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Current Fungal Infection Reports
Published in: Current Fungal Infection Reports 4/2011

01-12-2011 | Genomics and Pathogenesis (Shmuel Shoham, Section Editor)

Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome (IRIS): Pathogenesis and its Clinical Implications

Authors: Darin L. Wiesner, David R. Boulware

Published in: Current Fungal Infection Reports | Issue 4/2011

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Abstract

This review provides an overview of Cryptococcus neoformans immunology and focuses on the pathogenesis of Cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three phases: (1) before antiretroviral therapy (ART), with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance; (2) during initial ART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and (3) at IRIS, a cytokine storm with a predominant type-1 helper T-cell (Th1) interferon-gamma (IFN-γ) response. Understanding IRIS pathogenesis allows for risk stratification and customization of HIV/AIDS care. In brief, persons at high IRIS risk may benefit from enhancing microbiologic clearance by use of adjunctive agents in combination with amphotericin, prolonging initial induction therapy, and/or increasing the initial consolidation antifungal therapy dose to at least 800 mg of fluconazole daily until the 2-week CSF culture is known to be sterile. Prophylactic anti-inflammatory therapies or undue delay of ART initiation in an attempt to prevent IRIS is unwarranted and may be dangerous.
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Metadata
Title
Cryptococcus-Related Immune Reconstitution Inflammatory Syndrome (IRIS): Pathogenesis and its Clinical Implications
Authors
Darin L. Wiesner
David R. Boulware
Publication date
01-12-2011
Publisher
Current Science Inc.
Published in
Current Fungal Infection Reports / Issue 4/2011
Print ISSN: 1936-3761
Electronic ISSN: 1936-377X
DOI
https://doi.org/10.1007/s12281-011-0064-8

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