Immune Reconstitution Inflammatory Syndrome - Overview of IRIS What Is IRIS? • A state of hyperinflammatory response that usually occurs in the first six months of treatment of HIV/AIDS patients. • The newly reconstituted immune system may react more strongly to an existing infection, causing a worsening of that disease. Paradoxical IRIS: • The worsening of a previously diagnosed opportunistic infection after initiating antiretroviral therapy. Unmasking IRIS: • Worsening of an unrecognized infection with exaggerated inflammatory features after initiating antiretroviral therapy. Who Gets It? • 10-20% of HIV-infected patients starting on antiretroviral therapy ART: • ART ↓ viral load within the first 1 to 2 weeks after initiation • ART ↑ improves CD4 count in 3-6 months IRIS: Generally Diagnosis of Exclusion! No specific diagnostic criteria, but the following should be present: • AIDS with low pretreatment CD4 count (<100), except TB IRIS which can occur at any CD4 count! • Virologic and immunologic response to ART with a decrease in HIV-1 RNA level from baseline or an increase in CD4+ cells from baseline or both • Rule out drug-resistant infection, bacterial superinfection, drug reactions, noncompliance • Clinical manifestations of inflammation • Temporal association between ART initiation and onset of illness features - One week to a few months (median 48 days) Severity of IRIS Depends On: • CD4 count before ART initiation • Degree of viral suppression • CD4 recovery after ART initiation Clinical Presentation: • Related to the type and location of preexisting opportunistic infection • The physical findings of IRIS depend on the pathogen involved Pathogens: • M. TB - Lymphadenitis, pulmonary infiltrates, pleural effusions, CNS tuberculoma meningitis, pericarditis, peritoneal disease, osteitis, cutaneous lesions, serositis peritonitis, bowel perforation, epididymitis, granulomatous nephritis, fevers • MAC/NTM - Painful lymphadenitis, pulmonary infiltrates, peritonitis, osteomyelitis, cutaneous abscesses, cavitation • Cryptococcus species - Meningoencephalitis, lymphadenitis, cryptococcomas, cavitating pneumonia, skin lesions, ocular • PJP - Pneumonitis (fever, cough, hypoxia, and pulmonary infiltrates), organizing PNA • Mycobacterium Leprae - Cutaneous lesions • Histoplasmosis - Lymphadenitis, cutaneous histoplasmosis, mucocutaneous • JC Virus - Progressive multifocal leukoencephalopathy (PML), Confusion, visual symptoms such as double vision, blindness, or gait ataxia • Papillomavirus - Molluscum contagiosum • Herpes Simplex Virus - Genital ulceration • Varicella Zoster - Zoster flare, ocular lesions: keratitis, iritis • CMV - Retinitis, immune recovery uveitis, Extraocular symptoms: pneumonitis, colitis, pancreatitis • HBV, HCV - Hepatic flare, rapid progression of cirrhosis. Fever, chills, lack of appetite, unintentional weight loss, nausea, jaundice. • Kaposi sarcoma, HHV8 - Worsening of cutaneous lesions with swelling, tenderness, and peripheral edema Other Pathogens Associated with IRIS: • Parvovirus B19 • Candida albicans • Epstein Barr Virus • Herpes simplex • Bartonella henselae • Histoplasma capsulatum • Dermatophytosis • Leprosy • Bacillus Calmette-Guérin (BCG) • Talaromyces (Penicillium) marneffei • Schistosoma mansoni • Molluscum contagiosum virus • Leishmaniasis Differential Diagnosis: • Drug reaction/ART toxicity • Poor adherence to treatment • Persistently active infection/drug resistance • New opportunistic infection Treatment: • ART is usually continued when patients develop IRIS (exception: encephalitis secondary to IRIS) - Use NSAIDs or corticosteroids for IRIS • Treat for opportunistic infection ASAP • Paradoxical IRIS: • Therapy for previous infection continued • If already on ART, continue ART, use NSAIDs or corticosteroids for IRIS with severe symptoms • No need to prevent IRIS by delaying ART treatment, unless the patient has known cryptococcal or TB meningitis • Guidelines recommend starting ART < 2 weeks for most OI • Cryptococcal meningitis: ART 4-6 weeks after antifungal therapy (COAT TRIAL: Deferring ART for 5 weeks improved survival) • TB meningitis: ART should be delayed at least four weeks (and initiated within eight weeks) after treatment for TB meningitis is initiated. Corticosteroids should be considered adjuvant treatment #IRIS #Immune #Reconstitution #Inflammatory #Syndrome #Differential #Diagnosis #Management
