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.
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.
Authors: Satish Gopal; Monita R Patel; Chad J Achenbach; Elizabeth L Yanik; Stephen R Cole; Sonia Napravnik; Greer A Burkholder; W Christopher Mathews; Benigno Rodriguez; Steven G Deeks; Kenneth H Mayer; Richard D Moore; Mari M Kitahata; Kristy L Richards; Joseph J Eron Journal: Clin Infect Dis Date: 2014-04-21 Impact factor: 9.079
Authors: Peter R Williamson; Joseph N Jarvis; Anil A Panackal; Matthew C Fisher; Síle F Molloy; Angela Loyse; Thomas S Harrison Journal: Nat Rev Neurol Date: 2016-11-25 Impact factor: 42.937
Authors: Anil A Panackal; Mika Komori; Peter Kosa; Omar Khan; Dima A Hammoud; Lindsey B Rosen; Sarah K Browne; Yen-Chih Lin; Elena Romm; Charu Ramaprasad; Bettina C Fries; John E Bennett; Bibiana Bielekova; Peter R Williamson Journal: Clin Infect Dis Date: 2016-11-10 Impact factor: 9.079