Pediatric Drugs

, Volume 21, Issue 1, pp 33–39 | Cite as

Clinical Features and Treatment of Down Syndrome Arthropathy: Experience from Two US Tertiary Hospitals

  • Jordan T. JonesEmail author
  • Nasreen Talib
  • Daniel Lovell
  • Mara L. Becker
Short Communication



Arthropathy of Down syndrome (DA) is largely under-recognized, with an average 2-year delay in diagnosis. Most patients present with polyarthritis, and treatment has historically been challenging.


Our objective was to investigate the clinical features and treatment of DA in the largest cohort reported to date.


In a retrospective chart review at two tertiary care hospitals, International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes for Down syndrome (DS) and juvenile idiopathic arthritis (JIA), between 1 January 1995 and 31 December 2015, were identified and charts reviewed.


In total, 43 patients were identified, with an average (± standard deviation [SD]) follow-up period of 6 ± 4.4 years. The average age of symptom onset was 7.4 ± 3.9 years, with a mean delay of 19 ± 17 months from symptom onset to diagnosis. At diagnosis, 77% of patients had morning stiffness and 72% had abnormal laboratory values; there was an average of 15 ± 13 active joints (range 1–56). Treatment approaches varied, and there was a significant decrease in joints with active arthritis (p < 0.001), with 25% and 39% having at least one change in disease-modifying antirheumatic drug (DMARD) and biologic therapy, respectively. DMARD therapy was discontinued in 60% because of side effects, and 39% had inadequate response to first-line biologic therapy.


DA remains under-recognized, with delays in diagnosis and extensive musculoskeletal symptoms at presentation. While DA can improve with current therapy for JIA (corticosteroids, DMARDs, biologics), barriers include medication toxicity, intolerance, and ineffectiveness. Earlier diagnosis through improved screening and more targeted treatment may allow for earlier disease control and better outcomes.



The authors acknowledge Chelsey Smith of Children’s Mercy Kansas City for coordinator support, Leena Danawala of University of Missouri-Kansas City for help with data collection, and Judy Thomas of Cincinnati Children’s Medical Center for help obtaining medical records.

Compliance with Ethical Standards

Conflict of interest

Jordan T. Jones, Nasreen Talib, Daniel Lovell, and Mara L. Becker have no conflicts of interest that are directly relevant to the content of this article.


No sources of funding were used to conduct this study or prepare this manuscript.


  1. 1.
    de Graaf G, Buckley F, Skotko BG. Estimates of the live births, natural losses, and elective terminations with Down syndrome in the United States. Am J Med Genet Part A. 2015;167A(4):756–67.CrossRefGoogle Scholar
  2. 2.
    de Graaf G, Buckley F, Skotko BG. Estimation of the number of people with Down syndrome in the United States. Genet Med. 2017;19(4):439–47.CrossRefGoogle Scholar
  3. 3.
    Shin M, Siffel C, Correa A. Survival of children with mosaic Down syndrome. Am J Med Genet Part A. 2010;152A(3):800–1.CrossRefGoogle Scholar
  4. 4.
    Yancey CL, Zmijewski C, Athreya BH, Doughty RA. Arthropathy of Down’s syndrome. Arthritis Rheum. 1984;27(8):929–34.CrossRefGoogle Scholar
  5. 5.
    Juj H, Emery H. The arthropathy of Down syndrome: an underdiagnosed and under-recognized condition. J Pediatr. 2009;154(2):234–8.CrossRefGoogle Scholar
  6. 6.
    Olson JC, Bender JC, Levinson JE, Oestreich A, Lovell DJ. Arthropathy of Down syndrome. Pediatrics. 1990;86(6):931–6.Google Scholar
  7. 7.
    Krumrey-Langkammerer M, Haas J-P. Trisomy 21 and juvenile idiopathic arthritis: relevance of chromosomal aberrations for the diagnostic assessment of arthritis. Aktuelle Rheumatologie. 2016;41(5):390–5.CrossRefGoogle Scholar
  8. 8.
    Foley C, MacDermott E, Killeen O. Clinical and radiological features of down’s arthropathy. Pediatr Rheumatol. 2014;12(Suppl 1):P30.CrossRefGoogle Scholar
  9. 9.
    Peeters M, Poon A. Down syndrome and leukemia: unusual clinical aspects and unexpected methotrexate sensitivity. Eur J Pediatr. 1987;146(4):416–22.CrossRefGoogle Scholar
  10. 10.
    Petty RE, Laxer RM, Lindsley CB, Wedderburn L. Textbook of pediatric rheumatology. 7th ed. Philadelphia, PA: Saunders; 2016. p. 736.Google Scholar
  11. 11.
    Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2.Google Scholar
  12. 12.
    Brewer EJ Jr, Bass J, Baum J, Cassidy JT, Fink C, Jacobs J, et al. Current proposed revision of JRA Criteria. JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Section of the Arthritis Foundation. Arthritis Rheum. 1977;20(2 Suppl):195–9.Google Scholar
  13. 13.
    Cassidy JT, Levinson JE, Bass JC, Baum J, Brewer EJ Jr, Fink CW, et al. A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum. 1986;29(2):274–81.CrossRefGoogle Scholar
  14. 14.
    Ruperto N, Ravelli A, Murray KJ, Lovell DJ, Andersson-Gare B, Feldman BM, et al. Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis. Rheumatology. 2003;42(12):1452–9.CrossRefGoogle Scholar
  15. 15.
    Meiorin S, Pistorio A, Ravelli A, Iusan SM, Filocamo G, Trail L, et al. Validation of the Childhood Health Assessment Questionnaire in active juvenile systemic lupus erythematosus. Arthritis Rheum. 2008;59(8):1112–9.CrossRefGoogle Scholar
  16. 16.
    Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, Childhood Arthritis Rheumatology Research A, et al. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2011;63(7):929–36.Google Scholar
  17. 17.
    Malak R, Kotwicka M, Krawczyk-Wasielewska A, Mojs E, Samborski W. Motor skills, cognitive development and balance functions of children with Down syndrome. Ann Agric Environ Med AAEM. 2013;20(4):803–6.Google Scholar
  18. 18.
    Kim HI, Kim SW, Kim J, Jeon HR, Jung DW. Motor and cognitive developmental profiles in children with Down syndrome. Ann Rehabil Med. 2017;41(1):97–103.CrossRefGoogle Scholar
  19. 19.
    Padmakumar B, Evans Jones LG, Sills JA. Is arthritis more common in children with Down syndrome? Rheumatology. 2002;41(10):1191–3.CrossRefGoogle Scholar
  20. 20.
    Baum RA, Nash PL, Foster JE, Spader M, Ratliff-Schaub K, Coury DL. Primary care of children and adolescents with down syndrome: an update. Curr Probl Pediatr Adolesc Health Care. 2008;38(8):241–61.CrossRefGoogle Scholar
  21. 21.
    Bull MJ, Committee on G. Health supervision for children with Down syndrome. Pediatrics. 2011;128(2):393–406.CrossRefGoogle Scholar
  22. 22.
    Heiligenhaus A, Heinz C, Edelsten C, Kotaniemi K, Minden K. Review for disease of the year: epidemiology of juvenile idiopathic arthritis and its associated uveitis: the probable risk factors. Ocul Immunol Inflamm. 2013;21(3):180–91.CrossRefGoogle Scholar
  23. 23.
    Martin TM, Rosenbaum JT. An update on the genetics of HLA B27-associated acute anterior uveitis. Ocul Immunol Inflamm. 2011;19(2):108–14.CrossRefGoogle Scholar
  24. 24.
    Saurenmann RK, Levin AV, Feldman BM, Rose JB, Laxer RM, Schneider R, et al. Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study. Arthritis Rheum. 2007;56(2):647–57.CrossRefGoogle Scholar
  25. 25.
    Wallace CA, Giannini EH, Spalding SJ, Hashkes PJ, O’Neil KM, Zeft AS, et al. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis Rheum. 2012;64(6):2012–21.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Division of RheumatologyChildren’s Mercy Kansas CityKansas CityUSA
  2. 2.Division of General PediatricsChildren’s Mercy Kansas CityKansas CityUSA
  3. 3.Division of RheumatologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

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