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Clin Infect Dis. 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).

Author information

1
HIV and AIDS Malignancy Branch.
2
Viral Oncology Section, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research.
3
Laboratory of Pathology.
4
Positron Emission Tomography Department, Clinical Center, National Institutes of Health.
5
Laboratory of Cellular Oncology.
6
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda.
7
HIV Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.

Erratum in

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)

PMID:
26658701
PMCID:
PMC4772848
DOI:
10.1093/cid/civ996
[Indexed for MEDLINE]
Free PMC Article

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