Immune reconstitution inflammatory syndrome (IRIS)
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- Paradoxical deterioration in clinical status after ART initiation despite improved immune function due to inflammatory response against infectious antigen, which may or may not have been Dx’d at initiation of ART.
- Typically occurs in pts with low initial CD4 (usually < 50) and rapid decline in viral load; onset usually within 6 wks of ART initiation, but sometimes several mos later.
- Inciting pathogens: M. avium complex, M. tuberculosis (30% of cases), and other mycobacteria, CMV, Cryptococcus, Pneumocystis jiroveci, Leishmania, HSV, VZV, hepatitis B and C, JC virus, HHV8 (Kaposi’s and Castleman’s), JC virus (PML), and others.
- Common Sx (varies according to causative pathogen): fever, localized lymphadenophathy/lymphadenitis, abscesses, pneumonia, vitritis, CNS disease, hepatitis, and dermatologic manifestations.
- Presentations of OIs may be atypical (eg, MAC: localized granulomatous lymphadenopathy without mycobacteremia; CMV: vitritis; PML: enhancing CNS lesions; Cryptococcus: marked CSF leukocytosis).
- Autoimmune diseases (e.g.sarcoidosis, Grave’s disease) may be exacerbated
- Despite high risk (>25%) of paradoxical worsening in pts with active TB after initiation of ART, overall mortality improved in coinfected pts with CD4< 100 treated with ART.