Current HIV/AIDS Reports

, Volume 1, Issue 3, pp 122–127 | Cite as

Immune restoration inflammatory syndromes: Apparently paradoxical clinical events after the initiation of HAART

  • Matthias Stoll
  • Reinhold E. Schmidt
Article

Abstract

Immune reconstitution occurs after initiation of highly active antiretroviral therapy in immunodeficient HIV-positive individuals. Unexpected deterioration of inflammatory disease and atypical clinical features resembling symptoms of autoimmune disease may arise. These atypical inflammatory disorders, synonymously summarized as immune reconstitution syndrome, immune restoration disease, and immune restoration inflammatory syndrome (IRIS), are caused by augmentation of inflammation during immune reconstitution in an immunocompromised host. These disorders have to be distinguished from intercurrent infection and rheumatic disease, respectively. Treatment of IRIS consists of elements for both potential differential diagnoses (ie, anti-inflammatory and immunosuppressive drugs, such as in autoimmune disorders and antimicrobial chemotherapy, to decrease the burden of pathogen, such as in infectious disease). Therefore, awareness for IRIS is of increasing importance from a clinical point of view. However, diagnostic criteria and standards of treatment are still preliminary.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Stoll M, Schmidt RE: Immune restoration inflammatory syndromes: the dark side of successful antiretroviral treatment. Curr Infect Dis Rep 2003, 5:266–276.PubMedGoogle Scholar
  2. 2.
    Moubasher AD, Kamel NA, Zedan H, Raheem DD: Cytokines in leprosy: effect of treatment on serum cytokines in leprosy. Int J Dermatol 1998, 37:741–746.PubMedCrossRefGoogle Scholar
  3. 3.
    Lawn SD, Wood C, Lockwood DN: Borderline tuberculoid leprosy: an immune reconstitution phenomenon in a human immunodeficiency virus-infected person. Clin Infect Dis 2003, 36:e5-e6.PubMedCrossRefGoogle Scholar
  4. 4.
    Lees AJ, MacLeod AF, Marshall J: Cerebral tuberculomas developing during treatment of tuberculous meningitis. Lancet 1980, 1:1208–1211.PubMedCrossRefGoogle Scholar
  5. 5.
    Rooney JJ, Crocco JA, Kramer S, Lyons HA: Further observations on tuberculin reactions in active tuberculosis. Am J Med 1976, 60:517–522.PubMedCrossRefGoogle Scholar
  6. 6.
    Dooley DP, Carpenter JL, Rademacher S: Adjunctive corticosteroid therapy for tuberculosis: a critical reappraisal of the literature. Clin Infect Dis 1997, 25:872–887.PubMedGoogle Scholar
  7. 7.
    de Gans J, van de Beek D: Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002, 347:1549–1556.PubMedCrossRefGoogle Scholar
  8. 8.
    Mocroft A, Ledergerber B, Katlama C, et al.: Decline in the AIDS and death rates in the Euro SIDA study: an observational study. Lancet 2003, 362:22–29.PubMedCrossRefGoogle Scholar
  9. 9.
    Behrens G, Meyer D, Stoll M, Schmidt RE: Immune reconstitution syndromes in human immunodeficiency virus infection following effective antiretroviral therapy. Immunobiology 2000, 202:186–193.PubMedGoogle Scholar
  10. 10.
    French MA, Lenzo N, John M, et al.: Immune restoration disease after the treatment of immunodeficient HIVinfected patients with highly active antiretroviral therapy. HIV Med 2000, 1:107–115. An excellent overview of approximately 33 cases of immune restoration disease. The study was performed monocentric in Perth, Australia, involving 179 patients who started HAART during a consecutive 10-month period. The reported cases with IRIS reflect 25% of 132 patients successfully treated with HAART. Therefore, this study characterizes a realistic spectrum of disease. Pathophysiologic aspects of these cases have been investigated and discussed by a group of immunologists and clinicians.PubMedCrossRefGoogle Scholar
  11. 11.
    Cheng VC, Yuen KY, Chan WM, et al.: Immunorestitution disease involving the innate and adaptive response. Clin Infect Dis 2000, 30:882–892. The outstanding merit of this review of more than 100 cases is the broad definition of immune restoration inflammatory diseases, which is not exclusively related to HIV infection or T-cell immunodeficiencies.PubMedCrossRefGoogle Scholar
  12. 12.
    Shelburne SA, Hamill RJ: The immune reconstitution inflammatory syndrome. AIDS Rev 2003, 5:67–79.PubMedGoogle Scholar
  13. 13.
    Stone SF, Price P, Tay K, French MA: 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, 185:1813–1817.PubMedCrossRefGoogle Scholar
  14. 14.
    Righetti E, Ballon G, Ometto L, et al.: Dynamics of Epstein- Barr virus in HIV-1-infected subjects on highly active antiretroviral therapy. AIDS 2002, 16:63–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Morlese JF, Orkin CM, Abbas R, et al.: Plasma IL-6 as a marker of mycobacterial immune restoration disease in HIV-1 infection. AIDS 2003, 17:1411–1413.PubMedCrossRefGoogle Scholar
  16. 16.
    Weber K, Meyer D, Grosse V, et al.: Reconstitution of NK cell activity in HIV-1 infected individuals receiving antiretroviral therapy. Immunobiology 2000, 202:172–178.PubMedGoogle Scholar
  17. 17.
    Abino JF, Peraldi R, Lepidi H, et al.: Bacillary splenitis during immune restoration in an HIV-infected patient. AIDS 2002, 16:1429–1430.PubMedCrossRefGoogle Scholar
  18. 18.
    Goldsack NR, Allen S, Lipman MC: Adult respiratory distress syndrome as a severe immune reconstitution disease following the commencement of highly active antiretroviral therapy. Sex Transm Infect 2003, 79:337–338.PubMedCrossRefGoogle Scholar
  19. 19.
    Narita M, Ashkin D, Hollender ES, Pitchenik AE: Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. Am J Respir Crit Care Med 1998, 158:157–161.PubMedGoogle Scholar
  20. 20.
    Race EM, Adelson-Mitty J, Kriegel GR, et al.: Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease. Lancet 1998, 351:252–255.PubMedCrossRefGoogle Scholar
  21. 21.
    Whitcup SM: Cytomegalovirus retinitis in the era of highly active antiretroviral therapy. JAMA 2000, 283:653–657.PubMedCrossRefGoogle Scholar
  22. 22.
    Domingo P, Torres OH, Ris J, Vazquez G: Herpes zoster as an immune reconstitution disease after initiation of combination antiretroviral therapy in patients with human immunodeficiency virus type-1 infection. Am J Med 2001, 110:605–609.PubMedCrossRefGoogle Scholar
  23. 23.
    Fox PA, Barton SE, Francis N, et al.: Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease. HIV Med 1999, 1:10–18.PubMedCrossRefGoogle Scholar
  24. 24.
    Stone SF, Price P, Keane NM, et al.: Levels of IL-6 and soluble IL-6 receptor are increased in HIV patients with a history of immune restoration disease after HAART. HIV Med 2002, 3:21–27.PubMedCrossRefGoogle Scholar
  25. 25.
    Zietz C, Bogner JR, Goebel FD, Lohrs U: An unusual cluster of cases of Castleman’s disease during highly active antiretroviral therapy for AIDS. N Engl J Med 1999, 340:1923–1924.PubMedCrossRefGoogle Scholar
  26. 26.
    Soriano V, Sulkowski M, Bergin C, et al.: Care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel. AIDS 2002, 16:813–828.PubMedCrossRefGoogle Scholar
  27. 27.
    Stone SF, Lee S, Keane NM, et al.: Association of increased hepatitis C virus (HCV)-specific IgG and soluble CD26 dipeptidyl peptidase IV enzyme activity with hepatotoxicity after highly active antiretroviral therapy in human immunodeficiency virus-HCV-coinfected patients. J Infect Dis 2002, 186:1498–1502.PubMedCrossRefGoogle Scholar
  28. 28.
    Proia LA, Ngui SL, Kaur S, et al.: Reactivation of hepatitis B in patients with human immunodeficiency virus infection treated with combination antiretroviral therapy. Am J Med 2000, 108:249–251.PubMedCrossRefGoogle Scholar
  29. 29.
    Rockstroh JK, Theisen A, Kaiser R, et al.: Antiretroviral triple therapy decreases HIV viral load but does not alter hepatitis C virus (HCV) serum levels in HIV-HCV-coinfected haemophiliacs. AIDS 1998, 12:829–830.PubMedGoogle Scholar
  30. 30.
    Cinque P, Pierotti C, Vigano MG, et al.: The good and evil of HAART in HIV-related progressive multifocal leukoencephalopathy. J Neurovirol 2001, 7:358–363.PubMedCrossRefGoogle Scholar
  31. 31.
    Langford TD, Letendre SL, Marcotte TD, et al.: Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy. AIDS 2002, 16:1019–1029.PubMedCrossRefGoogle Scholar
  32. 32.
    Murray R, Mallal S, Heath C, French M: Cerebral mycobacterium avium infection in an HIV-infected patient following immune reconstitution and cessation of therapy for disseminated mycobacterium avium complex infection. Eur J Clin Microbiol Infect Dis 2001, 20:199–201.PubMedCrossRefGoogle Scholar
  33. 33.
    Nolan RC, Chidlow G, French MA: Parvovirus B19 encephalitis presenting as immune restoration disease after highly active antiretroviral therapy for human immunodeficiency virus infection. Clin Infect Dis 2003, 36:1191–1194.PubMedCrossRefGoogle Scholar
  34. 34.
    Makela P, Howe L, Glover S, et al.: Recurrent Guillain-Barre syndrome as a complication of immune reconstitution in HIV. J Infect 2002, 44:47–49.PubMedCrossRefGoogle Scholar
  35. 35.
    Behrens GM, Meyer D, Stoll M, Schmidt RE: Immune reconstitution syndromes in human immuno-deficiency virus infection following effective antiretroviral therapy. Immunobiology 2000, 202:186–193.PubMedGoogle Scholar
  36. 36.
    Behrens G, Knuth C, Schedel I, et al.: Highly active antiretroviral therapy. Lancet 1998, 351:1057–1058.PubMedCrossRefGoogle Scholar
  37. 37.
    Bell C, Nelson M, Kaye S: A case of immune reconstitution rheumatoid arthritis. Int J STD AIDS 2002, 13:580–581.PubMedCrossRefGoogle Scholar
  38. 38.
    Sellier P, Monsuez JJ, Evans J, et al.: Human immunodeficiency virus-associated polymyositis during immune restoration with combination antiretroviral therapy. Am J Med 2000, 109:510–512.PubMedCrossRefGoogle Scholar
  39. 39.
    Jubault V, Penfornis A, Schillo F, et al.: Sequential occurrence of thyroid autoantibodies and Graves’ disease after immune restoration in severely immunocompromised human immunodeficiency virus-1-infected patients. J Clin Endocrinol Metab 2000, 85:4254–4257.PubMedCrossRefGoogle Scholar
  40. 40.
    Sereti I, Sarlis NJ, Arioglu E, et al.: Alopecia universalis and Graves’ disease in the setting of immune restoration after highly active antiretroviral therapy. AIDS 2001, 15:138–140.PubMedCrossRefGoogle Scholar
  41. 41.
    Silvestre JF, Albares MP, Ramon R, Botella R: Cutaneous intolerance to tattoos in a patient with human immunodeficiency virus: a manifestation of the immune restoration syndrome. Arch Dermatol 2001, 137:669–670.PubMedGoogle Scholar
  42. 42.
    Wittram C, Fogg J, Farber H: Immune restoration syndrome manifested by pulmonary sarcoidosis. AJR Am J Roentgenol 2001, 177:1427.PubMedGoogle Scholar
  43. 43.
    Werwitzke S, Tiede A, Stoll M, von Depka M: Immune reconstitution inflammatory syndrome (IRIS) as a cause for inhibitor development in hemophilia. J Thromb Haemost 2004, 2:193–194.PubMedCrossRefGoogle Scholar
  44. 44.
    Behrens G, Stoll M, Schmidt RE: Lipodystrophy syndrome with protease inhibitors: what is it, what causes it and how can it be managed? Drug Saf 2000, 23:57–76.PubMedCrossRefGoogle Scholar
  45. 45.
    Grahame C, Alber DG, Lucas SB, et al.: Association between Kaposi’s sarcoma and atherosclerosis: implications for gammaherpesviruses and vascular disease. AIDS 2001, 15:1902–1904.CrossRefGoogle Scholar
  46. 46.
    Lewis W: Atherosclerosis in AIDS: potential pathogenetic roles of antiretroviral therapy and HIV. J Mol Cell Cardiol 2000, 32:2115–2129.PubMedCrossRefGoogle Scholar
  47. 47.
    Keane NM, Price P, Lee S, et al.: An evaluation of serum soluble CD30 levels and serum CD26 (DPPIV) enzyme activity as markers of type 2 and type 1 cytokines in HIV patients receiving highly active antiretroviral therapy. Clin Exp Immunol 2001, 126:111–116.PubMedCrossRefGoogle Scholar
  48. 48.
    Behbahani H, Landay A, Patterson BK, et al.: Normalization of immune activation in lymphoid tissue following highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2000, 25:150–156.PubMedCrossRefGoogle Scholar
  49. 49.
    Price P, Mathiot N, Krueger R, et al.: Immune dysfunction and immune restoration disease in HIV patients given highly active antiretroviral therapy. J Clin Virol 2001, 22:279–287.PubMedCrossRefGoogle Scholar
  50. 50.
    Price P, Morahan G, Huang D, et al.: Polymorphisms in cytokine genes define subpopulations of HIV-1 patients who experienced immune restoration diseases. AIDS 2002, 16:2043–2047. In addition to previously described associations of IRIS to certain histocompatibility antigens and distinct patterns of immunoreconstitution, this study demonstrates that polymorphisms of genetic factors have an impact on the manifestation of IRIS.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2004

Authors and Affiliations

  • Matthias Stoll
    • 1
  • Reinhold E. Schmidt
  1. 1.Department Clinical ImmunologyMedical School HannoverHannoverGermany

Personalised recommendations