Pediatric Kaposi sarcoma in context of the HIV epidemic in sub-Saharan Africa: current perspectives

Abstract

The global experience with pediatric Kaposi sarcoma (KS) has evolved immensely since the onset of HIV (human immunodeficiency virus). In this review, current perspectives on childhood KS are discussed in the context of the HIV epidemic in sub-Saharan Africa. Endemic (HIV-unrelated) KS was first described over 50 years ago in central and eastern Africa, regions where human herpesvirus-8, the causative agent of KS, is endemic. With the alarming rise in HIV prevalence over the past few decades, KS has become not only the most common HIV-related malignancy in Africa, but also one of the most common overall childhood cancers throughout the central, eastern, and southern regions of the continent. The unique clinical features of pediatric KS that were described in those early endemic KS reports have been re-affirmed by the contemporary experience with HIV-related KS. These characteristics include a predilection for primary lymph node involvement, significant proportions of patients lacking prototypical cutaneous lesions, and the potential for fulminant disease progression. Other clinical features that distinguish childhood KS from adult disease include disease presentation with severe cytopenias, and the common occurrence of childhood KS without severe CD4 count suppression. Distinct clinical heterogeneity in disease presentation and treatment response have been demonstrated. Long-term complete remission and event-free survival can be achieved—especially in children with lymphadenopathic KS—utilizing treatment with antiretroviral therapy plus mild–moderate chemotherapy regimens that are well tolerated, even in low-income settings. A pediatric-specific staging classification and risk-stratification platform have been retrospectively validated, and may help guide therapeutic strategies. With expansion of the HIV treatment infrastructure throughout Africa, coupled with recent developments in establishing comprehensive pediatric oncology programs, there is great potential for improving outcomes for children with KS. Increased awareness of the unique clinical nuances and collaborative evaluations of pediatric-specific treatment paradigms are required to optimize survival for children with KS.

KSHV viral load and Interleukin‐6 in HIV‐associated pediatric Kaposi sarcoma—Exploring the role of lytic activation in driving the unique clinical features seen in endemic regions

“…The Lilongwe Pediatric KS Staging Classification attempts to stratify four distinct groups with different responses to therapy—mild/moderate cutaneous/oral disease (stage 1), lymphadenopathic KS (stage 2), woody edema (stage 3) and visceral and/or disseminated cutaneous/oral disease (stage 4) . While the limited numbers of patients broken down by stage preclude definitive conclusions regarding associations with KSHV VL, we observed a distinct pattern with all 12 of the patients with detectable KSHV VL categorized as Stages 2 or 4, and 5/6 patients with undetectable KSHV VL being categorized as Stages 1 or 3.…”

Epidemic, Endemic, or Stewart–Bluefarb? When Several Forms of Kaposi Seem to Dispute Paternity

“…Endemic KD affects adults as well as children. Its transmission is more probably horizontal (child-child) or vertical (mother-child and parents-children) [1,3,[6][7][8]. It is diagnosed most often between 30 and 40 years with a marked predominance with males.…”

“…Since the advent of the HIV-AIDS (human immunodeficiency virus-acquired immunodeficiency syndrome) pandemic, it has experienced an epidemiological outbreak. e risk of developing KD is higher in areas where there is a high prevalence of HHV8 infection and HIV infection: Central, West, and South Africa [4][5][6][7][8].…”

Endemic Kaposi sarcoma in HIV-negative children and adolescents: an evaluation of overlapping and distinct clinical features in comparison with HIV-related disease

“…Patients were staged according to the Lilongwe Pediatric KS Staging Classification, a pediatric-specific staging paradigm that attempts to address the unique clinical features of childhood KS observed in KSHV-endemic regions of Africa [ 17 , 19 ]. Briefly, this staging classification differentiates four distinct clinical phenotypes with contrasting disease characteristics and treatment outcomes.…”

“…Stage 2 is defined as lymphadenopathic KS, while stage 3 is characterized by the presence of woody edema. Stage 4 is the group with the worst long-term survival and includes patients with visceral disease and those with 20 or more hyperpigmented skin/oral lesions in widespread distribution [ 17 , 19 ].…”