Dermatological Immune Restoration Syndrome in HIV Infected Patients

Charussri Wachirakaphan; Siri Chiewchavit

Authors

Charussri Wachirakaphan DEPARTMENT OF INTERNAL MEDICINE, FACULTY OF MEDICINE, CHIANG MAI UNIVERSITY, CHIANG MAI, THAILAND
Siri Chiewchavit DEPARTMENT OF INTERNAL MEDICINE, FACULTY OF MEDICINE, CHIANG MAI UNIVERSITY, CHIANG MAI, THAILAND

Keywords:

HIV, AID, Immune Restoration Syndrome, IRIS, immune restitution disease, IRD, immune reconstitution phenomenon, Dermatology

Abstract

Dermatological disease are common in HIV infected patients. The diagnosis and treatment of such problems are rapidly changing following HAART. In many developed countries, incidences of some dermatological disease are on the decline while some disease are emerging with unusual manifestation as a result of improved immunity in patients who receive HAART. Signs and symptoms of diseases may differ depending on pathogenic organisms and disease mechanisms involved. At present there are no clear treatment guidelines available and disease treatment depends on experience of individual physicians. The purpose of this review on dermatological immune restoration syndrome was to provide physicians with relevant information necessary for patient care.

References

Reynaud-Mendel B, Janier M, Gerbaka J, et al. Dermatological finding in HIV-infected patients: A prospective study with emphasis on CD4+ cell count. Dermatology 1996;192:325-8.

Schaub N, Gilli L,Rufli T, et al. Epidemiology of skin disease in HIV-infected patients: A prospective cohort study. Schweiz Rundsch Med Prax 1996;85:1162-6.

Coldiron BM,Bergstresser PR. Prevalence and clinical spectrum of skin disease in patients infected with human immunodeficiency virus. Arch Dermatol 1988;125:357-61.

Zalla MJ, SU WPD, Fransway AF. Dermatologic manifestation of human immunodeficiency virus infection. Mayo Clin Proc 1992;67:1089-108.

Handa S, Bingham JS. Dermatological immune restoration syndrome: does it exist .JEADV 2001;15:430-2.

Charle Darley. The prevalence of skin disease in HIV infection .AIDS Patient Care STDs 1998;12:849-52

Uthayakumar S,Nandwani R,Drinkwater T, Nayagam A, Darley C. The prevalence of skin disease in HIV infection and its relationship to the degree of immunosuppression. Br J Dermatol 1997;137:595-8.

Tschachler E , Berrgstresses PR , Stingl G. HIV-related skin disease. Lancet 1996;348:659-63.

Dyche JA,Hay RJ. HIV. the skin and the impact of antiretroviral therapy. Curr opin in infect Dis 2000;13:99-101.

Aftergut K, Cockerell CJ. Update on the cutaneous manifestationof HIV infection. Clinical and Pathologic features. Dermatol clin 1999;17:445-71.

Porras B, Costner M, Freidman-Kien AE,Cockerell CJ. Update on cutaneous manifestation of HIV infection. Med Clin North Am 1998;82:1033-80.

Ledermann MM, Valdez H. Immune restoration with antiretroviral therapies : implication for clinical management. JAMA 2000;284:223-8.

Sepkowitz KA .Effect of HAART on natural history of AIDS related opportunistic disorder. Lancet 1998;351:228-30.

Palella FJJr, Delaney KM, Moorman AC , et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338: 853-60.

Michaels S, Clark R, Kissinger P. Declining morbidity and mortality among patients with advance human immunodeficiency virus infection. N Engl J Med 1998; 339: 405-6.

Jacobson MA, French M. Altered natural history of AIDS – related opportunistic infections in the era of potent combination antiretroviral therapy. AIDS 1998; 12: S157-S163.

Powderly WG, Landay A, Ledermann MM. Recovery of the immune system with antiretroviral therapy: the end of opportunism. JAMA 1998; 280: 72-7.

Autran B, Carcelain G, Li TS et al .Positive effects of combined antiretroviral therapy on CD4+ T cells homeostasis and function in advanced HIV disease. Science 1997;277:112-6.

Li TS, Tubiana R, Katlama C et al. Long-lasting recovery in CD4 T-cell function and viral load reduction after highly active antiretroviral therapy in advanced HIV-1 disease. Lancet 1998;351:1682-6.

Nokta MA, Li XD, Nichols J, et al. Homeostasis of naïve and memory T cell subpopulations in peripheral blood and lymphoid tissue in the context of human immunodeficiency virus infection. J Infect Dis 2001;183:1336-42.

Fischer T, Schworer H, Vente C, Reich K, Ramadori G, et al. Clinical improvement of HIV-associated psoriasis parallels a reduction of HIV viral load induced by effective antiretroviral therapy AIDS 1999;13:628-9.

Costner M, Cockerell CJ. The changing spectrum of the cutaneous manifestations of HIV disease. Arch Dermatol 1998;134 : 1290–2.

Spach DH, Colvern R. Resolution of recalcitrant hand warts in an HIV-infected patient treated with potent antiretroviral therapy. J Am Acad Dermatol 1999;40:818-21.

Krischer J, Rutschmann O, Hirschel B et al. Regression of Kaposi’s sarcoma during therapy with HIV-1 protease inhibitors: a prospective pilot study. J Am Acad Dermatol 1998;38: 594–8.

De Milito A, Catucci M, Venturi G et al. Antiretroviral therapy with protease inhibitors in human immunodeficiency virus type-1 and human herpes virus 8-coinfected patients . J Med Virol 1999;57:140–4.

Hurni MA, Bohlen L, Furrer H, Braathenc R. Complete regression of giant molluscum contagiosum lesions in an HIV-infected patient following combined antiretroviral therapy with saquinavir, zidovudine and lamivudine. AIDS 1997;11: 1784–5.

Hicks CB, Myers SA, Giner J. Resolution of intractable molluscum contagiosum in a human immunodeficiency virus infected patient after institution of antiretroviral therapy with ritonavir. Clin Infect Dis 1997;24: 1023–5.

Lipman M, Breen R. Immune reconstitution inflammatory syndrome in HIV.Curr Opin Infect Dis 2006 Feb; 19(1):20-5.

Martinez E, Gatell JM, Moran Y et al. High incidence of herpes zoster after starting antiretroviral therapy with a protease inhibitor. Paper presented at: 5th Conference on Retrovirus and Opportunistic Infections; February 3. Chicago, IL , 1998: Abstr. 501.

Aldeen T, Hay P, Davidson F, Lau R. Herpes zoster infection in HIV- seropositive patients associated with highly active antiretroviral therapy. AIDS 1998;12(13): 1719–20.

Rodriguez-Rosado R, Soriano V, Dona C, Gonzalez-Lahoz J. Opportunistic infections shortly after beginning highly active antiretroviral therapy . Antivir Ther 1998; 3 (4): 229–31.

Martinez E, Gatell J, Moran Y, Aznar E, Guelar A, et al . High incidence of Herpes zoster in patients with AIDS soon after treatment with protease inhibitors. Clin Infect Dis 1998;27:1510-3.

French MA, Lenzo N, John M, et al. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med 2000;1(2):107–15

Fox PA, Barton SE, Francis N et al. Chronic erosive herpes simplex virus infection of the penis, a possible immune reconstitution disease. HIV Med 2000;1: 10–8.

Carcelain G, Debre P, Autran B. Reconstitution of CD4+ T lymphocytes in HIV-infected individuals following antiretroviral therapy. Curr Opin Immunol 2001;13:483-8.

Cheng VC, Yuen KY, Chan YM, et al. Immunorestitution disease involvement the innate and adaptive response. Clin Infect Dis 2000;30:882-92.

Deayton JR, Sabin CA, Britt WB , et al . Rapid reconstitution of humoral immunity against cytomegalovirus but not HIV following highly active antiretroviral therapy. AIDS 2002;16:2129-35.

Foudraine Na, Hovenkamp E, Notermans DW, et al . Immunopathology as a result of highly active antiretroviral therapy in HIV-1 infected patients. AIDS 1999;13:177-84.

Samuel A. Shelburne III and Richard J. Hamill. The Immune Reconstitution Inflammatory Syndrome. AIDS Rev 2003;5:67-79.

Michailidis C, Pozniak AL, Mandalia S, et al. Clinical characteristics of IRIS syndrome in patients with HIV and tuberculosis. Antivir Ther 2005;10:417-22.

Stone S., Price P, French M. Immune Restoration Disease: A Consequence of Dysregulated Immune Responses After HAART. Current HIV Research 2004; 2: 235-42.

French MA, Price P , Stone SF. Immune restoration disease after antiretroviral therapy [EDITORIAL REVIEW]. AIDS 2004 ;18(12):1615-27.

Shelburne S, Hamill R, Rodríguez-Barradas M, et al. Immune reconstitution inflammatory syndrome: emergence of a unique syndrome during highly active antiretroviral therapy. Medicine 2002 ;81:213-27.

Domingo B, Torres O, Ris J, et al. Varicella zoster virus as an immune reconstitution disease after initiation of combination antiretroviral therapy in HIV- infected patients. Am J Med 2001;110:605-9.

French M, Mallal SA, Dawkins RL. Zidovudine induced restoration of cell-mediated immunity to mycobacteria in immunodeficient HIV-infected patients. AIDS 1992; 6:1293-7.

Mallal SA, James IR, French MAH. Detection of subclinical Mycobacterium avium intracellulare complex infection in immunodeficient HIV-infected patients treated with zidovudine. AIDS 1994; 8:1263–9.

Dworkin MS, Fratkin MD. Mycobacterium avium complex lymph node abscess after use of highly active antiretroviral therapy in a patient with AIDS. Arch Intern Med 1998 ;158:1828-38.

Cabie A, Abel S, Brebion A, Desbois N, Sobesky G. Mycobacterial lymphadenitis after initiation of highly active antiretroviral therapy. Eur J Clin Microbiol Infect Dis 1998; 17:812–3.

Phillips P, Kwiatkowski MB, Copland M, Craib K, Montaner J. Mycobacterial lymphadenitis associated with the initiation of combination antiretroviral therapy. J Acquir Immune Defic Syndr Hum Retrovirol 1999; 20:122–8.

Schwietert M, Battegay M. Focal mycobacterial lymphadenitis after starting highly active antiretroviral treatment. Dtsch med Wschr 1999; 124:45–8.

Bartley PB, Allworth AM, Eisen DP. Mycobacterium avium complex causing endobronchial disease in AIDS patients after partial immune restoration. Int J Tuberculosis Lung Dis 1999; 3:1132–6.

Price LM, O’Mahoney C. Focal adenitis developing after immune reconstitution with HAART. Int J STD AIDS 2000; 11:685–6.

Hassell M, French MA. Mycobacterium avium infection and immune restoration disease after highly active antiretroviral therapy in a patient with HIV and normal CD4+ counts. Eur J Clin Microbiol Infect Dis 2001; 20:889–91.

Salama C, Policar M, Venkataraman M. Isolated pulmonary Mycobacterium avium complex infection in patients with human immunodeficiency virus infection: case reports and literature review. Clin Infect Dis 2003; 37:e35–e40.

del Giudice P, Durant J, Counillon E, et al . Mycobacterial cutaneous manifestations : a new sign of immune restoration syndrome in patients with acquired immunodeficiency syndrome. Arch Dermatol 1999 Sep;135:1129-30.

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;351:252-5.

Sotto A, Guillot B, Dandurand M, Jourdan J. Exacerbation of skin mycobacterial lesions under highly active antiretroviral therapy in an HIV-infected patient. AIDS 1999;13(3): 1790–1.

Brown M, Williams I, Miller R. Deterioration of disseminated cutaneous Mycobacterium avium complex infection with a leukemoid reaction following institution of highly active antiretroviral therapy. Sex Transm Infect 2001 ;77:149-50.

Lawn SD, Bicanic TA, Macallan DC. Pyomyositis and cutaneous abscesses due to Mycobacterium avium: an immune reconstitution manifestation in a patient with AIDS. Clin Infect Dis 2004; 38:461–3.

Puthanakit T, Oberdorfer P, Ukarapol N, et al. Immune reconstitution syndrome from nontuberculous mycobacterial infection after initiation of antiretroviral therapy in children with HIV infection . Pediatr Infect Dis J 2006; 25(7) : 645-7.

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: 157–61.

Crump JA, Tyrer MJ, Lloyd-Owen SJ. Miliary tuberculosis with paradoxical expansion of intracranial tuberculomas complicating human immunodeficiency virus infection in a patient receiving highly active antiretroviral therapy. Clin Infect Dis 1998; 26:1008–9.

Furrer H-J, Malinverni R. Systemic inflammatory reaction after starting highly active antiretroviral therapy in AIDS patients treated for extrapulmonary tuberculosis. Am J Med 1999;106:371–2.

Kunimoto DY, Chui L, Nobert E, Houston S. Immune mediated ‘HAART’ attack during treatment for tuberculosis. Highly active antiretroviral therapy. Int J Tuberc Lung Dis 1999;3:944–7.

Chien JW, Johnson JL. Paradoxical reactions in HIV and pulmonary TB. Chest 1998; 114:933–6.

Fishman JE, Saraf-Lavi E, Narita M, Hollender ES, RamsinghaniR, Ashkin D. Pulmonary tuberculosis in AIDS patients: transient chest radiographic worsening after initiation of antiretroviral therapy. Am J Roentgenol 2000; 174:43–9.

Navas E, Martin-Davila P, Moreno L, et al. Paradoxical reactions of tuberculosis in patients with the acquired immunodeficiency syndrome who are treated with highly active antiretroviral therapy. Arch Intern Med 2002; 162:97–9.

Lawn SD, Macallan DC. Hypercalcemia: a manifestation of immune reconstitution complicating tuberculosis in an HIVinfected person. Clin Infect Dis 2004; 38:154–5.

Sharp MJ, Mallon DFJ. Regional Bacillus Calmette-Guerin lymphadenitis after initiating anti-retroviral therapy in an infant with human immunodeficiency virus type 1 infection. Ped Infect Dis J 1998; 17:660–2.

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.

Pignataro P, Rocha Ada S,. Nery JA ,et al. Leprosy and AIDS: two cases of increasing inflammatory reactions at the start of highly active antiretroviral therapy. Eur J Clin Microbiol Infect Dis 2004;23:408–11.

Manfredi R, Pieri F, Pileri S, et al. The changing face of AIDS related opportunism: cryptococcosis in the highly active antiretroviral therapy (HAART) era. Case reports and literature review. Mycopathologia 1999;148:73-8.

Gilquin J, Piketty C, Thomas V, et al. Acute cytomegalovirus infection in AIDS patients with CD4+ counts above 100x106 cells/L following combination antiretroviral therapy including protease inhibitors. AIDS 1997;11:1159-60.

Qazi N, Morlese J, Walsh J, et al. Severe cutaneous ulceration secondary to cytomegalovirus inclusion disease during successful immune reconstitution with HAART. AIDS Read 2002 ; 12:452-7.

Greenspan D, Canchola AJ, MacPhail LA, Cheikh B, Greenspan JS. Effect of highly active antiretroviral therapy on frequency of oral warts. Lancet 2001; 357:1411–2.

King MD, Reznik DA, O’Daniels CM, Larsen NM, Osterholt D, Blumberg HM. Human papillomavirus-associated oral warts among human immunodeficiency virus-seropositive patients in the era of highly active antiretroviral therapy: an emerging infection. Clin Infect Dis 2002; 34:641–8.

Jevtovic DJ , Salemovic D, Ranin J, et al .The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Medicine 2005;6;140–3.

Weir A, Wansbrough-Jones M. Mucosal Kaposi’s sarcoma following protease inhibitor therapy in an HIV-infected patient. AIDS 1997; 11:1895–6.

Bouscarat F, Maubec E, Matheron S, Descamps V. Immune recovery inflammatory folliculitis. AIDS 2000; 14:617–8.

Delfos NM, Collen AF, Kroona FP . Demodex folliculitis: a skin manifestation of immune reconstitution disease AIDS 2004;18:701–8.

Blanche P, Gombert B, Rivoal O, Abad S, Salmon D, Brezin A. Uveitis due to Leishmania major as part of HAART-induced immune restitution syndrome in a patient with AIDS. Clin Infect Dis 2002; 34:1279–80.

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; 340:1923–4.

Leidner R,Aboulafia D. Recrudescent Kaposi’s Sarcoma After Initiation of HAART: A manifestation of Immune Reconstitution Syndrome AIDS Patitent Care STDs 2005;19:635-44.

Ridolfo AL, Gervasoni C, Antinori S, Pizzuto M, Santambrogio S, Trabattoni D, et al. Post-kala-azar dermal leishmaniasis during highly active antiretroviral therapy in an AIDS patient infected with Leishmania infantum. J Infect 2000; 40:199–202.

Kerob D,Bouaziz J.D,Sarfati C,et al. First Case of Cutaneous Reconstitution Inflammatory Syndrome Associated with HIV Infection and Leishmaniasis. CID 2006;43:664-5.

Neumann S, Kreth F, Schubert S, Mossner J, Caca K. Reiter’s syndrome as a manifestation of an immune reconstitution syndrome in an HIV-infected patient: successful treatment with doxycycline. Clin Infect Dis 2003; 36:1628–9.

Mirmirani P, Maurer TA, Herndier B, et al. Sarcoidosis in a patient with AIDS: a manifestation of immune restoration syndrome. J Am Acad Dermatol 1999;41: 285–6.

Blanche P, Passeron A, Gombert B, Ginsburg C, Salmon D, Sicard D. Sarcoidosis and HIV infection: influence of highly active antiretroviral therapy. Br J Dermatol 1999; 140:1185.

Trevenzoli M, Cattelan AM, Marino F, Marchioro U, Cadrobbi P. Sarcoidosis and HIV infection: a case report and a review of the literature. Postgrad Med J 2003; 79:535–8.

Foulon G, Wislez M, Naccache JM, et al. Sarcoidosis in HIV-infected patients in the era of highly active antiretroviral therapy. Clin Infect Dis 2004; 38:418–25.

A Kreuter, R Schlottmann, P Altmeyer, Nh Brockmeyer. Acne vulgaris as an immune reconstitution syndrome in a patient with AIDS after initiation of antiretroviral therapy. JEADV 2002;16: 638-49.

Phillips P, Chan K, Hogg R, Bessuille E, Black W, Talbot J, et al. Azithromycin prophylaxis for Mycobacterium avium complex during the era of highly active antiretroviral therapy: evaluation of a provincial program. Clin Infect Dis 2002; 34:371–8.

Price P, Keane NM, Stone SF, Cheong KYM, French MA. MHC haplotypes affect the expression of opportunistic infections in HIV patients. Hum Immunol 2001; 62:157–64.

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; 16:2043–7.

de Boer M, Kroon1 F.P , Kauffmann R.H. Immune restoration disease in HIV-infected individuals receiving highly active antiretroviral therapy: clinical and immunological characteristics . Neth J med 2003;61:408-12.

Tangsinmankong N, Kamchaisatian W, Zilbermann J,et al . Varicella zoster as a manifestation of immune restoration disease in HIV-infected children. J Allergy Clin Immunol 2004;113:742-6.

Robertson J , Meier M , Wall J , Ying J , Fichtenbaum C. Immune Reconstitution Syndrome in HIV: Validating a Case Definition and Identifying Clinical Predictors in Persons Initiating Antiretroviral Therapy.Clin Infect Dis 2006; 42:1639–46.

Shelburne SA, Visnegarwala F,Darcourt J, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy.AIDS 2005;19:399-406.

Hirsch H,Kaufmann G,Sendi P,Battegay M. Immune Reconstitution in HIV-Infected Patients.Clin Infect Dis 2004; 38:1159–66.

Burman WJ , Jones BE. Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy. Am J Respir Crit Care Med 2001; 164:7-12.

Kong H,Myers S. Cutaneous effects of highly active antiretroviral therapy in HIV-infected patients. Dermatol Ther 2005 ;18:58–66.