) that can inhibit cell growth and activate apoptosis (cell death). Patients tolerate the product well with only mild to moderate skin irritation at the site of application in some individuals. Duration of treatment is long term, with the patient seeing results after four to eight weeks of therapy. Treatment slows the progress of the disease and reduces the size of the lesions.

Other local treatments include cryotherapy (using a liquid nitrogen spray or probe to freeze the tumor), injections of vinblastine (a drug also used for systemic chemotherapy) directly into the tumor, laser therapy, or radiation therapy targeted at the tumor sites. These methods have some success, but they also have unpleasant side effects. Vinblastine injections are about 70% effective, but they do not resolve the lesions completely.

Systemic chemotherapy

With widespread KS lesions over the body surface, or evidence of spread to other parts of the body, physicians will consider systemic chemotherapy drugs. A new class of chemotherapy drugs, called liposomal anthracyclines, appears to produce good results with fewer toxic side effects than do more conventional chemotherapy drugs. Two of these drugs, liposomal doxorubicin (Doxil) and liposomal daunorubicin (DaunoXone) have become the treatment of choice. These drugs last longer in the human body, demonstrate higher concentrations of the drug in tumors, and have fewer toxic side effects.

Paclitaxel (Taxol) is the newest drug in the KS arsenal. It has a 75% effective rate and is very effective in patients who are resistant to anthracycline drugs. The 3-hour infusion time and the incidence of bone marrow suppression, hair loss, and joint and muscle pain make it less attractive to patients.

Antiretroviral therapy

Evidence suggests that for some individuals, the class of AIDS drugs called protease inhibitors, in combination with other anti-HIV drugs, can reduce the levels of detectable HIV in the blood to nearly zero, and in some patients stabilize or reverse KS tumors. A study late in 2003 showed that highly active antiretroviral therapy (HAART) containing a protease inhibitor helped block KS tumor growth, invasion and distant spread. HAART is a treatment used to treat HIV patients. Since the discovery of HHV-8, interest in an antiviral approach to KS has increased. There is no evidence, however, that two antiviral drugs commonly prescribed for herpes, acyclovir and ganciclovir, have any effect on the disease. One study of 20,000 patients with HIV and AIDS found that those who took foscarnet, another antretroiviral medication that works in a different way than acyclovir and ganciclovir, were less likely to develop KS tumors.

Another treatment source is interferon-alpha, which is made by the body and has powerful effects on the immune system. Investigators have tried injecting it directly into lesions, and also in combination with other anti-HIV drugs such as zidovudine, with some success. It has been used with patients who have KS limited only to the skin and who have little immunosuppression. Interferon-alpha has had poor tumor response and significant toxic effects in patients, especially those with seriously-depressed immune systems.

Still other avenues of therapy being researched are sex hormones, thalidomide, SU5516 (an endothelial growth factor inhibitor), and angiogenesis inhibitors, which prevent the growth of blood vessels within a cell that supplies oxygen and nutrients. There also is some research involving the oral administration of alitretinoin.

Alternative treatment

The Bastyr University AIDS Research Study has been investigating and collecting data on treatment for KS and other opportunistic conditions that are AIDS-related. Among the treatments under investigation are nutritional and herbal therapies (both internal and external). Bastyr University is located in Seattle, Washington.

Prognosis

The prognosis for patients with classic KS is good. Tumors can frequently be controlled and patients frequently die of other causes before any serious spread. African endemic KS can progress rapidly and lead to premature death, despite treatment. In AIDS-related KS, milder cases can frequently be controlled; the prognosis for more advanced and rapidly progressing cases is less certain and dependent on the patient's overall medical condition. There are indications that KS can be stabilized or reversed in patients whose level of HIV in the blood is reduced to undetectable levels via combined antiretroviral therapy.

KEY TERMS

African endemic Kaposi's sarcoma— Affects men and boys; can appear like classic KS or in a more lethal form.

AIDS-related Kaposi's sarcoma— Emerged as one of the first illnesses associated with AIDS patients. These tumors usually appear on the upper body, the soft palate and gum areas, and, as the disease advances, in the lymph nodes, stomach, intestines, and lungs.

Apoptosis— Cell death.

Classic Kaposi's sarcoma— Usually affects older men of Mediterranean or eastern European backgrounds, and produces tumors on the lower legs.

Cytokines— Regulatory proteins that are produced by the immune system.

Human herpesvirus 8— Also called Kaposi's sarcoma-associated herpesvirus (KSHV). Thought to be a viral cause for KS.

Iatrogenic Kaposi's sarcoma— Develops in transplant patients who take immunosuppressive drugs to prevent rejection of their organ transplant.

MCH-1— Major histocompatibility complex proteins that protect cells from invasion.

Prevention

Safer sex practices may help to prevent AIDS-related KS by decreasing the risk of transmission of HHV-8 through sexual means. However, the addition of avoidance of deep kissing to those precautions may be necessary. Intravenous drug users should still be urged not to share needles. Treatment with antiretrovirals may help to preserve the function of the immune system in HIV patients and delay the appearance and progression of KS lesions. In fact, since the introduction of HAART in those infected with HIV, KS has decreased substantially. However, it still remains the most common cancer among those infected with HIV.

Large clinical trials underway in 2003 were showing some promise for preventing infection with HHV-8 through prophylaxis (preventive medication) with antiherpes drugs.

Resources

PERIODICALS

"Alitretinoin Gel Effective for Treating Lesions." AIDS Weekly February 12, 2001.

Cannon, Michael J., A. Scott Laney, and Philip E. Pellett. "Human Herpesvirus 8: Current Issues." Clinical Infectious Diseases July 1, 2003: 82-86.

Dezube, Bruce J. "AIDS-Related Kaposi Sarcoma." Archives of Dermatology 136, no. 2 (December 2000): 1554.

Henderson, Charles W. "Kissing May Spread Cause of Kaposi's Sarcoma." Cancer Weekly November 21, 2000: NA.

Mann, Arnold. "Kaposi's Lesions Benefit from Long-Term Alitretinoin Gel Use." Family Practice News 30, no. 19 (October 1, 2000): 12.

"Protease Inhibitors Used for Treating HIV also Block Kaposi Sarcoma." Cancer Weekly 30, no. 19 (November 4, 2003): 125.

Rohrmus, Bettina, Eva M. Thoma-Greber, Hohannes R. Bogner, and Martin Rocken. "Outlook in Oral and Cutaneous Kaposi's Sarcoma." The Lancet 356, no. 9248 (December 23, 2000): 2160.

Kaposi's sarcoma

Definition

Kaposi's sarcoma (KS), also called multiple idiopathic hemorrhagic sarcoma, is a neoplastic disease associated especially with AIDS , usually affecting the skin and mucous membranes.

Description

Causes & symptoms

Kaposi's sarcoma (KS) is caused by herpesvirus 8. Malignant cells are found in the tissues under the skin or mucous membranes that line the mouth, nose, and anus. KS causes red or purple patches on the skin and/or mucous membranes and spread to other organs, such as the lungs, liver, or intestinal tract. KS is seen in three forms:

• indolent
• lymphadenopathic
• AIDS-related

The primary distinction between the three forms of KS is the rate of growth and the location of the lesions. In the past, the indolent form of Kaposi's sarcoma was the most common, and was most often seen in men over the age of 60 years of Jewish or Italian ancestry; in African men; and in patients who had organ transplants or had their immune systems impaired for other reasons. KS was frequently left untreated. Because of its slow growth, the cancer was not a threat to the patient. Since the 1980s, a far higher percentage of cases with rapid growth have been observed, usually accompanied by AIDS (HIV disease).

The aggressive form of KS is seen in about one-third of patients with AIDS, and has become endemic in equatorial African. In African nations, aggressive KS is seen most often among young men and children.

Lymphadenophic KS affects the lymph nodes as well as the skin structures.

Diagnosis

KS is traditionally diagnosed based on the red or purple patches on the skin or mucous membranes. A biopsy is usually performed in order to verify the diagnosis. Since other cancers may have a similar appearance to KS, it is often useful to test for the presence of human herpesvirus 8 in order to confirm the diagnosis.

Treatment

In indolent KS, localized treatment is often adequate. Superficial lesions may be removed surgically. Alternatives are radiation therapy, electrical curettage, in which the lesion is burned with an electrical current, or cryotherapy, in which a source of extreme cold, such as liquid nitrogen, is applied to the cancer in order to kill the cells.

Among patients who develop KS after an organ transplant, reduction in the dose of drugs used to control the immune response may be enough to control or eliminate the cancer, although this treatment increases the risk of transplant rejection. One report from the University of Barcelona in Spain states that a change of medication may resolve the problem of KS after transplantation.

In KS associated with AIDS, systemic chemotherapy is usually required.

The Gay Men's Health Crisis (GMHC) has reviewed a number of alternative therapies which have been tried in KS, but none have shown consistently favorable results. Among the treatments mentioned were shark cartilage, herbal and purifying massage therapies to enhance immune function, and transcendental meditation . Homeopathy has been tried, but here too the results have not been reliable.

Allopathic treatment

There are no current best-practice treatments for KS. For rapidly growing KS, a standard treatment is systemic chemotherapy with a combination of adriamycin, bleomycin, and vincristine (ABV); however, several studies have reported that single-agent treatments may be as effective as combinations. Single-agent treatments that have shown evidence of effectiveness are a liposomal form of adriamycin used alone; methotrexate, and trimetrexate. Interferon-alpha has also been reported to be effective in AIDS-related KS.

Expected results

The expected results depend primarily on the underlying condition of the patient. Those patients who have classic slow-growing KS may live many years, even in the absence of treatment. For patients with AIDS, a proposed staging system has divided patients into low- and high-risk groups, depending both on the extent of the sarcoma and their underlying immune function. Patients with well-functioning immune systems, no AIDS associated opportunistic infections , and KS confined to the skin have an estimated survival of about three years. Those with impaired immune systems, other infections, and more widespread KS have an estimated survival of about one year. Overall length of survival will depend on the patient's response to treatment.

Prevention

The United States Public Health Service (USPHS) guidelines for prevention of KS call for prophylactic administration of drugs that are effective against human herpesvirus-8. The primary drugs for this purpose are foscarnet and ganciclovir. In each case, the dose must be adjusted based on the patient's condition. While the USPHS recognizes that KS may affect children as well as adults, no formal recommendations for prevention have been published.

Resources

BOOKS

Abeloff M. D., J. O. Armitage, A. S. Lichter, and J. E. Nieder-huber, editors. Clinical Oncology, 2nd edition. New York: Churchill Livingston, 2000.

PERIODICALS

Campistol, J. M., A. Gutierrez-Dalmau, and J. V. Torregrosa. "Conversion to sirolimus: a successful treatment for post-transplantation Kaposi's sarcoma." Transplantation (March 2004): 760–2.

Chao, S. C., J. Y. Lee, and C. J. Tsao. "Treatment of classical type Kaposi's sarcoma with paclitaxel." Anticancer Res (January-February 2001): 571–3.

Cheuk, W., K. O. Wong, C. S. Wong, J. E. Dinkel, D. Ben-Dor, and J. K. Chan. "Immunostaining for human herpesvirus 8 latent nuclear antigen-1 helps distinguish Kaposi sarcoma from its mimickers." Am J Clin Pathol (March 2004): 335–42.

"DaunoXome offers KS treatment alternative." Aids Alert (June 1996): 67–8.

OTHER

"Prevention of disease recurrence." 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with HIV: Part III. United States Public Health Service/Infectious Diseases Society of America, 1999.

"Prevention of the first episode of disease." 1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with HIV: Part II. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention. U.S. Public Health Service/Infectious Diseases Society of America, 1999.

Samuel Uretsky, Pharm.D.

KAPOSI'S SARCOMA

DEFINITION

Kaposi's sarcoma (KS; pronounced kuh-PO-seez sar-KO-muh) is a very rare form of cancer (see cancer entry). The word "sarcom" refers to any form of cancer that affects muscle, bone, liver, kidneys, lungs, spleen, bladder, and other organs and tissues. At one time, Kaposi's sarcoma was seen almost entirely in older men of Mediterranean or eastern European background. In the 1980s, however, it began to show up in young men with AIDS (see AIDS entry). Mild forms of the disease can be treated with topical (local) agents. More serious forms are treated with chemotherapy (treatment with drugs). KS is a major cause of death among people with AIDS.

DESCRIPTION

Scientists know of four forms of Kaposi's sarcoma. One form, called classical KS, affects older men of Mediterranean or eastern European background. The disease appears as pink, purple, or brown patches on the lower legs. These patches can be painful and ugly, but they are usually not life-threatening.

A second form of KS is called African endemic KS. It affects boys and men of any ethnic background. Its earliest symptoms are similar to those of classical KS. The cancer soon spreads, however, to tissues under the skin, the bones, and the lymph system. The disease is difficult to treat and often causes death within a few years of diagnosis.

Iatrogenic (pronounced eye-a-truh-JE-nik) KS is a third form of the disease. An iatrogenic disorder is one that develops because a patient is being treated for some other disease. Iatrogenic KS usually occurs in patients who have had a liver or kidney transplant. It is able to develop because these patients have taken drugs to suppress (restrain) their immune systems. Iatrogenic KS tends to disappear when these patients stop taking the drugs.

The fourth form of KS is AIDS-related KS. This form of KS appeared among gay men who developed AIDS in the 1980s. AIDS-related KS tumors first appear on the skin. But the disease may then spread to the head, neck, back, mouth, stomach and intestines, lymph nodes, and lungs. In its advanced stages, AIDS-related KS is very difficult to cure and can often cause death.

CAUSES

A variety of factors appear to lead to the development of KS:

• Genetic background. People with classic and African KS appear to possess an abnormal gene. Genes are chemical substances in the body that determine a person's physical and biological characteristics.
• Sex hormones. KS occurs far more often in men than in women. This suggests that sex hormones may have something to do with how the disease develops.
• Immune suppression. In many cases, the immune system may be strong enough to defend the body against KS. When the immune system is weakened, however, it loses that ability. People who are taking immunosuppressant drugs are, therefore, at risk for KS. So are people with AIDS, whose immune systems are often very badly damaged.
• Infectious agents that are sexually transmitted. Gay and bisexual men and intravenous drug users are all at high risk for AIDS. But gay and bisexual men are ten times more likely to develop KS than are intravenous drug users. That suggests that KS may be caused by some agent that is transmitted sexually. Further support for this idea comes from the fact that the rate of KS cases among gay and bisexual men has dropped dramatically as safer sex practices have become more widespread.

Kaposi's Sarcoma: Words to Know

African endemic Kaposi's sarcoma:

A form of KS that affects boys and men, has symptoms like those of classic KS, and can spread rapidly and cause death.

AIDS-related Kaposi's sarcoma:

A form of KS that occurs primarily in gay and bisexual men; it is much more dangerous than classic KS.

Classic Kaposi's sarcoma:

A form of KS that usually affects older men of Mediterranean or eastern European background.

Iatrogenic Kaposi's sarcoma:

A form of KS that develops in people who have had organ transplants and are taking immunosuppressant drugs.

Researchers have already found viruses they think may cause KS. One of the most likely candidates is called human herpes virus 8. This virus belongs to the same family that causes cold sores and shingles. The virus has been found in samples of KS taken from patients with the disease. Additional studies are still needed to confirm this theory.

SYMPTOMS

The symptoms of KS are quite visible and take the form of pink, purple, or brown patches that usually first appear on the lower legs.

DIAGNOSIS

KS can often be diagnosed simply by the appearance of the lesions (blotches) on a patient's skin. An unexplained cough or chest pain, or unexplained stomach or intestinal pain or bleeding, may suggest that the disease has spread to internal organs. A visual diagnosis of KS is usually confirmed with a biopsy. A biopsy is a process by which a small sample of tissue is taken from a patient. The sample is studied under a microscope to see what kinds of cells are present. KS cells have a very distinctive appearance that a scientist can recognize.

TREATMENT

There is no single best treatment for KS. The choice of treatment depends on the type of KS a patient has and how far it has spread. Doctors sometimes use a combination of treatments to obtain the best possible results. Some common treatments include:

Topical Therapy

Topical therapy is used when there are few lesions and the disease seems to be progressing slowly. In such a case, a doctor may freeze the lesions, which kills them. Radiation therapy can also be used on individual lesions. Radiation therapy involves the use of some form of radiation, such as X rays, to kill cancer cells.

Systemic Chemotherapy

In systemic chemotherapy, a patient is given drugs that enter his or her bloodstream and are carried throughout the body. The drugs can thus attack and kill cancer cells in all parts of the body. Doctors have found that a combination of cancer-killing drugs often works better than a single drug. Some commonly used drugs include vinblastine (pronounced vin-BLAS-teen), bleomycin (pronounced blee-uh-MYS-uhn), and doxorubicin (dok-suh-ROO-buh-suhn).

Antiviral Therapy

A number of drugs have been developed for the treatment of AIDS. Some of these drugs also appear to be effective against KS. Among the most promising of these drugs is a group of chemicals known as protease inhibitors. Some widely used antiviral drugs (drugs that kill viruses) have not, however, been effective in treating KS. These drugs include acyclovir (pronounced a-SI-klo-veer) and ganciclovir (pronounced gan-SI-klo-veer).

Other Treatments

A number of other treatments for KS are being studied. These include:

Alpha-interferon. Alpha-interferon is a chemical produced naturally in the body that fights infectious agents. It has been tested as a treatment for KS by injecting it directly into lesions.

• Retinoids. Retinoids are related to vitamin A. They have long been used to treat acne (see acne entry) and other skin diseases (see skin disorders entry). Some researchers believe that they also may be effective against KS lesions.
• Laser therapy. Laser therapy is similar to radiation therapy except that it uses laser light instead of X rays or other forms of radiation. Laser therapy has had limited success in destroying small lesions.

WHAT ARE INTERFERONS?

Infections are caused by bacteria, viruses, fungi, and other organisms. Doctors now have a number of tools to fight most of these disease-causing agents. For example, many bacterial infections can be cured by antibiotics. Viral infections, however, are a more difficult problem. Scientists have discovered relatively few drugs that will kill viruses. Some of the most promising of these drugs belong to a group known as the interferons.

Interferons were discovered in 1957 by the Scottish virologist Alick Isaacs and the Swiss virologist Jean Lindenmann. While studying influenza, Isaacs and Lindenmann made an unexpected discovery. Viruses in a cell had a way of preventing other viruses from entering the same cell. The viruses originally present in the cell produced a protein (chemical) that killed newly-arrived viruses. Isaacs and Lindenmann called the protein interferon because it "interfered" with the presence of other viruses.

At first, scientists thought that only one kind of interferon existed. But they have now discovered more than two dozen. Alpha-interferon is one type. It is being used to treat patients with Kaposi' sarcoma. Scientists are now investigating ways in which they will be able to make interferons work for them in fighting a number of diseases, including cancer.

Alternative Treatment

There is little evidence that any form of alternative treatment is effective against KS. Some practitioners recommend the use of herbal medicines and special diets.

PROGNOSIS

The prognosis for KS differs significantly for various forms of the disease. Patients with classic KS stand a good chance of complete recovery if they receive treatment soon enough. The prognosis for African endemic KS is not very good. The disease tends to spread rapidly and causes death within a relatively short period of time. Milder forms of AIDS-related KS can often be controlled. If the disease spreads to internal organs, however, prognosis is much less certain.

PREVENTION

There are no known methods for preventing classic and African endemic KS. AIDS-related KS can be prevented if those who are at risk for the disease (primarily gay and bisexual men) practice safer-sex methods. These methods prevent the spread of the infectious agent—whatever it is—from an infected to a noninfected person.

FOR MORE INFORMATION

Organizations

American Academy of Dermatology. 930 N. Meacham Road, PO Box 4014, Schaumburg, IL 60173. (847) 330-0230; (888) 462–3376. http://www.aad.org.

Gay Men's Health Crisis. 119 West 24th Street, New York, NY 10011. (212) 367-1000. http://www.gmhc.org.

Kaposi's sarcoma (kap-oh-siz) n. a malignant tumour arising from blood vessels in the skin and appearing as purple to dark brown plaques or nodules. It is common in Africa but rare in the Western world, except in patients with AIDS. The tumour evolves slowly; radiotherapy is the treatment of choice for localized lesions and chemotherapy may be of value in metastatic disease. See AIDS. [ M. Kaposi (1837–1902), Austrian dermatologist]