Background:  Among the variants of immune reconstitution inflammatory syndrome (IRIS), Kaposi’s sarcoma-IRIS (KS-IRIS) is one of the least understood—especially in resource-limited settings where KS is epidemic. Now that ART is becoming available in Sub-Saharan Africa, we have hypothesized that KS-IRIS is likely to be most relevant in this region. This is because of the high prevalence of AIDS-related KS in Africa and because of factors that theoretically may predispose to KS-IRIS, specifically higher KS lesion burden and lower pre-ART CD4⁺ T cell count.

Methods:  In Uganda, we studied KS-IRIS among patients with AIDS-related KS who were participating in a randomized trial of 2 different ART regimens. Subjects were evaluated every 4 weeks with detailed physical examination and digital photography. KS-IRIS was defined as, within the first 12 weeks of ART, any of the following in pre-existing KS lesions—swelling, tenderness, erythema, warmth or paresthesia; or new or worse peripheral, facial, or genital edema; or new or worse chest X-ray findings.

Results:  Of the initial 55 subjects, the most common KS-IRIS finding was evidence of inflammation within existing KS lesions:  12-week cumulative incidences were 61% for lesion swelling, 75% for tenderness, 35% for erythema, 50% for warmth, and 42% for paresthesia. Most such findings resolved spontaneously, and there were several instances of dramatic lesion enlargement followed by spontaneous reduction. Peripheral edema occurred in 22% of subjects, facial edema in 3.6%, genital edema in 3.8%, and pulmonary findings in 19%. For both edema and pulmonary findings, only 2 subjects had spontaneous resolution; the remainder required chemotherapy or are still being evaluated. The 2 most fulminant KS-IRIS cases featured diffuse lesion swelling and pulmonary involvement; death ensued with KS-IRIS possibly being contributory.

Conclusions:  In Sub-Saharan Africa, KS-IRIS occurs at a clinically relevant frequency with a wide spectrum of manifestations. Patients with KS who initiate ART should be counseled about the potential risk of prematurely stopping ART. Many of the findings are difficult to distinguish from natural KS progression, and even some of the most dramatic cases can be self-limiting. This, coupled with general unavailability of effective KS chemotherapy in resource-limited settings, makes patient management complicated when KS-IRIS is suspected.