Immune reconstitution inflammatory syndrome

Background

• Also called IRIS
• Definition-Disease or pathogen specific inflammatory response in HIV infected patients after initiation or re-initiation of ARV therapy or after change to more active ARV therapy.
• Usually low CD4 counts and high viral loads at time of ARV initiation
• Can occur at any CD4 count
• Occurs usually within 4-8 weeks after initiation of therapy

Clinical Features

Major Presentations

• TB- worsening TB symptoms
• MAC- localized lymphadenitis, pulm disease, systemic inflammation indistinguishable from active MAC
  • MAC-IRIS patients are not bacteremic
• Crypto- worsening meningitis symptoms
• CMV-Retinitis, Vitritis, Uveitis
  • IRIS due to CMV can cause vision loss
    • mean time to vitritis 20 weeks
• Hepatitis B or C- transient transaminitis difficult to distinguish from drug induced cause
  • hepatic flares usually mild, may decompensate cirrhotics.
• Progressive Multifocal Leukoencephalopathy- worsening focal neuro lesions, changes on MRI
• Kaposi's Sarcoma- worsening Kaposi's
• Autoimmune diseases- Pre-existing autoimmune disorder exacerbation

Minor Presentations

• Herpes Simplex Virus and Varicella Zoster Virus reactivation
• Non-specific derm- many including oral and genital warts

Differential Diagnosis

• Opportunistic infection based on H&P

Diagnosis

• Index of suspicion with known recent initiation of ARV's

Management

Mild IRIS

• Standard therapy for offending opportunistic info (i.e. acyclovir for HSV)
• Largely supportive care
  • NSAID's for mild symptoms
  • Inhaled steroids for pulmonary symptoms
• Continue ARV except in severe IRIS (see below)

Severe IRIS

• Defined as a threat to functional status or permanent disability (i.e. vision loss from CMV)
• Severe IRIS- prednisone 1-2mg/kg (consult HIV/ID) for 1-2 weeks then taper