Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement
in a previously incompetent human immune system manifesting as worsening of clinical
symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory
response. IRIS was first recognized in the setting of human immunodeficiency virus,
and this clinical setting continues to be where it is most frequently encountered.
Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and
the underlying pathogen, include excessive activation of the immune system, with increased
circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory
markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking
IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening
for opportunistic infections before starting ART is a key element to prevent this
phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome
and exclusion of alternative diagnoses, particularly underlying infections and drug
resistance. Controlled studies supporting the use of pharmacologic interventions in
IRIS are scare, and recommendations are based on case series and expert opinions.
The only controlled trial published to date, showed reduction in morbidity in patients
with paradoxical tuberculosis–related IRIS with the use of oral corticosteroids. There
are currently limited data to recommend other anti-inflammatory or immunomodulatory
therapies that are discussed in this review, and further research is needed. Ongoing
research regarding the immune pathogenesis of IRIS will likely direct future rational
therapeutic approaches and clinical trials.
Abbreviations:
ART (antiretroviral therapy), CCR (chemokine receptor), CI (confidence interval), CMV (Cytomegalovirus), CNS (central nervous system), CRP (C-reactive protein), CSF (cerebrospinal fluid), HIV (human immunodeficiency virus), HR (hazard ratio), IFN (interferon), IP (interferon-γ-inducible protein 10), IL (interleukin), IRIS (immune reconstitution inflammatory syndrome), KS (Kaposi sarcoma), MAC (Mycobacterium avium complex), MHC (major histocompatibility complex), OI (opportunistic infection), OR (odds ratio), PML (progressive multifocal leukoencephalopathy), TB (tuberculosis), Tregs (regulatory T cells), TNF (tumor necrosis factor)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: August 06, 2015
Accepted:
July 31,
2015
Received in revised form:
July 14,
2015
Received:
March 30,
2015
Identification
Copyright
Published by Elsevier Inc.
