Vol 7, No 4 (2021)
Review paper
Published online: 2022-03-29
Systemic juvenile idiopathic arthritis — current diagnostic and therapeutic management
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DOI: 10.5603/FR.2021.0019
Rheumatol. Forum 2021;7(4):145-154.
Abstract
Juvenile idiopathic arthritis (JIA) is a heterogeneous group of arthritis that has seven subtypes under the currently applicable ILAR classification. It is the most common arthropathy diagnosed in children, a chronic disease affecting children and adolescents. The systemic form of juvenile idiopathic arthritis (SJIA) is the most frequent subtype of the disease with a different aetiopathogenesis, broad clinical picture, various courses, burdened with numerous complications and requiring a therapeutic approach that is different than in other subtypes of JIA. In the case of SJIA, it is essential to establish the
correct diagnosis as soon as possible and to initiate effective treatment and, if there is no effect after standard steroid therapy, use targeted anti-cytokine therapy. This review discusses current data on the aetiopathogenesis of the disease, clinical presentation and principles of diagnostic and therapeutic management.
Keywords: juvenile idiopathic arthritispathogenesiscytokinestreatment
References
- Nigrovic PA, Colbert RA, Holers VM, et al. Biological classification of childhood arthritis: roadmap to a molecular nomenclature. Nat Rev Rheumatol. 2021; 17(5): 257–269.
- Bruck N, Schnabel A, Hedrich CM. Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches. Clin Immunol. 2015; 159(1): 72–83.
- Pardeo M, Bracaglia C, De Benedetti F. Systemic juvenile idiopathic arthritis: New insights into pathogenesis and cytokine directed therapies. Best Pract Res Clin Rheumatol. 2017; 31(4): 505–516.
- Ombrello MJ, Arthur VL, Remmers EF, et al. British Society of Pediatric and Adolescent Rheumatology (BSPAR) Study Group, Inception Cohort of Newly Diagnosed Patients with Juvenile Idiopathic Arthritis (ICON-JIA) Study Group, Childhood Arthritis Prospective Study (CAPS) Group, Randomized Placebo Phase Study of Rilonacept in sJIA (RAPPORT) Investigators, Sparks-Childhood Arthritis Response to Medication Study (CHARMS) Group, Biologically Based Outcome Predictors in JIA (BBOP) Group. Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications. Ann Rheum Dis. 2017; 76(5): 906–913.
- van Loosdregt J, van Wijk F, Prakken B, et al. Update on research and clinical translation on specific clinical areas from biology to bedside: Unpacking the mysteries of juvenile idiopathic arthritis pathogenesis. Best Pract Res Clin Rheumatol. 2017; 31(4): 460–475.
- Bruck N, Schnabel A, Hedrich CM. Current understanding of the pathophysiology of systemic juvenile idiopathic arthritis (sJIA) and target-directed therapeutic approaches. Clin Immunol. 2015; 159(1): 72–83.
- Toplak N, Blazina Š, Avčin T. The role of IL-1 inhibition in systemic juvenile idiopathic arthritis: current status and future perspectives. Drug Des Devel Ther. 2018; 12: 1633–1643.
- Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014; 6(10): a016295.
- Vilaiyuk S, Lerkvaleekul B, Soponkanaporn S, et al. Correlations between serum interleukin 6, serum soluble interleukin 6 receptor, and disease activity in systemic juvenile idiopathic arthritis patients treated with or without tocilizumab. Cent Eur J Immunol. 2019; 44(2): 150–158.
- Ruperto N, Martini A. Current and future perspectives in the management of juvenile idiopathic arthritis. Lancet Child Adolesc Health. 2018; 2(5): 360–370.
- Thierry S, Fautrel B, Lemelle I, et al. Prevalence and incidence of juvenile idiopathic arthritis: a systematic review. Joint Bone Spine. 2014; 81(2): 112–117.
- Żuber Z, Kania U, Król-Zdechlikiewicz A, et al. Analysis of Clinical Symptoms and Laboratory Profiles in Children with Juvenile Idiopathic Arthritis in Malopolska Region (Poland) in the Years 2007-2010. Open Access Macedonian Journal of Medical Sciences. 2014; 2(1): 56–61.
- Martini A, Ravelli A, Avcin T, et al. Pediatric Rheumatology International Trials Organization (PRINTO). Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2019; 46(2): 190–197.
- Colafrancesco S, Manara M, Bortoluzzi A, et al. AOSD Consensus Group, AOSD Consensus Group. Management of adult-onset Still's disease with interleukin-1 inhibitors: evidence- and consensus-based statements by a panel of Italian experts. Arthritis Res Ther. 2019; 21(1): 275.
- Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004; 31(2): 390–392.
- Lee JJY, Schneider R. Systemic Juvenile Idiopathic Arthritis. Pediatr Clin North Am. 2018; 65(4): 691–709.
- Martini A, Ravelli A, Avcin T, et al. Pediatric Rheumatology International Trials Organization (PRINTO). Toward New Classification Criteria for Juvenile Idiopathic Arthritis: First Steps, Pediatric Rheumatology International Trials Organization International Consensus. J Rheumatol. 2019; 46(2): 190–197.
- Vignes S, Wechsler B, Yamaguchi M, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol. 1992; 19(3): 424–430.
- Fautrel B, Zing E, Golmard JL, et al. Proposal for a new set of classification criteria for adult-onset still disease. Medicine (Baltimore). 2002; 81(3): 194–200.
- Kumar S. Systemic Juvenile Idiopathic Arthritis: Diagnosis and Management. Indian J Pediatr. 2016; 83(4): 322–327.
- Smolewska E, Opoka-Winiarska V, Żuber Z. Młodzieńcze idiopatyczne zapalenie stawów. In: Smolewska E. ed. Reumatologia wieku rozwojowego. Kompendium. PZWL, Warszawa 2019: 127–138.
- Russo RAG, Katsicas MM. Patients with very early-onset systemic juvenile idiopathic arthritis exhibit more inflammatory features and a worse outcome. J Rheumatol. 2013; 40(3): 329–334.
- Shimizu M, Nakagishi Y, Yachie A. Distinct subsets of patients with systemic juvenile idiopathic arthritis based on their cytokine profiles. Cytokine. 2013; 61(2): 345–348.
- Woerner A, von Scheven-Gête A, Cimaz R, et al. Complications of systemic juvenile idiopathic arthritis: risk factors and management recommendations. Expert Rev Clin Immunol. 2015; 11(5): 575–588.
- Shimizu M, Nakagishi Y, Inoue N, et al. Interleukin-18 for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Clin Immunol. 2015; 160(2): 277–281.
- Mizuta M, Shimizu M, Inoue N, et al. Clinical significance of serum CXCL9 levels as a biomarker for systemic juvenile idiopathic arthritis associated macrophage activation syndrome. Cytokine. 2019; 119: 182–187.
- Minoia F, Davì S, Horne A, et al. Pediatric Rheumatology International Trials Organization, Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology Collaborative Study Group, Histiocyte Society. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol. 2014; 66(11): 3160–3169.
- Arthritis Foundation. Systemic Juvenile Idiopathic Arthritis. Available from:. https://arthritis.org/diseases/systemic-juvenile-idiopathic-arthritis (February 2020).
- 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.
- Nigrovic PA. Review: is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis? Arthritis Rheumatol. 2014; 66(6): 1405–1413.
- Hinze CH, Holzinger D, Lainka E, et al. PRO-KIND SJIA project collaborators. Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany. Pediatr Rheumatol Online J. 2018; 16(1): 7.
- DeWitt E, Kimura Y, Beukelman T, et al. Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis. Arthritis Care & Research. 2012; 64(7): 1001–1010.
- Vastert SJ, de Jager W, Noordman BoJ, et al. Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study. Arthritis Rheumatol. 2014; 66(4): 1034–1043.
- Ringold S, Weiss PF, Beukelman T, et al. American Collge of Rheumatology, American College of Rheumatology. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Care Res (Hoboken). 2013; 65(10): 1551–1563.
- Żuber Z, Rutkowska-Sak L, Smolewska E, et al. Zalecenia postępowania diagnostycznego i terapeutycznego w młodzieńczym idiopatycznym zapaleniu stawów (MIZS) o początku uogólnionym. Stanowisko Zespołu Ekspertów przy Konsultancie Krajowym w dziedzinie reumatologii. Reumatologia. 2013; 51(5): 328–331.
- Saccomanno B, Tibaldi J, Minoia F, et al. Predictors of Effectiveness of Anakinra in Systemic Juvenile Idiopathic Arthritis. J Rheumatol. 2019; 46(4): 416–421.
- Arthur VL, Shuldiner E, Remmers EF, et al. INCHARGE Consortium. IL1RN Variation Influences Both Disease Susceptibility and Response to Recombinant Human Interleukin-1 Receptor Antagonist Therapy in Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2018; 70(8): 1319–1330.
- Ruperto N, Brunner HI, Quartier P, et al. Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG), Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG), PRINTO, PRCSG. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012; 367(25): 2396–2406.
- Maritsi DN, Vougiouka O, Eleftheriou D. Discontinuation of Canakinumab following Clinical Disease Remission Is Feasible in Patients with Systemic Juvenile Idiopathic Arthritis. J Rheumatol. 2020; 47(4): 634–635.
- Brunner HI, Quartier P, Alexeeva E, et al. Paediatric Rheumatology International Trials Organisation, the Pediatric Rheumatology Collaborative Study Group. Efficacy and Safety of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis With and Without Fever at Baseline: Results From an Open-Label, Active-Treatment Extension Study. Arthritis Rheumatol. 2020; 72(12): 2147–2158.
- Verweyen EL, Pickering A, Grom AA, et al. Distinct gene expression signatures characterize strong clinical responders vs non-responders to Canakinumab in children with sJIA. Arthritis Rheumatol. 2021; 73(7): 1334–1340.
- Hinze T, Kessel C, Hinze CH, et al. A dysregulated interleukin-18-interferon-γ-CXCL9 axis impacts treatment response to canakinumab in systemic juvenile idiopathic arthritis. Rheumatology (Oxford). 2021; 60(11): 5165–5174.
- De Benedetti F, Brunner HI, Ruperto N, et al. PRINTO, PRCSG. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012; 367(25): 2385–2395.
- Horneff G, Schulz AC, Klotsche J, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017; 19(1): 256.
- Bielak M, Husmann E, Weyandt N, et al. IL-6 blockade in systemic juvenile idiopathic arthritis - achievement of inactive disease and remission (data from the German AID-registry). Pediatr Rheumatol Online J. 2018; 16(1): 22.
- Erkens R, Esteban Y, Towe C, et al. Pathogenesis and Treatment of Refractory Disease Courses in Systemic Juvenile Idiopathic Arthritis: Refractory Arthritis, Recurrent Macrophage Activation Syndrome and Chronic Lung Disease. Rheum Dis Clin North Am. 2021; 47(4): 585–606.
- Ruperto N, Brunner HI, Zuber Z, et al. Pediatric Rheumatology International Trials Organization (PRINTO), Pediatric Rheumatology Collaborative Study Group (PRCSG). Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study. Pediatr Rheumatol Online J. 2017; 15(1): 86.
- Ruperto N, Lovell DJ, Quartier P, et al. Paediatric Rheumatology INternational Trials Organization, Pediatric Rheumatology Collaborative Study Group. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008; 372(9636): 383–391.
