Wednesday, October 7, 2009

New type of Kaposi’s sarcoma seen in HIV-negative gay men

A new variant of Kaposi’s sarcoma (KS) has been described by French skin specialists in middle-aged, HIV-negative gay men with normal immune function. The skin cancer, which is caused by HHV-8, a virus of the herpes family, is an AIDS-defining illness when it occurs in HIV-positive men. The cases seen in HIV-negative men were less aggressive and rapidly-progressing than those in people with AIDS. However they tended to be more aggressive than in the ‘classical’, originally described type of KS which is seen most often in men of Mediterranean origin, and occurred at an earlier age (mid-50s instead of late 60s). In addition the researchers found a worrying association with other cancers. One in seven of the HIV-negative KS sufferers went on to develop other cancers – in one case, another skin cancer, but in other cases cancers of the lymphatic system. This is the same proportion of patients who go on to develop other cancers as in HIV-positive KS cases. Most patients had some form of treatment – the majority topical treatment such as surgery or radiotherapy. But one in six had systemic chemotherapy. While only a minority treated with conventional anti-cancer drugs had a complete response, better results were obtained with interferon-alpha, with a complete response in two out of five patients treated and a partial response in the other three. Anecdotal cases of KS in HIV-negative people have been described in scientific literature from the late 1980s but this was the first systematic search for such patients in the post-HAART era. The researchers retrospectively studied all consecutive patients seen between 1995 and 2007 at the dermatology clinics of two Paris hospitals. During this period, approximately 300 cases of KS were seen in HIV-negative people. Of these, 28 (9%) were identified as gay or bisexual men. The researchers were unable to calculate directly whether this represented a greater prevalence of KS than in heterosexual patients, but a previous study found HHV-8 seropositivity rates of 4% in heterosexual white men attending a sexual health clinic and 24% in gay men. It is thought that HHV-8, which was only discovered in 1994, was already widespread in gay men before the advent of HIV, because prevalence figures did not increase significantly in the HIV era. HHV-8 is carried in saliva and the higher rates seen in gay men are attributed to oral sex. The average age at the onset of symptoms was 53 and at diagnosis 56 – considerably younger than the 64-72 age range for diagnosis of classical KS. The youngest person diagnosed was 35. All but two patients were white – the others were French-Caribbean and Japanese. Eleven patients had travelled in Africa, where HHV-8 is considerably more prevalent in the general population, (causing an aggressive form of KS in HIV-positive and negative people including children as young as six), and six had lived in other southern Mediterranean countries. None had immunosuppression (average CD4 count 920, range 465-1648) and only one had a history of taking immunomodulating drugs (steroids). There were no cases of the rapidly progressing type of KS involving internal organs seen in AIDS. 54% had ‘indolent’, slowly progressing lesions on one or more limbs; 32% had more aggressive, periodically inflamed lesions; while 14% had more severe disease such as widely disseminated multiple lesions or evidence of systemic disease such as swollen lymph nodes and oedema (fluid accumulation). Four patients (14%) developed other cancers after the KS diagnosis: one the skin cancer basal cell carcinoma, the other three different lymphomas; follicular lymphoma, Castleman’s disease and Burkitt lymphoma, with an average gap of five years between KS and lymphoma diagnosis. 14% of patients also had diabetes, suggesting a possible link. HHV-8 antibodies were detected in the blood of 22 of the 25 patients that were tested for them (88%). In the three negative cases antibodies were detected when more sensitive antibody tests were used on KS tissue samples. Only two of 22 patients who underwent HHV-8 DNA tests had HHV-8 virus detectable in their blood at the time of diagnosis, one with mild disease and one with severe disease. But perhaps significantly, when two out of three patients who developed lymphomas were tested, both had detectable HHV-8 viral loads at the time of these later diagnoses. In conclusion, the researchers say, they have identified a fourth type of KS to go alongside the three already known: the relatively benign ‘classical’ type seen in older Mediterranean men, the AIDS-related type, and the endemic type seen in Africa that often affects children. It appears midway in virulence between the classical and other types. Cases of KS with a similar presentation and progression pattern have also been seen in HIV-positive gay men with normal CD4 counts. While the disease was relatively benign on most cases and not life-threatening in any, KS apears to be triggered or exacerbated in HHV-8-positive people given immunomodulating drugs such as steroids, and it is of concern that in one patient that responded partially to interferon, KS later reappeared in a more aggressive form. The researchers suggest that all men who have sex with men should have their HHV-8 antibody status ascertained, especially if immunosuppressive drugs such as steroids are prescribed.


Post a Comment

Subscribe to Post Comments [Atom]

<< Home

Your Ad Here