Immune reconstitution syndrome

Background

Immune reconstitution syndrome, or immune reconstitution inflammatory syndrome (IRIS), refers to the paradoxical worsening of pre-existing infections after antiretroviral therapy (ART) is intiated for HIV.^[1] It occurs due to increases in T lymphocyte numbers that occurs after ART is started as well as increased immune response.

Clinical Features

Symptoms of underlying illness within 1 week to a few months after initiating ART
Fever (especially with mycobacterial or cryptococcal infections)^[2]
Manifestations of the underlying disease process:
- Tuberculosis
- Mycobacterium avium
- Cryptococcus neoformans
- Cytomegalovirus
- Progressive multifocal leukoencephalopathy (associated with the JC virus)
- Pneumocystis jirovecii pneumonia
- Herpes zoster
- Hepatitis B
- Leishmaniasis
- Kaposi sarcoma

Differential Diagnosis

Progression of HIV/AIDS
Antimicrobial resistance
Medication noncompliance
Development of new opportunistic infection rather than recrudescence
Drug toxicity

Evaluation

Diagnostic Criteria

The diagnosis of IRIS is clinical. Most of the following criteria should be present to make the diagnosis:^[3]

Presence of AIDS with low pretreatment CD4 count. Usually this is <100, but tuberculosis can be reactivated with CD4 cells >200.
Positive virologic and immunologic response to ART
Absence of evidence of drug-resistant infection, bacterial superinfection, adverse drug reaction, patient noncompliance, or reduced serum drug levels
Presence of clinical manifestations consistent with inflammatory condition
Temporal association between ART initiation and the onset of clinical features of illness

Commonly Associated Pathogens

Management

Continue ART
Treatment of underlying opportunistic infection
Glucocorticoids may be indicated as adjunct therapy for severe cases

Disposition

Disposition depends on severity of the immune response as well as the specific underlying disease process. Consider admission if unstable, poor follow-up, or severe illness.

External Links

References

↑ DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med. 2000;133(6):447–454. doi:10.7326/0003-4819-133-6-200009190-00013
↑ Cheng VC, Yuen KY, Chan WM, Wong SS, Ma ES, Chan RM. Immunorestitution disease involving the innate and adaptive response. Clin Infect Dis. 2000;30(6):882–892. doi:10.1086/313809
↑ Haddow LJ, Easterbrook PJ, Mosam A, et al. Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort. Clin Infect Dis. 2009;49(9):1424–1432. doi:10.1086/630208
↑ Shelburne SA 3rd, Hamill RJ, Rodriguez-Barradas MC, et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine (Baltimore). 2002;81(3):213–227. doi:10.1097/00005792-200205000-00005

Authors:

[1] DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy. Ann Intern Med. 2000;133(6):447–454. doi:10.7326/0003-4819-133-6-200009190-00013

[2] Cheng VC, Yuen KY, Chan WM, Wong SS, Ma ES, Chan RM. Immunorestitution disease involving the innate and adaptive response. Clin Infect Dis. 2000;30(6):882–892. doi:10.1086/313809

[3] Haddow LJ, Easterbrook PJ, Mosam A, et al. Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort. Clin Infect Dis. 2009;49(9):1424–1432. doi:10.1086/630208

[4] Shelburne SA 3rd, Hamill RJ, Rodriguez-Barradas MC, et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine (Baltimore). 2002;81(3):213–227. doi:10.1097/00005792-200205000-00005

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