Article

Defining Immune Reconstitution Inflammatory Syndrome: Evaluation of Expert Opinion versus 2 Case Definitions in a South African Cohort

Department of HIV and Genitourinary Medicine, King's College London, London, UK.
Clinical Infectious Diseases (Impact Factor: 9.42). 09/2009; 49(9):1424-32. DOI: 10.1086/630208
Source: PubMed

ABSTRACT There is no validated case definition for human immunodeficiency virus-associated immune reconstitution inflammatory syndrome (IRIS). We measured the level of agreement of 2 published case definitions (hereafter referred to as CD1 and CD2) with expert opinion in a prospective cohort of patients who were starting antiretroviral therapy in South Africa.
A total of 498 adult patients were monitored for the first 6 months of antiretroviral therapy. All new or worsening clinical events were reviewed by 2 investigators and classified on the basis of expert opinion, CD1, and CD2. Events were categorized according to whether they were paradoxical or unmasking in presentation. We measured positive, negative, and chance-corrected agreement (kappa) with expert opinion for CD1 and CD2, and reviewed areas of disagreement.
A total of 620 clinical events were recorded, of which, on the basis of expert opinion, 144 (23.2%) were defined as probable IRIS and 112 (18.1%) were defined as possible IRIS. Of the 144 probable IRIS events, 93 (64.6%) were unmasking in presentation, 99 (68.8%) were associated with dermatological or orogenital disease, and 45 (31.3%) were associated with tuberculosis or major opportunistic infections. Of the 620 clinical events recorded, 41 (6.6%) were classified as IRIS on the basis of CD1, and 156 (25.2%) were classified as IRIS on the basis of CD2. Positive agreement between CD1 and expert opinion was low for both unmasking (17.2%; kappa = 0.24) and paradoxical events (37.3%; kappa = 0.43), mainly because 1 major criterion requires IRIS to be atypical and either an opportunistic infection or a tumor, although negative agreement was >98%. In contrast, CD2 had good positive agreement (>75% for most event types), with a kappa value of 0.75 for paradoxical and 0.62 for unmasking.
CD2 agreed well with expert opinion, with additional clinical events, such as arthropathy and inflammatory dermatoses, being classified as IRIS and added to CD2. We propose revised case definitions for both paradoxical and unmasking IRIS.

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    ABSTRACT: We describe two HIV-infected patients with tuberculosis-associated immune reconstruction inflammatory syndrome (TB-IRIS): one with "paradoxical" IRIS and the other with "unmasking" IRIS. TB-IRIS in HIV-infected subjects is an exacerbation of the symptoms, signs, or radiological manifestations of a pathogenic antigen, related to recovery of the immune system after immunosuppression. We focused on the radiological characteristics of TB-IRIS and the briefly literature review on this syndrome.
    04/2013; 2013:323208. DOI:10.1155/2013/323208
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    • "The frequency of TB-IRIS among Croatian patients in the study of Puljiz and colleagues in 2006 was 40.7% [5]. IRIS is a condition that results from rapid restoration of pathogen-specific immune responses to opportunistic infections , causing either the deterioration of a treated infection or the new presentation of a previously subclinical infection [6] [7]. There is no diagnostic test for IRIS, and a confirmation of the disease relies heavily upon case definitions incorporating clinical and laboratory data [7]. "
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    • "A case of IRIS was defined as a patient with unexpected deterioration in clinical condition with signs and symptoms of inflammation/infection soon after commencing ART (<6 months of regular ART). IRIS cases were classified as paradoxical or unmasking according to established clinical guidelines [11–13]. "
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