Langfristentwicklungen in der Kinder- und Jugendrheumatologie

Zusammenfassung

Im Gebiet der Kinderrheumatologie gab es in den letzten Jahrzehnten immense Fortschritte, die sowohl die Diagnostik, als auch die Therapie nachhaltig verbessert haben. Obwohl erst seit 2003 in Deutschland offiziell als Zusatzbezeichnung anerkannt, stehen heutzutage über 200 Kinder- und Jugendrheumatologen (d. h. 1,4 Kinderrheumatologen pro 100 000 Kinder) für die Erkennung und Behandlung von rheumatischen Erkrankungen bei Kindern und Jugendlichen bundesweit zur Verfügung. Neue Erkenntnisse in der Pathogenese rheumatischer Erkrankungen und die sich stetig weiterentwickelnde genetische Diagnostik haben das rheumatische Krankheitsspektrum und die Behandlungsmöglichkeiten dramatisch erweitert Internationale Forschungsnetzwerke und eine spezielle Gesetzgebung für die Entwicklung von pädiatrischen Medikamenten führten zur Zulassung von zahlreichen neuen Rheumamedikamenten, deren Sicherheit im klinischen Alltag seit der Jahrtausendwende systematisch in Deutschland untersucht wird. Maßnahmen zur Sicherung der Versorgungsqualität wurden implementiert, Standardinstrumente zur Bewertung der Krankheitsaktivität und Krankheitslast aus Patientensicht eingeführt sowie Initiativen zur Verbesserung der Versorgung Betroffener (z. B. die ProKind-Initiative) auf den Weg gebracht. Diese Veränderungen haben die Prognose und Lebensperspektive rheumakranker Kinder und Jugendlicher verbessert, wenngleich noch weiterer Optimierungsbedarf besteht.

Abstract

In the past 2 decades, there has been significant progress within the field of paediatric rheumatology. Paediatric rheumatology was introduced as a paediatric speciality in 2003. Today, more than 200 specialised consultants are practicing all over Germany (1.4 specialists/100.000 children). The rapid development in molecular medicine has led to a better understanding of the pathogenesis of rheumatic diseases, provided new diagnostic procedures and, eventually, new and more effective drugs. International research networks and a special legislation for the development of paediatric medication have led to the approval of many new drugs in paediatric rheumatology. Registers collect data on drug safety, disease activity and disease-associated damage. Evidence-based protocols developed by national and international boards of experts have helped to significantly improve outcomes and overall medical care for patients.

Schlüsselwörter

Kinderrheumatologie - Juvenile idiopathische Arthritis - Versorgungsstruktur - Biologika

Key words

juvenile idiopathic arthritis - biologics - medical care - paediatric rheumatology

Publication History

Article published online:
15 November 2021

• Literatur

• 1 Haas JP, Häfner R, Truckenbrodt H. Juvenile Idiopathische Arthritis. In: Manger B, Schulze-Koops, H., Hrsg. Checkliste: Rheumatologie. 4^th. Aufl. Stuttgart – New York: Georg Thieme Verlag; 2012: 377-400
• 2 Haas JP, Häfner R, Truckenbrodt H. Weitere rheumatische Erkankungen im Kindes- und Jugendalter. In: Manger B, Schulze-Koops, H., Hrsg. Checkliste: Rheumatologie. 4^th. Aufl. Stuttgart – New York: Georg Thieme Verlag; 2012: 401-431
• 3 Heiligenhaus A, Klotsche J, Niewerth M. et al. Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany. Arthritis Res Ther 2020; 22: 81
• 4 Petty RE, Southwood TR, Manners P. et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. The Journal of rheumatology 2004; 31: 390-392
• 5 Krumrey-Langkammerer M, Hafner R. Evaluation of the ILAR criteria for juvenile idiopathic arthritis. The Journal of rheumatology 2001; 28: 2544-2547
• 6 Bertilsson L, Andersson-Gare B, Fasth A. et al. Disease course, outcome, and predictors of outcome in a population-based juvenile chronic arthritis cohort followed for 17 years. The Journal of rheumatology 2013; 40: 715-724
• 7 Hugle B, Hinze C, Lainka E. et al. Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course. Pediatr Rheumatol Online J 2014; 12: 28
• 8 Dhaliwal KK, Lile NA, Tan CL et al.. Life-threatening complications of Henoch-Schonlein purpura: diffuse alveolar haemorrhage, venous thrombosis and bowel ischaemia. BMJ Case Rep. 2020 Sep 29 13(9).
• 9 Lim LSH, Pullenayegum E, Lim L. et al. From Childhood to Adulthood: The Trajectory of Damage in Patients With Juvenile-Onset Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken) 2017; 69: 1627-1635
• 10 Twilt M, Benseler SM. CNS vasculitis in children. Mult Scler Relat Disord 2013; 2: 162-171
• 11 Ozen S, Pistorio A, Iusan SM. et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Annals of the rheumatic diseases 2010; 69: 798-806
• 12 Ruperto N, Ozen S, Pistorio A. et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation. Annals of the rheumatic diseases 2010; 69: 790-797
• 13 Lainka E, Haas JP, Horneff G. et al. Systemic Juvenile Idiopathic Arthritis – New Aspects of Clinical Features, Diagnostic Tools and Treatment Strategies. Ann Paediatr Rheumatol. 2013
• 14 Weiss PF, Colbert RA. Juvenile Spondyloarthritis: A Distinct Form of Juvenile Arthritis. Pediatr Clin North Am 2018; 65: 675-690
• 15 Zisman D, Stoll ML, Butbul Aviel Y. et al. Juvenile Psoriatic Arthritis: A Report from the GRAPPA 2017 Annual Meeting. J Rheumatol Suppl 2018; 94: 11-16
• 16 Brunner HI, Ivaskova E, Haas JP. et al. Class I associations and frequencies of class II HLA-DRB alleles by RFLP analysis in children with rheumatoid-factor-negative juvenile chronic arthritis. Rheumatology international 1993; 13: 83-88
• 17 Hall PJ, Burman SJ, Barash J. et al. HLA and complement C4 antigens in polyarticular onset seronegative juvenile chronic arthritis: association of early onset with HLA-DRw8. The Journal of rheumatology 1989; 16: 55-59
• 18 Oen K, Malleson PN, Cabral DA. et al. Early predictors of longterm outcome in patients with juvenile rheumatoid arthritis: subset-specific correlations. The Journal of rheumatology 2003; 30: 585-593
• 19 Hameed K, Bowman S, Kondeatis E. et al. The association of HLA-DRB genes and the shared epitope with rheumatoid arthritis in Pakistan. Br J Rheumatol 1997; 36: 1184-1188
• 20 Haas JP, Andreas A, Rutkowski B. et al. A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis. Rheumatology international 1991; 11: 191-197
• 21 Haas JP, Kimura A, Truckenbrodt H. et al. Early-onset pauciarticular juvenile chronic arthritis is associated with a mutation in the Y-box of the HLA-DQA1 promoter. Tissue antigens 1995; 45: 317-321
• 22 Haas JP, Metzler M, Frank C. et al. HLA-DQA1 gene expression profiling in oligoarticular JIA. Autoimmunity 2009; 42: 389-391
• 23 Hinks A, Cobb J, Marion MC. et al. Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis. Nature genetics 2013; 45: 664-669
• 24 Han B, Diogo D, Eyre S. et al. Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity. Am J Hum Genet 2014; 94: 522-532
• 25 Hinks A, Marion MC, Cobb J. et al. Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis. Arthritis Rheumatol 2018; 70: 957-962
• 26 Lachmann HJ. Periodic fever syndromes. Best Pract Res Clin Rheumatol 2017; 31: 596-609
• 27 McGonagle D, Aziz A, Dickie LJ. et al. An integrated classification of pediatric inflammatory diseases, based on the concepts of autoinflammation and the immunological disease continuum. Pediatr Res 2009; 65: 38R-45R
• 28 Charras A, Hedrich CM. The role of epigenetics in paediatric rheumatic disease. Curr Opin Rheumatol 2019; 31: 450-463
• 29 Nagamine K, Peterson P, Scott HS. et al. Positional cloning of the APECED gene. Nat Genet 1997; 17: 393-398
• 30 Bennett CL, Christie J, Ramsdell F. et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001; 27: 20-21
• 31 Fisher GH, Rosenberg FJ, Straus SE. et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell 1995; 81: 935-946
• 32 Wu J, Wilson J, He J. et al. Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J Clin Invest 1996; 98: 1107-1113
• 33 Bolze A, Byun M, McDonald D. et al. Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet 2010; 87: 873-881
• 34 Wang J, Zheng L, Lobito A. et al. Inherited human Caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 1999; 98: 47-58
• 35 Chun HJ, Zheng L, Ahmad M. et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 2002; 419: 395-399
• 36 Deng Y, Tsao BP. Updates in Lupus Genetics. Curr Rheumatol Rep 2017; 19: 68
• 37 d'Angelo DM, Di Filippo P, Breda L. et al. Type I Interferonopathies in Children: An Overview. Front Pediatr 2021; 9: 631329
• 38 McDermott MF, Aksentijevich I. The autoinflammatory syndromes. Curr Opin Allergy Clin Immunol 2002; 2: 511-516
• 39 Brydges S, Kastner DL. The systemic autoinflammatory diseases: inborn errors of the innate immune system. Curr Top Microbiol Immunol 2006; 305: 127-160
• 40 Ozen S, Bakkaloglu A, Yilmaz E. et al. Mutations in the gene for familial Mediterranean fever: do they predispose to inflammation?. The Journal of rheumatology 2003; 30: 2014-2018
• 41 Yamasaki Y, Takei S, Imanaka H. et al. S100A12 and vascular endothelial growth factor can differentiate Blau syndrome and familial Mediterranean fever from systemic juvenile idiopathic arthritis. Clin Rheumatol 2019; 38: 835-840
• 42 Normand S, Massonnet B, Delwail A. et al. Specific increase in caspase-1 activity and secretion of IL-1 family cytokines: a putative link between mevalonate kinase deficiency and inflammation. Eur Cytokine Netw 2009; 20: 101-107
• 43 Rosen-Wolff A, Kreth HW, Hofmann S. et al. Periodic fever (TRAPS) caused by mutations in the TNFalpha receptor 1 (TNFRSF1A) gene of three German patients. Eur J Haematol 2001; 67: 105-109
• 44 Aksentijevich I, Masters SL, Ferguson PJ. et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med 2009; 360: 2426-2437
• 45 Mahler EA, Johannsen J, Tsiakas K. et al. Exome Sequencing in Children. Dtsch Arztebl Int 2019; 116: 197-204
• 46 Dueckers G, Guellac N, Arbogast M. et al. Evidence and consensus based GKJR guidelines for the treatment of juvenile idiopathic arthritis. Clin Immunol 2012; 142: 176-193
• 47 Truckenbrodt H, Hafner R. Methotrexate therapy in juvenile rheumatoid arthritis: a retrospective study. Arthritis and rheumatism 1986; 29: 801-807
• 48 Minden K, Horneff G, Niewerth M. et al. Time of Disease-Modifying Antirheumatic Drug Start in Juvenile Idiopathic Arthritis and the Likelihood of a Drug-Free Remission in Young Adulthood. Arthritis Care Res (Hoboken) 2019; 71: 471-481
• 49 Armaroli G, Klein A, Ganser G. et al. Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BiKeR registry. Arthritis Res Ther 2020; 22: 258
• 50 Klein A, Becker I, Minden K. et al. Biologic Therapies in Polyarticular Juvenile Idiopathic Arthritis. Comparison of Long-Term Safety Data from the German BIKER Registry. ACR Open Rheumatol 2020; 2: 37-47
• 51 Klotsche J, Klein A, Niewerth M. et al. Re-treatment with etanercept is as effective as the initial firstline treatment in patients with juvenile idiopathic arthritis. Arthritis Res Ther 2021; 23: 118
• 52 Huang B, Qiu T, Chen C. et al. Timing matters: real-world effectiveness of early combination of biologic and conventional synthetic disease-modifying antirheumatic drugs for treating newly diagnosed polyarticular course juvenile idiopathic arthritis. RMD open. 2020 Jan 6(1).
• 53 Wallace CA, Giannini EH, Spalding SJ. et al. Clinically inactive disease in a cohort of children with new-onset polyarticular juvenile idiopathic arthritis treated with early aggressive therapy: time to achievement, total duration, and predictors. The Journal of rheumatology 2014; 41: 1163-1170
• 54 Ravelli A, Consolaro A, Horneff G. et al. Treating juvenile idiopathic arthritis to target: recommendations of an international task force. Annals of the rheumatic diseases 2018; 77: 819-828
• 55 Oommen PT, Schütz K, Baltruschat K. et al. S2k-Leitlinie „Therapie der Juvenilen Idiopathischen Arthritis“. In: www.awmf.org/leitlinien/aktuelle-leitlinien.html AWMF; 2019
• 56 Angeles-Han ST, Ringold S, Beukelman T. et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Screening, Monitoring, and Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis. Arthritis Care Res (Hoboken) 2019; 71: 703-716
• 57 Kuemmerle-Deschner JB, Hansmann S, Wulffraat NM. et al. Recommendations for collaborative paediatric research including biobanking in Europe: a Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative. Annals of the rheumatic diseases 2018; 77: 319-327
• 58 Constantin T, Foeldvari I, Anton J. et al. Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative. Annals of the rheumatic diseases 2018; 77: 1107-1117
• 59 Groot N, de Graeff N, Avcin T. et al. European evidence-based recommendations for diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Annals of the rheumatic diseases 2017; 76: 1788-1796
• 60 Groot N, de Graeff N, Marks SD. et al. European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative. Annals of the rheumatic diseases 2017; 76: 1965-1973
• 61 Groot N, de Graeff N, Avcin T. et al. European evidence-based recommendations for diagnosis and treatment of paediatric antiphospholipid syndrome: the SHARE initiative. Annals of the rheumatic diseases 2017; 76: 1637-1641
• 62 de Graeff N, Groot N, Brogan P. et al. European consensus-based recommendations for the diagnosis and treatment of rare paediatric vasculitides – the SHARE initiative. Rheumatology 2019; 58: 656-671
• 63 de Graeff N, Groot N, Ozen S. et al. European consensus-based recommendations for the diagnosis and treatment of Kawasaki disease – the SHARE initiative. Rheumatology 2019; 58: 672-682
• 64 Ozen S, Marks SD, Brogan P. et al. European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis-the SHARE initiative. Rheumatology 2019; 58: 1607-1616
• 65 Hansmann S, Lainka E, Horneff G. et al. Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative. Pediatr Rheumatol Online J 2020; 18: 17
• 66 Thomschke S, Schulz M, Bätzing J. Epidemiologie der juvenilen idiopathischen Arthritis (JIA) in der ambulanten Versorgung – eine Analyse anhand bundesweiter vertragsärztlicher Abrechnungsdaten der Jahre 2009 bis 2015. In: Versorgungsatlasde. Berlin: Zentralinstitut für die kassenärztliche Versorgung in Deutschland (Zi); 2018: 1-16
• 67 Bundesamt S. Mikrozensus – Haushalte und Familien 2019 In 2019; 147
• 68 Minden K, Niewerth M, Klotsche J. et al. Versorgung von Kindern, Jugendlichen und jungen Erwachsenen mit juveniler idiopathischer Arthritis [Healthcare of Children, Adolescents and Young Adults with Juvenile Idiopathic Arthritis]. Akt Rheumatol 2018; 43: 375-382
• 69 Hospach A, Trauzeddel R, Windschall D. et al. Protokolle zur Klassifikation, Überwachung und Therapie in der Kinderrheumatologie (PRO-KIND): Enthesitis-assoziierte Arthritis. Arthritis & Rheuma 2018; 38: 132-140
• 70 Hinze CH, Holzinger D, Lainka E. et al. Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany. Pediatr Rheumatol Online J 2018; 16: 7
• 71 Hinze CH, Oommen PT, Dressler F. et al. Development of practice and consensus-based strategies including a treat-to-target approach for the management of moderate and severe juvenile dermatomyositis in Germany and Austria. Pediatr Rheumatol Online J 2018; 16: 40
• 72 Horneff G, Klein A, Ganser G. et al. Protocols on classification, monitoring and therapy in children's rheumatology (PRO-KIND): results of the working group Polyarticular juvenile idiopathic arthritis. Pediatr Rheumatol Online J 2017; 15: 78
• 73 Schwarz T, Oommen PT, Windschall D. et al. Protokolle zur Klassifikation, Überwachung und Therapie in der Kinderrheumatologie (PRO-KIND): Chronisch nicht-bakterielle Osteomyelitis (CNO). Arthritis & Rheuma 2018; 38: 282-288
• 74 Ringold S, Nigrovic PA, Feldman BM. et al. The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans: Toward Comparative Effectiveness in the Pediatric Rheumatic Diseases. Arthritis Rheumatol 2018; 70: 669-678