Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar 15;62(6):730-738.
doi: 10.1093/cid/civ996. Epub 2015 Dec 12.

Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS)

Mark N Polizzotto  1 , Thomas S Uldrick  1 , Kathleen M Wyvill  1 , Karen Aleman  1 , Vickie Marshall  2 , Victoria Wang  1 , Denise Whitby  2 , Stefania Pittaluga  3 , Elaine S Jaffe  3 , Corina Millo  4 , Giovanna Tosato  5 , Richard F Little  1 , Seth M Steinberg  6 , Irini Sereti  7 , Robert Yarchoan  1
Affiliations

Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS)

Mark N Polizzotto et al. Clin Infect Dis. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Clin Infect Dis. 2018 Mar 5;66(6):985. doi: 10.1093/cid/cix831. Clin Infect Dis. 2018. PMID: 29370384 Free PMC article. No abstract available.

Abstract

Background: Kaposi sarcoma herpesvirus (KSHV) is the cause of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a form of Castleman disease (KSHV-MCD). Recently a KSHV-associated inflammatory cytokine syndrome (KICS) distinct from KSHV-MCD was reported.

Methods: We prospectively characterized the clinical, laboratory, virologic and immunologic features of KICS by evaluating symptomatic adults with KSHV using a prespecified definition. These features and overall survival were compared with controls from 2 prospectively characterized human immunodeficiency virus (HIV)-infected cohorts, including 1 with KSHV coinfection.

Results: All 10 KICS subjects were HIV infected males; 5 had HIV viral load (VL) suppressed <50 copies mL (median 72, range <50-74 375); all had KS and 2 also had PEL. All had multiple severe symptoms attributable to KICS: median number of symptoms 8 (6-11), median grade of worst symptom 3 (2-4). These included gastrointestinal disturbance (present in 9); edema (9); respiratory (6); and effusions (5). Laboratory abnormalities included anemia (all); hypoalbuminemia (all) and thrombocytopenia (6). None developed KSHV-MCD; 6 died with median survival from KICS diagnosis 13.6 months. KICS subjects compared with controls had more severe symptoms; lower hemoglobin and albumin; higher C-reactive protein; higher KSHV VL; elevated interleukin (IL)-6 and IL-10; and an increased risk of death (all P < .05). Anemia and hypoalbuminemia at presentation were independently associated with early death.

Conclusions: KICS subjects demonstrated diverse severe symptoms, a high rate of KSHV-associated tumors, high mortality, and a distinct IL-6/IL-10 signature. KICS may be an important unrecognized cause of morbidity and mortality, including symptoms previously ascribed to HIV. Exploration of KSHV-directed therapy is warranted.

Keywords: HIV; Human Herpesvirus 8 (HHV-8); IL-10; IL-6; Kaposi sarcoma herpesvirus (KSHV).

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Clinical manifestations and clinical course of a representative patient with Kaposi sarcoma herpesvirus (KSHV)-associated inflammatory cytokine syndrome (KICS). Note: Functional and structural imaging, histopathology, and laboratory abnormalities of a representative subject are illustrated. Presenting symptoms included respiratory failure, gastrointestinal symptoms, and generalized hemorrhage in the setting of thrombocytopenia. Kaposi sarcoma (KS) was present with limited cutaneous involvement (B) but severe pulmonary involvement shown in bronchoscopy and computed tomography (C) together with hepatic and lymph node involvement demonstrated by histopathology (D). There were bilateral pleural effusions (C), ascites, and severe soft tissue edema. 18F-fluoro deoxyglucose positron emission tomography with computed tomography (18FDG-PET) (A) demonstrated tracer uptake at sites of KS, including limited lymph nodes, without adenopathy or splenomegaly. Laboratory abnormalities (E) included markedly elevated C-reactive protein (CRP), severe thrombocytopenia, severe hypoalbuminemia and anemia. KSHV viral load (VL) in PBMCs at presentation was 20 250 copies/106 peripheral blood mononuclear cells (PBMCs) and in plasma 3.99 × 106 copies/mL. There was no evidence of intercurrent infection, no evidence of KSHV-MCD on lymph node biopsy (D) and no evidence of primary effusion lymphoma. The patient was treated with liposomal doxorubicin and antiretroviral therapy together intravenous immunoglobulin and a single dose of rituximab and made a gradual improvement (E) before succumbing to a pulmonary complication. Abbreviation: MCD, multicentric Castleman disease.
Figure 2.
Figure 2.
Systemic inflammation, Kaposi sarcoma herpesvirus (KSHV) activation and human interleukin (IL)-6 and IL-10 elevation in patients with KSHV-associated inflammatory cytokine syndrome (KICS) compared with controls. Note: Systemic inflammation measured by C-reactive protein (CRP), KSHV replication measured by viral load (VL) in peripheral blood mononuclear cells (PBMCs), and circulating IL-6 and IL-10 were each markedly elevated in KICS subjects compared with each of the 4 control groups, including the 2 groups with uncontrolled human immunodeficiency virus (HIV) viremia. P values are by Wilcoxon rank sum test for comparison to KICS patients. Note: all values are log transformed.
Figure 3.
Figure 3.
Overall survival in Kaposi sarcoma herpesvirus-associated inflammatory cytokine syndrome (KICS) subjects compared with controls. Note: Survival was significantly worse among KICS subjects than controls (P < .0001). Note that the 4 control cohorts are grouped here for the purposes of analysis, as only 1 death occurred among all 40 patients in those 4 groups. Abbreviation: HIV, human immunodeficiency virus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Chang Y, Cesarman E, Pessin MS et al. . Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994; 266:1865–9. - PubMed
    1. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995; 332:1186–91. - PubMed
    1. Soulier J, Grollet L, Oksenhendler E et al. . Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 1995; 86:1276–80. - PubMed
    1. Moore PS, Gao SJ, Dominguez G et al. . Primary characterization of a herpesvirus agent associated with Kaposi's sarcomae. J Virol 1996; 70:549–58. - PMC - PubMed
    1. Aoki Y, Tosato G, Fonville TW, Pittaluga S. Serum viral interleukin-6 in AIDS-related multicentric Castleman disease. Blood 2001; 97:2526. - PubMed

Publication types

MeSH terms