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Arthritis und Rheuma 2022; 42(03): 185-192
DOI: 10.1055/a-1825-7194
Kinderrheumatologie
Übersichtsartikel

Lyme-Arthritis

Von der Borrelien-Infektion zur postinfektiösen ArthritisLyme-arthritisFrom borrelia infection to postinfectious arthritis
Henner Morbach
1   Pädiatrische Rheumatologie und Osteologie, Kinderklinik und Poliklinik, Universitätsklinikum Würzburg
2   Pädiatrische Infektiologie und Immunologie, Kinderklinik und Poliklinik, Universitätsklinikum Würzburg
,
Annette Holl-Wieden
1   Pädiatrische Rheumatologie und Osteologie, Kinderklinik und Poliklinik, Universitätsklinikum Würzburg
,
Johannes Dirks
2   Pädiatrische Infektiologie und Immunologie, Kinderklinik und Poliklinik, Universitätsklinikum Würzburg
,
Johannes Forster
3   Institut für Hygiene und Mikrobiologie, Julius-Maximilians-Universität Würzburg
,
Johannes Liese
2   Pädiatrische Infektiologie und Immunologie, Kinderklinik und Poliklinik, Universitätsklinikum Würzburg
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ZUSAMMENFASSUNG

Die Lyme-Arthritis ist die häufigste Spätmanifestation einer Infektion durch Borrelia burgdorferi und manifestiert sich meist als mono- oder oligoartikuläre Arthritis. Serologisch ist sie durch positive IgG-Antikörper und in der Regel negative IgM-Antikörper gegen Borrelien gekennzeichnet. Das Ansprechen auf eine initiale antibiotische Therapie (Doxycyclin oder Amoxicillin) ist in der Regel gut mit Ansprechraten von 80–90 %. Bei etwa 10 % der Patienten entwickelt sich trotz erneuter antibiotischer Therapie eine persistierende Arthritis. Bei diesem postinfektiösen („Antibiotika-refraktären“) Verlauf stehen immunopathologische Mechanismen im Vordergrund. Eine Persistenz nicht lebender Borrelienbestandteile (Peptidoglykane) scheint hierbei die Entzündung zu unterhalten. Entzündungshemmende bzw. immunmodulatorische Therapien können den postinfektiösen Verlauf der Lyme-Arthritis verkürzen. Als weitere Therapieoption kann bei refraktären Verläufen eine arthroskopische Synovektomie erwogen werden.

ABSTRACT

Lyme-arthritis is a common late manifestation of Lyme borreliosis and usually manifests as mono- or oligorticular arthritis. The serological constellation is characterized by positive IgG antibodies against borrelia with absence of IgM antibodies. Response to antibiotic therapy (initially doxycycline or amoxicillin) is usually good, with response rates of 80–90 %. In 10 % of cases, persistent arthritis develops despite repeated antibiotic treatment. In this post-infectious (“antibiotic-refractory”) course, immunopathological mechanisms are in the foreground. A persistence of avital borrelial components (peptidoglycans) also seems to maintain the inflammation. Anti-inflammatory or immunomodulatory therapies can shorten the post-infectious course of Lyme-arthritis. Arthroscopic synovectomy can be considered as a further treatment option in refractory cases.

Schlüsselwörter

Borreliose - Lyme-Arthritis - Antibiotika-refraktäre Lyme-Arthritis

Keywords

Lyme borreliosis - Lyme arthritis - Antibiotic-refractory Lyme arthritis


Publication History

Article published online:
07 June 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Steere AC, Malawista SE, Snydman DR. et al Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum 1977; 20: 7-17
    CrossrefPubMedSearch in Google Scholar
  • 2 Burgdorfer W, Barbour AG, Hayes SF. et al Lyme disease-a tick-borne spirochetosis?. Science 1982; 216: 1317-1319
    CrossrefPubMedSearch in Google Scholar
  • 3 Steere AC, Grodzicki RL, Kornblatt AN. et al The spirochetal etiology of Lyme disease. N Engl J Med 1983; 308: 733-740
    CrossrefPubMedSearch in Google Scholar
  • 4 Steere AC, Green J, Schoen RT. et al Successful parenteral penicillin therapy of established Lyme arthritis. N Engl J Med 1985; 312: 869-874
    CrossrefPubMedSearch in Google Scholar
  • 5 Steere AC, Malawista SE, Newman JH. et al Antibiotic therapy in Lyme disease. Ann Intern Med 1980; 93: 1-8
    CrossrefPubMedSearch in Google Scholar
  • 6 Steere AC, Strle F, Wormser GP. et al Lyme borreliosis. Nat Rev Dis Primers 2016; 02: 16090
    CrossrefPubMedSearch in Google Scholar
  • 7 Branda JA, Steere AC. Laboratory Diagnosis of Lyme Borreliosis. Clin Microbiol Rev 2021: 34
    CrossrefPubMedSearch in Google Scholar
  • 8 Steere AC. Posttreatment Lyme disease syndromes: distinct pathogenesis caused by maladaptive host responses. J Clin Invest 2020; 130: 2148-2151
    CrossrefPubMedSearch in Google Scholar
  • 9 Huppertz HI, Bentas W, Haubitz I. et al Diagnosis of paediatric Lyme arthritis using a clinical score. Eur J Pediatr 1998; 157: 304-308
    CrossrefPubMedSearch in Google Scholar
  • 10 Deanehan JK, Nigrovic PA, Milewski MD. et al Synovial fluid findings in children with knee monoarthritis in lyme disease endemic areas. Pediatr Emerg Care 2014; 30: 16-19
    CrossrefPubMedSearch in Google Scholar
  • 11 Deanehan JK, Kimia AA, Tan Tanny SP. et al Distinguishing Lyme from septic knee monoarthritis in Lyme disease-endemic areas. Pediatrics 2013; 131: e695-e701
    CrossrefPubMedSearch in Google Scholar
  • 12 Szer IS, Taylor E, Steere AC. The long-term course of Lyme arthritis in children. N Engl J Med 1991; 325: 159-163
    CrossrefPubMedSearch in Google Scholar
  • 13 Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987; 107: 725-731
    CrossrefPubMedSearch in Google Scholar
  • 14 Lawson JP, Steere AC. Lyme arthritis: radiologic findings. Radiology 1985; 154: 37-43
    CrossrefPubMedSearch in Google Scholar
  • 15 Steere AC, Levin RE, Molloy PJ. et al Treatment of Lyme arthritis. Arthritis Rheum 1994; 37: 878-888
    CrossrefPubMedSearch in Google Scholar
  • 16 Dattwyler RJ, Halperin JJ, Volkman DJ. et al Treatment of late Lyme borreliosis--randomised comparison of ceftriaxone and penicillin. Lancet 1988; 01: 1191-1194
    CrossrefPubMedSearch in Google Scholar
  • 17 Lantos PM, Rumbaugh J, Bockenstedt LK. et al Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clin Infect Dis 2021; 72: e1-e48
    CrossrefPubMedSearch in Google Scholar
  • 18 Gaubitz M, Dressler F, Huppertz HI. et al [Diagnosis and treatment of Lyme arthritis. Recommendations of the Pharmacotherapy Commission of the Deutsche Gesellschaft fur Rheumatologie (German Society for Rheumatology)]. Z Rheumatol 2014; 73: 469-474
    CrossrefPubMedSearch in Google Scholar
  • 19 Brunner J, Christen H-J, Fingerle V. et al Borreliose. In: DGPI Handbuch – Infektionen bei Kindern und Jugendlichen. Stuttgart: Georg Thieme 2018
    PubMedSearch in Google Scholar
  • 20 Horton DB, Taxter AJ, Davidow AL. et al Pediatric Antibiotic-refractory Lyme Arthritis: A Multicenter Case-control Study. J Rheumatol 2019; 46: 943-951
    CrossrefPubMedSearch in Google Scholar
  • 21 Carlson D, Hernandez J, Bloom BJ. et al Lack of Borrelia burgdorferi DNA in synovial samples from patients with antibiotic treatment-resistant Lyme arthritis. Arthritis Rheum 1999; 42: 2705-2709 42:12 2705::AIDL42:DASHANR29 > 3.0.CO;2L42:DASHHL42:URLEND
    CrossrefPubMedSearch in Google Scholar
  • 22 Lochhead RB, Strle K, Arvikar SL. et al Lyme arthritis: linking infection, inflammation and autoimmunity. Nat Rev Rheumatol 2021; 17: 449-461
    CrossrefPubMedSearch in Google Scholar
  • 23 Lochhead RB, Arvikar SL, Aversa JM. et al Robust interferon signature and suppressed tissue repair gene expression in synovial tissue from patients with postinfectious, Borrelia burgdorferi-induced Lyme arthritis. Cell Microbiol 2019; 21: e12954
    CrossrefPubMedSearch in Google Scholar
  • 24 Bentas W, Karch H, Huppertz HI. Lyme arthritis in children and adolescents: outcome 12 months after initiation of antibiotic therapy. J Rheumatol 2000; 27: 2025-2030
    PubMedSearch in Google Scholar
  • 25 Glaude PD, Huber AM, Mailman T. et al Clinical characteristics, treatment and outcome of children with Lyme arthritis in Nova Scotia. Paediatr Child Health 2015; 20: 377-380
    CrossrefPubMedSearch in Google Scholar
  • 26 Grillon A, Scherlinger M, Boyer PH. et al Characteristics and clinical outcomes after treatment of a national cohort of PCR-positive Lyme arthritis. Semin Arthritis Rheum 2019; 48: 1105-1112
    CrossrefPubMedSearch in Google Scholar
  • 27 Rose CD, Fawcett PT, Eppes SC. et al Pediatric Lyme arthritis: clinical spectrum and outcome. J Pediatr Orthop 1994; 14: 238-241
    CrossrefPubMedSearch in Google Scholar
  • 28 Steere AC, Angelis SM. Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis. Arthritis Rheum 2006; 54: 3079-3086
    CrossrefPubMedSearch in Google Scholar
  • 29 Tory HO, Zurakowski D, Sundel RP. Outcomes of children treated for Lyme arthritis: results of a large pediatric cohort. J Rheumatol 2010; 37: 1049-1055
    CrossrefPubMedSearch in Google Scholar
  • 30 Badawi A, Arora P, Brenner D. Biologic Markers of Antibiotic-Refractory Lyme Arthritis in Human: A Systematic Review. Infect Dis Ther 2019; 08: 5-22
    CrossrefPubMedSearch in Google Scholar
  • 31 Lochhead RB, Ordonez D, Arvikar SL. et al Interferon-gamma production in Lyme arthritis synovial tissue promotes differentiation of fibroblast-like synoviocytes into immune effector cells. Cell Microbiol 2019; 21: e12992
    CrossrefPubMedSearch in Google Scholar
  • 32 Vudattu NK, Strle K, Steere AC. et al Dysregulation of CD4 + CD25(high) T cells in the synovial fluid of patients with antibiotic-refractory Lyme arthritis. Arthritis Rheum 2013; 65: 1643-1653
    CrossrefPubMedSearch in Google Scholar
  • 33 Strle K, Sulka KB, Pianta A. et al T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate With Borrelia burgdorferi Antibodies During Early Infection and With Autoantibodies Late in the Illness in Patients With Antibiotic-Refractory Lyme Arthritis. Clin Infect Dis 2017; 64: 930-938
    CrossrefPubMedSearch in Google Scholar
  • 34 Strle K, Jones KL, Drouin EE. et al Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease. Am J Pathol 2011; 178: 2726-2739
    CrossrefPubMedSearch in Google Scholar
  • 35 Bockenstedt LK, Gonzalez DG, Haberman AM. et al Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. J Clin Invest 2012; 122: 2652-2660
    CrossrefPubMedSearch in Google Scholar
  • 36 Jutras BL, Lochhead RB, Kloos ZA. et al Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proc Natl Acad Sci U S A 2019; 116: 13498-13507
    CrossrefPubMedSearch in Google Scholar
  • 37 DeHart TG, Kushelman MR, Hildreth SB. et al The unusual cell wall of the Lyme disease spirochaete Borrelia burgdorferi is shaped by a tick sugar. Nat Microbiol 2021; 06: 1583-1592
    CrossrefPubMedSearch in Google Scholar
  • 38 Strle K, Shin JJ, Glickstein LJ. et al Association of a Toll-like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic-refractory Lyme arthritis. Arthritis Rheum 2012; 64: 1497-1507
    CrossrefPubMedSearch in Google Scholar
  • 39 Steere AC, Klitz W, Drouin EE. et al Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide. J Exp Med 2006; 203: 961-971
    CrossrefPubMedSearch in Google Scholar
  • 40 Iliopoulou BP, Guerau-de-Arellano M, Huber BT. HLA-DR alleles determine responsiveness to Borrelia burgdorferi antigens in a mouse model of self-perpetuating arthritis. Arthritis Rheum 2009; 60: 3831-3840
    CrossrefPubMedSearch in Google Scholar
  • 41 Crowley JT, Drouin EE, Pianta A. et al A Highly Expressed Human Protein, Apolipoprotein B-100, Serves as an Autoantigen in a Subgroup of Patients With Lyme Disease. J Infect Dis 2015; 212: 1841-1850
    CrossrefPubMedSearch in Google Scholar
  • 42 Crowley JT, Strle K, Drouin EE. et al Matrix metalloproteinase-10 is a target of T and B cell responses that correlate with synovial pathology in patients with antibiotic-refractory Lyme arthritis. J Autoimmun 2016; 69: 24-37
    CrossrefPubMedSearch in Google Scholar
  • 43 Pianta A, Drouin EE, Crowley JT. et al Annexin A2 is a target of autoimmune T and B cell responses associated with synovial fibroblast proliferation in patients with antibiotic-refractory Lyme arthritis. Clin Immunol 2015; 160: 336-341
    CrossrefPubMedSearch in Google Scholar
  • 44 Steere AC, Gross D, Meyer AL. et al Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis. J Autoimmun 2001; 16: 263-268
    CrossrefPubMedSearch in Google Scholar
  • 45 Sulka KB, Strle K, Crowley JT. et al Correlation of Lyme Disease-Associated IgG4 Autoantibodies With Synovial Pathology in Antibiotic-Refractory Lyme Arthritis. Arthritis Rheumatol 2018; 70: 1835-1846
    CrossrefPubMedSearch in Google Scholar
  • 46 Kalish RA, Kaplan RF, Taylor E. et al Evaluation of study patients with Lyme disease, 10–20-year follow-up. J Infect Dis 2001; 183: 453-460
    CrossrefPubMedSearch in Google Scholar
  • 47 Schoen RT, Aversa JM, Rahn DW. et al Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy. Arthritis Rheum 1991; 34: 1056-1060
    CrossrefPubMedSearch in Google Scholar
  • 48 Horton DB, Taxter AJ, Davidow AL. et al Intraarticular Glucocorticoid Injection as Second-line Treatment for Lyme Arthritis in Children. J Rheumatol 2019; 46: 952-959
    CrossrefPubMedSearch in Google Scholar
  • 49 Nimmrich S, Becker I, Horneff G. Intraarticular corticosteroids in refractory childhood Lyme arthritis. Rheumatol Int 2014; 34: 987-994
    CrossrefPubMedSearch in Google Scholar