Skip to main content
Erschienen in: Zeitschrift für Rheumatologie 2/2006

01.03.2006 | Leitthema

Systemischer Lupus erythematodes: Aktivität und Outcome

verfasst von: Prof. Dr. M. Aringer, J. S. Smolen

Erschienen in: Zeitschrift für Rheumatologie | Ausgabe 2/2006

Einloggen, um Zugang zu erhalten

Zusammenfassung

Der systemische Lupus erythematodes (SLE) mit seinem vielfältigen Spektrum an Organmanifestationen stellt den Rheumatologen klinisch wie wissenschaftlich vor besondere Herausforderungen. Validierte Scores für die Aktivität (BILAG, ECLAM, SIS, SLAM, SLEDAI), den verursachten Organschaden oder „damage“ (SLICC) und die Lebensqualität (MOS SF-36) sind seit Jahren erfolgreich im Einsatz. Neue Therapien müssen ihre Wirksamkeit aber in erster Linie anhand von Outcome-Parametern konkreter Organe unter Beweis stellen — und die sind häufig schlecht definiert. Für die proliferative Lupusnephritis gibt es seit Jahren adäquate Studien, die aber mit sehr harten Parametern (Nierenversagen, Tod) arbeiten und bis zum endgültigen Beweis zumindest 5 Jahre benötigen. Keiner der Surrogatmarker kann dabei als gesichert gelten. Daher erscheinen überschaubare Studien zur Erarbeitung erfolgversprechende Strategien und Langzeitstudien zur endgültigen Sicherung derzeit als beste Lösung.
Literatur
1.
Zurück zum Zitat Albrecht J, Taylor L, Berlin JA et al. (2005) The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus. J Invest Dermatol 125:889–894CrossRefPubMedPubMedCentral Albrecht J, Taylor L, Berlin JA et al. (2005) The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus. J Invest Dermatol 125:889–894CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Allen E, Farewell VT, Isenberg DA, Gordon C (2005) A statistical analysis of the interrelationships between disease activity in different systems in systemic lupus erythematosus. Rheumatology (Oxford) Allen E, Farewell VT, Isenberg DA, Gordon C (2005) A statistical analysis of the interrelationships between disease activity in different systems in systemic lupus erythematosus. Rheumatology (Oxford)
3.
Zurück zum Zitat American College of Rheumatology (2004) The American College of Rheumatology response criteria for systemic lupus erythematosus clinical trials: measures of overall disease activity. Arthritis Rheum 50:3418–3426CrossRef American College of Rheumatology (2004) The American College of Rheumatology response criteria for systemic lupus erythematosus clinical trials: measures of overall disease activity. Arthritis Rheum 50:3418–3426CrossRef
4.
Zurück zum Zitat Aringer M, Smolen JS (2004) TNF and other proinflammatory cytokines in SLE: A rationale for therapeutic intervention. Lupus 13:344–347CrossRefPubMed Aringer M, Smolen JS (2004) TNF and other proinflammatory cytokines in SLE: A rationale for therapeutic intervention. Lupus 13:344–347CrossRefPubMed
5.
Zurück zum Zitat Aringer M, Smolen JS, Graninger WB (1998) Severe infections in plasmapheresis-treated systemic lupus erythematosus. Arthritis Rheum 41:414–420CrossRefPubMed Aringer M, Smolen JS, Graninger WB (1998) Severe infections in plasmapheresis-treated systemic lupus erythematosus. Arthritis Rheum 41:414–420CrossRefPubMed
6.
Zurück zum Zitat Aringer M, Graninger WB, Steiner G, Smolen JS (2004) Safety and efficacy of TNFα blockade in systemic lupus erythematosus — an open label study. Arthritis Rheum 50:3161–3169CrossRefPubMed Aringer M, Graninger WB, Steiner G, Smolen JS (2004) Safety and efficacy of TNFα blockade in systemic lupus erythematosus — an open label study. Arthritis Rheum 50:3161–3169CrossRefPubMed
7.
Zurück zum Zitat Balow JE, Austin HA III (2004) Maintenance therapy for lupus nephritis — something old, something new. N Engl J Med 350:1044–1046CrossRefPubMed Balow JE, Austin HA III (2004) Maintenance therapy for lupus nephritis — something old, something new. N Engl J Med 350:1044–1046CrossRefPubMed
8.
Zurück zum Zitat Bencivelli W, Vitali C, Isenberg DA et al. (1992) Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. III. Development of a computerised clinical chart and its application to the comparison of different indices of disease activity. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol 10:549–554PubMed Bencivelli W, Vitali C, Isenberg DA et al. (1992) Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. III. Development of a computerised clinical chart and its application to the comparison of different indices of disease activity. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol 10:549–554PubMed
9.
Zurück zum Zitat Bjornadal L, Yin L, Granath F et al. (2004) Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964–95. J Rheumatol 31:713–719PubMed Bjornadal L, Yin L, Granath F et al. (2004) Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964–95. J Rheumatol 31:713–719PubMed
10.
Zurück zum Zitat Bombardier C, Gladman DD, Urowitz MB et al. (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640CrossRefPubMed Bombardier C, Gladman DD, Urowitz MB et al. (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640CrossRefPubMed
11.
Zurück zum Zitat Boumpas DT, Balow JE (1998) Outcome criteria for lupus nephritis trials: a critical overview. Lupus 7:622–629CrossRefPubMed Boumpas DT, Balow JE (1998) Outcome criteria for lupus nephritis trials: a critical overview. Lupus 7:622–629CrossRefPubMed
12.
Zurück zum Zitat Buyon JP, Kalunian KC, Ramsey-Goldman R et al. (1999) Assessing disease activity in SLE patients during pregnancy. Lupus 8:677–684CrossRefPubMed Buyon JP, Kalunian KC, Ramsey-Goldman R et al. (1999) Assessing disease activity in SLE patients during pregnancy. Lupus 8:677–684CrossRefPubMed
13.
Zurück zum Zitat Cervera R, Khamashta MA, Font J et al. (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82:299–308 Cervera R, Khamashta MA, Font J et al. (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82:299–308
14.
Zurück zum Zitat Christopher-Stine L, Petri M, Astor BC, Fine D (2004) Urine protein-to-creatinine ratio is a reliable measure of proteinuria in lupus nephritis. J Rheumatol 31:1557–1559PubMed Christopher-Stine L, Petri M, Astor BC, Fine D (2004) Urine protein-to-creatinine ratio is a reliable measure of proteinuria in lupus nephritis. J Rheumatol 31:1557–1559PubMed
15.
Zurück zum Zitat Contreras G, Pardo V, Leclercq B et al. (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980CrossRefPubMed Contreras G, Pardo V, Leclercq B et al. (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980CrossRefPubMed
16.
Zurück zum Zitat Ginzler EM, Dooley MA, Aranow C et al. (2005) Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 353:2219–2228CrossRefPubMed Ginzler EM, Dooley MA, Aranow C et al. (2005) Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 353:2219–2228CrossRefPubMed
17.
Zurück zum Zitat Gladman D, Ginzler E, Goldsmith C et al. (1996 a) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–369CrossRefPubMed Gladman D, Ginzler E, Goldsmith C et al. (1996 a) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–369CrossRefPubMed
18.
Zurück zum Zitat Gladman DD, Urowitz MB, Ong A et al. (1996 b) A comparison of five health status instruments in patients with systemic lupus erythematosus (SLE). Lupus 5:190–195CrossRefPubMed Gladman DD, Urowitz MB, Ong A et al. (1996 b) A comparison of five health status instruments in patients with systemic lupus erythematosus (SLE). Lupus 5:190–195CrossRefPubMed
19.
Zurück zum Zitat Gladman DD, Goldsmith CH, Urowitz MB et al. (2000) The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index for systemic lupus erythematosus international comparison. J Rheumatol 27:373–376PubMed Gladman DD, Goldsmith CH, Urowitz MB et al. (2000) The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index for systemic lupus erythematosus international comparison. J Rheumatol 27:373–376PubMed
20.
Zurück zum Zitat Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed
21.
Zurück zum Zitat Gourley MF, Austin HA, Scott D et al. (1996) Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 125:549–557CrossRefPubMed Gourley MF, Austin HA, Scott D et al. (1996) Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 125:549–557CrossRefPubMed
22.
Zurück zum Zitat Hay EM, Bacon PA, Gordon C et al. (1993) The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 86:447–458PubMed Hay EM, Bacon PA, Gordon C et al. (1993) The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med 86:447–458PubMed
23.
Zurück zum Zitat Hebert LA, Dillon JJ, Middendorf DF et al. (1995) Relationship between appearance of urinary red blood cell/white blood cell casts and the onset of renal relapse in systemic lupus erythematosus. Am J Kidney Dis 26:432–438CrossRefPubMed Hebert LA, Dillon JJ, Middendorf DF et al. (1995) Relationship between appearance of urinary red blood cell/white blood cell casts and the onset of renal relapse in systemic lupus erythematosus. Am J Kidney Dis 26:432–438CrossRefPubMed
24.
Zurück zum Zitat Houssiau FA, Vasconcelos C, D’Cruz D et al. (2002) Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 46:2121–2131CrossRefPubMed Houssiau FA, Vasconcelos C, D’Cruz D et al. (2002) Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 46:2121–2131CrossRefPubMed
25.
Zurück zum Zitat Illei GG, Austin HA, Crane M et al. (2001) Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 135:248–257CrossRefPubMed Illei GG, Austin HA, Crane M et al. (2001) Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 135:248–257CrossRefPubMed
26.
Zurück zum Zitat Illei GG, Tackey E, Lapteva L, Lipsky PE (2004) Biomarkers in systemic lupus erythematosus: II. Markers of disease activity. Arthritis Rheum 50:2048–2065CrossRefPubMed Illei GG, Tackey E, Lapteva L, Lipsky PE (2004) Biomarkers in systemic lupus erythematosus: II. Markers of disease activity. Arthritis Rheum 50:2048–2065CrossRefPubMed
27.
Zurück zum Zitat Krupp LB, LaRocca NG, Muir J, Steinberg AD (1990) A study of fatigue in systemic lupus erythematosus. J Rheumatol 17:1450–1452PubMed Krupp LB, LaRocca NG, Muir J, Steinberg AD (1990) A study of fatigue in systemic lupus erythematosus. J Rheumatol 17:1450–1452PubMed
28.
Zurück zum Zitat Liang MH, Socher SA, Larson MG, Schur PH (1989) Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 32:1107–1118CrossRefPubMed Liang MH, Socher SA, Larson MG, Schur PH (1989) Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 32:1107–1118CrossRefPubMed
29.
Zurück zum Zitat Looney RJ, Anolik JH, Campbell D et al. (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50:2580–2589CrossRefPubMed Looney RJ, Anolik JH, Campbell D et al. (2004) B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50:2580–2589CrossRefPubMed
30.
Zurück zum Zitat Moroni G, Quaglini S, Maccario M et al. (1996) „Nephritic flares“ are predictors of bad long-term renal outcome in lupus nephritis. Kidney Int 50:2047–2053CrossRefPubMed Moroni G, Quaglini S, Maccario M et al. (1996) „Nephritic flares“ are predictors of bad long-term renal outcome in lupus nephritis. Kidney Int 50:2047–2053CrossRefPubMed
31.
Zurück zum Zitat Moss KE, Ioannou Y, Sultan SM et al. (2002) Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades. Ann Rheum Dis 61:409–413CrossRefPubMedPubMedCentral Moss KE, Ioannou Y, Sultan SM et al. (2002) Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades. Ann Rheum Dis 61:409–413CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Omdal R, Mellgren SI, Koldingsnes W et al. (2002) Fatigue in patients with systemic lupus erythematosus: lack of associations to serum cytokines, antiphospholipid antibodies, or other disease characteristics. J Rheumatol 29:482–486PubMed Omdal R, Mellgren SI, Koldingsnes W et al. (2002) Fatigue in patients with systemic lupus erythematosus: lack of associations to serum cytokines, antiphospholipid antibodies, or other disease characteristics. J Rheumatol 29:482–486PubMed
33.
Zurück zum Zitat Omdal R, Sjoholm H, Koldingsnes W et al. (2005) Fatigue in patients with lupus is not associated with disturbances in cerebral blood flow as detected by SPECT. J Neurol 252:78–83CrossRefPubMed Omdal R, Sjoholm H, Koldingsnes W et al. (2005) Fatigue in patients with lupus is not associated with disturbances in cerebral blood flow as detected by SPECT. J Neurol 252:78–83CrossRefPubMed
34.
Zurück zum Zitat Petri M, Buyon J, Kim M (1999) Classification and definition of major flares in SLE clinical trials. Lupus 8:685–691CrossRefPubMed Petri M, Buyon J, Kim M (1999) Classification and definition of major flares in SLE clinical trials. Lupus 8:685–691CrossRefPubMed
35.
Zurück zum Zitat Ruperto N, Ravelli A, Cuttica R et al. (2005) The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set. Arthritis Rheum 52:2854–2864CrossRefPubMed Ruperto N, Ravelli A, Cuttica R et al. (2005) The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set. Arthritis Rheum 52:2854–2864CrossRefPubMed
36.
Zurück zum Zitat Schett G, Rubin RL, Steiner G et al. (2000) The lupus erythematosus cell phenomenon: comparative analysis of antichromatin antibody specificity in lupus erythematosus cell-positive and -negative sera. Arthritis Rheum 43:420–428CrossRefPubMed Schett G, Rubin RL, Steiner G et al. (2000) The lupus erythematosus cell phenomenon: comparative analysis of antichromatin antibody specificity in lupus erythematosus cell-positive and -negative sera. Arthritis Rheum 43:420–428CrossRefPubMed
37.
Zurück zum Zitat Schett G, Smole J, Zimmermann C et al. (2002) The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity. Lupus 11:704–715CrossRefPubMed Schett G, Smole J, Zimmermann C et al. (2002) The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity. Lupus 11:704–715CrossRefPubMed
38.
Zurück zum Zitat Smolen JS (1987) Clinical and serologic features: Incidence and diagnostic approach. In: Smolen JS, Zielinski CC (eds) Systemic lupus erythematosus. Springer, Berlin Heidelberg New York Tokyo, pp 171–196 Smolen JS (1987) Clinical and serologic features: Incidence and diagnostic approach. In: Smolen JS, Zielinski CC (eds) Systemic lupus erythematosus. Springer, Berlin Heidelberg New York Tokyo, pp 171–196
39.
Zurück zum Zitat Steinberg AD, Steinberg SC (1991) Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 34:945–950CrossRefPubMed Steinberg AD, Steinberg SC (1991) Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 34:945–950CrossRefPubMed
40.
Zurück zum Zitat Strand V, Gladman D, Isenberg D et al. (1999) Outcome measures to be used in clinical trials in systemic lupus erythematosus. J Rheumatol 26:490–497PubMed Strand V, Gladman D, Isenberg D et al. (1999) Outcome measures to be used in clinical trials in systemic lupus erythematosus. J Rheumatol 26:490–497PubMed
41.
Zurück zum Zitat Strand V, Gladman D, Isenberg D et al. (2000) Endpoints: consensus recommendations from OMERACT IV. Outcome measures in rheumatology. Lupus 9:322–327CrossRefPubMed Strand V, Gladman D, Isenberg D et al. (2000) Endpoints: consensus recommendations from OMERACT IV. Outcome measures in rheumatology. Lupus 9:322–327CrossRefPubMed
42.
Zurück zum Zitat Studnicka-Benke A, Steiner G, Petera P, Smolen JS (1996) Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. Br J Rheumatol 35:1067–1074CrossRefPubMed Studnicka-Benke A, Steiner G, Petera P, Smolen JS (1996) Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. Br J Rheumatol 35:1067–1074CrossRefPubMed
43.
Zurück zum Zitat Stummvoll GH, Aringer M, Smolen JS et al. (2005) IgG immunoadsorption reduces systemic lupus erythematosus activity and proteinuria: a long term observational study. Ann Rheum Dis 64:1015–1021CrossRefPubMedPubMedCentral Stummvoll GH, Aringer M, Smolen JS et al. (2005) IgG immunoadsorption reduces systemic lupus erythematosus activity and proteinuria: a long term observational study. Ann Rheum Dis 64:1015–1021CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Trager J, Ward MM (2001) Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol 13:345–351CrossRefPubMed Trager J, Ward MM (2001) Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol 13:345–351CrossRefPubMed
45.
Zurück zum Zitat Vitali C, Bencivelli W, Isenberg DA et al. (1992) Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol 10:541–547PubMed Vitali C, Bencivelli W, Isenberg DA et al. (1992) Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol 10:541–547PubMed
46.
Zurück zum Zitat Wang B, Gladman DD, Urowitz MB (1998) Fatigue in lupus is not correlated with disease activity. J Rheumatol 25:892–895PubMed Wang B, Gladman DD, Urowitz MB (1998) Fatigue in lupus is not correlated with disease activity. J Rheumatol 25:892–895PubMed
47.
Zurück zum Zitat Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30:473–483CrossRefPubMed Ware JE Jr, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 30:473–483CrossRefPubMed
48.
Zurück zum Zitat Wollaston SJ, Farewell VT, Isenberg DA et al. (2004) Defining response in systemic lupus erythematosus: a study by the Systemic Lupus International Collaborating Clinics Group. J Rheumatol 31:2390–2394PubMed Wollaston SJ, Farewell VT, Isenberg DA et al. (2004) Defining response in systemic lupus erythematosus: a study by the Systemic Lupus International Collaborating Clinics Group. J Rheumatol 31:2390–2394PubMed
Metadaten
Titel
Systemischer Lupus erythematodes: Aktivität und Outcome
verfasst von
Prof. Dr. M. Aringer
J. S. Smolen
Publikationsdatum
01.03.2006
Verlag
Springer Berlin Heidelberg
Erschienen in
Zeitschrift für Rheumatologie / Ausgabe 2/2006
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI
https://doi.org/10.1007/s00393-006-0040-9

Weitere Artikel der Ausgabe 2/2006

Zeitschrift für Rheumatologie 2/2006 Zur Ausgabe

Wegbereiter in der Rheumatologie

Hans Tichy (1888–1970), der Unermüdliche

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.