Objective: Enthesitis-related arthritis is a subtype of juvenile idiopathic arthritis category, characterized by enthesitis, arthritis, and the risk of axial involvement. We aimed to summarize the demographics, clinical, and laboratory findings of enthesitis-related arthritis patients and to identify the distinguishing features of enthesitis-related arthritis patients with HLA B27 positive compared to the patients who were HLA B27 negative. Materials and Methods: This retrospective study included patients with Enthesitis-related arthritis who followed up between 2015 and 2018. Demographical, clinical, and laboratory data were retrospectively reviewed from the patient files and computerized medical charts. Results: A total of 72 patients diagnosed with enthesitis-related arthritis were included in the study. The male/female ratio was 2.1/1. Fifty-three (73%) of them presented with peripheral arthritis. The most commonly affected joint was knee (81.1%), followed by the ankle (43%), hips (32%), and wrist (5%). HLA B27 was positive in 36 (50%) patients. During followup, the number of patients who developed enthesitis-related arthritis -associated uveitis was 8 (11.1%). During follow-up, 56 patients with inflammatory back pain and/or sacroiliac tenderness underwent spinal MRI. Ten (17.8%) patients had only thoracal and/or lumbar involvement, 18 (32%) had only sacroiliitis, and 9 (16%) patients had both of them on spinal MRI. In comparison with HLA-B27-negative children, HLAB27- positive patients were more likely to have enthesitis (16 (44.4%) vs 8 (22.2%), p=0.046), MRI proven sacroiliitis (19 (52.7%) vs 8 (22.2%), p=0.031), MRI proven spinal involvement (13 (36.1%) vs 6 (16.6%), p=0.031), and uveitis (8 (100%) vs 0(0%), p=0.014). During follow up, 65/72 (90.2 %) of them needed disease-modifying antirheumatic drugs (DMARD), and 51/72 (70.8%) needed anti-tumor necrosis factor-α (TNF-α) therapy. Conclusion: We found that patients who were HLA-B27- positive had significantly more enthesitis, MRI-proven sacroiliitis, MRI-proven spinal involvement, and acute anterior uveitis, in comparison to patients who were HLA B27 negative. It is crucial to carefully assess those patients with concern for enthesitis-related arthritis to determine the expected prognosis and make therapeutic decisions appropriately.
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[1] Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet 2011; 377(9783): 2138-2149.
[2] Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004; 31(2): 390-392.
[3] Burgos-Vargas R. The juvenile-onset spondyloarthritides. Rheum Dis Clin North Am 2002; 28(3): 531-560, vi
[4] Weiss PF, Beukelman T, Schanberg LE, et al. Enthesitisrelated arthritis is associated with higher pain intensity and poorer health status in comparison with other categories of juvenile idiopathic arthritis: the Childhood Arthritis and Rheumatology Research Alliance Registry. J Rheumatol 2012; 39(12): 2341-2351.
[5] Poddubnyy D. Axial spondyloarthritis: is there a treatment of choice? Ther Adv Musculoskelet Dis 2013; 5(1): 45-54.
[6] Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Rheumatol 2019; 71(6): 846-863.
[7] Adrovic A, Barut K, Sahin S, et al. Juvenile Spondyloarthropathies. Curr Rheumatol Rep 2016; 18(8): 55.
[8] Weiss PF, Fuhlbrigge RC, von Scheven E, et al. Children with enthesitis-related arthritis could benefit from treatments targeted for adults with spondyloarthritis. Arthritis Care Res (Hoboken) 2020
[9] Srivastava R, Phatak S, Yadav A, et al. HLA B27 typing in 511 children with juvenile idiopathic arthritis from India. Rheumatol Int 2016; 36(10): 1407-1411.
[10] Nordal E, Zak M, Aalto K, et al. Ongoing disease activity and changing categories in a long-term nordic cohort study of juvenile idiopathic arthritis. Arthritis Rheum 2011; 63(9): 2809-2818.
[11] Gmuca S, Weiss PF. Evaluation and Treatment of Childhood Enthesitis-Related Arthritis. Curr Treatm Opt Rheumatol 2015; 1(4): 350-364.
[12] Minden K, Niewerth M, Listing J, et al. Long-term outcome in patients with juvenile idiopathic arthritis. Arthritis Rheum 2002; 46(9): 2392-2401.
[13] Gmuca S, Xiao R, Brandon TG, et al. Multicenter inception cohort of enthesitis-related arthritis: variation in disease characteristics and treatment approaches. Arthritis Res Ther 2017; 19(1): 84.
[14] Vendhan K, Sen D, Fisher C, et al. Inflammatory changes of the lumbar spine in children and adolescents with enthesitis-related arthritis: magnetic resonance imaging findings. Arthritis Care Res (Hoboken) 2014; 66(1): 40-46.
[15] Kurugoglu S, Kanberoglu K, Kanberoglu A, et al. MRI appearances of inflammatory vertebral osteitis in early ankylosing spondylitis. Pediatr Radiol 2002; 32(3): 191-194.
[16] Weiss PF, Xiao R, Biko DM, et al. Assessment of Sacroiliitis at Diagnosis of Juvenile Spondyloarthritis by Radiography, Magnetic Resonance Imaging, and Clinical Examination. Arthritis Care Res (Hoboken) 2016; 68(2): 187-194.
[17] Kunjir V, Venugopalan A, Chopra A. 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 2010; 37(8): 1756-1762.
[18] Burgos-Vargas R, Pacheco-Tena C, Vazquez-Mellado J. A short-term follow-up of enthesitis and arthritis in the active phase of juvenile onset spondyloarthropathies. Clin Exp Rheumatol 2002; 20(5): 727-731.
[19] Berntson L, Damgard M, Andersson-Gare B, et al. HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis. J Rheumatol 2008; 35(10): 2055-2061.
[20] Chang JH, McCluskey PJ, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol 2005; 50(4): 364- 388.
[21] Haibel H, Brandt HC, Song IH, et al. No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis 2007; 66(3): 419-421.
[22] Katsicas MM, Russo R. Biologic agents in juvenile spondyloarthrop
[23] Henrickson M, Reiff A. Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. J Rheumatol 2004; 31(10): 2055-2061.
[24] Sulpice M, Deslandre CJ, Quartier P. Efficacy and safety of TNFalpha antagonist therapy in patients with juvenile spondyloarthropathies. Joint Bone Spine 2009; 76(1): 24- 27.
[25] Horneff G, Burgos-Vargas R, Constantin T, et al. 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 2014; 73(6): 1114-1122.
[26] Burgos-Vargas R, Tse SM, Horneff G, et al. A Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis-Related Arthritis. Arthritis Care Res (Hoboken) 2015; 67(11): 1503- 1512.