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

• Published in: Clinical infectious diseases Vol. 62; no. 6; pp. 730 - 738
• Main Authors: Polizzotto, Mark N., Uldrick, Thomas S., Wyvill, Kathleen M., Aleman, Karen, Marshall, Vickie, Wang, Victoria, Whitby, Denise, Pittaluga, Stefania, Jaffe, Elaine S., Millo, Corina, Tosato, Giovanna, Little, Richard F., Steinberg, Seth M., Sereti, Irini, Yarchoan, Robert
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.03.2016
• Subjects: Adult; and Commentaries; ARTICLES AND COMMENTARIES; C-Reactive Protein - analysis; Coinfection - virology; Cytokines; Cytokines - adverse effects; Cytokines - blood; Drug therapy; Female; Herpes viruses; Herpesviridae; Herpesvirus; Herpesvirus 8, Human - immunology; HIV; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Humans; Immunology; Inflammation - immunology; Inflammation - mortality; Inflammation - physiopathology; Inflammation - virology; Interleukin-10 - blood; Interleukin-6 - blood; Kaposi's sarcoma-associated herpesvirus; Lentivirus; Male; Middle Aged; Outcome Assessment, Health Care; Patient Outcome Assessment; Prospective Studies; Retroviridae; Sarcoma, Kaposi - epidemiology; Sarcoma, Kaposi - immunology; Sarcoma, Kaposi - mortality; Sarcoma, Kaposi - virology; Survival analysis; Viral Load; Virology; Young Adult; HIV; Human Herpesvirus 8 (HHV-8); IL-10; IL-6; Kaposi sarcoma herpesvirus (KSHV)
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/civ996

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.