Neurologic Consequences of the Immune Reconstitution Inflammatory Syndrome (IRIS)

Abstract

Although major advancements have been made in the treatment of HIV infection, graft-versus-host reactions, and autoimmune diseases, an unexpected consequence of treatment has been the emergence of a devastating inflammatory syndrome, termed the immune reconstitution inflammatory syndrome (IRIS). The pathophysiology of the syndrome is poorly understood, and the syndrome poses unique challenges for diagnosis and treatment. We have reviewed the neurologic manifestations of IRIS in the context of HIV infection as well as in the setting of treatment of autoimmune diseases such as multiple sclerosis, in which compartmental immune suppression may occur without an obvious underlying immune suppression. The purpose of this review is to identify common themes that may assist in the diagnosis and management of these IRIS syndromes.

Multiple sclerosis reactivation postfingolimod cessation: Is it IRIS?

“…This challenge translates into a therapeutic dilemma as to whether to rapidly remove the offending drug or to initiate the treatment of IRIS. Corticosteroids in the form of intravenous methylprednisolone for 3–5 days followed by an oral taper for 6–8 days remain the recommended treatment for acute IRIS based on retrospective studies 11 23. Although corticosteroids are not the most ideal drug for controlling IRIS because of the lack of specificity, they remain the most effective class of drugs in patients with severe inflammation 11.…”

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

“…30 In an HIV+ patient noncompliant to antiretroviral therapy and to treatment for CMV colitis, CMV encephalitis developed, characterized by both typical and atypical imaging features. 54 Instead of the more typical MR imaging findings of ventriculitis or even solitary focal mass lesions, this patient, who died from his CMV encephalitis, had MR imaging showing widespread multifocal areas of restricted diffusion and faint solid or peripheral enhancement in both the supra- and infratentorial compartments.…”

“…IRIS occurs in approximately 16% of patients with AIDS with TB and antiretroviral therapy, of whom 3% die. 30 In fact, TB is reported to be the infection most commonly associated with IRIS extracranially 8 and usually occurs within 2 months of antiretroviral therapy when not involving the CNS. 25 In HIV+ patients with M tuberculosis whose antituberculous therapy was started within 1–6 months before initiation of HAART, 43% developed extracranial TB-IRIS at 2–114 days (12-day median) after HAART, manifested systemically by lymphadenopathy, fever recurrence, skin lesions, worsening lung infiltrates, and gastrointestinal symptoms.…”

“…69 It was only the TB abscesses that were noted to be more frequent in this HIV+ population than in the non-HIV cohort. 69 Finally, although some investigators have suggested that meningeal enhancement and a communicating hydrocephalus in a patient with antitubercular and antiretroviral therapy should point to a diagnosis of TB-CNS-IRIS, 19,30 these imaging findings are not exclusive to this group of patients, even if some authors have reported them more commonly in the IRIS cohort.…”

Immune reconstitution inflammatory syndrome and the central nervous system

“…Onset and clinical forms of central nervous system-immune reconstitution inflammatory syndrome CNS-IRIS typically occurs within 2 months after the initiation of ART; however, IRIS may occur as late as 2 years after ART initiation [11 ]. Although the exact mechanisms of IRIS are currently unclear, the syndrome appears to be related with immune restoration.…”