Cryptococcal immune reconstitution inflammatory syndrome

Curr Opin Infect Dis. 2013 Feb;26(1):26-34. doi: 10.1097/QCO.0b013e32835c21d1.

Abstract

Purpose of review: The epidemiology and pathogenesis of, and risk factors for, cryptococcal immune reconstitution inflammatory syndrome (CM-IRIS) are reviewed with an emphasis on how new insights inform a rational management approach and prevention strategies.

Recent findings: Risk factors for paradoxical CM-IRIS are a low inflammatory response and CD4 cell count at baseline, rapid immune restoration from this low baseline, and a high organism or antigen load at baseline and at antiretroviral therapy (ART) initiation. Detailed immune mechanisms are still unclear. Rapidly fungicidal induction therapy, allowing prompt initiation of ART (from around 3 weeks in resource-limited settings in the context of amphotericin B induction) at a time when organism and antigen loads are low, may reduce overall mortality without exacerbating paradoxical CM-IRIS, compared with initiation of ART at later time points. Recent cohorts suggest early recognition and management can reduce the mortality associated with paradoxical CM-IRIS. Unmasking CM-IRIS is preventable through screening for cryptococcal antigen prior to ART and preemptive antifungal treatment for those testing positive, although prospective studies are needed.

Summary: Optimal antifungal induction and judicious ART timing, together with early recognition and management of developing cases, with thorough exclusion of alternative diagnoses, should help reduce paradoxical CM-IRIS-related mortality. Unmasking CM-IRIS cases should be preventable.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / immunology
  • AIDS-Related Opportunistic Infections / prevention & control
  • Anti-HIV Agents / therapeutic use*
  • Antifungal Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • HIV Infections / drug therapy
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / drug therapy*
  • Immune Reconstitution Inflammatory Syndrome / immunology
  • Immune Reconstitution Inflammatory Syndrome / prevention & control
  • Meningitis, Cryptococcal / diagnosis
  • Meningitis, Cryptococcal / drug therapy*
  • Meningitis, Cryptococcal / prevention & control
  • Risk Factors

Substances

  • Anti-HIV Agents
  • Antifungal Agents