What is IRIS?
Immune reconstitution inflammatory syndrome (IRIS) is the dysfunctional operation of the immune system when ART treatment for an HIV infection allows the immune system to become effective again. In essence, the immune system is acting as if an infection is still present and reacts to it, causing the inflammatory manifestations typical of the original disease. Paradoxical IRIS occurs when the reaction is to a previously known infection in the person, while unmasking IRIS is when the reactions is to an infection that wasn't previously diagnosed in the person (Kelley & Armstrong, 2009).
People who are just starting their ART therapy for the first time or who are restarting their therapy after being off the therapy for while. Diseases and infections most associated with IRIS are tuberculosis, herpes simplex, herpes zoster, Hepatitis B & C, Karposi sarcoma, Cryptococcal neoformans, and mycobacterium avium complex.
Low CD4+ count at the start of ART therapy, usually less than 100cells/mm3, was found in multiple studies. Recent research indicates the possibility that starting ART soon after an opportunistic infection has been found, the serum antigen from that infection will be elevated, and stimulate IRIS.
How is IRIS diagnosed?
No diagnostic marker exists, so no definitive lab test can identify the syndrome. Diagnosis is complicated by the fact that the immune system's reaction to the absent infection (IRIS) is identical to its reaction to an infection that actually exists. This is particularly difficult with unmasking IRIS, since the disease wasn't previously diagnosed in the individual, and it is unknown whether the signs and symptoms are related to a new infection or unmasking IRIS. Care must be taken to confirm that the symptoms do not represent an actual new or recurring infection, or are not result of a drug interaction.
What is the treatment?
Generally, the inflammatory process dies down after an average of about 2 months, requiring only supportive care. Occasionally, hospitalization and corticosteroid treatment are necessary.
What is IRIS in relation to tuberculosis?
In 2006, over 100 researchers gathered to define three different syndromes or conditions with similar symptomology: paradoxical TB-IRIS and unmasking TB-IRIS, both noted above, and ART-associated TB. The main difference in relating IRIS to TB is that if the patient was not diagnosed with TB prior to initiation to ART, and the disease is "unmasked" by ART, the immune system will most likely not have resolved the TB infection. Thus, it is likely that true unmasking TB-IRIS is rare, and instead the patient has active TB! For this reason, the consensus of the researchers was that patients who present with symptoms of previously undiagnosed active TB while on ART be diagnosed with ART-associated TB. A sub-category of unmasking TB-IRIS was defined as well. A rough outline of the definitions is listed below (Meintjes et al., 2008):
For paradoxical TB-IRIS, since TB would have been already diagnosed, the patient will have at least started TB therapy and most likely be on that therapy at the time of initiation of ART therapy (the latter is not a requirement of diagnosis). The patient would also need to have responded to TB therapy and be free of symptoms of active TB at the time of initiation of ART therapy. In addition, clinical symptoms of TB must be present as well, such as fever, lymphadenopathy, cough, or evidence of additional pulmonary infiltrates (if the patient had pulmonary TB). Other clinical diagnoses must be ruled out, such as TB drug resistance, drug interactions or other opportunistic infections.
For ART-associated TB, TB treatment would not have been started by the time of ART initiation, and active TB is diagnosed subsequently by means of WHO criteria.
For unmasking TB-IRIS, the same criteria as for ART-associated TB plus either: a disproportionate response of the immune system to active TB particularly in regards to inflammatory presentation or a paradoxical reaction after a patient has been established on the TB treatment.
References
Kelley, C. F., & Armstrong, W. S. (2009). Update on immune reconstitution inflammatory syndrome: progress and unanswered questions. Current Infectious Disease Reports, 11(6), 486-493.
Meintjes, G., Lawn, S. D., Scano, F., Maartens, G., French, M. A., Worodria, W., et al. (2008). Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. The Lancet Infectious Diseases, 8(8), 516-523. doi: 10.1016/S1473-3099(08)70184-1
No comments:
Post a Comment