Immune reconstitution inflammatory syndrome
Immune reconstitution inflammatory syndrome (IRIS) is paradoxical deterioration of a pre-existing illness following abrupt improvement in an individual's immune function. It is classically seen in HIV/AIDS patients following initiation of highly active anti-retroviral therapy (HAART). Increasingly, however, it is also seen in the setting of other diseases treated with immunomodulation (e.g. Natalizumab-associated progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome (PML-IRIS) in multiple sclerosis).
This article focuses on IRIS in the setting of HIV/AIDS.
IRIS 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 decrease in CD4+count or HIV RNA following initiation of therapy
- initiation of HAART soon after diagnosis of an opportunistic infection
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.
- "paradoxical" IRIS has been postulated to arise from the restoration of the previously suppressed inflammatory immune response, in the absence of active infection 1. This is thought to occur 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 infection 6
CMV, VZV, and HIV itself rarely cause IRIS.
The imaging features are widespread either reflecting the imaging appearances of the underlying pathogen or may mimic worsening of the underlying condition, or be atypical. Typically enhancing masses gain mass effect rapidly. Enhancement is variable and may appear bizarre or wild 9.
- 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 lesions 2
- pulmonary Kaposi sarcoma
- similar to Kaposi sarcoma alone (reticular and reticulonodular opacities, consolidation, septal lines and pleural effusions), but increasing in extent 5
- non-IRIS associated opportunistic infection
- CNS lymphoma
Treatment and prognosis
Treatment is with corticosteroid therapy, alongside ongoing HAART. Fatal cases have been reported in under 5% of cases 6.
- 1. Chen KC, Chen JY, Tung GA. Case 149: Immune reconstitution inflammatory syndrome. Radiology. 2009;252 (3): 924-8. doi:10.1148/radiol.2523080402 - Pubmed citation
- 2. Smith AB, Smirniotopoulos JG, Rushing EJ. From the archives of the AFIP: central nervous system infections associated with human immunodeficiency virus infection: radiologic-pathologic correlation. Radiographics. 28 (7): 2033-58. doi:10.1148/rg.287085135 - Pubmed citation
- 3. Rajeswaran G, Becker JL, Michailidis C et-al. The radiology of IRIS (immune reconstitution inflammatory syndrome) in patients with mycobacterial tuberculosis and HIV co-infection: Appearances in 11 patients. Clin Radiol. 2006;61 (10): 833-43. doi:10.1016/j.crad.2006.04.007 - Pubmed citation
- 4. Venkataramana A, Pardo CA, Mcarthur JC et-al. Immune reconstitution inflammatory syndrome in the CNS of HIV-infected patients. Neurology. 2006;67 (3): 383-8. doi:10.1212/01.wnl.0000227922.22293.93 - Pubmed citation
- 5. Godoy MC, Rouse H, Brown JA et-al. Imaging features of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome. AJR Am J Roentgenol. 2007;189 (4): 956-65. doi:10.2214/AJR.07.2458 - Pubmed citation
- 6. Martin-blondel G, Delobel P, Blancher A et-al. Pathogenesis of the immune reconstitution inflammatory syndrome affecting the central nervous system in patients infected with HIV. Brain. 2011;134 (Pt): 928-46. doi:10.1093/brain/awq365 - Pubmed citation
- 7. Kleinschmidt-DeMasters BK, Miravalle A, Schowinsky J et-al. Update on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab. J. Neuropathol. Exp. Neurol. 2012;71 (7): 604-17. doi:10.1097/NEN.0b013e31825caf2c - Pubmed citation
- 8. Pornsuriyasak P, Suwatanapongched T. Thoracic manifestations of paradoxical immune reconstitution inflammatory syndrome during or after antituberculous therapy in HIV-negative patients. Diagn Interv Radiol. 2015;21 (2): 134-9. doi:10.5152/dir.2014.14212 - Free text at pubmed - Pubmed citation
- 9. FACR AGOMD. Osborns Brain. Lippincott Williams & Wilkins. ISBN:1931884218. Read it at Google Books - Find it at Amazon
- manifestations of HIV/AIDS
- CNS manifestations
- pulmonary manifestations
- cardiovascular manifestations
- gastrointestinal manifestations
- hepatobiliary manifestations
- genitourinary manifestations
- musculoskeletal manifestations
- AIDS defining illnesses
- HIV associated neoplasms
- immune reconstitution inflammatory syndrome (IRIS)
- AIDS embryopathy