Neurologische Immunrekonstitutionssyndrome bei HIV

Zusammenfassung

Das inflammatorische Immunrekonstitutionssyndrom (IRS) ist eine Erkrankung, die als Folge der Einführung einer hochaktiven antiretroviralen Therapie (HAART) erst in den letzten Jahren beschrieben wurde. Im Rahmen des IRS kommt es vermehrt zu atypischen Verläufen opportunistischer Infektionen des zentralen Nervensystems. Zudem scheint es nach Initiierung der HAART häufig zu autoimmunen entzündlichen Erkrankungen des zentralen und peripheren Nervensystems zu kommen. Das IRS tritt dabei zumeist nur wenige Wochen nach dem Beginn einer HAART auf und führt zu paradoxen Verschlechterungen bei eigentlichem Ansprechen des Immunsystems und der HIV-Erkrankung auf die HAART. Das IRS führt dadurch zu einer erhöhten Mortalität der betroffenen Patienten. Gerade neurologische Manifestationen eines IRS sind schwer von den bekannten opportunistischen Infektionen des ZNS, insbesondere einer progressiven multifokalen Leukoenzephalopathie zu differenzieren. Momentan fehlen noch Studien, die eine Therapie des IRS systematisch überprüft hätten. In der Therapie von HIV-Patienten engagierte Ärzte sollten das Krankheitsbild kennen, um die Abgrenzung zu opportunistischen Infektionen vorzunehmen

Summary

The inflammatory immune reconstitution syndrome (IRS) appears in conjunction with initiation of a highly active antiretroviral therapy (HAART) and is recognized only in the last few years. The IRS is mainly characterized by atypical clinical presentations of opportunistic CNS infections. In addition, IRS might develop directly after initiation of HAART as an inflammatory autoimmune disease of the peripheral and central nervous system. The IRS often begins only a few weeks after initiation of HAART und leads to paradoxical clinical deterioration while the immune system and HIV disease appear to respond to treatment. IRS is accompanied by an increased mortality of affected patients. Especially neurological manifestations of IRS are difficult to differentiate from opportunistic CNS infections, in particular from progressive multifocal leucoencephalopathy. Studies that systematically investigated treatment options of IRS are still lacking. Neurologists who are engaged in treatment of HIV patients should be aware of clinical signs of IRS given that they have to distinguish IRS from opportunistic infections and that they have to decide about discontinuation of HAART in affected patients.

Schlüsselwörter

Immunrekonstitutionssyndrom - HIV - progressive multifokale Leukoenzephalopathie - HAART

Keywords

Immune reconstitution syndrome - HIV - progressive multifocal leukoencephalopathy - HAART

• Literatur

• 1 Breen RA. et al. Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection. Thorax 2004; 59 (Suppl. 08) 704-707.
• 2 Buckingham SJ. et al. Immune reconstitution inflammatory syndrome in HIV-infected patients with mycobacterial infections starting highly active anti-retroviral therapy. Clin Radiol 2004; 59 (Suppl. 06) 505-513.
• 3 Cinque P. et al. The good and evil of HAART in HIV-related progressive multifocal leukoencephalopathy. J Neurovirol 2001; 7 (Suppl. 04) 358-363.
• 4 Corral I. et al. Focal monophasic demyelinating leukoencephalopathy in advanced HIV infection. Eur Neurol 2004; 52 (Suppl. 01) 36-41.
• 5 Couppié P. et al. Increased incidence of genital herpes after HAART initiation: a frequent presentation of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients. AIDS Patient Care STDS 2006; 20 (Suppl. 03) 143-145.
• 6 De Luca A. et al. The effect of potent antiretroviral therapy and JC virus load in cerebrospinal fluid on clinical outcome of patients with AIDS-associated progressive multifocal leukoencephalopathy. J Infect Dis 2000; 182: 1077-1083.
• 7 Dore GJ. et al. National HIV Surveillance Committee. Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 2003; 17 (Suppl. 10) 1539-1545.
• 8 Feller L, Wood NH, Lemmer J. Herpes zoster infection as an immune reconstitution inflammatory syndrome in HIV-seropositive subjects: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 104 (Suppl. 04) 455-460.
• 9 French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS 2004; 18: 1615-1627.
• 10 Goebel FD. Immune reconstitution inflammatory syndrome (IRIS)--another new disease entity following treatment initiation of HIV infection. Infection 2005; 33: 43-45.
• 11 Hirsch HH. et al. Immune reconstitution in HIV-infected patients. Clin Infect Dis 2004; 38: 1159-1166.
• 12 Hoffmann C. et al. Progressive multifocal leucoencephalopathy with unusual inflammatory response during antiretroviral treatment. J Neurol Neurosurg Psychiatry 2003; 74 (Suppl. 08) 1142-1144.
• 13 Jenny-Avital ER, Abadi M. Immune reconstitution cryptococcosis after initiation of successful highly active antiretroviral therapy. Clin Infect Dis 2002; 35 (Suppl. 12) e128-133.
• 14 Kastrup O. et al. Evolution of purely infratentorial PML under HAART--negative outcome under rapid immune reconstitution. Clin Neurol Neurosurg 2005; 107 (Suppl. 06) 509-513.
• 15 Lipman M, Breen R. Immune reconstitution inflammatory syndrome in HIV. Curr Opin Infect Dis 2006; 19 (Suppl. 01) 20-25.
• 16 Maschke M. et al. Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). J Neurol Neurosurg Psychiatry 2000; 69: 376-380.
• 17 Patel AK. et al. Immune reconstitution syndrome presenting with cerebral varicella zoster vasculitis in HIV-1-infected patient: a case report. J Int Assoc Physicians AIDS Care (Chic Ill) 2006; 5 (Suppl. 04) 157-160.
• 18 Sacktor N. et al. HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology 2001; 56: 257-260.
• 19 Shelburne SA, Hamill RJ. The immune reconstitution inflammatory syndrome. AIDS Rev 2003; 5 (Suppl. 02) 67-79.
• 20 Shelburne SA. et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005; 19 (Suppl. 04) 399-406.
• 21 Shelburne SA. et al. The role of immune reconstitution inflammatory syndrome in AIDS-related Cryptococcus neoformans disease in the era of highly active antiretroviral therapy. Clin Infect Dis 2005; 40 (Suppl. 07) 1049-1052.
• 22 Skiest DJ, Hester LJ, Hardy RD. Cryptococcal immune reconstitution inflammatory syndrome: report of four cases in three patients and review of the literature. J Infect 2005; 51 (Suppl. 05) e289-297.
• 23 Staudinger R, Henry K. Remission of HIV myelopathy after highly active antiretroviral therapy. Neurology 2000; 54: 267-268.
• 24 Stone SF. et al. Cytomegalovirus (CMV) retinitis immune restoration disease occurs during highly active antiretroviral therapy-induced restoration of CMV-specific immune responses within a predominant Th2 cytokine environment. J Infect Dis 2002; 185 (Suppl. 12) 1813-1817.
• 25 Tuon FF. et al. Immune reconstitution inflammatory syndrome associated with disseminated mycobacterial infection in patients with AIDS. AIDS Patient Care STDS 2007; 21 (Suppl. 08) 527-532.
• 26 Zandman-Goddard G, Peeva E, Barland P. Combined autoimmune disease in a patient with AIDS. Clin Rheumatol 2002; 21 (Suppl. 01) 70-72.