Infektionsrisiko bei rheumatischen Erkrankungen – mit und ohne Therapie

Zusammenfassung

Das Risiko, an einer schweren Infektion zu erkranken, ist bei rheumatologischen Erkrankungen erhöht, wobei besonders Patienten mit systemischem Lupus erythematodes und solche unter intensiver immunsuppressiver Therapie gefährdet sind. Dabei kommt der Höhe der Dosis und der Dauer einer Therapie mit Kortikosteroiden, dem Alter der Betroffenen sowie dem Vorliegen möglicher Komorbiditäten eine besondere Bedeutung zu. Vor Einleitung einer immusuppressiven Therapie ist es daher erforderlich, die vorhandenen Risiken gegen den Nutzen einer möglichen Therapie abzuwägen und – soweit möglich – auf eine Minimierung der vorhandenen Risiken hinzuwirken. So lässt sich beispielsweise durch eine effektive Verminderung der Kortikosteroid-Dosis und durch prophylaktische Maßnahmen, wie eine konsequente Durchführung der zur Verfügung stehenden Impfungen, das Risiko für schwere Infektionen deutlich vermindern. Besonders für neue immunsuppressive Therapien sind die mit Infektionen verbundenen Risiken kritisch zu prüfen, um die Therapiesicherheit zu erhöhen.

Summary

Patients suffering from rheumatic diseases were endangered by severe infections. Important risk factors were dosage and length of corticosteroid therapy, older age or comorbidities like lung diseases or diabetes. Before starting an immunosuppressive therapy, the risk to suffer from a severe infection should be calculated. It can be diminished by minimizing risk factors like reducing corticosteroid dosage and performing recommended vaccinations. Thereby, safety of immunosuppressive therapy can be ameliorated.

Schlüsselwörter

Infektion - rheumatische Erkrankungen - immunsuppressive Therapie - Kortikoide

Keywords

Infection - rheumatic diseases - immunsuppressive treatment - corticosteroids

• Literatur

• 1 Prior P, Symmons DP, Scott DL. et al. Cause of death in rheumatoid arthritis. Br J Rheumatol 1984; 23: 92-99.
• 2 Reilly PA, Cosh JA, Maddison PJ. et al. Mortality and survival in rheumatoid arthritis: a 25 year prospective study of 100 patients. Ann Rheum Dis 1990; 49: 363-369.
• 3 Wagner UG, Koetz K, Weyand CM, Goronzy JJ. Perturbation of the T cell repertoire in rheumatoid arthritis. Proc Natl Acad Sci 1998; 95: 14447-14452.
• 4 Koetz K, Bryl E, Spickschen K. et al. T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci U S A 2000; 97: 9203-9208.
• 5 Doran MF, Crowson CS, Pond GR. et al. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum 2002; 46: 2287-2293.
• 6 Doran MF, Crowson CS, Pond GR. et al. Predictors of infection in rheumatoid arthritis. Arthritis Rheum 2002; 46: 2294-2300.
• 7 Dougados M, Soubrier M, Antunez A. et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA). Ann Rheum Dis. published online October 4 2013 doi:
• 8 Wolfe F, Caplan L, Michaud K. Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum 2006; 54: 628-634.
• 9 Strangfeld A, Eveslage M, Schneider M. et al. Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient?. Ann Rheum Dis 2011; 70: 1914-1920.
• 10 Geri G, Dadoun S, Bui T. et al. Risk of infections in bronchiectasis during disease-modifying treatment and biologics for rheumatic diseases. BMC Infect Dis 2011; 11: 304.
• 11 Sheane B, Ibanez D, Gladman D, Urowitz MB. Causes Of Mortality In Lupus Patients Followed Prospectively At a Large Single-Centre Lupus Clinic. ACR. 2013 Abstract #614
• 12 Falagas M, Manta KG, Betsi GI, Pappas G. Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review. Clin Rheumatol 2007; 26: 663-670.
• 13 Feller B. Infectious diseases in systemic lupus erythematosus: risc factors, management and prophylaxis. Best Pract Res Clin Rheum 2002; 16: 281-291.
• 14 Kang I, Park SH. Infectious complications in SLE after immunosuppressive therapies. Curr Opin Rheumatol 2003; 15: 528-534.
• 15 Kim WU, Min JK, Lee SH. et al. Causes of death in Korean patients with systemic lupus erythematosus: a single center retrospective study. Clin Exp Rheumatol 1999; 17: 539-545.
• 16 Bosch X, Guilabert A, Pallarés L. et al. Infections in systemic lupus erythemtosus: a prospective and controlled study of 110 patients. Lupus 2005; 15: 584-589.
• 17 Kinder BW, Freemer MM, King TE. et al. Clinical and genetic risk factors for pneumonia in systemic lupus erythematosus. Arthritis Rheum 2007; 56: 2679-2686.
• 18 Stohl W, Elliott JE, Li L. et al. Impaired nonrestricted cytolytic activity in systemic lupus erythematosus: involvement of a pathway independent of Fas, tumor necrosis factor, and extracellular ATP that is associated with little detectable perforin. Arthritis Rheum 1997; 40: 1130-1137.
• 19 Stohl W, Hamilton AS, Deapen DM. et al. Impaired cytotoxic T lymphocyte activity in systemic lupus erythematosus following in vitro polyclonal T cell stimulation: a contributory role for non-T cells. Lupus 1999; 8: 293-299.
• 20 Ng WL, Chu CM, Wu AKL. et al. Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus. Q J Med 2006; 99: 37-47.
• 21 Feldman C, Hiraki L, Marty F. et al. Serious Infection Rates Among Patients With Systemic Lupus Erythematosus Receiving Corticosteroids and Immunosuppressants. ACR. 2013 Abstract #780
• 22 Merayo-Chalico J. et al. Lymphopenia as risk factor for development of severe infections in patients with systemic lupus erythematosus: a case-control study. Q J Med 2013; 106: 451-457.
• 23 Van der Straeten C, Wei N, Rothschild J. et al. Rapidly fatal pneumococcal septicemia in systemic lupus erythematosus. J Rheumatol 1987; 14: 1177-1180.
• 24 Lim E, Koh WH, Loh SF. et al. Non-typhoidal salmonellosis in patients with systemic lupus erythematosus. A study of fifty patients and a review of the literature. Lupus 2001; 10: 87-92.
• 25 Yun JE, Lee SW, Kim TH. et al. The incidence and clinical characteristics of Mycobacterium tuberculosis infection among systemic lupus erythematosus and rheumatoid arthritis patients in Korea. Clin Exp Rheumatol 2002; 20: 127-132.
• 26 Gladman DD, Hussain F, Ibanez D. et al. The nature and outcome of infection in systemic lupus erythematosus. Lupus 2002; 11: 234-239.
• 27 Nagasawa K, Yamauchi Y, Tada Y. et al. High incidence of herpes zoster in patients with systemic lupus erythematosus: an immunological analysis. Ann Rheum Dis 1990; 49: 630-633.
• 28 Pryor BD, Bologna SG, Kahl LE. Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythematosus. Arthritis Rheum 1996; 39: 1475-1482.
• 29 Staples PJ, Gerding DN, Decker JL. et al. Incidence of infection in systemic lupus erythematosus. Arthritis Rheum 1974; 17: 1-10.
• 30 Hellmann DB, Petri M, Whiting-O’Keefe Q. Fatal infections in systemic lupus erythematosus: the role of opportunistic organisms. Medicine (Baltimore) 1987; 66: 341-348.
• 31 Marie I, Hachulla E, Che’ Rin P. et al. Opportunistic Infections In Polymyositis And Dermatomyositis. Arthritis Rheum 2005; 53: 155-165.
• 32 Durand M, Thomas SL. Incidence of Infections in Patients With Giant Cell Arteritis: A Cohort Study. Arthritis Care Res 2012; 64: 581-588.
• 33 Harigai M, Sada K, Fujii T. et al. High Clinical Remission Rate With Relatively High Incidence Of Serious Infection In Newly-Onset ANCA-Associated Vasculitides In Japan - A Report From The Nationwide Prospective Cohort Study. ACR. 2013 Abstract #749
• 34 Zink A, Manger B, Kaufmann J. et al. Evaluation of the RABBIT risk score for serious infections. Ann Rheum Dis. 2013 June 28, online first
• 35 Ruiz-Irastorza G, Olivares N, Ruiz-Arruza I. et al. Predictors of major infections in systemic lupus erythematosus. Arthritis Res Ther 2009; 11: R109.
• 36 Borba EF. et al. Influenza a/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?. Rheumatology. 2012 Jan 31, advanced access
• 37 Schneeweiss S, Setoguchi S, Weinblatt ME. et al. Anti-Tumor Necrosis Factor alpha Therapy and the Risk of Serious Bacterial Infektions in Elderly Patients with Rheumatoid Arthritis. Arthritis Rheum 2007; 6: 1754-1764.
• 38 Dixon WG. et al. The association between systemic glucocorticoid therapy and the risk of infection in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Res Ther 2011; 13: R139.
• 39 Dixon WG, Kezouh A, Bernatsky S, Suissa S. The influence of systemic glucocorticoid therapy upon the risk of non-serious infection in older patients with rheumatoid arthritis: a nested case-control study. ARD. 2011 February 1, online first
• 40 Jick SS, Lieberman ES, Rahman MU, Choi HK. Glucocorticoid use, other associated factors, and the risk of tuberculosis. Arthritis Rheum (Arthritis Care and Research) 2006; 55: 19-26.
• 41 Limper AH, Knox KS, Sarosi GA. et al. An official American Thoracic Society Statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011; 183: 96-128.
• 42 Cornberg M, Protzer U, Petersen J. et al. Prophylaxis, Diagnosis and Therapy of Hepatitis B Virus Infection - The German Guideline. Z Gastroenterol 2011; 49: 871-930.
• 43 Droz N, Gilardin L, Cacoub P. et al. Kinetic Profiles and management of Hepatitis B Virus reactivation in patients with immune-mediated inflammatory diseases. Arthritis Care Res 2013; 65: 1504-1514.
• 44 Singh JA, Wells GA, Christensen R. et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview (Review). The Cochrane Library; 2012. Issue 3
• 45 Van Vollenhoven RF, Emery P, Bingham III CO. et al. Long-term safety of rituximab in rheumatoid adverse events of interest in RA patients clinical trial programme with a focus on arthritis: 9.5-year follow-up of the global. Ann Rheum Dis 2013; 2: 1496-1502.
• 46 Hua C, Barnetche T, Combe B, Morel J. Effect of Methotrexate, anti-TNF alpha and Rituximab on the Immune Response to Influenza and Pneumococcal Vaccines in Patients with Rheumatoid Arthritis: a systematic review and meta-analysis. Arthritis Care Res. 2013 DOI
• 47 Kim EM, Uhm WS, Bae SC. et al. Incidence of tuberculosis among korean patients with ankylosing spondylitis who are taking tumor necrosis factor blockers. J Rheumatol 2011; 38: 2218-2223 Epub 2011 Aug 15
• 48 Dixon WG, Hyrich KL, Watson KD. et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: Results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis. 2009 Oct 22, published online
• 49 Tubach F, Salmon D, Ravaud P. et al. for the Research Axed on Tolerance of Biotherapies Group Risk of Tuberculosis Is Higher With Anti-Tumor Necrosis Factor Monoclonal Antibody Therapy Than With Soluble Tumor Necrosis Factor Receptor Therapy The Three-Year Prospective French Research Axed on Tolerance of Biotherapies. Registry. Arthritis Rheum 2009; 60: 1884-1894
• 50 Baddley JW, Winthrop KL, Chen L. et al. Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) Study. Annals Rheum Dis. 2013 July 13, online first
• 51 Kim PS, Ho GY, Prete PE, Furst DE. Safety And Efficacy Of Abatacept In Eight Rheumatoid Arthritis Patients With Chronic Hepatitis B. Arthritis Care Res 2012; 64: 1265-1268.
• 52 Fanouriakis A, Vassilopoulos D, Repa A. et al. Hepatitis B reactivation following treatment with abatacept in a patient with past hepatitis B virus infection. Rheumatology. 2013 June 14, advance access
• 53 Strangfeld A, Listing J, Herzer P. et al. Risk of Herpes Zoster in Patients With Rheumatoid Arthritis Treated With Anti-TNF-alpha Agents. JAMA 2009; 301: 737-744.
• 54 Galloway JB, Mercer LK, Moseley A. et al. Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2012 April 24, online first
• 55 Warnatz K, Goldacker S, Gause AM. die Kommission Pharmakotherapie der DGRh. Vaccination recommendations of the comission for Pharmacotherapy of the german society of rheumatology. Z Rheumatol 2013; 9: 909.
• 56 Arkema EV, van Vollenhoven RF, Askling J. for the ARTIS Study Group. Incidence of progressive multifocal leukoencephalopathy in patients with rheumatoid arthritis: a national population-based study. Ann Rheum Dis. 2012 June 27, online first
• 57 Molloy ES, Calabrese LH. Progressive Multifocal Leukoenzephalopathy. A national estimate of frequency in Systemic Lupus Erythematosus and other rheumatic diseases. Arthritis Rheum 2009; 60: 3761.
• 58 Molloy ES, Calabrese LH. Progressive Multifocal Leukoencephalopathy Associated With Immunosuppressive Therapy in Rheumatic Diseases Evolving Role of Biologic Therapies. Arthritis Rheum 2012; 64: 3043-3051.
• 59 Schmedt N, Andersohn F, Garbe E. Signals of progressive multifocal leukoencephalopathy for immunosuppressants: a disproportionality analysis of spontaneous reports within the US Adverse Event Reporting System (AERS). pharmacoepidemiology and drug safety. 2012 published online in Wiley Online Library ( wileyonlinelibrary.com ) DOI:
• 60 Bharat A, Xie F, Baddley JW. et al. Incidence and Risk Factors for Progressive Multifocal Leukoencephalopathy Among Patients With Selected Rheumatic Diseases. Arthritis Care Res 2012; 64: 612-615.