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Rheumatology and Therapy
Published in: Rheumatology and Therapy 2/2016

Open Access 01-12-2016 | Review

Juvenile Idiopathic Arthritis: Diagnosis and Treatment

Authors: Gabriella Giancane, Alessandro Consolaro, Stefano Lanni, Sergio Davì, Benedetta Schiappapietra, Angelo Ravelli

Published in: Rheumatology and Therapy | Issue 2/2016

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Abstract

Juvenile idiopathic arthritis is a broad term that describes a clinically heterogeneous group of arthritides of unknown cause, which begin before 16 years of age. This term encompasses several disease categories, each of which has distinct presentation, clinical manifestations, and, presumably, genetic background and etiopathogenesis. Although none of the available drugs has curative potential, prognosis has greatly improved as a result of substantial progresses in disease management. The most important new development has been the introduction of the biologic medications, which constitute a valuable treatment option for patients who are resistant to conventional antirheumatic agents. Further insights into the disease pathogenesis and treatment will be provided by the continuous advances in understanding of the mechanisms related to the immune response and inflammatory process, and by the development of new drugs that are capable of selectively inhibiting single molecules or pathways.
Literature
1.
2.
Petty RE, Cassidy JT. Textbook of pediatric rheumatology. Philadelphia: Saunders Elsevier; 2011.
3.
Szer I, Kimura Y, Malleson P, Southwood T. Arthritis in children and adolescents. Oxford: Oxford University Press; 2006.
4.
Fujikawa S, Okuni M. Clinical analysis of 570 cases with juvenile rheumatoid arthritis: results of a nationwide retrospective survey in Japan. Acta Paediatr Jpn. 1997;39:245–9.PubMedCrossRef
5.
Consolaro A, Ruperto N, Filocamo G, et al. Seeking insights into the EPidemiology, treatment and Outcome of Childhood Arthritis through a multinational collaborative effort: introduction of the EPOCA study. Pediatr Rheumatol Online J. 2012;10:39.PubMedPubMedCentralCrossRef
6.
Consolaro A, Ravelli A. Unraveling the phenotypic variability of juvenile idiopathic arthritis across races or geographic areas - key to understanding etiology and genetic factors? J Rheumatol. 2016;43:683–5.PubMedCrossRef
7.
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;31:390–2.PubMed
8.
Fink CW. Proposal for the development of classification criteria for idiopathic arthritides of childhood. J Rheumatol. 1995;22:1566–9.PubMed
9.
Petty RE, Southwood TR, Baum J, et al. Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol. 1998;25:1991–4.PubMed
10.
Ramsey SE, Bolaria RK, Cabral DA, Malleson PN, Petty RE. Comparison of criteria for the classification of childhood arthritis. J Rheumatol. 2000;27:1283–6.PubMed
11.
Foeldvari I, Bidde M. Validation of the proposed ILAR classification criteria for juvenile idiopathic arthritis. International League of Associations for Rheumatology. J Rheumatol. 2000;27:1069–72.PubMed
12.
Fantini F. Classification of chronic arthritides of childhood (juvenile idiopathic arthritis): criticisms and suggestions to improve the efficacy of the Santiago-Durban criteria. J Rheumatol. 2001;28:456–9.PubMed
13.
Krumrey-Langkammerer M, Häfner R. Evaluation of the ILAR criteria for juvenile idiopathic arthritis. J Rheumatol. 2001;28:2544–7.PubMed
14.
Berntson L, Fasth A, Andersson-Gäre B, et al. Construct validity of ILAR and EULAR criteria in juvenile idiopathic arthritis: a population based incidence study from the Nordic countries. International League of Associations for Rheumatology. European League Against Rheumatism. J Rheumatol. 2001;28:2737–43.PubMed
15.
Berntson L, Fasth A, Andersson-Gäre B, et al. The influence of heredity for psoriasis on the ILAR classification of juvenile idiopathic arthritis. J Rheumatol. 2002;29:2454–8.PubMed
16.
Burgos-Vargas R, Rudwaleit M, Sieper J. The place of juvenile onset spondyloarthropathies in the Durban 1997 ILAR classification criteria of juvenile idiopathic arthritis. International League of Associations for Rheumatology. J Rheumatol. 2002;29:869–74.PubMed
17.
Martini A. Are the number of joints involved or the presence of psoriasis still useful tools to identify homogeneous disease entities in juvenile idiopathic arthritis? J Rheumatol. 2003;30:1900–3.PubMed
18.
Ravelli A, Felici E, Magni-Manzoni S, et al. Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease. Arthritis Rheum. 2005;52:826–32.PubMedCrossRef
19.
Ravelli A, Varnier GC, Oliveira S, et al. Antinuclear antibody-positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis. Arthritis Rheum. 2011;63:267–75.PubMedCrossRef
20.
Martini A. It is time to rethink juvenile idiopathic arthritis classification and nomenclature. Ann Rheum Dis. 2012;71:1437–9.PubMedCrossRef
21.
22.
Ravelli A, Magni-Manzoni S, Pistorio A, et al. Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr. 2005;146:598–604.PubMedCrossRef
23.
Davì S, Minoia F, Pistorio A, et al. Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 2014;66:2871–80.PubMedCrossRef
24.
Davì S, Consolaro A, Guseinova D, et al. An international consensus survey of diagnostic criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis. J Rheumatol. 2011;38:764–8.PubMedCrossRef
25.
Minoia F, Davì S, Bovis F, et al. Development of new classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. Pediatr Rheumatol. 2014;12(Suppl 1). doi:10.​1002/​art.​39332.
26.
Ravelli A, Minoia F, Davì S, et al. 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Arthritis Rheumatol. 2016;68:566–76.PubMedCrossRef
27.
Ravelli A, Minoia F, Davì S, et al. 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Iniative. Ann Rheum Dis. 2016;75(3):481-9.PubMedCrossRef
28.
29.
Al-Matar MJ, Petty RE, Tucker LB, Malleson PN, Schroeder ML, Cabral DA. The early pattern of joint involvement predicts disease progression in children with oligoarticular (pauciarticular) juvenile rheumatoid arthritis. Arthritis Rheum. 2002;46:2708–15.PubMedCrossRef
30.
Felici E, Novarini C, Magni-Manzoni S, et al. Course of joint disease in patients with antinuclear antibody-positive juvenile idiopathic arthritis. J Rheumatol. 2005;32:1805–10.PubMed
31.
Tsitsami E, Bozzola E, Magni-Manzoni S, et al. Positive family history of psoriasis does not affect the clinical expression and course of juvenile idiopathic arthritis patients with oligoarthritis. Arthritis Rheum. 2003;49:488–93.PubMedCrossRef
32.
Ravelli A, Consolaro A, Schiappapietra B, Martini A. The conundrum of juvenile psoriatic arthritis. Clin Exp Rheumatol. 2015;33:S40–3.PubMed
33.
Ravelli A, Viola S, Ruperto N, Corsi B, Ballardini G, Martini A. Correlation between conventional disease activity measures in juvenile chronic arthritis. Ann Rheum Dis. 1997;56:197–200.PubMedPubMedCentralCrossRef
34.
Filocamo G, Davì S, Pistorio A, et al. Evaluation of 21-numbered circle and 10-centimeter horizontal line visual analog scales for physician and parent subjective ratings in juvenile idiopathic arthritis. J Rheumatol. 2010;37:1534–41.PubMedCrossRef
35.
Filocamo G, Consolaro A, Ferrari C, Ravelli A. Introducing new tools for assessment of parent- and child-reported outcomes in paediatric rheumatology practice: a work in progress. Clin Exp Rheumatol. 2013;31:964–8.PubMed
36.
Brunner HI, Ravelli A. Developing outcome measures for paediatric rheumatic diseases. Best Pract Res Clin Rheumatol. 2009;23:609–24.PubMedCrossRef
37.
Brunner HI, Giannini EH. Health-related quality of life in children with rheumatic diseases. Curr Opin Rheumatol. 2003;15:602–12.PubMedCrossRef
38.
Luca NJC, Feldman BM. Health outcomes of pediatric rheumatic diseases. Best Pract Res Clin Rheumatol. 2014;28:331–50.PubMedCrossRef
39.
Feldman BM, Grundland B, McCullough L, Wright V. Distinction of quality of life, health related quality of life, and health status in children referred for rheumatologic care. J Rheumatol. 2000;27:226–33.PubMed
40.
Pincus T, Yazici YSC. Quality control of a medical history: improving accuracy with patient participation, supported by a four-page version of the multidimensional health assessment questionnaire (MDHAQ). Rheum Dis Clin North Am. 2009;35:851–60.PubMedCrossRef
41.
42.
Consolaro A, Negro G, Chiara Gallo M, et al. Defining criteria for disease activity states in nonsystemic juvenile idiopathic arthritis based on a three-variable juvenile arthritis disease activity score. Arthritis Care Res (Hoboken). 2014;66:1703–9.PubMedCrossRef
43.
Ravelli A. The time has come to include assessment of radiographic progression in juvenile idiopathic arthritis clinical trials. J Rheumatol. 2008;35:553–7.PubMed
44.
Reed MH, Wilmot DM. The radiology of juvenile rheumatoid arthritis. A review of the English language literature. J Rheumatol Suppl. 1991;31:2–22.PubMed
45.
Van Rossum MA, Zwinderman AH, Boers M, et al. Radiologic features in juvenile idiopathic arthritis: a first step in the development of a standardized assessment method. Arthritis Rheum. 2003;48:507–15.PubMedCrossRef
46.
Magni-Manzoni S, Rossi F, Pistorio A, et al. Prognostic factors for radiographic progression, radiographic damage, and disability in juvenile idiopathic arthritis. Arthritis Rheum. 2003;48:3509–17.PubMedCrossRef
47.
Rossi F, Di Dia F, Galipò O, et al. Use of the sharp and larsen scoring methods in the assessment of radiographic progression in juvenile idiopathic arthritis. Arthritis Care Res. 2006;55:717–23.CrossRef
48.
Ravelli A, Ioseliani M, Norambuena X, et al. Adapted versions of the Sharp/van der Heijde score are reliable and valid for assessment of radiographic progression in juvenile idiopathic arthritis. Arthritis Rheum. 2007;56:3087–95.PubMedCrossRef
49.
Doria AS, de Castro CC, Kiss MHB, et al. Inter- and intrareader variability in the interpretation of two radiographic classification systems for juvenile rheumatoid arthritis. Pediatr Radiol. 2003;33:673–81.PubMedCrossRef
50.
Mason T, Reed AM, Nelson AM, Thomas KB. Radiographic progression in children with polyarticular juvenile rheumatoid arthritis: a pilot study. Ann Rheum Dis. 2005;64:491–3.PubMedPubMedCentralCrossRef
51.
Van Rossum MAJ, Boers M, Zwinderman AH, et al. Development of a standardized method of assessment of radiographs and radiographic change in juvenile idiopathic arthritis: introduction of the Dijkstra composite score. Arthritis Rheum. 2005;52:2865–72.PubMedCrossRef
52.
Cannizzaro E, Schroeder S, Müller LM, Kellenberger CJ, Saurenmann R. Temporomandibular joint involvement in children with juvenile idiopathic arthritis. J Rheumatol. 2011;38:510–5.PubMedCrossRef
53.
Pedersen TK, Kuseler A, Gelineck J, Herlin T. A prospective study of magnetic resonance and radiographic imaging in relation to symptoms and clinical findings of the temporomandibular joint in children with juvenile idiopathic arthritis. J Rheumatol. 2008;35:1668–75.PubMed
54.
Argyropoulou MI, Fanis SL, Xenakis T, Efremidis SC, Siamopoulou A. The role of MRI in the evaluation of hip joint disease in clinical subtypes of juvenile idiopathic arthritis. Br J Radiol. 2002;75:229–33.PubMedCrossRef
55.
Nistala K, Babar J, Johnson K, et al. Clinical assessment and core outcome variables are poor predictors of hip arthritis diagnosed by MRI in juvenile idiopathic arthritis. Rheumatology. 2007;46:699–702.PubMedCrossRef
56.
Malattia C, Damasio MB, Basso C, et al. Dynamic contrast-enhanced magnetic resonance imaging in the assessment of disease activity in patients with juvenile idiopathic arthritis. Rheumatology (Oxford). 2010;49:178–85.CrossRef
57.
58.
Müller L, Avenarius D, Damasio B, et al. The paediatric wrist revisited: redefining MR findings in healthy children. Ann Rheum Dis. 2011;70:605–10.PubMedCrossRef
59.
Walther M, Harms H, Krenn V, Radke S, Kirschner S, Gohlke F. Synovial tissue of the hip at power Doppler US: correlation between vascularity and power Doppler US signal. Radiology. 2002;225:225–31.PubMedCrossRef
60.
Albrecht K, Müller-Ladner U, Strunk J. Quantification of the synovial perfusion in rheumatoid arthritis using Doppler ultrasonography. Clin Exp Rheumatol. 2006;25:630–8.
61.
Brown AK, Quinn MA, Karim Z, et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. Arthritis Rheum. 2006;54:3761–73.PubMedCrossRef
62.
Spannow AH, Pfeiffer-Jensen M, Andersen NT, Herlin T, Stenbøg E. Ultrasonographic measurements of joint cartilage thickness in healthy children: age- and sex-related standard reference values. J Rheumatol. 2010;37:2595–601.PubMedCrossRef
63.
64.
Lanni S, Wood M, Ravelli A, et al. Towards a role of ultrasound in children with juvenile idiopathic arthritis. Rheumatology (Oxford). 2013;52:413–20.CrossRef
65.
Scott C, Meiorin S, Filocamo G, et al. A reappraisal of intra-articular corticosteroid therapy in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2010;28:774–81.PubMed
66.
Consolaro A, Varnier GC, Martini A, Ravelli A. Advances in biomarkers for paediatric rheumatic diseases. Nat Rev Rheumatol. 2014;11:1–11.CrossRef
67.
Hunter PJ, Nistala K, Jina N, et al. Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression. Arthritis Rheum. 2010;62:896–907.PubMedPubMedCentralCrossRef
68.
Gibson DS, Finnegan S, Jordan G, et al. Stratification and monitoring of juvenile idiopathic arthritis patients by synovial proteome analysis. J Proteom Res. 2009;8:5601–9.CrossRef
69.
Myles A, Aggarwal A. 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). 2011;50:481–8.CrossRef
70.
Viswanath V, Myles A, Dayal R, Aggarwal A. Levels of serum matrix metalloproteinase-3 correlate with disease activity in the enthesitis-related arthritis category of juvenile idiopathic arthritis. J Rheumatol. 2011;38:2482–7.PubMedCrossRef
71.
Aoki C, Inaba Y, Choe H, et al. Discrepancy between clinical and radiological responses to tocilizumab treatment in patients with systemic-onset juvenile idiopathic arthritis. J Rheumatol. 2014;41:1171–7.PubMedCrossRef
72.
Foell D, Roth J. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum. 2004;50:3762–71.PubMedCrossRef
73.
Holzinger D, Frosch M, Kastrup A, et al. The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis. Ann Rheum Dis. 2012;71:974–80.PubMedCrossRef
74.
De Jager W, Hoppenreijs EP, Wulffraat NM, Wedderburn LR, Kuis W, Prakken BJ. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann Rheum Dis. 2007;66:589–98.PubMedCrossRef
75.
Lotito APN, Campa A, Silva CAA, Kiss MHB, Mello SBV. Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis. J Rheumatol. 2007;34:823–30.PubMed
76.
Moncrieffe H, Ursu S, Holzinger D, et al. A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein. Rheumatology (Oxford). 2013;52:1467–76.CrossRef
77.
Foell D, Wulffraat N, Wedderburn LR, et al. Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA. 2010;303:1266–73.PubMedCrossRef
78.
Gerss J, Roth J, Holzinger D, et al. Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study. Ann Rheum Dis. 2012;71:1991–7.PubMedCrossRef
79.
Vastert S, Prakken B. Update on research and clinical translation on specific clinical areas: from bench to bedside: how insight in immune pathogenesis can lead to precision medicine of severe juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 2014;28:229–46.PubMedCrossRef
80.
Vastert SJ, de Jager W, Noordman BJ, 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 (Hoboken). 2014;66:1034–43.CrossRef
81.
Behrens EM, Beukelman T, Paessler M, Cron RQ. Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol. 2007;34:1133–8.PubMed
82.
Bleesing J, Prada A, Siegel DM, et al. The diagnostic significance of soluble CD163 and soluble interleukin-2 receptor alpha-chain in macrophage activation syndrome and untreated new-onset systemic juvenile idiopathic arthritis. Arthritis Rheum. 2007;56:965–71.PubMedCrossRef
83.
Reddy VV, Myles A, Cheekatla SS, Singh S, Aggarwal A. Soluble CD25 in serum: a potential marker for subclinical macrophage activation syndrome in patients with active systemic onset juvenile idiopathic arthritis. Int J Rheum Dis. 2014;17:261–7.PubMedCrossRef
84.
Gorelik M, Fall N, Altaye M, et al. Follistatin-like protein 1 and the ferritin/erythrocyte sedimentation rate ratio are potential biomarkers for dysregulated gene expression and macrophage activation syndrome in systemic juvenile idiopathic arthritis. J Rheumatol. 2013;40:1191–9.PubMedCrossRef
85.
Häfner R, Truckenbrodt H, Spamer M. Rehabilitation in children with juvenile chronic arthritis. Baillieres Clin Rheumatol. 1998;12:329–61.PubMedCrossRef
86.
Wallace CA. Current management of juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 2006;20:279–300.PubMedCrossRef
87.
Toledo MMM, Martini G, Gigante C, Da Dalt L, Tregnaghi A, Zulian F. Is there a role for arthroscopic synovectomy in oligoarticular juvenile idiopathic arthritis? J Rheumatol. 2006;33:1868–72.PubMed
88.
Beukelman T, Patkar NM, Saag KG, et al. 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 (Hoboken). 2011;63:465–82.PubMedPubMedCentralCrossRef
89.
Ruperto N, Nikishina I, Pachanov ED, et al. A randomized, double-blind clinical trial of two doses of meloxicam compared with naproxen in children with juvenile idiopathic arthritis: short- and long-term efficacy and safety results. Arthritis Rheum. 2005;52:563–72.PubMedCrossRef
90.
Reiff A, Lovell DJ, Van Adelsberg J, et al. Evaluation of the comparative efficacy and tolerability of rofecoxib and naproxen in children and adolescents with juvenile rheumatoid arthritis: a 12-week randomized controlled clinical trial with a 52-week open-label extension. J Rheumatol. 2006;33:985–95.PubMed
91.
92.
Lanni S, Bertamino M, Consolaro A, et al. Outcome and predicting factors of single and multiple intra-articular corticosteroid injections in children with juvenile idiopathic arthritis. Rheumatology. 2011;50:1627–34.PubMedCrossRef
93.
Papadopoulou C, Gonzalez MI, Nieto JC, et al. Delineating the role of multiple corticosteroid joint injections in the management of juvenile idiopathic arthritis in the biologic ERA. Arthritis Rheum. 2012;64:S503–S503.
94.
Neidel J, Boehnke M, Küster RM. The efficacy and safety of intraarticular corticosteroid therapy for coxitis in juvenile rheumatoid arthritis. Arthritis Rheum. 2002;46:1620–8.PubMedCrossRef
95.
Tynjälä P, Honkanen V, Lahdenne P. Intra-articular steroids in radiologically confirmed tarsal and hip synovitis in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2004;22:643–8.PubMed
96.
97.
Hashkes PJ, Laxer RM. Medical treatment of juvenile idiopathic arthritis. JAMA. 2005;294:1671–84.PubMedCrossRef
98.
Ravelli A, Martini A. Methotrexate in juvenile idiopathic arthritis: answers and questions. J Rheumatol. 2000;27:1830–3.PubMed
99.
Gutiérrez-Suárez R, Burgos-Vargas R. The use of methotrexate in children with rheumatic diseases. Clin Exp Rheumatol. 2010;28:S122–7.PubMed
100.
Giannini EH, Brewer EJ, Kuzmina N, et al. Methotrexate in resistant juvenile rheumatoid arthritis. Results of the USA-USSR double-blind, placebo-controlled trial. The Pediatric Rheumatology Collaborative Study Group and The Cooperative Children’s Study Group. N Engl J Med. 1992;326:1043–9.PubMedCrossRef
101.
Ruperto N, Murray KJ, Gerloni V, et al. A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate. Arthritis Rheum. 2004;50:2191–201.PubMedCrossRef
102.
Klein A, Kaul I, Foeldvari I, Ganser G, Urban A, Horneff G. Efficacy and safety of oral and parenteral methotrexate therapy in children with juvenile idiopathic arthritis: an observational study with patients from the German Methotrexate Registry. Arthritis Care Res (Hoboken). 2012;64:1349–56.PubMedCrossRef
103.
Tuková J, Chládek J, Němcová D, Chládková J, Doležalová P. Methotrexate bioavailability after oral and subcutaneous administration in children with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2009;27:1047–53.PubMed
104.
Alsufyani K, Ortiz-Alvarez O, Cabral DA, Tucker LB, Petty RE, Malleson PN. The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate. J Rheumatol. 2004;31:179–82.PubMed
105.
Ravelli A, Viola S, Ramenghi B, Beluffi G, Zonta LA, Martini A. Radiologic progression in patients with juvenile chronic arthritis treated with methotrexate. J Pediatr. 1998;133:262–5.PubMedCrossRef
106.
Harel L, Wagner-Weiner L, Poznanski AK, Spencer CH, Ekwo E, Magilavy DB. Effects of methotrexate on radiologic progression in juvenile rheumatoid arthritis. Arthritis Rheum. 1993;36:1370–4.PubMedCrossRef
107.
Ortiz-Alvarez O, Morishita K, Avery G, et al. Guidelines for blood test monitoring of methotrexate toxicity in juvenile idiopathic arthritis. J Rheumatol. 2004;31:2501–6.PubMed
108.
Ravelli A, Migliavacca D, Viola S, Ruperto N, Pistorio A, Martini A. Efficacy of folinic acid in reducing methotrexate toxicity in juvenile idiopathic arthritis. Clin Exp Rheumatol. 1999;17:625–7.PubMed
109.
Silverman E, Mouy R, Spiegel L, et al. Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med. 2005;352:1655–66.PubMedCrossRef
110.
Lovell DJ, Giannini EH, Reiff A, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med. 2000;342:763–9.PubMedCrossRef
111.
Quartier P, Taupin P, Bourdeaut F, et al. Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum. 2003;48:1093–101.PubMedCrossRef
112.
Giannini EH, Ilowite NT, Lovell DJ, et al. Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2794–804.PubMedCrossRef
113.
Horneff G, Schmeling H, Biedermann T, et al. The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis. 2004;63:1638–44.PubMedPubMedCentralCrossRef
114.
Prince FHM, Geerdink LM, Borsboom GJJM, et al. Major improvements in health-related quality of life during the use of etanercept in patients with previously refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2010;69:138–42.PubMedCrossRef
115.
Giannini EH, Ilowite NT, Lovell DJ, et al. Effects of long-term etanercept treatment on growth in children with selected categories of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:3259–64.PubMedCrossRef
116.
Billiau AD, Loop M, Le PQ, et al. Etanercept improves linear growth and bone mass acquisition in MTX-resistant polyarticular-course juvenile idiopathic arthritis. Rheumatology. 2010;49:1550–8.PubMedCrossRef
117.
Nielsen S, Ruperto N, Gerloni V, et al. Preliminary evidence that etanercept may reduce radiographic progression in juvenile idiopathic arthritis. Clin Exp Rheumatol. 2008;26:688–92.PubMed
118.
Otten MH, Prince FHM, Armbrust W, et al. Factors associated with treatment response to etanercept in juvenile idiopathic arthritis. JAMA. 2011;306:2340–7.PubMedCrossRef
119.
Solari N, Palmisani E, Consolaro A, et al. Factors associated with achievement of inactive disease in children with juvenile idiopathic arthritis treated with etanercept. J Rheumatol. 2013;40:192–200.PubMedCrossRef
120.
Ruperto N, Lovell DJ, Cuttica R, et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007;56:3096–106.PubMedCrossRef
121.
Lovell DJ, Ruperto N, Goodman S, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359:810–20.PubMedCrossRef
122.
Schmeling H, Minden K, Foeldvari I, Ganser G, Hospach T, Horneff G. Efficacy and safety of adalimumab as the first and second biologic agent in juvenile idiopathic arthritis: the German Biologics JIA Registry. Arthritis Rheumatol. 2014;66:2580–9.PubMedCrossRef
123.
Brunner H, Ruperto N, Tzaribachev N, et al. A148: a multi-center, double-blind, randomized-withdrawal trial of subcutaneous golimumab in pediatric patients with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy: week 48 results. Arthritis Rheumatol. 2014;66:S191–2.CrossRef
124.
Tynjala P, Vahasalo P, Tarkiainen M, et al. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis. 2011;70:1605–12.PubMedCrossRef
125.
Horneff G, De Bock F, Foeldvari I, et al. Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis. 2009;68:519–25.PubMedCrossRef
126.
Wallace CA, Giannini EH, Spalding SJ, et al. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis Rheum. 2012;64:2012–21.PubMedCrossRef
127.
Hugle B, Burgos-Vargas R, Inman RD, et al. Long-term outcome of anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondyloarthritis. Clin Exp Rheumatol. 2014;32:424–31.PubMed
128.
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;73:1114–22.PubMedCrossRef
129.
Kremer JM. Cytotoxic T-lymphocyte antigen 4-immunoglobulin in rheumatoid arthritis. Rheum Dis Clin North Am. 2004;30:381–91, viii.
130.
Ruperto N, Lovell DJ, Quartier P, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372:383–91.PubMedCrossRef
131.
Ruperto N, Lovell DJ, Quartier P, et al. Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:1792–802.PubMedCrossRef
132.
Ruperto N, Lovell DJ, Li T, et al. Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2010;62:1542–51.PubMedCrossRef
133.
Brunner HI, Ruperto N, Zuber Z, et al. Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial. Ann Rheum Dis. 2015;74:1110–7.PubMedCrossRef
134.
De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini A. Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest. 1994;93:2114–9.PubMedPubMedCentralCrossRef
135.
De Benedetti F, Martini A. Is systemic juvenile rheumatoid arthritis an interleukin 6 mediated disease? J Rheumatol. 1998;25:203–7.PubMed
136.
Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005;201:1479–86.PubMedPubMedCentralCrossRef
137.
Verbsky JW, White AJ. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol. 2004;31:2071–5.PubMed
138.
Ruperto N, Quartier P, Wulffraat N, et al. A phase II, multicenter, open-label study evaluating dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features. Arthritis Rheum. 2012;64:557–67.PubMedCrossRef
139.
Ruperto N, Brunner HI, Quartier P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2396–406.PubMedCrossRef
140.
Ilowite NT, Prather K, Lokhnygina Y, et al. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of rilonacept in the treatment of systemic juvenile idiopathic arthritis. Arthritis Rheumatol. 2014;66:2570–9.PubMedPubMedCentralCrossRef
141.
Nigrovic PA, Mannion M, Prince FHM, et al. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 2011;63:545–55.PubMedCrossRef
142.
Nigrovic PA. Review: is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis? Arthritis Rheumatol (Hoboken). 2014;66:1405–13.CrossRef
143.
Yokota S, Miyamae T, Imagawa T, et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2005;52:818–25.PubMedCrossRef
144.
Woo P, Wilkinson N, Prieur A-M, et al. Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged cli. Arthritis Res Ther. 2005;7:R1281–8.PubMedPubMedCentralCrossRef
145.
Yokota S, Imagawa T, Mori M, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008;371:998–1006.PubMedCrossRef
146.
De Benedetti F, Brunner HI, Ruperto N, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2385–95.PubMedCrossRef
147.
Alexeeva EI, Valieva SI, Bzarova TM, et al. Efficacy and safety of repeat courses of rituximab treatment in patients with severe refractory juvenile idiopathic arthritis. Clin Rheumatol. 2011;30:1163–72.PubMedCrossRef
148.
Southwood TR, Foster HE, Davidson JE, et al. Duration of etanercept treatment and reasons for discontinuation in a cohort of juvenile idiopathic arthritis patients. Rheumatology. 2011;50:189–95.PubMedCrossRef
149.
Horneff G, Foeldvari I, Minden K, Moebius D, Hospach T. Report on malignancies in the German juvenile idiopathic arthritis registry. Rheumatology. 2011;50:230–6.PubMedCrossRef
150.
Prince FHM, Twilt M, ten Cate R, et al. Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register. Ann Rheum Dis. 2009;68:635–41.PubMedCrossRef
151.
Dekker L, Armbrust W, Rademaker CM, Prakken B, Kuis W, Wulffraat NM. Safety of anti-TNFalpha therapy in children with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2004;22:252–8.PubMed
152.
Diak P, Siegel J, La Grenade L, Choi L, Lemery S, McMahon A. Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration. Arthritis Rheum. 2010;62:2517–24.PubMedCrossRef
153.
Lehman TJ. Should the Food and Drug Administration warning of malignancy in children receiving tumor necrosis factor alpha blockers change the way we treat children with juvenile idiopathic arthritis? Arthritis Rheum. 2010;62:2183–4.PubMedCrossRef
154.
Beukelman T, Haynes K, Curtis JR, et al. Rates of malignancy associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum. 2012;64:1263–71.PubMedPubMedCentralCrossRef
155.
Nordstrom BL, Mines D, Gu Y, Mercaldi C, Aquino P, Harrison MJ. Risk of malignancy in children with juvenile idiopathic arthritis not treated with biologic agents. Arthritis Care Res (Hoboken). 2012;64:1357–64.PubMedCrossRef
156.
Cron RQ, Beukelman T. Guilt by association—what is the true risk of malignancy in children treated with etanercept for JIA? Pediatr Rheumatol Online J. 2010;8:23.PubMedPubMedCentralCrossRef
157.
Ruperto N, Martini A. Juvenile idiopathic arthritis and malignancy. Rheumatology (Oxford). 2014;53(6):968–74.CrossRef
158.
Quartier P, Allantaz F, Cimaz R, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70:747–54.PubMedCrossRef
159.
Yokota S, Tanaka T, Kishimoto T. Efficacy, safety and tolerability of tocilizumab in patients with systemic juvenile idiopathic arthritis. Ther Adv Musculoskelet Dis. 2012;4:387–97.PubMedPubMedCentralCrossRef
160.
Imagawa T, Yokota S, Mori M, et al. Safety and efficacy of tocilizumab, an anti-IL-6-receptor monoclonal antibody, in patients with polyarticular-course juvenile idiopathic arthritis. Mod Rheumatol. 2012;22:109–15.PubMedCrossRef
Metadata
Title
Juvenile Idiopathic Arthritis: Diagnosis and Treatment
Authors
Gabriella Giancane
Alessandro Consolaro
Stefano Lanni
Sergio Davì
Benedetta Schiappapietra
Angelo Ravelli
Publication date
01-12-2016
Publisher
Springer Healthcare
Published in
Rheumatology and Therapy / Issue 2/2016
Print ISSN: 2198-6576
Electronic ISSN: 2198-6584
DOI
https://doi.org/10.1007/s40744-016-0040-4

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