Chapter 217. AIDS and Kaposi's Sarcoma

A 35-year-old gay man presented with papular lesions on his elbow (Figure 217-1). Shave biopsy demonstrated Kaposi's sarcoma (KS). He subsequently tested positive for HIV and began treatment with antiretroviral combination therapy. The KS resolved with topical alitretinoin gel treatment.

In the United States, KS is most often seen in patients with AIDS and patients on immunosuppressants after organ transplantation. KS can also be classic (older Mediterranean men) or endemic (young men in sub-Saharan Africa). KS is caused by Kaposi's sarcoma-associates herpesvirus (KSHV), which promotes oncogenesis. KS cannot be cured, but treatment can result in improvement or disease stabilization. Current therapies improve the immune system or target KSHV. Therapies that modulate KSHV-mediated signaling are being studied.

• KS can be classic (older Mediterranean men), endemic (young men in sub-Saharan Africa), epidemic (AIDS patients), or posttransplantation (organ recipients).1
• In the United States, 81.6% of KS is seen in patients with AIDS2 (Figure 217-1).
• In HIV-positive patients, the prevalence is 7.2/1000 person years; 451 times higher than general population.3
• In transplant patients, the prevalence is 1.4/1000 person years; 128 times higher than general population.3
• The prevalence of classic KS in the general population of southern Italy is 2.5/100,0004 (Figure 217-2).
• The male-to-female ratio for epidemic KS in the United States is approximately 50:1 but is falling as the prevalence of AIDS increases among women.5 The male-to-female ratio has been approximately 10:1 for classic and endemic KS.
• KS is the most common malignancy seen in AIDS patients.

• KS is caused by KSHV, also known as human herpes virus 8 (HHV-8). KSHV acts through host cell signal transduction to activate multiple oncogenic pathways.6
• KS is an angioproliferative neoplasm, with abnormal proliferation of endothelial cells, myofibroblasts, and monocyte cells.
• Lesions often begin as papules or patches and progress to plaques as proliferation continues.
• Some lesions ulcerate (nodular stage), and lymphedema can occur.

• Immunodeficiency as a consequence of AIDS.
• Immunosuppressants for solid-organ transplantation.

The diagnosis is often made clinically in a patient who has AIDS and a typical presentation of KS. In atypical presentations, diagnosis is made by biopsy.

Clinical Features

• Cutaneous lesions are usually multifocal, papular, and reddish-purple in color (Figures 217-1 and 217-2).
• Plaques or fungating lesions can be seen on the lower extremities, including the soles of the feet (Figure 217-3).
  • Vascular-appearing papules on the feet and lower legs are typical of classic KS without AIDS (Figure 217-4).
• Oral cavity lesions can be flat or nodular and are red to purple in color (Figure 217-5).
• GI lesions can be asymptomatic or can cause abdominal pain, nausea, vomiting, bleeding, or weight loss.
• Pulmonary lesions can cause shortness of breath or may appear as infiltrates, nodules, or pleural effusions on chest radiographs.

Typical Distribution

AIDS-related KS7:

• Skin lesions are seen mainly on the lower extremities (Figure 217-6), face, and genitalia. Presence of skin lesions should prompt an oral examination as oral involvement may change prognosis and management.
• Lesions in the oral cavity are common (33%), typically seen on the palate or gingiva (Figure 217-5).
• GI involvement is noted in 40% of newly diagnosed KS in HIV patients at diagnosis and up to 80% in autopsy studies. GI lesions can occur without skin lesions.
• Pulmonary involvement is also common, and up to 15% may occur without skin lesions in patients with KS and HIV. A chest radiograph often demonstrates pulmonary involvement.
• Any organ can be involved.

Laboratory Testing

• Check an HIV test in any person with KS who is not known to be HIV-positive.
• CD4+ T lymphocyte count is an important prognostic indicator.

Imaging

Chest radiograph if there is pulmonary involvement. GI endoscopy if GI involvement if suspected.

Biopsy

Often required for definitive diagnosis. If the lesions are nodular a simple shave biopsy should be sufficient. If the lesions are flat, a 4-mm punch biopsy should provide adequate tissue for diagnosis.

The diagnosis of KS requires a biopsy as several other lesions can mimic early KS.7

• Purpura—Bleeding under the skin caused by a variety of platelet, vascular, or coagulation disorders; usually not palpable and more widespread.
• Hematomas—Localized swelling usually from a break in a blood vessel; history of trauma and usually not palpable.
• Hemangiomas or angiomas—Benign growths of small blood vessels that blanch with pressure (Chapter 201, Acquired Vascular Skin Lesions).
• Dermatofibromas—Small, firm, red-to-brown nodules made up of hystiocytes and collagen deposits in the mid dermis, often seen on the legs; lesions are usually small (<6 mm) and dimple downward when compressed laterally (Chapter 160, Dermatofibroma).
• Bacillary angiomatosis—A systemic infectious disease caused by Bartonella species. Cutaneous lesions appear as scattered papules and nodules or an abscess. Bacillary angiomatosis may occur when the CD4 count is below 200 and is treated with antibiotics (Figure 217-7).

KS is not curable, but treatments can reduce disease burden and slow progression (Figure 217-8).

Medications

• In patients with HIV/AIDS, HAART (highly active antiretroviral therapy) therapy improves KS. Treat with antiretroviral drugs or refer to a physician with experience initiating and following antiretroviral therapy. Antiretroviral therapy inhibits HIV replication, decreases the response to KSHV, and has antiangiogenic activity. SOR A
• Avoid high-dose steroids, as they can severely aggravate KS, especially pulmonary KS.
• Consider KS-specific therapies:
  • Alitretinoin gel 0.1%—Patient applies gel to lesions 2 times a day, increasing to 3 to 4 times a day if tolerated, for 4 to 8 weeks (66% response rate).8 SOR A
  • Liposomal doxorubicin 20 mg/m2 every 3 weeks or liposomal daunorubicin 40 mg/m2 every 2 weeks (50% response rate).9 SOR A
  • Paclitaxel 100 mg/m2 every 2 weeks or 135 mg/m2 every 3 weeks; response rates 60% to 70% in patients who had failed a prior chemotherapy regiment.10 SOR A Premedication with dexamethasone is recommended.10
  • Interferon-α at 1 million U/day demonstrated the most benefit to patients with KS limited to the skin and CD4+ T-lymphocyte counts more than 200.11
  • Intralesional vinblastine (70% response rate)12 or radiation therapy (80% response rate) are also effective for skin lesions.13 SOR A
• Classic and endemic KS are rare in the United States and are often treated with radiation or surgical excision.
• Removing immunosuppressants or radiation can treat transplant-related KS.

In addition to the medications that target KSHV, new therapies are undergoing study that target KSHV-mediating signaling.6

• In severe disease requiring systemic therapy, 50% to 85% of patients will respond with either improvement or disease stability; however, the response lasts only 6 to 7 months before therapy has to be repeated. When therapy is repeated, the response times generally decrease.6
• Patients with AIDS-related KS have 5-year survival rates of greater than 80% when KS is the AIDS-defining illness and the CD4+ T-lymphocyte count is greater than 200. Survival rates fall to less than 10% when the patient is older than age 50 years and there is another AIDS-defining illness at the time of presentation.14

KS, particularly AIDS-related KS, is generally treated by physicians with advanced training in HIV/AIDS management and oncology. Follow-up is determined by disease progression and response to therapy.

• KS is not curable, but several treatments can result in regression of the lesions for a better cosmetic result.
• KS can affect most parts of the body, commonly the skin, oral cavity, GI tract, and lungs.
• During treatment, lesions typically flatten, shrink, and fade (Figure 217-8).
• Rarely, starting antiretroviral therapy may cause lesions to flare because of an inflammatory reaction as the immune system begins to recover (immune reconstitution).

Patient Resource

• The National Cancer Institute. Kaposi Sarcoma Treatment—http://www.cancer.gov/cancertopics/pdq/treatment/kaposis/patient/.

Provider Resource

• The National Cancer Institute has information for health professionals—http://www.cancer.gov/cancertopics/pdq/treatment/kaposis/HealthProfessional.