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Erschienen in: Modern Rheumatology 3/2012

01.06.2012 | Original Article

Reactivation of cytomegalovirus predicts poor prognosis in patients on intensive immunosuppressive treatment for collagen-vascular diseases

verfasst von: Ryosuke Hanaoka, Kazuhiro Kurasawa, Reika Maezawa, Kotaro Kumano, Satoko Arai, Takashi Fukuda

Erschienen in: Modern Rheumatology | Ausgabe 3/2012

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Abstract

Reactivation of cytomegalovirus (CMV) occurs during intensive immunosuppressive therapies. However, the influence of CMV reactivation on prognosis in patients with immunosuppressive therapies for collagen-vascular diseases (CVD) is not fully understood. To determine whether CMV reactivation affects the prognosis of patients with CVD and to identify risk factors of CMV reactivation, we reviewed, retrospectively, the medical records of 109 CVD patients who were treated with glucocorticoid (prednisolone ≥20 mg/day) and were tested for CMV antigen (CMV-Ag). CMV-Ag was detected in 34 of the 109 patients. First-time CMV-Ag detection was within 50 days from the start of intensive immunosuppressive therapy in 82% of the patients. Common manifestations at first-time CMV-Ag detection were fever, arthralgia, and rash, although 52.9% of the patients were asymptomatic. The risk factors for CMV reactivation were old age (>65 years) and high-dose glucocorticoids (PSL ≥50 mg). During the 4-year study period, 18% of patients with positive CMV-Ag and 5% of those without CMV-Ag died. Patients with CMV-Ag (max CMV number ≥5/105 WBC) had a significantly poorer prognosis. Multivariate analysis confirmed CMV reactivation as an independent poor prognostic factor in CVD patients. Causes of death were exacerbation of pre-existing interstitial pneumonia and infection other than CMV. Our results demonstrate that CMV reactivation, particularly with a high CMV-Ag number, is a poor prognostic factor in CVD patients. Patients with older age and high-dose glucocorticoids have a high risk of CMV reactivation.
Literatur
1.
Zurück zum Zitat Griffiths PD. Cytomegalovirus. In: Zuckerman AZ, editor. Principles and practice of clinical virology. 6th ed. Hoboken: Wiley; 2009. p. 161–98.CrossRef Griffiths PD. Cytomegalovirus. In: Zuckerman AZ, editor. Principles and practice of clinical virology. 6th ed. Hoboken: Wiley; 2009. p. 161–98.CrossRef
2.
Zurück zum Zitat Krech U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull World Health Organ. 1973;49:103–6.PubMed Krech U. Complement-fixing antibodies against cytomegalovirus in different parts of the world. Bull World Health Organ. 1973;49:103–6.PubMed
3.
Zurück zum Zitat Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis. 2004;4:725–38.PubMedCrossRef Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis. 2004;4:725–38.PubMedCrossRef
4.
Zurück zum Zitat Soderberg-Naucler C, Fish KN, Nelson JA. Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell. 1997;91:119–26.PubMedCrossRef Soderberg-Naucler C, Fish KN, Nelson JA. Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell. 1997;91:119–26.PubMedCrossRef
5.
Zurück zum Zitat Rubin RH. Impact of cytomegalovirus infection on organ transplant recipients. Rev Infect Dis. 1990;12:S754–66.PubMedCrossRef Rubin RH. Impact of cytomegalovirus infection on organ transplant recipients. Rev Infect Dis. 1990;12:S754–66.PubMedCrossRef
6.
Zurück zum Zitat Mori T, Kameda H, Ogawa H, et al. Incidence of cytomegalovirus reactivation in patients with inflammatory connective tissue disease who are under immunosuppressive therapy. J Rheumatol. 2004;31:1349–51.PubMed Mori T, Kameda H, Ogawa H, et al. Incidence of cytomegalovirus reactivation in patients with inflammatory connective tissue disease who are under immunosuppressive therapy. J Rheumatol. 2004;31:1349–51.PubMed
7.
Zurück zum Zitat Yoda Y, Hanaoka R, Ide H, et al. Clinical evaluation of patients with inflammatory connective tissue diseases complicated by cytomegalovirus antigenemia. Mod Rheumatol. 2006;16:137–42.PubMedCrossRef Yoda Y, Hanaoka R, Ide H, et al. Clinical evaluation of patients with inflammatory connective tissue diseases complicated by cytomegalovirus antigenemia. Mod Rheumatol. 2006;16:137–42.PubMedCrossRef
8.
Zurück zum Zitat Takizawa Y, Inokuma S, Tanaka Y, et al. Clinical characteristics of cytomegalovirus infection in rheumatic diseases: multicentre survey in a large patient population. Rheumatology. 2008;47:1373–8.PubMedCrossRef Takizawa Y, Inokuma S, Tanaka Y, et al. Clinical characteristics of cytomegalovirus infection in rheumatic diseases: multicentre survey in a large patient population. Rheumatology. 2008;47:1373–8.PubMedCrossRef
9.
Zurück zum Zitat Kurihara T, Hayashi J, Matsuoka T, Ito A. HCMV pp65 antigenemia assay using indirect alkaline phosphatase staining method. Biomed Res. 1995;16:125–9. Kurihara T, Hayashi J, Matsuoka T, Ito A. HCMV pp65 antigenemia assay using indirect alkaline phosphatase staining method. Biomed Res. 1995;16:125–9.
10.
Zurück zum Zitat Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34:1094–7.PubMedCrossRef Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34:1094–7.PubMedCrossRef
11.
Zurück zum Zitat Yamashita M, Ishii T, Iwama N, Takahashi H. Incidence and clinical features of cytomegalovirus infection diagnosed by cytomegalovirus pp65 antigenemia assay during high dose corticosteroid therapy for collagen vascular diseases. Clin Exp Rheumatol. 2006;24:649–55.PubMed Yamashita M, Ishii T, Iwama N, Takahashi H. Incidence and clinical features of cytomegalovirus infection diagnosed by cytomegalovirus pp65 antigenemia assay during high dose corticosteroid therapy for collagen vascular diseases. Clin Exp Rheumatol. 2006;24:649–55.PubMed
12.
Zurück zum Zitat Döcke WD, Prösch S, Fietze E, et al. Cytomegalovirus reactivation and tumor necrosis factor. Lancet. 1994;343:268–9.PubMedCrossRef Döcke WD, Prösch S, Fietze E, et al. Cytomegalovirus reactivation and tumor necrosis factor. Lancet. 1994;343:268–9.PubMedCrossRef
13.
Zurück zum Zitat Limaye AP, Kirby KA, Rubenfeld GD, et al. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA. 2008;300:413–22.PubMedCrossRef Limaye AP, Kirby KA, Rubenfeld GD, et al. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA. 2008;300:413–22.PubMedCrossRef
14.
Zurück zum Zitat Raftery MJ, Schwab M, Eibert SM, Samstag Y, Walczak H, Schönrich G. Targeting the function of mature dendritic cells by human cytomegalovirus: a multilayered viral defense strategy. Immunity. 2001;15:997–1009.PubMedCrossRef Raftery MJ, Schwab M, Eibert SM, Samstag Y, Walczak H, Schönrich G. Targeting the function of mature dendritic cells by human cytomegalovirus: a multilayered viral defense strategy. Immunity. 2001;15:997–1009.PubMedCrossRef
15.
Zurück zum Zitat Boeckh M, Nichols WG. Immunosuppressive effects of betaherpesviruses. Herpes. 2003;10:12–6.PubMed Boeckh M, Nichols WG. Immunosuppressive effects of betaherpesviruses. Herpes. 2003;10:12–6.PubMed
16.
Zurück zum Zitat Varani S, Frascaroli G, Landini MP, Söderberg-Nauclér C. Human cytomegalovirus targets different subsets of antigen-presenting cells with pathological consequences for host immunity: implications for immunosuppression, chronic inflammation and autoimmunity. Rev Med Virol. 2009;19:131–45.PubMedCrossRef Varani S, Frascaroli G, Landini MP, Söderberg-Nauclér C. Human cytomegalovirus targets different subsets of antigen-presenting cells with pathological consequences for host immunity: implications for immunosuppression, chronic inflammation and autoimmunity. Rev Med Virol. 2009;19:131–45.PubMedCrossRef
17.
Zurück zum Zitat van den Berg AP, Klompmaker IJ, Haagsma EB, et al. Evidence for an increased rate of bacterial infections in liver transplant patients with cytomegalovirus infection. Clin Transplant. 1996;10:224–31.PubMed van den Berg AP, Klompmaker IJ, Haagsma EB, et al. Evidence for an increased rate of bacterial infections in liver transplant patients with cytomegalovirus infection. Clin Transplant. 1996;10:224–31.PubMed
18.
Zurück zum Zitat George MJ, Snydman DR, Werner BG, et al. The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Am J Med. 1997;103:106–13.PubMedCrossRef George MJ, Snydman DR, Werner BG, et al. The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Am J Med. 1997;103:106–13.PubMedCrossRef
19.
Zurück zum Zitat Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis. 2002;185:273–82.PubMedCrossRef Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis. 2002;185:273–82.PubMedCrossRef
20.
Zurück zum Zitat Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet. 2005;365:2105–15.PubMedCrossRef Hodson EM, Jones CA, Webster AC, et al. Antiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trials. Lancet. 2005;365:2105–15.PubMedCrossRef
21.
Zurück zum Zitat Compton T, Kurt-Jones EA, Boehme KW, et al. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol. 2003;77:4588–96.PubMedCrossRef Compton T, Kurt-Jones EA, Boehme KW, et al. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol. 2003;77:4588–96.PubMedCrossRef
22.
Zurück zum Zitat Fasth AE, Snir O, Johansson AA, et al. Skewed distribution of proinflammatory CD4+ CD28 null T cells in rheumatoid arthritis. Arthritis Res Ther. 2007;9:R87.PubMedCrossRef Fasth AE, Snir O, Johansson AA, et al. Skewed distribution of proinflammatory CD4+ CD28 null T cells in rheumatoid arthritis. Arthritis Res Ther. 2007;9:R87.PubMedCrossRef
23.
Zurück zum Zitat Zhu H, Cong JP, Yu D, Bresnahan WA, Shenk TE. Inhibition of cyclooxygenase2 blocks human cytomegalovirus replication. Proc Natl Acad Sci USA. 2002;99:3932–7.PubMedCrossRef Zhu H, Cong JP, Yu D, Bresnahan WA, Shenk TE. Inhibition of cyclooxygenase2 blocks human cytomegalovirus replication. Proc Natl Acad Sci USA. 2002;99:3932–7.PubMedCrossRef
24.
Zurück zum Zitat Reinke P, Fietze E, Ode-Hakim S, et al. Late-acute renal allograft rejection and symptomless cytomegalovirus infection. Lancet. 1994;344:1737–8.PubMedCrossRef Reinke P, Fietze E, Ode-Hakim S, et al. Late-acute renal allograft rejection and symptomless cytomegalovirus infection. Lancet. 1994;344:1737–8.PubMedCrossRef
25.
Zurück zum Zitat Cainelli F, Vento S. Infections and solid organ transplant rejection: a cause-and-effect relationship? Lancet Infect Dis. 2002;2:539–49.PubMedCrossRef Cainelli F, Vento S. Infections and solid organ transplant rejection: a cause-and-effect relationship? Lancet Infect Dis. 2002;2:539–49.PubMedCrossRef
26.
Zurück zum Zitat Sagedal S, Nordal KP, Hartmann A, et al. The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients. Am J Transplant. 2002;2:850–6.PubMedCrossRef Sagedal S, Nordal KP, Hartmann A, et al. The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients. Am J Transplant. 2002;2:850–6.PubMedCrossRef
Metadaten
Titel
Reactivation of cytomegalovirus predicts poor prognosis in patients on intensive immunosuppressive treatment for collagen-vascular diseases
verfasst von
Ryosuke Hanaoka
Kazuhiro Kurasawa
Reika Maezawa
Kotaro Kumano
Satoko Arai
Takashi Fukuda
Publikationsdatum
01.06.2012
Verlag
Springer Japan
Erschienen in
Modern Rheumatology / Ausgabe 3/2012
Print ISSN: 1439-7595
Elektronische ISSN: 1439-7609
DOI
https://doi.org/10.1007/s10165-011-0519-3

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