Immunosuppressive Treatment–Related Kaposi Sarcoma
In 1969, the first case of KS in association with immunosuppression in a renal transplant patient was described. Since that time, a number of renal and other organ allograft recipients who received prednisone and azathioprine developed KS shortly after the onset of immunosuppressive therapy. Estimates of the incidence of KS in immunosuppressed renal transplant recipients are between 150 and 200 times the expected incidence of the tumor in the general population. The average time to develop KS after transplantation is 16 months. Although the KS tumor in iatrogenically immunosuppressed patients often remains localized to the skin, widespread dissemination with mucocutaneous or visceral organ involvement is common. In some cases, the KS tumors have regressed as a result of reduction or changes in immunosuppressive therapy. Clinical management of renal transplant patients who develop KS is difficult and requires a balance between the risk of death from generalized KS and the risk of graft rejection and complications of renal failure that may occur if the immunosuppressive therapy is discontinued.
Epidemic Kaposi Sarcoma
In 1981, a fulminant and disseminated form of KS in young homosexual or bisexual men was first reported as part of an epidemic now known as AIDS. The etiology of AIDS is a T-cell lymphotropic retrovirus known as HIV. The underlying immunologic deficiency that characterizes HIV disease is an acquired profound disorder of cell-mediated immune functions. This immunologic deficiency and immune dysregulation predisposes the host to a variety of opportunistic infections and unusual neoplasms, especially KS. HIV may play an indirect role in the development of KS.
Approximately 95% of all the cases of epidemic KS in the United States have been diagnosed in homosexual or bisexual men. In the past, approximately 26% of all homosexual males with HIV disease presented with, or eventually developed, KS during the course of their illness. By comparison, fewer than 3% of all heterosexual intravenous drug users with HIV disease developed KS. The proportion of HIV disease patients with KS has steadily decreased since the epidemic was first identified in 1981. About 48% of AIDS patients in 1981 had KS as their presenting AIDS diagnosis. By August 1987, the cumulative proportion of AIDS patients with KS had diminished to fewer than 20%. The introduction of highly active antiretroviral therapy (HAART) has delayed or prevented the emergence of drug-resistant HIV strains, profoundly decreased viral load, led to increased survival, and lessened the risk of opportunistic infections.[17,18,19] The use of HAART has been associated with a sustained and substantial decline in KS incidence in multiple large cohorts.[20,21,22,23,24,25]
The lesions that develop may involve the skin; oral mucosa; lymph nodes; and visceral organs, such as the gastrointestinal tract, lung, liver, and spleen. Most patients with HIV disease who present with the mucocutaneous lesions of KS feel healthy and are usually free of systemic symptoms, as compared to patients with HIV disease who first develop an opportunistic infection. The sites of disease at presentation of epidemic KS are much more varied than the sites seen in other types of this neoplasm. In an early report on the clinical manifestations of the disease, 49 patients were described. Of these patients, 8% had no skin involvement, 27% had localized or fewer than five skin lesions, and 63% had innumerable skin lesions widely distributed over the skin surface area. Of these patients, 61% had generalized lymphadenopathy at the time of the first examination. Four of these patients, who had generalized lymphadenopathy in the absence of skin lesions or detectable visceral organ involvement at the time of presentation, were found to have biopsy-proven KS localized to the lymph nodes. In 45% of the patients studied, KS lesions were found in one or more sites along the gastrointestinal tract. Of these patients, 29% had either unexplained fever or unexplained weight loss when first seen. While most patients present with skin disease, KS involvement of lymph nodes or the gastrointestinal tract may occasionally precede the appearance of the cutaneous lesions.