Kaposi Sarcoma (KS) in HIV Negative Men Who Have Sex with Men

Red and brownish bilateral plaques presenting as a classical Kaposi sarcoma in a 59-year-old HIV negative bisexual man of Japanese origin.

Kaposi sarcoma (KS) was among the first opportunistic conditions that signalled the impending HIV/AIDS epidemic in the early 1980s.

A sarcoma is a cancer that develops in connective tissues such as cartilage, bone, fat, muscle, blood vessels, or fibrous tissues (related to tendons or ligaments). KS was named for Dr. Moritz Kaposi, who first described it in 1872.

In 1994, Y. Chang and colleagues identified human herpesvirus-8 (HHV-8), aka Kaposi sarcoma-associated herpes virus (KSHV), as the etiologic agent of Kaposi sarcoma*.

In the June 19, 2008 issue of AIDS, French researchers reported findings from a retrospective study of HIV negative and HIV positive homosexual and bisexual male patients with histologically proven KS. In this article, they described the 4 epidemiological forms of KS that have been reported, each associated with HHV-8.

Classical KS - which mostly occurs in men aged 60 years or older from Mediterranean areas or Central and East European countries, presents as nodules or plaques predominantly located on the lower extremities.

Endemic KS - which occurs in Africa and mainly affects men and women aged 35 years or older, may present as a nodule on the lower extremities, local invasive, or visceral disease. In Africa, KS may also affect young children, with few skin lesions observed but frequent lymph node and visceral involvement, resulting in a poor prognosis.

Iatrogenic KS -- is mostly observed in organ transplant recipients on immunosuppressive therapy.

Epidemic KS -- occurs in HIV positive, predominantly homosexual men, and presents as multifocal skin lesions, frequently with either mucosal or visceral involvement, or both.

Multiple small inflammatory nodules of the palm of a 74-year-old HIV negative homosexual man.

HHV-8 seroprevalence is strongly correlated with KS, and epidemiologic studies have shown that HHV-8 infection precedes KS. However, HHV-8 seroprevalence is highly heterogeneous worldwide. Prevalence is high in East and Central Africa (> 50%), where transmission is mainly horizontal, probably through contact with saliva during childhood, with rare cases of vertical transmission from mother-to-child.

HHV-8 seroprevalence is intermediate (10% to 20%) in Mediterranean countries such as Italy and Greece, where the routes of transmission remain undetermined.

Seroprevalence is low (< 5%) among the general population of Northern Europe and the U.S. In countries with a low prevalence of HHV-8, the virus predominantly infects men who have sex with men (MSM) through oral and genital sexual contact.

Independent epidemiologic studies carried out in the U.S. and Europe have shown that about 25% of MSM are infected with HHV-8. Given the high prevalence of HHV-8 in homosexual and bisexual men, and the strong association between KS and HHV-8, immunocompetent MSM could also be at risk of developing KS. However, only anecdotal cases of KS in HIV negative MSM had been reported to date.

Between 1995 and 2007, the French researchers studied a cohort of 28 HIV negative MSM with KS from 2 centers, describing their clinical and epidemiologic characteristics and their HHV-8 status.

Results

• The mean age at first symptoms of KS was 53 years.

• Clinical presentation resembled classical KS, with limited disease in most patients.

• No cellular or humoral immunodeficiency was observed.

• Serological tests for HHV-8 were positive in 88% of patients.

• Only 2 patients displayed HHV-8 viremia at the time of KS diagnosis.

• 3 patients developed lymphoproliferative disorders (Castleman disease, follicular lymphoma, and Burkitt lymphoma).

• In this population, interferon alfa was well tolerated, and led to a complete response, but most patients required only local treatment, if any.

Based on their findings, the study team wrote, "Kaposi's sarcoma may develop in homosexual or bisexual men without HIV infection. This type of Kaposi's sarcoma has clinical features in common with classical Kaposi's sarcoma, but occurs in younger patients."

Further, they noted, "Its prognosis is good, as Kaposi's sarcoma is generally limited, but clinicians should be aware of the association with lymphoproliferative diseases, which may affect prognosis."

In conclusion, the authors observed that based on their data, KS has the following characteristics when it occurs in HIV negative MSM, particularly in those frequently staying in areas of medium to high HHV-8 seroprevalence: "Classical Kaposi sarcoma-like clinical presentation in patients significantly younger than for classical Kaposi sarcoma; and possible association with type 2 diabetes and lymphoproliferative disorders, related or unrelated to HHV-8."

Finally they recommended, "As the prevalence of HHV-8 is high in MSM, we recommend serologic testing for HHV-8 in this population when prescribing immunosuppressive [therapies], as these patients seem to be at risk of developing Kaposi sarcoma."

Department of Dermatology, Cochin Hospital, APHP, Faculte de Medecine Rene Descartes, Department of Virology, Pitie Salpetriere Hospital, APHP; Dermatology, Virology, and Pathology, INSERM U716, Saint-Louis Hospital, APHP, Paris, France.

6/24/08

Reference
F Lanternier, C Lebbe, N Schartz, and others. Kaposi's sarcoma in HIV-negative men having sex with men. AIDS 22(10): 1163-1168. June 19, 2008.

Citation
*Y Chang, E Cesarman, MS Pessin, and others. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865.