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An IRIS to Remember

Published:September 20, 2010DOI:https://doi.org/10.1016/j.amjmed.2010.06.002
      To the Editor:
      A 48-year-old man with acquired immunodeficiency syndrome presented to our clinic with 6 days of worsening frontal headache, vomiting, diffuse myalgias, and weakness. On examination he had profound lower extremity weakness, increased patellar tendon reflexes, sensory loss in his feet, and Babinski signs present bilaterally. The patient was hospitalized, and a lumbar puncture revealed a cerebral spinal fluid leukocyte count of 4277 cells/uL with 94% atypical lymphocytes, erythrocyte count of 8673 cells/uL, glucose of 63 mg/dL, and protein of 3480 mg/dL. Magnetic resonance imaging (MRI) found diffuse edema of the thoracic spinal cord consistent with meningomyelitis (Figure).
      Figure thumbnail gr1
      FigureSagittal magnetic resonance images of the thoracic spine. T1-weighted precontrast image (left) shows diffuse swelling (thick white arrows) of the spinal cord. T2-weighted image (right) demonstrates cord edema (increased signal, outlined arrows). Postcontrast T1-weighted fat-suppressed image (center) shows extensive leptomeningeal enhancement (small white arrows) with nodular intramedullary enhancement at T6 (large white arrow).
      Of note, he had restarted highly active antiretroviral therapy 3 weeks prior. His CD4+ count and human immunodeficiency virus (HIV)-1 viral load at that time were 103 cells/uL and 284,370 copies/mL, respectively. On admission, his CD4+ count was 79 cells/uL and HIV-1 viral load was 606 copies/mL.
      The diagnosis of immune reconstitution inflammatory syndrome (IRIS) was made, highly active antiretroviral therapy was discontinued and dexamethasone 10 mg intravenously (IV) every 6 hours was initiated. The patient's strength and sensation improved. Cerebrospinal fluid polymerase chain reaction was positive for varicella zoster virus at day 4 and IV acyclovir was added. Two months after admission, he was able to ambulate with a walker.

      Discussion

      IRIS is a pathologic immune recognition of antigens that occurs after highly active antiretroviral therapy initiation. Although lethal in <10% of AIDS patients,
      • Castelnuovo B.
      • Manabe Y.C.
      • Kiragga A.
      • et al.
      Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort.
      IRIS is an increasingly recognized complication of highly active antiretroviral therapy initiation, with an incidence between 15% and 25%.
      • Manabe T.C.
      • Campbell J.D.
      • Sydnor E.
      • Moore R.D.
      Immune reconstitution inflammatory syndrome.
      Risk factors for this syndrome include use of a protease inhibitor, CD4+ nadir <100 cells/uL, and a decrease in the HIV viral load of >2.5 on logarithmic scale.
      • Manabe T.C.
      • Campbell J.D.
      • Sydnor E.
      • Moore R.D.
      Immune reconstitution inflammatory syndrome.
      An increase in the total CD4 count may also be seen.
      • Manabe T.C.
      • Campbell J.D.
      • Sydnor E.
      • Moore R.D.
      Immune reconstitution inflammatory syndrome.
      Clinicians should suspect central nervous system IRIS when patients have an unexplained neurological decline accompanied by new or progressive neuroradiological findings, a decrease in plasma viral load of ≥1 log10, or histopathology demonstrating T-cell infiltration.
      • Riedel D.J.
      • Pardo C.A.
      • McArthur J.
      • Nath A.
      Therapy insight: CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome.
      Central nervous system IRIS accounts for approximately 75% of deaths from IRIS.
      • Castelnuovo B.
      • Manabe Y.C.
      • Kiragga A.
      • et al.
      Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort.
      There are only 2 prior reports of varicella zoster virus-mediated central nervous system IRIS in the literature.
      • Chang C.C.
      • McLean C.
      • Vujovic O.
      • et al.
      Fatal acute varicella-zoster virus hemorrhagic meningomyelitis with necrotizing vasculitis in an HIV-infected patient.
      • Clark B.M.
      • Krueger R.G.
      • Price P.
      • French M.A.
      Compartmentalization of the immune response in varicella zoster virus immune restoration disease causing transverse myelitis.
      Our patient demonstrated neurologic deterioration, transverse myelitis on MRI, and >3 log10 decrease in viral load. His lack of CD4+ recovery is consistent with previous case reports of varicella zoster virus central nervous system IRIS.
      • Chang C.C.
      • McLean C.
      • Vujovic O.
      • et al.
      Fatal acute varicella-zoster virus hemorrhagic meningomyelitis with necrotizing vasculitis in an HIV-infected patient.
      • Clark B.M.
      • Krueger R.G.
      • Price P.
      • French M.A.
      Compartmentalization of the immune response in varicella zoster virus immune restoration disease causing transverse myelitis.
      Although there are no prospective trials to guide the treatment of varicella zoster virus central nervous system IRIS, high dose IV steroids followed by an oral prednisone taper and IV acyclovir have been employed with clinical improvement.
      • Chang C.C.
      • McLean C.
      • Vujovic O.
      • et al.
      Fatal acute varicella-zoster virus hemorrhagic meningomyelitis with necrotizing vasculitis in an HIV-infected patient.
      • Clark B.M.
      • Krueger R.G.
      • Price P.
      • French M.A.
      Compartmentalization of the immune response in varicella zoster virus immune restoration disease causing transverse myelitis.
      The decision to discontinue highly active antiretroviral therapy is a difficult one. In mild IRIS, the symptoms are generally self-limited, and highly active antiretroviral therapy should be continued.
      • Riedel D.J.
      • Pardo C.A.
      • McArthur J.
      • Nath A.
      Therapy insight: CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome.
      However, interruption of highly active antiretroviral therapy may be necessary in cases of life-threatening IRIS, especially if the patient is unresponsive to corticosteroids.
      • Race E.M.
      • Adelson-Mitty J.
      • Kriegel G.R.
      • et al.
      Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease.
      Yet, discontinuing highly active antiretroviral therapy risks life-threatening opportunistic infections, and IRIS may still recur after its re-initiation.
      • Race E.M.
      • Adelson-Mitty J.
      • Kriegel G.R.
      • et al.
      Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease.

      References

        • Castelnuovo B.
        • Manabe Y.C.
        • Kiragga A.
        • et al.
        Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort.
        Clin Infect Dis. 2009; 49: 965-972
        • Manabe T.C.
        • Campbell J.D.
        • Sydnor E.
        • Moore R.D.
        Immune reconstitution inflammatory syndrome.
        J Acquir Immune Defic Syndr. 2007; 46: 456-462
        • Riedel D.J.
        • Pardo C.A.
        • McArthur J.
        • Nath A.
        Therapy insight: CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome.
        Nat Clin Pract Neurol. 2006; 2: 557-565
        • Chang C.C.
        • McLean C.
        • Vujovic O.
        • et al.
        Fatal acute varicella-zoster virus hemorrhagic meningomyelitis with necrotizing vasculitis in an HIV-infected patient.
        Clin Infect Dis. 2009; 48: 372-373
        • Clark B.M.
        • Krueger R.G.
        • Price P.
        • French M.A.
        Compartmentalization of the immune response in varicella zoster virus immune restoration disease causing transverse myelitis.
        AIDS. 2004; 18: 1218-1221
        • Race E.M.
        • Adelson-Mitty J.
        • Kriegel G.R.
        • et al.
        Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease.
        Lancet. 1998; 351: 252-255