Answer: B

The development of new cutaneous lesions in the setting of AIDS is disconcerting. The widespread nature of the lesions and the violaceous morphologic pattern seen in this case suggest the development of AIDS-related Kaposi sarcoma (KS), which was confirmed by biopsy. KS is considered a malignancy characterized by proliferation of spindle cells of endothelial origin with varying degrees of abnormal vascularity that proliferate in the skin, oral mucosa, lymph nodes, and visceral organs.

Originally described in 1872 by a Hungarian dermatologist, Moritz Kaposi,9 KS was of little epidemiologic concern in America, or other Western countries, until the AIDS epidemic began in the 1980s. For the first several decades of the AIDS epidemic, KS was a well-recognized complication, mostly affecting Haitians and individuals who contracted HIV through sexual contact. At that time, the viral etiology for each condition was not known, so co-infection with the 2 sexually transmitted viruses was not recognized.


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Many years after HIV was identified as the cause of AIDS, the pathogenesis of KS was linked to the human herpes virus 8 (HHV-8) or KS-associated herpesvirus (KSHV). HHV-8 contributes to the development of this typically low-grade neoplasm by stimulating processes of inflammation, proliferation, and angiogenesis within virally infected host endothelial cells.10  Host cell cycle regulatory genes, such as p53 and RB, are inhibited by processes that HHV-8 uses to maintain latency in the human host, allowing for more lenient progression through the cell cycle and decreased apoptosis.10 HHV-8 also confers changes in the transcriptional programming of infected endothelial cells allowing the lineage of the classic spindle cell to develop. It is still controversial whether these spindle cells are of vascular or lymphatic origin; however, their endothelial origin is clearly demonstrated with cell markers including CD31, CD34, and CD36.11

Fortunately, widespread use of highly active retroviral therapy (HAART) has greatly reduced the incidence of KS, at least in the HIV-infected population in developed countries. However, it remains an issue in certain parts of the world.  We now recognize 4 distinct variants of KS: classic, iatrogenic, AIDS-related epidemic, and African endemic.11,12 Recently, cases of indolent KS resembling classic KS have been discovered in men who have sex with men, without the presence of HIV; this may become a fifth type of KS: nonepidemic KS.12

KS is a relatively rare disease worldwide, with less than 2 cases annually per 100,000 people. It is more common in patients with immunosuppression, with a worldwide annual incidence of 482 per 100,000 in HIV-infected patients and 69 per 100,000 in transplant patients.13 Classic KS occurs in the elderly, especially individuals of Jewish or Eastern European descent, and its onset may be associated with age-related immunosenescence. While Iatrogenic KS occurs in patients who are immunosuppressed because of taking systemic medications, often in transplant patients taking cyclosporine.14 AIDS-related epidemic KS is seen predominately in HIV-infected men who have sex with men. African endemic KS predominately affects black Africans, most commonly children. The AIDS-related epidemic variant typically occurs when CD4 T-cell numbers are below 500 cells/mm³ and is considered an AIDS-defining disease; however, the exact timing of onset is variable. KS may be the initial presenting sign, especially in underserved areas.10

AIDs-related epidemic KS lesions most commonly arise on the trunk or face with a propensity for regions around the nose, eyes, and ears. Early lesions appear as red-pink oval-shaped macules or papules, which can progress to form larger purple-black plaques or nodules causing significant disfigurement, with a potential to ulcerate and erode.10 In 10% to 15% of patients, blue or violaceous oral lesions appear. Classic and iatrogenic variants tend to have pink to red-violet macules on the lower extremities, with a more indolent course. It is important to note that KS can affect visceral organs, especially the gastrointestinal tract and lungs, so these systems should also be evaluated.15

The diagnosis of KS is made histologically. Histologic findings depend on the stage of the lesion: patch, plaque, or nodule, and diagnostic changes are more readily identified in more mature lesions. The abnormal spindle cell of KS appears as an elongated endothelial cell and increases in number in more advanced lesions; however, these are not pathognomonic for KS. KS-specific changes are seen within the vasculature. Early patch stage lesions display subtle jagged-appearing blood vessels that dissect the collagen of the superficial dermis. In plaque stage lesions, these vascular structures have matured and extend deeper into the dermis and subcutis, eventually forming a characteristic sieve-like pattern as the spindled endothelial cells replace the dermal collagen in the final nodular or tumor stage. The use of an immunohistochemical stain for a latent gene of HHV-8, called the latency-associated nuclear antigen (LANA), has demonstrated a high diagnostic sensitivity and specificity for diagnosing KS.16

The clinical appearance of KS similarly depends upon the stage of the disease. Lesions can resemble vasculitis, lymphatic or vascular malformations, leukemia or lymphoma cutis, lichen planus, sarcoidosis, and other early stage vascular tumors. Histologically,  KS must be differentiated from bacillary angiomatosis, acroangiodermatitis, Kaposiform hemangioendothelioma (in children), spindle cell hemangioma, angiosarcoma, and other fibrohistiocytic tumors.15

Treatment for KS varies with the subtype. Patients with the AIDS-related epidemic variant, like our patient, should be treated with highly active antiretroviral therapy (HAART). Improving the T-cell count and decreasing the HIV viral load both contribute to KS regression. Iatrogenic KS also responds to immune reconstitution; however, in these cases it is a complex task to decrease immunosuppression without risking organ rejection. More advanced cases of KS may require cytotoxic chemotherapy and topical regimens may be possible for more localized lesions. Overall clinical response depends on the stage and variant of KS, but generally high recurrence rates are common.16

Once our patient was able to resume her HAART medications her CD4 count slowly rose, her viral load became undetectable, and the cutaneous lesions slowly resolved.

Ronald Scott Bukoski, MS, is a medical student and Julia R. Nunley, MD, is a professor of dermatology at the Medical College of Virginia Hospitals, Virginia Commonwealth University, Richmond, Virginia.

References

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