Skip to main content
SpringerLink
Log in

Enthesitis-related arthritis

  • Review Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Juvenile idiopathic arthritis (JIA) is the most common chronic arthritis of childhood. Currently, it is characterized by seven categories. The enthesitis-related arthritis (ERA) category usually affects boys older than 6 years and presents with lower limb asymmetrical arthritis associated with enthesitis. Later, these children can develop inflammatory lumbosacral pain (IBP). These children are at risk of developing acute anterior uveitis. A recently devised disease activity index, Juvenile Spondyloarthropathy Disease Activity Index (JSpADA), has been validated in retrospective cohorts. The corner stone of treatment is NSAIDs, local corticosteroid injections, and exercise. Methotrexate and sulfasalazine can be used for peripheral arthritis while anti-tumor necrosis factor (TNF) agents are sometimes used to treat refractory enthesitis and sacroiliitis. Almost two third of patients with ERA have persistent disease and often have impairments in their quality of life. The presence of hip or ankle arthritis and a family history of spondyloarthropathy or polyarticular joint involvement at onset are associated with poorer prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Petty RE, Southwood TR, Manners P et al (2001) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision. Edmonton J Rheumatol 31:390–392

    Google Scholar 

  2. Rosenberg AM, Petty RE (1982) A syndrome of seronegative enthesopathy and arthropathy in children. Arthritis Rheum 125:1041–1047

    Article  Google Scholar 

  3. Oen K, Tucker L, Huber AM et al (2009) Predictors of early inactive disease in a juvenile idiopathic arthritis cohort: results of a Canadian multicenter, prospective inception cohort study. Arthritis Rheum 61:1077–1086

    Article  PubMed  Google Scholar 

  4. Kunjir V, Venuopalan A, Chopra A (2010) Disease using the ILAR classification criteria for JIA: a community-based profile of Indian patients with juvenile onset chronic inflammatory joint disease using the ILAR classification criteria for JIA: a community-based cohort study. J Rheumatol 37:1756–1762

    Article  PubMed  Google Scholar 

  5. Saurenmann RK, Rose JB, Tyrrell P et al (2007) Epidemiology of juvenile idiopathic arthritis in a multiethnic cohort: ethnicity as a risk factor. Arthritis Rheum 56:1974–1984

    Article  CAS  PubMed  Google Scholar 

  6. Hinks A, Martin P, Flynn E et al (2011) Subtype specific genetic associations for juvenile idiopathic arthritis: ERAP1 with the enthesitis related arthritis subtype and IL23R with juvenile psoriatic arthritis. Arthritis Res Ther 13(1):R12

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Saxena N, Misra R, Aggarwal A (2006) Is the enthesitis-related arthritis subtype of juvenile idiopathic arthritis a form of chronic reactive arthritis? Rheumatology 45:1129–1132

    Article  CAS  PubMed  Google Scholar 

  8. Ramanathan A, Srinivasulu H, Colbert RA (2013) Update on juvenile spondyloarthropathy. Rheum Dis Clin N Am 39:767–788

    Article  Google Scholar 

  9. Aggarwal A, Agarwal S, Misra R (2007) Chemokine and chemokine receptor analysis reveals elevated interferon-inducible protein-10 (IP)-10/CXCL10 levels and increased number of CCR5+ and CXCR3+ CD4 T cells in synovial fluid of patients with enthesitis-related arthritis (ERA). Clin Exp Immunol 148:515–519

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Saxena N, Aggarwal A, Misra R (2007) Elevated concentrations of monocyte derived cytokines in synovial fluid of children with enthesitis related arthritis and polyarticular types of juvenile idiopathic arthritis. J Rheumatol 32:1349–1353

    Google Scholar 

  11. Myles A, Aggarwal A (2011) Expression of Toll-like receptors 2 and 4 is increased in peripheral blood and synovial fluid monocytes of patients with enthesitis-related arthritis subtype of juvenile idiopathic arthritis. Rheumatology (Oxford) 50:481–488

    Article  CAS  Google Scholar 

  12. Zeng L, Lindstrom MJ, Smith JA (2011) Ankylosing spondylitis macrophage production of higher levels of interleukin-23 in response to lipopolysaccharide without induction of a significant unfolded protein response. Arthritis Rheum 63:3807–3817

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Mahendra A, Misra R, Aggarwal A (2009) Th1 and Th17 predominance in the enthesitis-related arthritis form of juvenile idiopathic arthritis. J Rheumatol 36:1730–1736

    Article  CAS  PubMed  Google Scholar 

  14. Chan AT, Kollnberger SD, Wedderburn LR et al (2005) Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheum 52:3586–3595

    Article  CAS  PubMed  Google Scholar 

  15. D’Agostino MA, Said-Nahal R, Hacquard-Bouder C et al (2003) Assessment of peripheral enthesitis in the spon-dylarthropathies by ultrasonography combined with power Doppler: a cross-sectional study. Arthritis Rheum 48:523–533

    Article  PubMed  Google Scholar 

  16. Weiss PF, Klink AJ, Behrens EM et al (2011) Enthesitis in an inception cohort of enthesitis-related arthritis. Arthritis Care Res 63:1307–1312

    Article  Google Scholar 

  17. Giannini EH, Ruperto N, Ravelli A et al (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40:1202–1209

    Article  CAS  PubMed  Google Scholar 

  18. Aquino MR, Tse SM, Gupta S et al (2015) Whole-body MRI of juvenile spondyloarthritis: protocols and pictorial review of characteristic patterns. Pediatr Radiol 45:754–762

    Article  PubMed  Google Scholar 

  19. Gensler LS, Ward MM, Reviella JD et al (2008) Clinical, radiographic and functional differences between juvenile-onset and adult-onset ankylosing spondylitis: results from the PSOAS cohort. Ann Rheum Dis 67:233–237

    Article  CAS  PubMed  Google Scholar 

  20. Stoll ML, Bhore R, Dempsey-Robertson M et al (2010) Spondyloarthritis in a pediatric population: risk factors for sacroiliitis. J Rheumatol 37:2402–2408

    Article  PubMed Central  PubMed  Google Scholar 

  21. Oen K, Duffy CM, Tse SM et al (2010) Early outcomes and improvement of patients with juvenile idiopathic arthritis enrolled in a Canadian multicenter inception cohort. Arthritis Care Res 62:527–536

    Article  Google Scholar 

  22. Pagnini I, Sevelli S, Matucci-Cerinic M et al (2010) Early predictors of juvenile sacroiliitis in enthesitis-related arthritis. J Rheumatol 37:2395–2401

    Article  PubMed  Google Scholar 

  23. Petty RE, Cassidy JT (2011) Enthesitis-related arthritis (juvenile ankylosing spondylitis). In: Cassidy JT (ed) Textbook of pediatric rheumatology, 6th edn. Saunders Elsevier Publishers, Philadelphia, pp 272–280

    Chapter  Google Scholar 

  24. Stoll ML, Patel AS, Punaro M et al (2012) MR enterography to evaluate sub-clinical intestinal inflammation in children with spondyloarthritis. Pediatr Rheumatol Online J 10:6

    Article  PubMed Central  PubMed  Google Scholar 

  25. Reimold AM, Chandran V (2014) Nonpharmacologic therapies in spondyloarthritis. Best Pract Res Clin Rheumatol 28:779–792

    Article  PubMed  Google Scholar 

  26. Ozgocmen S, Akgul O, Altay Z et al (2012) Expert opinion and key recommendations for the physical therapy and rehabilitation of patients with ankylosing spondylitis. Int J Rheum Dis 15:229–238

    Article  PubMed  Google Scholar 

  27. Haroon N, Kim T, Inman RD (2012) NSAIDs and radiographic progression in ankylosing spondylitis. Bagging big game with small arms? Ann Rheum Dis 71:1593–1595

    Article  PubMed  Google Scholar 

  28. Beukelman T, Patkar NM, Saag KG et al (2011) 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res 63:465–482

    Article  Google Scholar 

  29. Poddubnyy D (2013) Axial spondyloarthritis: is there a treatment of choice? Ther Adv Musculoskelet Disord 5:45–54

    Article  CAS  Google Scholar 

  30. Poddubnyy D, van der Heijde D (2012) Therapeutic controversies in spondyloarthritis: nonsteroidal anti-inflammatory drugs. Rheum Dis Clin N Am 38:601–611

    Article  Google Scholar 

  31. Marti P, Molinari L, Bolt IB et al (2008) Factors influencing the efficacy of intra-articular steroid injections in patients with juvenile idiopathic arthritis. Eur J Pediatr 167:425–430

    Article  PubMed  Google Scholar 

  32. Van Rossum MAJ, van Soesbergen RM, Boers M et al (2007) Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment. Ann Rheum Dis 66:1518–1524

    Article  PubMed Central  PubMed  Google Scholar 

  33. van Rossum MA, Fiselier TJ, Franssen MJ et al (1998) Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group. Arthritis Rheum 41:808–816

    Article  PubMed  Google Scholar 

  34. Tse SM, Burgos-Vargas R, Laxer RM (2005) Anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondylarthropathy. Arthritis Rheum 52:2103–2108

    Article  CAS  PubMed  Google Scholar 

  35. Otten MH, Prince FH, Twilt M et al (2011) Tumor necrosis factor-blocking agents for children with enthesitis-related arthritis—data from the Dutch arthritis and biological in children register, 1999–2010. J Rheumatol 38:2258–2263

    Article  CAS  PubMed  Google Scholar 

  36. Horneff G, Burgos-Vargas R, Constantin T et al (2014) Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study. Ann Rheum Dis 73:1114–1122

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Horneff G, Foeldvari I, Minden K et al (2015) Efficacy and safety of etanercept in enthesitis-related arthritis juvenile idiopathic arthritis: results from a phase 3 randomized double-blind study. Arthritis Rheumatol. doi:10.1002/art.39145

    PubMed  Google Scholar 

  38. Horneff G, Fitter S, Foeldvari I et al (2012) Double-blind, placebo-controlled randomized trial with adalimumab for treatment of juvenile onset ankylosing spondylitis (JoAS): significant short term improvement. Arthritis Res Ther 14:R230

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Haroon N, Inman RD, Learch TJ et al (2013) The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. Arthritis Rheum 65:2645–2654

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Wallace CA, Ruperto N, Giannini E et al (2004) Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheum 31:2290–2294

    PubMed  Google Scholar 

  41. Prince FHM, Twilt M, Simon SCM et al (2009) When and how to stop etanercept after successful treatment of patients with juvenile idiopathic arthritis. Ann Rheum Dis 68:1228–1229

    Article  CAS  PubMed  Google Scholar 

  42. Prince FHM, Twilt M, ten Cate R et al (2009) Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register. Ann Rheum Dis 68:635–641

    Article  CAS  PubMed  Google Scholar 

  43. Gerloni V, Pontikaki I, Gattinara M et al (2008) Focus on adverse events of tumour necrosis factor alpha blockade in juvenile idiopathic arthritis in an open monocentric long-term prospective study of 163 patients. Ann Rheum Dis 67:1145–1152

    Article  CAS  PubMed  Google Scholar 

  44. Weiss PF, Colbert RA, Xiao R et al (2014) Development and retrospective validation of the juvenile spondyloarthritis disease activity index. Arthritis Care Res 66:1775–1782

    Article  Google Scholar 

  45. Berntson L, Damgård M, Andersson-Gäre B et al (2008) HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis. J Rheumatol 35:2055–2061

    CAS  PubMed  Google Scholar 

  46. Colbert RA (2010) Classification of juvenile spondyloarthritis: enthesitis-related arthritis and beyond. Nat Rev Rheumatol 6:477–485

    Article  PubMed Central  PubMed  Google Scholar 

  47. Selvaag AM, Lien G, Sørskaar D et al (2005) Early disease course and predictors of disability in juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3 year prospective study. J Rheumatol 32:1122–1130

    PubMed  Google Scholar 

  48. Flatø B, Hoffmann-Vold AM, Reiff A et al (2006) Long-term outcome and prognostic factors in enthesitis-related arthritis: a case–control study. Arthritis Rheum 54:3573–3582

    Article  PubMed  Google Scholar 

Download references

Disclosures

None.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareily Road, Lucknow, Uttar Pradesh, 226014, India

    Amita Aggarwal & Durga Prasanna Misra

Authors
  1. Amita Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Durga Prasanna Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amita Aggarwal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aggarwal, A., Misra, D.P. Enthesitis-related arthritis. Clin Rheumatol 34, 1839–1846 (2015). https://doi.org/10.1007/s10067-015-3029-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-015-3029-4

Keywords

Search

Navigation