Abstract
While uncommon, CNS-IRIS developing after the initiation of HAART in the setting of HIV-related severe immunosuppression is characterized by an intense inflammatory reaction to dead or latent organisms or to self-antigens due to a heightened but dysregulated immune response. While this reaction can range from mild to fulminating, encompassing a very wide clinical spectrum, it is important to recognize because changes in medical management may be necessary to prevent neurologic decline and even death. Once contained, however, this inflammatory response can be associated with improved patient outcome as immune function is restored. Among the infectious organisms that are most commonly associated with CNS-IRIS are the JC virus and Cryptococcus organisms, which will be the subject of this review. CD8 cell infiltration in the leptomeninges, perivascular spaces, blood vessels, and even parenchyma seems to be the pathologic hallmark of CNS-IRIS. While recognition of CNS-IRIS may be difficult, the onset of new or progressive clinical symptoms, despite medical therapy and despite improved laboratory data, and the appearance on neuroimaging studies of contrast enhancement, interstitial edema, mass effect, and restricted diffusion in infections not typically characterized by these findings in the untreated HIV-infected patient should raise the strong suspicion for CNS-IRIS. While CNS-IRIS is a diagnosis of exclusion, the neuroradiologist can play a critical role in alerting the clinician to the possibility of this syndrome.
Highlights
Fungus: Cryptococcal Meningitis–IRIS Cryptococcus neoformans is an organism that can cause infection frequently seen in association with IRIS.[88]
Cryptococcal-IRIS can be manifested in many different ways—as lymphadenitis, pneumonitis, cryptococcal meningitis, or cryptococcomas—and can result in considerable morbidity and mortality.[20,89]
A prospective study of 101 Ugandans with AIDS without any prior ART exposure who developed cryptococcal meningitis after ART initiation, IRIS developed in a median time of 8.8 weeks in 45%, with 30% exhibiting CNS symptoms.[90]
Summary
Fungus: Cryptococcal Meningitis–IRIS Cryptococcus neoformans is an organism that can cause infection frequently seen in association with IRIS.[88] Cryptococcal-IRIS can be manifested in many different ways—as lymphadenitis, pneumonitis, cryptococcal meningitis, or cryptococcomas—and can result in considerable morbidity and mortality.[20,89] In CM-IRIS, mortality rates have ranged between 8% and 30%.20 according to some investigators, the morbidity and mortality rates have increased in CM-IRIS.[20] For example, in a prospective study of 65 HIV-positive patients with proved cryptococcal meningitis on antifungal medication (amphotericin B) who were ART-naïve, IRIS-associated cryptococcal meningitis developed in 17% (11 patients) at a median of 29 days after the initiation of ART.[20] While there was a greater immune restoration (as measured by a greater CD4 rise from baseline after 6 months) noted in patients with CM-IRIS as opposed to those with CM without IRIS, there was a higher mortality rate in the patients with CM-IRIS (4/11 versus 14/54).[20] There was a trend for those patients developing CM-IRIS to have a higher fungal burden at the end of Ն7 days of initial treatment with amphotericin B.20 In another investigation, a prospective study of 101 Ugandans with AIDS without any prior ART exposure who developed cryptococcal meningitis after ART initiation, IRIS developed in a median time of 8.8 weeks in 45%, with 30% exhibiting CNS symptoms.[90] Thirty-six percent of those with CM-IRIS died, compared with 21% with CM without IRIS.[90]
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