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Immune Reconstitution Inflammatory Syndrome (IRIS)

Last Updated: October 1, 2018

Open Table of Contents: Immune Reconstitution Inflammatory Syndrome (IRIS)

Figure 1: The images above are from an HIV positive patient with low CD4 count. The initial imaging demonstrated left dorsolateral frontal T1 hypointense (top row left), FLAIR hyperintense (top row right) signal that extends through the white matter even to involve the subcortical U fibers, findings that represent PML. The initial imaging was without abnormal enhancement. Six weeks after initiating HAART, the patient developed worsened neurologic deficits and shortly thereafter became obtunded. Followup imaging demonstrated significant interval worsening in the almost mass-like T1 hypointense signal (middle row right) with corresponding FLAIR hyperintense signal (bottom row left), increased mass effect with near complete effacement of the left lateral ventricle and mild left-to-right midline shift. There has been increased mild curvilinear enhancement in the left subinsular white matter (bottom row right), which is typical of IRIS.


  • First described in 1992 and occurs most commonly in the setting of HIV shortly after beginning highly active antiretroviral therapy (HAART) as an exuberant immune response to existing cerebral infection
  • Occurs in weeks, months or years after initiation of HAART
  • Up to 30% of HIV patients will develop IRIS
  • Also seen in patients on immune modulators such as natalizumab (often used for multiple sclerosis) after cessation of these medications


  • Two forms: paradoxical and unmasking
    • Paradoxical: restoration of previously suppressed inflammatory immune response in the absence of active infection
    • Unmasking: unmasks a previously subclinical cerebral infection

Clinical Features

  • Symptoms
    • New and worsening symptoms despite adequate treatment that mimic those of the underlying condition
    • Highly variable – some patients have mild symptoms with eventual immune restoration while others have more fulminant symptoms that can lead to death in a short time period after symptom onset
  • Age and Gender

    • No predilection


  • General
    • Atypical or worsening appearance of infection following HAART initiation or immunomodulator cessation
    • Variability due to differing underlying conditions
  • PML

    • Increasing mass effect and enhancement of previously identified white matter lesions
  • TB

    • Increased size, surrounding edema, and enhancement
  • Cryptococcosis

    • Increased size and enhancement of gelatinous pseudocysts
  • Imaging Recommendations

    • MR with contrast
  • Mimic

    • Can be a difficult diagnosis to make as the differential is broad, including HIV encephalitis, new opportunistic infections, or lymphoma. Often the clinical history and followup are most helpful.

For more information, please see the corresponding chapter in Radiopaedia.

Contributor: Sean Dodson, MD

DOI: https://doi.org/10.18791/nsatlas.v1.03.02.18


Cabral RF, et al. Immune Reconstitution Inflammatory Syndrome and Cerebral Toxoplasmosis. AJNR. 2010; 31:E65-69.

Post MJD, et al. CNS-Immune Reconstitution Inflammatory Syndrome in the Setting of HIV Infection, Part 1: Overview and Discussion of Progressive Multifocal Leukoencephalopathy-Immune Reconstitution Inflammatory Syndrome and Cryptococcal-Immune Reconstitution Inflammatory Syndrome. AJNR. 2012; 1-11. 10.3174/ajnr.A3183.

Post MJD, et al. CNS-Immune Reconstitution Inflammatory Syndrome in the Setting of HIV Infection, Part 2: Discussion of Neuro-Immune Reconstitution Inflammatory Syndrome with and without Other Pathogens. AJNR. 2012; 1-10. 10.3174/ajnr.A3184.

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