Kaposi's sarcoma

Definition

Kaposi's sarcoma is a form of skin cancer that can involve internal organs. It is most often 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 are not generally 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, and in more advanced cases, they can be found in the stomach and intestines, the lymph nodes, and the lungs,

Kaposi's sarcoma is reported to be found in 20% of 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.

— Janie F. Franz

A cancer characterized by numerous bluish-red nodules on the skin, usually on the lower extremities, that is endemic to equatorial Africa and often occurs in a particularly virulent form in people with AIDS.

[After Moritz Kaposi (1837–1902), Austrian dermatologist.]

Key Terms: Angiogenesis, Cryotherapy, Disseminated, Highly active antiretroviral therapy, Iatrogenic, Immunosuppressive, Indolent, Liposomes.

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 herpes virus.

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 2005, 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 fibroblasts, 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 ray. 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.
• 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 anticancer 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 2005, 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 angiogenesis 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 2005, 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 (seaweed); 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

By 2001, there were 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, interleukin-12, cidofovir, and filgrastim. One is a study of the effects of HAART on AIDS-related KS. 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

The only known preventive strategy for reducing one's risk for epidemic KS is abstinence from inter-course 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

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Hematology and Oncology." Section 11 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

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.

Periodicals

Correspondence: Kaposi's Sarcoma. New England Journal of Medicine 343, no. 8 (August 24, 2000).

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

Organizations

AIDS Clinical Trials Group (ACTG). c/o William Duncan, PhD, 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: .

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: .

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.

A condition affecting blood vessels; believed to be of a neoplastic nature and of multicentric origin. Skin lesions appear as multiple red-brown nodules ranging from a few mm to 1 cm in size. Histologically, endothelial proliferation in sheets or small vessels, hemosiderin deposits, fibroblastic proliferation, and an inflammatory infiltrate of lymphocytes are seen. Associated with HIV infection.

Kaposi’s sarcoma. (Regezi/Sciubba/Jordan, 2003)

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.

[Article by: Samuel Uretsky, Pharm.D.]

For more information on Kaposi sarcoma, visit Britannica.com.

Kaposi's sarcoma
Classification and external resources
Papular cutaneous Kaposi's Sarcoma
ICD-10	C46.
ICD-9	176
ICD-O:	M9140/3
OMIM	148000
DiseasesDB	7105
MedlinePlus	000661
eMedicine	med/1218  derm/203 oph/481
MeSH	D012514

Kaposi's sarcoma (KS) is a tumor caused by Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). It was originally described by Moritz Kaposi, a Hungarian dermatologist practicing at the University of Vienna in 1872.^[1] It became more widely known as one of the AIDS defining illnesses in the 1980s. The viral cause for this cancer was discovered in 1994. Although KS is now well-established to be caused by a virus infection, there is widespread lack of awareness of this even among persons at risk for KSHV/HHV-8 infection^[2].

Contents 1 Epidemiological varieties 2 Types 3 Clinical features 3.1 Skin 3.2 Mouth 3.3 Gastrointestinal tract 3.4 Respiratory tract 4 Pathophysiology and diagnosis 5 Treatment and prevention 6 History and theories 6.1 Discovery 6.2 Relationship to AIDS 6.3 Viral cause isolated 6.4 Unknown factors 7 Awareness 8 References 9 External links

Epidemiological varieties

HHV-8 is responsible for all varieties of KS.

Classic KS as originally described was a relatively indolent disease affecting elderly men from the Mediterranean region, or of Eastern European descent. Countries bordering the Mediterranean basin have higher rates of KSHV/HHV-8 infection than the remainder of Europe ^[3][4]

Endemic KS was described later in young African people, mainly from sub-Saharan Africa, as a more aggressive disease which infiltrated the skin extensively, especially on the lower limbs. This, it should be noted, is unrelated to HIV infection. The high rate of KS in sub-Saharan countries is due to the high rates of HHV 8 infection in their general populations, frequently greater than 50%.^[5][6]

Transplant Related KS had been described, but only rarely until the advent of calcineurin inhibitors (such as ciclosporin, which are inhibitors of T-cell function) for transplant patients in the 1980s, when its incidence grew rapidly. The tumor arises either when an HHV 8-infected organ is transplanted into someone who has not been exposed to the virus or when the transplant recipient already harbors pre-existing HHV 8 infection.^[7][8]

Epidemic KS was described during the 1980s as an aggressive disease in AIDS patients (HIV also causes a defect in T-cell immunity). It is over 300 times more common in AIDS patients than in renal transplant recipients. In this case, HHV 8 is sexually transmitted among people who are also at risk for sexually transmitted HIV infection. ^[9]

Types

Since Moritz Kaposi first described this malignant neoplasm, the disease has been reported in five separate clinical settings, with different presentations, epidemiology, and prognoses^[10]:599:

• Classic Kaposi sarcoma
• African cutaneous Kaposi sarcoma
• African lymphadenopathic Kaposi sarcoma
• AIDS-associated Kaposi sarcoma
• Immunosuppression-associated Kaposi sarcoma

Clinical features

KS lesions are nodules or blotches that may be red, purple, brown, or black, and are usually papular (i.e. palpable or raised).

They are typically found on the skin, but spread elsewhere is common, especially the mouth, gastrointestinal tract and respiratory tract. Growth can range from very slow to explosively fast, and is associated with significant mortality and morbidity.^[11]

Skin

Commonly affected areas include the lower limbs, face, mouth and genitalia. The lesions are usually as described above, but may occasionally be plaque-like (often on the soles of the feet) or even involved in skin breakdown with resulting fungating lesions. Associated swelling may be from either local inflammation or lymphoedema (obstruction of local lymphatic vessels by the lesion). Skin lesions may be quite disfiguring for the sufferer, and a cause of much psychosocial pathology.

Mouth

Intraoral Kaposi’s sarcoma lesion with an overlying candidiasis infection

Is involved in about 30%, and is the initial site in 15% of AIDS related KS. In the mouth, the hard palate is most frequently affected, followed by the gums.^[12] Lesions in the mouth may be easily damaged by chewing and bleed or suffer secondary infection, and even interfere with eating or speaking.

Gastrointestinal tract

Involvement can be common in those with transplant related or AIDS related KS, and it may occur in the absence of skin involvement. The gastrointestinal lesions may be silent or cause weight loss, pain, nausea/vomiting, diarrhea, bleeding (either vomiting blood or passing it with bowel motions), malabsorption, or intestinal obstruction.^[13]

Respiratory tract

Involvement of the airway can present with shortness of breath, fever, cough, hemoptysis (coughing up blood), or chest pain, or as an incidental finding on chest x-ray.^[14] The diagnosis is usually confirmed by bronchoscopy when the lesions are directly seen, and often biopsied.

Pathophysiology and diagnosis

Despite its name, it is generally not considered a true sarcoma, which is a tumor arising from mesenchymal tissue. KS actually arises as a cancer of lymphatic endothelium and forms vascular channels that fill with blood cells, giving the tumor its characteristic bruise-like appearance. KSHV proteins are uniformly detected in KS cancer cells.

KS lesions contain tumor cells with a characteristic abnormal elongated shape, called spindle cells. The tumor is highly vascular, containing abnormally dense and irregular blood vessels, which leak red blood cells into the surrounding tissue and give the tumor its dark color. Inflammation around the tumor may produce swelling and pain.

Although KS may be suspected from the appearance of lesions and the patient's risk factors, a definite diagnosis can only be made by biopsy and microscopic examination, which will show the presence of spindle cells. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.

Treatment and prevention

Blood tests to detect antibodies against KSHV have been developed and can be used to determine if a patient is at risk for transmitting infection to their sexual partner, or if an organ is infected prior to transplantation. Unfortunately, these tests are not available except as research tools and thus there is little screening for persons at risk for becoming infected with KSHV, such as transplant patients.

Kaposi's sarcoma is not curable, in the usual sense of the word, but it can often be effectively palliated for many years and this is the aim of treatment. In KS associated with immunodeficiency or immunosuppression, treating the cause of the immune system dysfunction can slow or stop the progression of KS. In 40% or more of patients with AIDS-associated Kaposi's sarcoma, the Kaposi lesions will shrink upon first starting highly active antiretroviral therapy (HAART). However, in a certain percentage of such patients, Kaposi's sarcoma may again grow after a number of years on HAART, especially if HIV is not completely suppressed. Patients with a few local lesions can often be treated with local measures such as radiation therapy or cryosurgery. Surgery is generally not recommended as Kaposi's sarcoma can appear in wound edges. More widespread disease, or disease affecting internal organs, is generally treated with systemic therapy with interferon alpha, liposomal anthracyclines (such as Doxil) or paclitaxel.

With the decrease in the death rate among AIDS patients receiving new treatments in the 1990s, the incidence and severity of epidemic KS also decreased. However, the number of patients living with AIDS is increasing substantially in the United States, and it is possible that the number of patients with AIDS-associated Kaposi's sarcoma will again rise as these patients live longer with HIV infection.

History and theories

Discovery

The disease is named after Moritz Kaposi (1837–1902), a Hungarian dermatologist who first described the symptoms in 1872. Research over the next century suggested that KS, like some other forms of cancer, might be caused by a virus or genetic factors, but no definite cause was found.

Relationship to AIDS

With the rise of the AIDS epidemic, KS, as initially one of the most common AIDS symptoms, was researched more intensively in hopes that it might reveal the cause of AIDS.

In 2007, San Francisco doctors reported a Kaposi's sarcoma cluster among gay men. All 15 patients undergoing treatment were long-term HIV patients whose HIV infections were firmly controlled with antiviral drugs. None appeared to be in any danger. The new cases were not aggressive, invasive or lethal as was typical with uncontrolled HIV during the 1980s. The unsightly, difficult to treat lesions raised questions about the immune response aging of HIV patients.^[15]

Viral cause isolated

Further information: Kaposi's sarcoma-associated herpesvirus

In 1994, Yuan Chang, Patrick S. Moore, and Ethel Cesarman at Columbia University in New York isolated genetic pieces of a virus from a KS lesion. They used representational difference analysis (a method to subtract out all of the human DNA from a sample) to isolate the viral genes. They then used these small DNA fragments as starting points to sequence the rest of the viral genome in 1996. This, the eighth human herpesvirus (HHV-8)—now known as Kaposi's sarcoma-associated herpesvirus (KSHV)—has since been found in all KS lesions tested, and is considered the cause of the disease. KSHV is a unique human tumor virus that has incorporated cellular genes that cause tumors into its genome ("molecular piracy"); the stolen cellular genes may help the virus escape from the immune system, but in doing so it also causes cells to proliferate. It is related to Epstein-Barr virus, a very common herpesvirus that can also cause human cancers. KSHV is readily found in all forms of KS. The virus is sexually transmitted among men having sex with men [1] and can be transmitted through organ donation [2]. In Africa, high rates of KSHV infection has led to KS becoming the most common cancer in sub-Saharan Africa [3]. KSHV infection is thought to be life-long so that persons infected with KSHV may develop KS years later if they develop AIDS or other immunosuppression.

Unknown factors

Like other tumor viruses, KSHV infection only leads to cancer in a minority of infected persons. Other factors are required, such as pre-existing immune system damage, for disease to erupt. In Africa has shown that even in the absence of HIV/AIDS, KS is more common in men than women although KSHV infection is equal between both sexes. This suggests that sex hormones may either protect from or predispose to KS in persons infected with the virus. Although older theories suggested that HIV might directly initiate KS, aside from its effects on the immune system, HIV and KSHV infect different cells and HIV is not found in KS tumors making this theory obsolete.

Awareness

Only 6% of men having sex with men are aware that KS is caused by a virus different from HIV^[16]. Thus, there is little community effort to prevent KSHV infection. Similarly, no systematic screening of organ donations is in place.

In AIDS patients, Kaposi's sarcoma is considered an opportunistic infection, a disease that is able to gain a foothold in the body because the immune system has been weakened. With the rise of HIV/AIDS in Africa, where KSHV is widespread, KS has become the most frequently reported cancer in some countries, such as Zimbabwe.

Nigerian bandleader Fela Kuti succumbed to the disease in 1997.

Because of their highly visible nature, external lesions are sometimes the presenting symptom of AIDS. Kaposi's sarcoma entered the awareness of the general public with the release of the film Philadelphia, in which the main character was fired after his employers found out he was HIV-positive due to visible lesions. Unfortunately, by the time KS lesions appear, it is likely that the immune system has already been severely weakened.

References

1. ^ Kaposi, M (1872). "Idiopathisches multiples Pigmentsarkom der Haut". Arch. Dermatol. Syph. 4: 265–273. doi:10.1007/BF01830024. 
2. ^ Phillips AM, Jones AG, Osmond DH, Pollack LM, Catania JA, Martin JN (July 2008). "Awareness of Kaposi's Sarcoma-Associated Herpesvirus Among Men Who Have Sex With Men". Sex Transm Dis. doi:10.1097/OLQ.0b013e318182c91f (inactive 2008-09-09). PMID 18665016. 
3. ^ Iscovich, J (Oct 22 1998). "Classic Kaposi's sarcoma in Jews living in Israel, 1961-1989: a population-based incidence study". AIDS 12 (15): 2067–72. doi:10.1097/00002030-199815000-00019. http://www.aidsonline.com/pt/re/aids/abstract.00002030-199815000-00019.htm;jsessionid=Gy0NY0Y2b5lXKwJTGkQv1C1SdhTymxKmhpM4Hkrdvvz3pyXQ9GPV!-1804036389!-949856145!8091!-1. 
4. ^ Fenig, E (October 1998). "Classic Kaposi sarcoma: experience at Rabin Medical Center in Israel". Am J Clin Oncol 21 (5): 498–500. doi:10.1097/00000421-199810000-00016. http://www.amjclinicaloncology.com/pt/re/ajco/abstract.00000421-199810000-00016.htm;jsessionid=Gy0Jys29KWqzWg4RWhQN9vCyvP3tMPn24WG35BQbdLHGlhJc1y7S!-1804036389!-949856145!8091!-1. 
5. ^ Cook-Mozaffari, P (December 1998). "The geographical distribution of Kaposi's sarcoma and of lymphomas in Africa before the AIDS epidemic". Br J Cancer 78 (11): 1521–8. PMID 9836488. 
6. ^ Olsen, SJ (October 1998). "Increasing Kaposi's sarcoma-associated herpesvirus seroprevalence with age in a highly Kaposi's sarcoma endemic region, Zambia in 1985" (PDF). AIDS 12 (14): 1921–5. doi:10.1097/00002030-199814000-00024. http://dceg.cancer.gov/pdfs/olsen1219211998.pdf. 
7. ^ Qunibi, W (Feb 27 1998). "Serologic association of human herpesvirus eight with posttransplant Kaposi's sarcoma in Saudi Arabia". Transplantation 65 (4): 583–5. doi:10.1097/00007890-199802270-00024. http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-199802270-00024.htm;jsessionid=Gy4Gq82dl1t9ppllm80G1PDjkbpmqFFkp2ypLSLnW2DthLg22DcM!220059229!-949856144!8091!-1. 
8. ^ Luppi, Mario (Nov 9 2000). "Bone marrow failure associated with human herpesvirus 8 infection after transplantation". N Engl J Med 343 (19): 1378–85. doi:10.1056/NEJM200011093431905. PMID 11070102. 
9. ^ Beral V, Peterman TA, Berkelman RL, Jaffe HW (January 1990). "Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection?". Lancet 335 (8682): 123–8. doi:10.1016/0140-6736(90)90001-L. PMID 1967430. http://linkinghub.elsevier.com/retrieve/pii/0140-6736(90)90001-L. 
10. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0721629210.
11. ^ Dezube, BJ (October 1996). "Clinical presentation and natural history of AIDS--related Kaposi's sarcoma". Hematol Oncol Clin North Am 10 (5): 1023–9. doi:10.1016/S0889-8588(05)70382-8. PMID 8880194. 
12. ^ Nichols, CM (01 November 1993). "Treating Kaposi's lesions in the HIV-infected patient". J Am Dent Assoc 124 (11): 78–84. PMID 8227776. http://jada.ada.org/cgi/content/abstract/124/11/78. Retrieved on 2007-06-11. 
13. ^ Danzig, JB (June 1991). "Gastrointestinal malignancy in patients with AIDS". Am J Gastroenterol 86 (6): 715–8. PMID 2038993. 
14. ^ Garay, SM (January 1987). "Pulmonary manifestations of Kaposi's sarcoma". Chest 91 (1): 39–43. doi:10.1378/chest.91.1.39. PMID 3792084. http://www.chestjournal.org/cgi/reprint/91/1/39. Retrieved on 2007-06-11. 
15. ^ Russell, Sabin (2007-10-11). "Unsettling re-emergence of 'gay cancer'". San Francisco Chronicle. http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2007/10/11/MNEESOFRG.DTL. Retrieved on 2007-10-12. 
16. ^ Phillips AM, Jones AG, Osmond DH, Pollack LM, Catania JA, Martin JN (July 2008). "Awareness of Kaposi's Sarcoma-Associated Herpesvirus Among Men Who Have Sex With Men". Sex Transm Dis. doi:10.1097/OLQ.0b013e318182c91f (inactive 2008-09-09). PMID 18665016. 

External links

• http://hivinsite.ucsf.edu/InSite?page=kb-authors&doc=kb-06-02-01
• Kaposi's sarcoma photo library at Dermnet
• Kaposi Sarcoma information
• Office of HIV and AIDS Malignancy in the National Cancer Institute

v • d • e Diseases of the skin and appendages by morphology Growths Epidermal wart · callus · seborrheic keratosis · acrochordon · molluscum contagiosum · actinic keratosis · squamous cell carcinoma · basal cell carcinoma · merkel cell carcinoma · nevus sebaceous · trichoepithelioma Pigmented Freckles · lentigo · melasma · nevus · melanoma Dermal and subcutaneous epidermal inclusion cyst · hemangioma · dermatofibroma · keloid · lipoma · neurofibroma · xanthoma · Kaposi's sarcoma · infantile digital fibromatosis · granular cell tumor · leiomyoma · lymphangioma circumscriptum · myxoid cyst Rashes With epidermal involvement Eczematous contact dermatitis · atopic dermatitis · seborrheic dermatitis · stasis dermatitis · lichen simplex chronicus · Darier's disease · glucagonoma syndrome · langerhans cell histiocytosis · lichen sclerosus · pemphigus foliaceus · Wiskott-Aldrich syndrome · Zinc deficiency Scaling psoriasis · tinea (corporis · cruris · pedis · manuum · faciei) · pityriasis rosea · secondary syphillis · mycosis fungoides · systemic lupus erythematosus · pityriasis rubra pilaris · parapsoriasis · ichthyosis Blistering herpes simplex · herpes zoster · varicella · bullous impetigo · acute contact dermatitis · pemphigus vulgaris · bullous pemphigoid · dermatitis herpetiformis · porphyria cutanea tarda · epidermolysis bullosa simplex Papular scabies · insect bite reactions · lichen planus · miliaria · keratosis pilaris · lichen spinulosus · transient acantholytic dermatosis · lichen nitidus · pityriasis lichenoides et varioliformis acuta Pustular acne vulgaris · acne rosacea · folliculitis · impetigo · candidiasis · gonococcemia · dermatophyte · coccidioidomycosis · subcorneal pustular dermatosis Hypopigmented tinea versicolor · vitiligo · pityriasis alba · postinflammatory hyperpigmentation · tuberous sclerosis · idiopathic guttate hypomelanosis · leprosy · hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized drug eruptions · viral exanthems · toxic erythema · systemic lupus erythematosus Localized cellulitis · abscess · boil · erythema nodosum · carcinoid syndrome · fixed drug eruption Specialized urticaria · erythema (multiforme · migrans · gyratum repens · annulare centrifugum · ab igne) Nonblanchable Purpura Macular thrombocytopenic purpura · actinic purpura Papular disseminated intravascular coagulation · vasculitis Indurated scleroderma/morphea · granuloma annulare · lichen sclerosis et atrophicus · necrobiosis lipoidica Miscellaneous disorders Ulcers Hair telogen effluvium · androgenic alopecia · trichotillomania · alopecia areata · systemic lupus erythematosus · tinea capitis · loose anagen syndrome · lichen planopilaris · folliculitis decalvans · acne keloidalis nuchae Nail onychomycosis · psoriasis · paronychia · ingrown nail Mucous membrane aphthous stomatitis · oral candidiasis · lichen planus · leukoplakia · pemphigus vulgaris · mucous membrane pemphigoid · cicatricial pemphigoid · herpesvirus · coxsackievirus · syphilis · systemic histoplasmosis · squamous cell carcinoma

v • d • e Vascular tissue neoplasm (ICD-O 9120-9179) (C49/D18, 171/215) Blood Hemangioma/hemangiosarcoma · Blue rubber bleb nevus syndrome · Hemangioendothelioma (Infantile hemangioendothelioma) · Kaposi's sarcoma · Hemangiopericytoma · Angiokeratoma · Capillary hemangioma (Hemangioblastoma) · Cavernous hemangioma Lymphatic Lymphangioma/lymphangiosarcoma · PEComa (Lymphangioleiomyomatosis) · Cystic hygroma Either Angioma/angiosarcoma · Angiofibroma see also vascular diseases, congenital

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