TreatmentUpdate
190

June 2012 

Two types of Kaposi’s sarcoma

There are two forms of Kaposi’s sarcoma (KS), as follows:

  • classical KS
  • HIV-related KS

Classical KS

This is the mild form of KS that particularly affects older men in the Mediterranean region or men of Mediterranean ancestry. Lesions generally appear on the skin, particularly the legs. Sometimes lesions can resolve without therapy. Classical KS rarely causes life-threatening complications.

HIV-related KS

Among HIV-positive people, KS is generally much more aggressive, with lesions affecting many parts of the skin. Lesions gradually become thicker and swollen. HIV-related KS can cause life-threatening complications because lesions grow near or within vital organs such as the lungs. This can cause fluid to build up in the lungs, leading to problems breathing. KS lesions can also occur in the gastrointestinal tract, where they can cause bleeding.

KS and inflammation

In the time before potent combination anti-HIV therapy (commonly called ART or HAART),  doctors noticed that among HIV-positive people who had stable KS, lesions would grow or spread during or after severe systemic infection. KS lesions would suddenly arise in HIV-positive people on skin that had previously been affected by inflammation, such as places where surgeons had cut the skin to gain entry to the body or places that had previously been affected by shingles (herpes zoster). These observations suggested that inflammation likely plays a role in helping to incite the development and growth of KS lesions.

KS—from patch to lesion

In HIV-positive people, KS usually starts as a small flat patch on the skin. Such lesions may appear deep red in colour due to the growth of blood vessels that feed the growing collection of KS-transformed cells.

Over time, the patch becomes thicker and firm, which means that it has entered the plaque stage where it turns deep red or even violet in colour.

As KS-transformed cells accumulate within the plaque, it grows and enters the nodular phase. Here the lesion becomes more like a nodule. Vessels within the nodule leak fluid and red blood cells. The buildup of leaked red blood cells within the spaces of the nodule gives it a purple colour. If the nodule is large it can affect other parts of the body, causing swelling of the skin or nearby tissues. Nodules can also leak lymphatic fluid and blood when irritated.

KS treatment

Before ART became available, treatment (usually chemotherapy) for HIV-related KS was generally not effective. If the lesions did initially resolve, they could later return or new ones would form.

In the ART era, HIV-related KS eventually clears as the immune system repairs the damage caused by HIV infection. As CD4+ cell counts rise, KS lesions may temporarily become swollen and hard. This is because the immune system has become stronger (due to ART) and can attack KS lesions and HHV-8-infected cells. This fight between the immune system and HHV-8 causes temporary inflammation of KS lesions.

As a result of initiating ART, most of these lesions will eventually stabilize in size and then begin to shrink and resolve. Over time, lesions may return if ART is interrupted or if HIV develops resistance to treatment, as both of these situations weaken the immune system, allowing HHV-8 production and infection to resume or intensify. HIV-infected cells also produce a protein called Tat that helps KS tumours grow. Only in rare cases is additional therapy—usually chemotherapy—required.

Therefore, for most HIV-positive people with KS in high-income countries, doctors generally favour instituting ART and closely monitoring the situation, as ART alone is often enough to cause KS to eventually resolve.

— Sean R. Hosein

REFERENCES:

  1. Taylor GS, Blackbourn DJ. Infectious agents in human cancers: lessons in immunity and immunomodulation from gammaherpesviruses EBV and KSHV. Cancer Letters. 2011 Jun 28;305(2):263-78.
  2. Myoung J, Ganem D. Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells. Journal of Clinical Investigation. 2011 Mar;121(3):1130-40.
  3. Ganem D. KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. Journal of Clinical Investigation. 2010 Apr;120(4):939-49