Clinical Manual for Management of the HIV-Infected Adult
2006 Edition

Section 6: Disease-Specific Treatment

Kaposi Sarcoma

Background

Kaposi sarcoma (KS) is an endothelial neoplasm that usually occurs as skin or oral lesions but may involve the internal organs. It is the most common AIDS-associated neoplasm and is an AIDS-defining disease. AIDS-associated KS is 1 of 4 types of KS, along with classic, endemic, and organ transplant-associated KS. Although the types vary in epidemiology and clinical presentation, all are associated with human herpesvirus type 8 (HHV-8), also known as KS-associated herpesvirus. The clinical manifestations of AIDS-associated KS (sometimes called epidemic KS) range in severity from mild to life threatening. The progression of disease may be rapid or slow, but the overall prognosis is poor in the absence of treatment. The skin lesions of KS, even when they do not cause medical morbidity, may cause significant disfigurement and emotional distress.

AIDS-associated KS usually occurs in HIV-infected persons with advanced immunosuppression (CD4 count <200 cells/µL), but may occur at any CD4 count. In the United States and Europe, KS occurs in all HIV risk groups, but most frequently in men who have sex with men (MSM). Risk factors in MSM include multiple sexual partners and a history of sexually transmitted infections (STIs); risk factors in other groups have not been clearly identified. The transmission of HHV-8 is not well understood. Although experts believe HHV-8 is transmitted sexually, it apparently also passes from person to person by other routes.

The incidence of KS in resource-abundant countries has declined markedly since the early 1990s, in part because of the widespread availability of effective combination antiretroviral therapy (ART). In parts of sub-Saharan Africa, where endemic KS has long existed in people with normal immune function, the incidence of KS has risen sharply in people with HIV/AIDS. ART appears to be effective in reducing the risk of AIDS-associated KS, particularly when initiated before the development of advanced immunosuppression.

S: Subjective

The cutaneous presentation of KS is the most common, occurring in 95% of cases. The patient may complain of a new painless pigmented (often purplish) lesion or lesions on the skin (usually of the extremities, face, or torso), or in the mouth. Lesions on the lower extremities, genitals, or face may be accompanied by swelling and pain. The patient may complain only of swelling or edema, without skin lesions, or may note enlarged lymph nodes. Oral lesions, if extensive, may cause tooth loss, pain, and ulceration.

Pulmonary KS may cause intractable cough, bronchospasm, hemoptysis, chest pain, and dyspnea.

Gastrointestinal KS may cause no symptoms, or the patient may have bleeding, pain, and symptoms of bowel obstruction.

During the history, ask about the symptoms noted above and associated characteristics, including the following:

• Duration of lesion(s)
• Pain
• Frequency of new lesions
• Respiratory or gastrointestinal symptoms
• Edema or swelling
• Recent CD4 cell counts

O: Objective

Physical Examination

Perform a careful physical examination, with particular attention to the following:

• Vital signs
• Skin (examine the entire skin surface)
• Oropharynx
• Extremities and external genitals (look for lesions, edema)
• Lymph nodes

Examine the lungs, abdomen, rectum, and other systems as indicated.

Common Manifestations

Skin lesions

Skin lesions may occur anywhere on the skin. Common sites include the face (under the eyes and on the tip of the nose), behind the ears, and on the extremities and torso. Lesions may be macules, papules, plaques, or nodules. At first, the lesions are small and may be flat. Their color may vary from pink or red to purple or brown-black (the latter particularly in dark-skinned individuals), and they are nonblanching, nonpruritic, and painless. Over time, the lesions often increase in size and number, darken, and rise from the surface; they may progress to tumor plaques (eg, on the thighs or soles of the feet), or to exophytic tumor masses, which can cause bleeding, necrosis, or extreme pain.

Oral lesions

Oral lesions may be flat or nodular and are red or purplish. They usually appear on the hard palate, but may develop on the soft palate, gums, tongue, or elsewhere.

Lymphedema

Lymphedema associated with KS usually appears in patients with visible cutaneous lesions, and edema may be out of proportion to the extent of visible lesions. Lymphedema may also occur in patients with no visible skin lesions. Common sites include the face, neck, external genitals, and lower extremities. Usually, a contiguous area of skin is also involved. Lymph nodes may be enlarged.

Pulmonary KS

Pulmonary KS usually causes severe, pneumonia-like symptoms and is rapidly progressive. The patient may exhibit difficulty breathing, bronchospasm, cough (sometimes with hemoptysis), and hypoxemia. The chest x-ray typically shows diffuse interstitial infiltrates, often accompanied by nodules or pleural effusion.

Gastrointestinal KS

Gastrointestinal KS may arise anywhere in the gastrointestinal tract. Patients are usually asymptomatic except in cases of intestinal obstruction or bleeding. KS may also cause protein-losing enteropathy. Visceral disease is uncommon in the absence of extensive cutaneous disease.

A: Assessment

The partial differential diagnosis depends on the type of symptoms present.

For cutaneous, oral, and lymph node presentations, consider the following:

• Bacillary angiomatosis
• Lymphoma
• Dermatofibromas
• Bacterial or fungal skin infections
• Stasis

For pulmonary symptoms, consider:

• Pneumocystis jiroveci pneumonia (PCP)
• Cytomegalovirus (CMV) pneumonia
• Pulmonary lymphoma (rare)

P: Plan

Diagnostic Evaluation

For cutaneous or oral KS, a presumptive diagnosis can often be made by the appearance of skin or mucous membrane lesions. Biopsy of a lesion (or a suspect lymph node) is recommended to verify the diagnosis and rule out infectious or other neoplastic causes. Biopsy is particularly important if the lesions are unusual in appearance or if the patient has systemic or atypical symptoms.

If respiratory symptoms are present, obtain chest x-rays or computed tomography (CT) studies. Radiographic findings may be suggestive of KS, but cannot provide a definitive diagnosis. Bronchoscopy with visualization of characteristic endobronchial lesions is usually adequate for diagnosis.

For patients with gastrointestinal symptoms and suspected KS, perform endoscopy.

Review recent CD4 cell counts. The CD4 count is typically low (<200 cells/µL) but KS can occur with any CD4 count.

If the patient has fever or respiratory, gastrointestinal, or constitutional symptoms, evaluate for other infectious and malignant causes (eg, by culture or biopsy) as suggested by the history and physical examination.

Treatment

Treatment of KS is not considered curative, and no single therapy is completely efficacious. ART is a key component of the treatment of KS and should be initiated (or maximized) in all persons with KS, unless contraindicated (for further information, see chapter Antiretroviral Therapy). KS often regresses and sometimes resolves in patients treated with effective ART. Other treatment modalities may be used concurrently, depending on the severity of KS and the speed of progression. Consult with a KS-experienced oncologist or dermatologist.

Specific treatment of KS depends on various factors such as the number, extent, severity, and location of lesions; cosmetic considerations; and presence of visceral involvement. The goals of therapy may also vary according to the clinical presentation and may include controlling symptoms, improving cosmetic appearance, reducing edema, eliminating pain, and clearing lesions.

Local treatment (preferably in conjunction with ART) is usually given to patients who have a few small lesions causing only minor symptoms. Systemic therapy (in conjunction with ART) is needed for more extensive or more severe disease, including symptomatic visceral disease, widespread skin involvement, significant edema, and rapidly progressive KS.

Local treatment of limited disease

Options for local treatment of limited disease include the following:

• ART followed by observation for response (limited, stable cutaneous disease may require no specific treatment)
• Topical treatment with alitretinoin gel (Panretin) 0.1%
• Intralesional chemotherapy (eg, vinblastine)
• Radiation therapy, for localized or facial lesions (may cause mucositis when used for oropharyngeal lesions)
• Cryotherapy
• Laser therapy

Treatment of extensive or rapidly progressing disease

Extensive or rapidly progressing disease may include lymphedema, intraoral or pharyngeal disease that interferes with eating, pulmonary KS, and painful or bulky lesions. Options for treatment include:

• Intralesional chemotherapy (eg, vinblastine)
• Systemic chemotherapy (eg, liposomal formulations of doxorubicin or daunorubicin, vincristine, paclitaxel [Taxol], etoposide [VP16], or bleomycin; these agents can be used alone or in combination for visceral or extensive cutaneous disease)
• Interferon-alfa

Patient Education

• KS often responds to treatment. Educate patients that ART is a cornerstone of treatment; encourage them to start and adhere to ART.
• Swollen or edematous lesions increase the risk of cellulitis, whereupon lesions can become infected and progress rapidly. Advise patients to avoid injuring swollen or edematous lesions, to keep them clean, and to call their health care provider if lesions appear to be spreading or if swelling worsens.
• Advise patients to return to the clinic if respiratory or gastrointestinal symptoms develop.
• Patients may use cosmetic preparations to cover facial lesions. Refer patients to support groups or counseling services if they are having difficulty coping with their physical appearance.

References

• Centers for Disease Control and Prevention, National Institutes of Health, HIV Medicine Association/Infectious Diseases Society of America. Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents. MMWR Recomm Rep. 2004 Dec 17; 53(RR15);1-112. Available online at aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=14. Accessed June 16, 2006.
• Jones JL, Hanson DL, Dworkin MS, et al. Incidence and trends in Kaposi's sarcoma in the era of effective antiretroviral therapy. J Acquir Immune Defic Syndr. 2000 Jul 1;24(3):270-4.
• Kaplan LD, Northfelt DW. Malignancies Associated with AIDS. In: Sande MA, Volberding PA, eds. The Medical Management of AIDS, 6th Edition. Philadelphia: WB Saunders; 1999:467-496.
• Paparizos VA, Kyriakis KP, Papastamopoulos V, et al. Response of AIDS-associated Kaposi sarcoma to highly active antiretroviral therapy alone. J Acquir Immune Defic Syndr. 2002 Jun 1;30(2):257-8.
• Saif MW, Little RF. AIDS-Related Malignancies. In: Abraham J, Allegra CJ, Gulley J, eds. Bethesda Handbook of Clinical Oncology; 2nd ed. New York: Lippincott, Williams and Wilkins; 2005:356-357.
• Tam HK, Zhang ZF, Jacobson LP, et al. Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer. 2002 Apr 20;98(6):916-22.