Immune reconstitution inflammatory syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a T-cell mediated encephalitis characterised by paradoxical deterioration of an AIDS related illness following initiation of highly active anti-retroviral therapy (HAART) or post treatment of autoimmune disease such as multiple sclerosis.

Epidemiology

It has been reported to affect 10-25% of patients with AIDS ¹.

Patients at highest risk are those with:

• low CD4+ count (less than 50cells/microl) and high plasma HIV RNA prior to initiation of therapy 
• rapid increasedecrease in CD4+count / increase inor HIV RNA following initiation of therapy
• initiation of HAART soon after diagnosis of an opportunistic infection

Clinical presentation

Symptoms typically develop within 60 days following initiation of HAART ¹, and generally mimic worsening of the underlying condition, despite rising CD4 counts and a falling viral load.  

The precise clinical picture depends on the underlying condition and body region involved.  

Pathology

• "paradoxical" IRIS has been postulated to arise due tofrom restoration of the previously suppressed inflammatory immune response, in the absence of active infection¹. This is thought to occur due due to reactivation of memory cells that had been previously activated by antigen exposure 
• "unmasking" IRIS is a second mechanism postulated in a separate clinical subgroup (rather than competing with the former) may relate to unmasking of a previously subclinical infection⁶

IRIS has been described with several opportunistic pathogens, including TB, PML and cryptococcosis, as well as Kaposi sarcoma.

CMV, VZV, and HIV itself are rarely cause IRIS. Natalizumab associated PML-IRIS has also been been reported.

Radiographic features

The imaging features may mimic worsening on the underlying condition, or be atypical.

• mycobacterial tuberculosis
  • new lymphadenopathy +/- central necrosis, pulmonary nodules or worsening or new abscesses ³
• progressive multifocal leukoencephalopathy (PML)
  • new enhancement and mass effect of the pre-existing white matter lesions²
• pulmonary Kaposi sarcoma
  • similar to Kaposi sarcoma alone (reticular and reticulonodular opacities, consolidation, septal lines and pleural effusions), but increasing in extent⁵

Treatment and prognosis

Treatment is with corticosteroid therapy, alongside ongoing HAART.  Fatal cases have been reported in under 5% of cases ⁶.