Abstract
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of joints in childhood. Glucocorticoids are being used in JIA treatment effectively for decades. Although systemic glucocorticoid use decreased with the introduction of biologic drugs, intraarticular glucocorticoid injections (IAGI) with nonsteroidal anti-inflammatory drugs and non-biologic disease modifying anti-rheumatic drugs (DMARDs) still remain the primary treatment in JIA, especially in oligoarticular subcategory. Systemic glucocorticoids are used mainly for severe JIA-associated complications such as macrophage activation syndrome (MAS), myocarditis, pericarditis, pleuritis, peritonitis, and severe anemia; as bridging therapy while waiting for the full therapeutic effect of DMARDs; and in certain occasions for patients with severe refractory uveitis. Since glucocorticoid administration is associated with many adverse events, it is important to use glucocorticoids in an optimum way balancing the risks and benefits. The aim of this review is to summarize the current knowledge on glucocorticoid treatment in JIA. A comprehensive literature search was conducted utilizing the Cochrane Library and MEDLINE/PubMed databases. The main topics include mechanism of action, dose, duration, adverse events, vaccination during glucocorticoid treatment, the place of glucocorticoids in JIA treatment guidelines and consensus treatment plans, glucocorticoid use in JIA-associated uveitis, MAS, and IAGI. Data from the literature provide guidance on how to use glucocorticoids in JIA treatment especially for IAGI and systemic use in systemic JIA and MAS. However, there is lack of evidence and need for prospective randomized studies in most parts including the indications in different JIA subcategories, optimum dose/route of administration/duration of treatment, and tapering strategies.
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Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, He X, Maldonado-Cocco J, Orozco-Alcala J, Prieur AM, Suarez-Almazor ME, Woo P, International League of Associations for R (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton 2001. J Rheumatol 31:390–392
Blazina S, Markelj G, Avramovic MZ, Toplak N, Avcin T (2016) Management of juvenile idiopathic arthritis: a clinical guide. Paediatr Drugs 18:397–412. https://doi.org/10.1007/s40272-016-0186-0
Beukelman T, Ringold S, Davis TE, DeWitt EM, Pelajo CF, Weiss PF, Kimura Y, Investigators CR (2012) Disease-modifying antirheumatic drug use in the treatment of juvenile idiopathic arthritis: a cross-sectional analysis of the CARRA Registry. J Rheumatol 39:1867–1874. https://doi.org/10.3899/jrheum.120110
Stoll ML, Cron RQ (2014) Treatment of juvenile idiopathic arthritis: a revolution in care. Pediatr Rheumatol Online J 12:13. https://doi.org/10.1186/1546-0096-12-13
Beukelman T, Kimura Y, Ilowite NT, Mieszkalski K, Natter MD, Burrell G, Best B, Jones J, Schanberg LE, Investigators CR (2017) The new Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry: design, rationale, and characteristics of patients enrolled in the first 12 months. Pediatr Rheumatol Online J 15:30. https://doi.org/10.1186/s12969-017-0160-6
Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, Scuccimarri R, Berard R, Tse SM, Morishita K, Stringer E, Johnson N, Levy DM, Duffy KW, Cabral DA, Rosenberg AM, Larche M, Dancey P, Petty RE, Laxer RM, Silverman E, Miettunen P, Chetaille AL, Haddad E, Houghton K, Spiegel L, Turvey SE, Schmeling H, Lang B, Ellsworth J, Ramsey S, Bruns A, Campillo S, Benseler S, Chedeville G, Schneider R, Yeung R, Duffy CM, Re A-Oi (2015) The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis 74:1854–1860. https://doi.org/10.1136/annrheumdis-2014-205372
Klotsche J, Raab A, Niewerth M, Sengler C, Ganser G, Kallinich T, Niehues T, Hufnagel M, Thon A, Hospach T, Horneff G, Minden K (2016) Outcome and trends in treatment of systemic juvenile idiopathic arthritis in the German National Pediatric Rheumatologic Database, 2000–2013. Arthritis Rheumatol 68:3023–3034. https://doi.org/10.1002/art.39796
Guzman J, Kerr T, Ward LM, Ma J, Oen K, Rosenberg AM, Feldman BM, Boire G, Houghton K, Dancey P, Scuccimarri R, Bruns A, Huber AM, Watanabe Duffy K, Shiff NJ, Berard RA, Levy DM, Stringer E, Morishita K, Johnson N, Cabral DA, Larche M, Petty RE, Laxer RM, Silverman E, Miettunen P, Chetaille AL, Haddad E, Spiegel L, Turvey SE, Schmeling H, Lang B, Ellsworth J, Ramsey SE, Roth J, Campillo S, Benseler S, Chedeville G, Schneider R, Tse SML, Bolaria R, Gross K, Feldman D, Cameron B, Jurencak R, Dorval J, LeBlanc C, St Cyr C, Gibbon M, Yeung RSM, Duffy CM, Tucker LB (2017) Growth and weight gain in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort. Pediatr Rheumatol Online J 15:68. https://doi.org/10.1186/s12969-017-0196-7
Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD (2011) Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int 31:1409–1417. https://doi.org/10.1007/s00296-011-1999-3
Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, Brown JP, Cohen A, Kim H (2013) A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 9:30. https://doi.org/10.1186/1710-1492-9-30
Cruz-Topete D, Cidlowski JA (2015) One hormone, two actions: anti- and pro-inflammatory effects of glucocorticoids. Neuroimmunomodulation 22:20–32. https://doi.org/10.1159/000362724
Uhlenhaut NH, Barish GD, Yu RT, Downes M, Karunasiri M, Liddle C, Schwalie P, Hubner N, Evans RM (2013) Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes. Mol Cell 49:158–171. https://doi.org/10.1016/j.molcel.2012.10.013
Stahn C, Buttgereit F (2008) Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol 4:525–533. https://doi.org/10.1038/ncprheum0898
Ayroldi E, Cannarile L, Migliorati G, Nocentini G, Delfino DV, Riccardi C (2012) Mechanisms of the anti-inflammatory effects of glucocorticoids: genomic and nongenomic interference with MAPK signaling pathways. FASEB J 26:4805–4820. https://doi.org/10.1096/fj.12-216382
Buttgereit F, da Silva JA, Boers M, Burmester GR, Cutolo M, Jacobs J, Kirwan J, Kohler L, Van Riel P, Vischer T, Bijlsma JW (2002) Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 61:718–722
Heijstek MW, Ott de Bruin LM, Bijl M, Borrow R, van der Klis F, Kone-Paut I, Fasth A, Minden K, Ravelli A, Abinun M, Pileggi GS, Borte M, Wulffraat NM, Eular (2011) EULAR recommendations for vaccination in paediatric patients with rheumatic diseases. Ann Rheum Dis 70:1704–1712. https://doi.org/10.1136/ard.2011.150193
Schimmer BPPK (2001) Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Gilman AG (eds) Goodman and Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, Medical Pub. Division, New York, pp 1469–1679
Panoulas VF, Douglas KM, Stavropoulos-Kalinoglou A, Metsios GS, Nightingale P, Kita MD, Elisaf MS, Kitas GD (2008) Long-term exposure to medium-dose glucocorticoid therapy associates with hypertension in patients with rheumatoid arthritis. Rheumatology 47:72–75. https://doi.org/10.1093/rheumatology/kem311
Strehl C, Bijlsma JW, de Wit M, Boers M, Caeyers N, Cutolo M, Dasgupta B, Dixon WG, Geenen R, Huizinga TW, Kent A, de Thurah AL, Listing J, Mariette X, Ray DW, Scherer HU, Seror R, Spies CM, Tarp S, Wiek D, Winthrop KL, Buttgereit F (2016) Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis 75:952–957. https://doi.org/10.1136/annrheumdis-2015-208916
Malattia C, Martini A (2014) Glucocorticoids in juvenile idiopathic arthritis. Ann N Y Acad Sci 1318:65–70. https://doi.org/10.1111/nyas.12436
Schiappapietra B, Varnier G, Rosina S, Consolaro A, Martini A, Ravelli A (2015) Glucocorticoids in juvenile idiopathic arthritis. Neuroimmunomodulation 22:112–118. https://doi.org/10.1159/000362732
Morrow SA, Stoian CA, Dmitrovic J, Chan SC, Metz LM (2004) The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. Neurology 63:1079–1080
Ilowite NT, Sandborg CI, Feldman BM, Grom A, Schanberg LE, Giannini EH, Wallace CA, Schneider R, Kenney K, Gottlieb B, Hashkes PJ, Imundo L, Kimura Y, Lang B, Miller M, Milojevic D, O’Neil KM, Punaro M, Ruth N, Singer NG, Vehe RK, Verbsky J, Woodward A, Zemel L (2012) Algorithm development for corticosteroid management in systemic juvenile idiopathic arthritis trial using consensus methodology. Pediatr Rheumatol Online J 10:31. https://doi.org/10.1186/1546-0096-10-31
Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Martini A, Rabinovich CE, Ruperto N (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. https://doi.org/10.1002/acr.20460
Huppertz HI (2011) Recommendations for juvenile idiopathic arthritis by the American College of Rheumatology: comment on the article by Beukelman et al. Arthritis Care Res 63:1354–1355. https://doi.org/10.1002/acr.20521 author reply 1355–1356.
Ringold S, Weiss PF, Beukelman T, Dewitt EM, Ilowite NT, Kimura Y, Laxer RM, Lovell DJ, Nigrovic PA, Robinson AB, Vehe RK, American College of R (2013) 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 65:1551–1563. https://doi.org/10.1002/acr.22087
Cellucci T, Guzman J, Petty RE, Batthish M, Benseler SM, Ellsworth JE, Houghton KM, Le BC, Huber AM, Luca N, Schmeling H, Shiff NJ, Soon GS, Tse SM, Pediatric Committee of the Canadian Rheumatology A (2016) Management of juvenile idiopathic arthritis 2015: a position statement from the Pediatric Committee of the Canadian Rheumatology Association. J Rheumatol 43:1773–1776. https://doi.org/10.3899/jrheum.160074
DeWitt EM, Kimura Y, Beukelman T, Nigrovic PA, Onel K, Prahalad S, Schneider R, Stoll ML, Angeles-Han S, Milojevic D, Schikler KN, Vehe RK, Weiss JE, Weiss P, Ilowite NT, Wallace CA,, Research A (2012) Juvenile Idiopathic Arthritis Disease-specific Research Committee of Childhood Arthritis R. Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis. Arthritis Care Res 64:1001–1010. https://doi.org/10.1002/acr.21625
Kimura Y, DeWitt EM, Beukelman T, Stoll ML, Nigrovic PA, Onel K, Prahalad S, Angeles-Han S, Schneider R, Juvenile Idiopathic Arthritis Disease-Specific Research Committee of the Childhood A, Rheumatology Research A (2014) Adding canakinumab to the Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for systemic juvenile idiopathic arthritis: comment on the article by DeWitt et al. Arthritis Care Res 66:1430–1431. https://doi.org/10.1002/acr.22343
Ringold S, Weiss PF, Colbert RA, DeWitt EM, Lee T, Onel K, Prahalad S, Schneider R, Shenoi S, Vehe RK, Kimura Y, Juvenile Idiopathic Arthritis Research Committee of the Childhood A, Rheumatology Research A (2014) Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for new-onset polyarticular juvenile idiopathic arthritis. Arthritis Care Res 66:1063–1072. https://doi.org/10.1002/acr.22259
Kimura Y, Grevich S, Beukelman T, Morgan E, Nigrovic PA, Mieszkalski K, Graham TB, Ibarra M, Ilowite N, Klein-Gitelman M, Onel K, Prahalad S, Punaro M, Ringold S, Toib D, Van Mater H, Weiss JE, Weiss PF, Schanberg LE, Investigators CR (2017) Pilot study comparing the childhood arthritis & rheumatology research alliance (CARRA) systemic juvenile idiopathic arthritis consensus treatment plans. Pediatr Rheumatol Online J 15:23. https://doi.org/10.1186/s12969-017-0157-1
Nigrovic PA, Beukelman T, Tomlinson G, Feldman BM, Schanberg LE, Kimura Y, Childhood A, Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis Consensus Treatment Plan W (2018) Bayesian comparative effectiveness study of four consensus treatment plans for initial management of systemic juvenile idiopathic arthritis: FiRst-Line options for systemic juvenile idiopathic arthritis treatment (FROST). Clin Trials 15:268–277. https://doi.org/10.1177/1740774518761367
Dueckers G, Guellac N, Arbogast M, Dannecker G, Foeldvari I, Frosch M, Ganser G, Heiligenhaus A, Horneff G, Illhardt A, Kopp I, Krauspe R, Markus B, Michels H, Schneider M, Singendonk W, Sitter H, Spamer M, Wagner N, Niehues T (2012) Evidence and consensus based GKJR guidelines for the treatment of juvenile idiopathic arthritis. Clin Immunol 142:176–193. https://doi.org/10.1016/j.clim.2011.10.003
Hinze CH, Holzinger D, Lainka E, Haas JP, Speth F, Kallinich T, Rieber N, Hufnagel M, Jansson AF, Hedrich C, Winowski H, Berger T, Foeldvari I, Ganser G, Hospach A, Huppertz HI, Monkemoller K, Neudorf U, Weissbarth-Riedel E, Wittkowski H, Horneff G, Foell D, Collaborators P-KSp (2018) Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany. Pediatr Rheumatol Online J 16:7. https://doi.org/10.1186/s12969-018-0224-2
Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG (2017) Prevention and management of glucocorticoid-induced side effects: a comprehensive review: a review of glucocorticoid pharmacology and bone health. J Am Acad Dermatol 76:1–9. https://doi.org/10.1016/j.jaad.2016.01.062
Higgins GC (2018) Complications of treatments for pediatric rheumatic diseases. Pediatr Clin N Am 65:827–854. https://doi.org/10.1016/j.pcl.2018.04.008
Aljebab F, Choonara I, Conroy S (2017) Systematic review of the toxicity of long-course oral corticosteroids in children. PloS One 12:e0170259. https://doi.org/10.1371/journal.pone.0170259
Amann J, Wessels AM, Breitenfeldt F, Huscher D, Bijlsma JWJ, Jacobs JWG, Buttgereit F (2017) Quantifying cutaneous adverse effects of systemic glucocorticoids in patients with rheumatoid arthritis: a cross-sectional cohort study. Clin Exp Rheumatol 35:471–476
Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG (2017) Prevention and management of glucocorticoid-induced side effects: a comprehensive review: ocular, cardiovascular, muscular, and psychiatric side effects and issues unique to pediatric patients. J Am Acad Dermatol 76:201–207. https://doi.org/10.1016/j.jaad.2016.02.1241
McErlane F, Carrasco R, Kearsley-Fleet L, Baildam EM, Wedderburn LR, Foster HE, Ioannou Y, Chieng SEA, Davidson JE, Thomson W, Hyrich KL (2018) Growth patterns in early juvenile idiopathic arthritis: results from the Childhood Arthritis Prospective Study (CAPS). Semin Arthritis Rheum 48:53–60. https://doi.org/10.1016/j.semarthrit.2017.11.002
Frittoli RB, Longhi BS, Silva AM, Filho AAB, Monteiro M, Appenzeller S (2017) Effects of the use of growth hormone in children and adolescents with juvenile idiopathic arthritis: a systematic review. Rev Bras Reumatol Engl Ed 57:100–106. https://doi.org/10.1016/j.rbre.2016.07.009
Kim JY, Kim HS, Park SH (2015) Disease flare after 7 year-remission of systemic type juvenile idiopathic arthritis: is growth hormone therapy a culprit or innocent bystander? Int J Rheum Dis 18:377–378. https://doi.org/10.1111/1756-185X.12385
Simon D, Prieur AM, Quartier P, Charles Ruiz J, Czernichow P (2007) Early recombinant human growth hormone treatment in glucocorticoid-treated children with juvenile idiopathic arthritis: a 3-year randomized study. J Clin Endocrinol Metab 92:2567–2573. https://doi.org/10.1210/jc.2006-2877
Bozzola M, De Benedetti F, De Amici M, Jouret B, Travaglino P, Pagani S, Conte F, Tauber M (2003) Stimulating effect of growth hormone on cytokine release in children. Eur J Endocrinol 149:397–401
Ahmet A, Brienza V, Tran A, Lemieux J, Aglipay M, Barrowman N, Duffy C, Roth J, Jurencak R (2017) Frequency and duration of adrenal suppression following glucocorticoid therapy in children with rheumatic diseases. Arthritis Care Res (Hoboken) 69:1224–1230. https://doi.org/10.1002/acr.23123
Rao RT, Scherholz ML, Androulakis IP (2018) Modeling the influence of chronopharmacological administration of synthetic glucocorticoids on the hypothalamic-pituitary-adrenal axis. Chronobiol Int. https://doi.org/10.1080/07420528.2018.1498098
Shulman DI, Palmert MR, Kemp SF, Lawson Wilkins D, Therapeutics C (2007) Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics 119:e484–e494. https://doi.org/10.1542/peds.2006-1612
Ahmet A, Kim H, Spier S (2011) Adrenal suppression: a practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy. Allergy Asthma Clin Immunol 7:13. https://doi.org/10.1186/1710-1492-7-13
Fisher LE, Ludwig EA, Wald JA, Sloan RR, Middleton E Jr, Jusko WJ (1992) Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 am versus 4 pm. Clin Pharmacol Ther 51:677–688
Maguire AM, Biesheuvel CJ, Ambler GR, Moore B, McLean M, Cowell CT (2008) Evaluation of adrenal function using the human corticotrophin-releasing hormone test, low dose Synacthen test and 9am cortisol level in children and adolescents with central adrenal insufficiency. Clin Endocrinol (Oxf) 68:683–691. https://doi.org/10.1111/j.1365-2265.2007.03100.x
Alves C, Robazzi TC, Mendonca M (2008) Withdrawal from glucocorticosteroid therapy: clinical practice recommendations. J Pediatr (Rio J) 84:192–202. https://doi.org/10.2223/JPED.1773 doi
Zhang Y, Milojevic D (2017) Protecting bone health in pediatric rheumatic diseases: pharmacological considerations. Paediatr Drugs 19:193–211. https://doi.org/10.1007/s40272-017-0219-3
Huber AM, Ward LM (2016) The impact of underlying disease on fracture risk and bone mineral density in children with rheumatic disorders: a review of current literature. Semin Arthritis Rheum 46:49–63. https://doi.org/10.1016/j.semarthrit.2016.02.003
Huber AM, Gaboury I, Cabral DA, Lang B, Ni A, Stephure D, Taback S, Dent P, Ellsworth J, LeBlanc C, Saint-Cyr C, Scuccimarri R, Hay J, Lentle B, Matzinger M, Shenouda N, Moher D, Rauch F, Siminoski K, Ward LM, Canadian Steroid-Associated Osteoporosis in the Pediatric Population C (2010) Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthritis Care Res (Hoboken) 62:516–526. https://doi.org/10.1002/acr.20171
LeBlanc CM, Ma J, Taljaard M, Roth J, Scuccimarri R, Miettunen P, Lang B, Huber AM, Houghton K, Jaremko JL, Ho J, Shenouda N, Matzinger MA, Lentle B, Stein R, Sbrocchi AM, Oen K, Rodd C, Jurencak R, Cummings EA, Couch R, Cabral DA, Atkinson S, Alos N, Rauch F, Siminoski K, Ward LM, Canadian S-AOiPPC (2015) Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res 30:1667–1675. https://doi.org/10.1002/jbmr.2511
Rodd C, Lang B, Ramsay T, Alos N, Huber AM, Cabral DA, Scuccimarri R, Miettunen PM, Roth J, Atkinson SA, Couch R, Cummings EA, Dent PB, Ellsworth J, Hay J, Houghton K, Jurencak R, Larche M, LeBlanc C, Oen K, Saint-Cyr C, Stein R, Stephure D, Taback S, Lentle B, Matzinger M, Shenouda N, Moher D, Rauch F, Siminoski K, Ward LM, Canadian Steroid-Associated Osteoporosis in the Pediatric Population C (2012) Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res (Hoboken) 64:122–131. https://doi.org/10.1002/acr.20589
Gordon CM, Leonard MB, Zemel BS, International Society for Clinical D (2014) 2013 Pediatric Position Development Conference: executive summary and reflections. J Clin Densitom 17:219–224. https://doi.org/10.1016/j.jocd.2014.01.007
Chinappen-Horsley U, Blake GM, Fogelman I, Spector TD (2007) A method for determining skeletal lengths from DXA images. BMC Musculoskelet Disord 8:113. https://doi.org/10.1186/1471-2474-8-113
Lecouvet FE, Malghem J, Maldague BE, Vande Berg BC (2005) MR imaging of epiphyseal lesions of the knee: current concepts, challenges, and controversies. Radiol Clin N Am 43:655–672, vii-viii. https://doi.org/10.1016/j.rcl.2005.02.002
Murphey MD, Foreman KL, Klassen-Fischer MK, Fox MG, Chung EM, Kransdorf MJ (2014) From the radiologic pathology archives imaging of osteonecrosis: radiologic-pathologic correlation. Radiographics 34:1003–1028. https://doi.org/10.1148/rg.344140019
Weinstein RS (2012) Glucocorticoid-induced osteoporosis and osteonecrosis. Endocrinol Metab Clin N Am 41:595–611. https://doi.org/10.1016/j.ecl.2012.04.004
Nash JJ, Nash AG, Leach ME, Poetker DM (2011) Medical malpractice and corticosteroid use. Otolaryngol Head Neck Surg 144:10–15. https://doi.org/10.1177/0194599810390470
Horton DB, Haynes K, Denburg MR, Thacker MM, Rose CD, Putt ME, Leonard MB, Strom BL (2017) Oral glucocorticoid use and osteonecrosis in children and adults with chronic inflammatory diseases: a population-based cohort study. BMJ Open 7:e016788. https://doi.org/10.1136/bmjopen-2017-016788
Tsampalieros A, Lam CK, Spencer JC, Thayu M, Shults J, Zemel BS, Herskovitz RM, Baldassano RN, Leonard MB (2013) Long-term inflammation and glucocorticoid therapy impair skeletal modeling during growth in childhood Crohn disease. J Clin Endocrinol Metab 98:3438–3445. https://doi.org/10.1210/jc.2013-1631
Thorne JE, Woreta FA, Dunn JP, Jabs DA (2010) Risk of cataract development among children with juvenile idiopathic arthritis-related uveitis treated with topical corticosteroids. Ophthalmology 117:1436–1441. https://doi.org/10.1016/j.ophtha.2009.12.003
Stroh IG, Moradi A, Burkholder BM, Hornbeak DM, Leung TG, Thorne JE (2017) Occurrence of and risk factors for ocular hypertension and secondary glaucoma in juvenile idiopathic arthritis-associated uveitis. Ocul Immunol Inflamm 25:503–512. https://doi.org/10.3109/09273948.2016.1142573
Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG (2017) Prevention and management of glucocorticoid-induced side effects: a comprehensive review: gastrointestinal and endocrinologic side effects. J Am Acad Dermatol 76:11–16. https://doi.org/10.1016/j.jaad.2016.02.1239
Angeles-Han S, Yeh S (2012) Prevention and management of cataracts in children with juvenile idiopathic arthritis-associated uveitis. Curr Rheumatol Rep 14:142–149. https://doi.org/10.1007/s11926-011-0229-z
Covar RA, Leung DY, McCormick D, Steelman J, Zeitler P, Spahn JD (2000) Risk factors associated with glucocorticoid-induced adverse effects in children with severe asthma. J Allergy Clin Immunol 106:651–659. https://doi.org/10.1067/mai.2000.109830
Beukelman T, Xie F, Chen L, Baddley JW, Delzell E, Grijalva CG, Lewis JD, Ouellet-Hellstrom R, Patkar NM, Saag KG, Winthrop KL, Curtis JR, Collaboration S (2012) Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 64:2773–2780. https://doi.org/10.1002/art.34458
Caplan A, Fett N, Rosenbach M, Werth VP, Micheletti RG (2017) Prevention and management of glucocorticoid-induced side effects: a comprehensive review: Infectious complications and vaccination recommendations. J Am Acad Dermatol 76:191–198. https://doi.org/10.1016/j.jaad.2016.02.1240
Hiraki LT, Feldman CH, Marty FM, Winkelmayer WC, Guan H, Costenbader KH (2017) Serious infection rates among children with systemic lupus erythematosus enrolled in medicaid. Arthritis Care Res 69:1620–1626. https://doi.org/10.1002/acr.23219
Singh JA, Hossain A, Kotb A, Wells G (2016) Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta-analysis. BMC Med 14:137. https://doi.org/10.1186/s12916-016-0673-8
Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement (2000). Am J Respir Crit Care Med 161:S221-247. https://doi.org/10.1164/ajrccm.161.supplement_3.ats600
Kimura Y, Fieldston E, Devries-Vandervlugt B, Li S, Imundo L (2000) High dose, alternate day corticosteroids for systemic onset juvenile rheumatoid arthritis. J Rheumatol 27:2018–2024
Groot N, Heijstek MW, Wulffraat NM (2015) Vaccinations in paediatric rheumatology: an update on current developments. Curr Rheumatol Rep 17:46. https://doi.org/10.1007/s11926-015-0519-y
Sousa S, Duarte AC, Cordeiro I, Ferreira J, Goncalves MJ, Meirinhos T, Rocha TM, Romao VC, Santos MJ (2017) Efficacy and safety of vaccination in pediatric patients with systemic inflammatory rheumatic diseases: a systematic review of the literature. Acta Reumatol Port 42:8–16
Hoes JN, Jacobs JW, Boers M, Boumpas D, Buttgereit F, Caeyers N, Choy EH, Cutolo M, Da Silva JA, Esselens G, Guillevin L, Hafstrom I, Kirwan JR, Rovensky J, Russell A, Saag KG, Svensson B, Westhovens R, Zeidler H, Bijlsma JW (2007) EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 66:1560–1567. https://doi.org/10.1136/ard.2007.072157
Matoulkova P, Pavek P, Maly J, Vlcek J (2014) Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of drug interaction. Expert Opin Drug Metab Toxicol 10:425–435. https://doi.org/10.1517/17425255.2014.878703
Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, Humphrey MB, Lane NE, Magrey M, Miller M, Morrison L, Rao M, Byun Robinson A, Saha S, Wolver S, Bannuru RR, Vaysbrot E, Osani M, Turgunbaev M, Miller AS, McAlindon T (2017) 2017 American college of rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 69:1095–1110. https://doi.org/10.1002/acr.23279
Inoue Y, Mitsunaga K, Yamamoto T, Chiba K, Yamaide F, Nakano T, Morita Y, Yamaide A, Suzuki S, Arima T, Yamaguchi KI, Tomiita M, Shimojo N, Kohno Y (2018) Early use of alendronate as a protective factor against the development of glucocorticoid-induced bone loss in childhood-onset rheumatic diseases: a cross-sectional study. Pediatr Rheumatol Online J 16:36. https://doi.org/10.1186/s12969-018-0258-5
Baroncelli GI, Bertelloni S (2014) The use of bisphosphonates in pediatrics. Horm Res Paediatr 82:290–302. https://doi.org/10.1159/000365889
Le Jeunne C, Aslangul E (2013) Prolonged corticosteroid therapy and diet. Rev Med Interne 34:284–286. https://doi.org/10.1016/j.revmed.2012.11.014
Bloom BJ, Alario AJ, Miller LC (2011) Intra-articular corticosteroid therapy for juvenile idiopathic arthritis: report of an experiential cohort and literature review. Rheumatol Int 31:749–756. https://doi.org/10.1007/s00296-010-1365-x
Jennings H, Hennessy K, Hendry GJ (2014) The clinical effectiveness of intra-articular corticosteroids for arthritis of the lower limb in juvenile idiopathic arthritis: a systematic review. Pediatr Rheumatol Online J 12:23. https://doi.org/10.1186/1546-0096-12-23
Ravelli A, Manzoni SM, Viola S, Pistorio A, Ruperto N, Martini A (2001) Factors affecting the efficacy of intraarticular corticosteroid injection of knees in juvenile idiopathic arthritis. J Rheumatol 28:2100–2102
Papadopoulou C, Kostik M, Gonzalez-Fernandez MI, Bohm M, Nieto-Gonzalez JC, Pistorio A, Lanni S, Consolaro A, Martini A, Ravelli A (2013) Delineating the role of multiple intraarticular corticosteroid injections in the management of juvenile idiopathic arthritis in the biologic era. Arthritis Care Res (Hoboken) 65:1112–1120. https://doi.org/10.1002/acr.21947
Ravelli A, Davi S, Bracciolini G, Pistorio A, Consolaro A, van Dijkhuizen EHP, Lattanzi B, Filocamo G, Verazza S, Gerloni V, Gattinara M, Pontikaki I, Insalaco A, De Benedetti F, Civino A, Presta G, Breda L, Marzetti V, Pastore S, Magni-Manzoni S, Maggio MC, Garofalo F, Rigante D, Gattorno M, Malattia C, Picco P, Viola S, Lanni S, Ruperto N, Martini A, Italian Pediatric Rheumatology Study G (2017) Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial. Lancet 389:909–916. https://doi.org/10.1016/S0140-6736(17)30065-X
Eberhard BA, Sison MC, Gottlieb BS, Ilowite NT (2004) Comparison of the intraarticular effectiveness of triamcinolone hexacetonide and triamcinolone acetonide in treatment of juvenile rheumatoid arthritis. J Rheumatol 31:2507–2512
Zulian F, Martini G, Gobber D, Plebani M, Zacchello F, Manners P (2004) Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a double-blind trial. Rheumatology 43:1288–1291. https://doi.org/10.1093/rheumatology/keh313
Scott C, Meiorin S, Filocamo G, Lanni S, Valle M, Martinoli C, Martini A, Ravelli A (2010) A reappraisal of intra-articular corticosteroid therapy in juvenile idiopathic arthritis. Clin Exp Rheumatol 28:774–781
Job-Deslandre C, Menkes CJ (1990) Complications of intra-articular injections of triamcinolone hexacetonide in chronic arthritis in children. Clin Exp Rheumatol 8:413–416
Goldzweig O, Carrasco R, Hashkes PJ (2013) Systemic adverse events following intraarticular corticosteroid injections for the treatment of juvenile idiopathic arthritis: two patients with dermatologic adverse events and review of the literature. Semin Arthritis Rheum 43:71–76. https://doi.org/10.1016/j.semarthrit.2012.12.006
Gondwe JS, Davidson JE, Deeley S, Sills J, Cleary AG (2005) Secondary Cushing’s syndrome in children with juvenile idiopathic arthritis following intra-articular triamcinolone acetonide administration. Rheumatology 44:1457–1458. https://doi.org/10.1093/rheumatology/kei154
Huppertz HI, Pfuller H (1997) Transient suppression of endogenous cortisol production after intraarticular steroid therapy for chronic arthritis in children. J Rheumatol 24:1833–1837
McKinney C, Sharma N, Jerath RS (2014) Livedoid dermatitis (Nicolau syndrome) following intra-articular glucocorticoid injection. J Clin Rheumatol 20:339–340. https://doi.org/10.1097/RHU.0000000000000146
Holland GN, Denove CS, Yu F (2009) Chronic anterior uveitis in children: clinical characteristics and complications. Am J Ophthalmol 147:667–678 e665. https://doi.org/10.1016/j.ajo.2008.11.009
Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. Lancet 369:767–778. https://doi.org/10.1016/S0140-6736(07)60363-8
Angeles-Han ST, Lo MS, Henderson LA, Lerman MA, Abramson L, Cooper AM, Parsa MF, Zemel LS, Ronis T, Beukelman T, Cox E, Sen HN, Holland GN, Brunner HI, Lasky A, Rabinovich CE, Juvenile Idiopathic Arthritis Disease-Specific Uveitis Subcommittee of Childhood Arthritis Rheumatology Research A (2018) Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for juvenile idiopathic arthritis-associated and idiopathic chronic anterior uveitis. Arthritis Care Res (Hoboken). https://doi.org/10.1002/acr.23610
Bou R, Adan A, Borras F, Bravo B, Calvo I, De Inocencio J, Diaz J, Escudero J, Fonollosa A, de Vicuna CG, Hernandez V, Merino R, Peralta J, Rua MJ, Tejada P, Anton J (2015) Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus. Rheumatol Int 35:777–785. https://doi.org/10.1007/s00296-015-3231-3
Constantin T, Foeldvari I, Anton J, de Boer J, Czitrom-Guillaume S, Edelsten C, Gepstein R, Heiligenhaus A, Pilkington CA, Simonini G, Uziel Y, Vastert SJ, Wulffraat NM, Haasnoot AM, Walscheid K, Palinkas A, Pattani R, Gyorgyi Z, Kozma R, Boom V, Ponyi A, Ravelli A, Ramanan AV (2018) Consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis: the SHARE initiative. Ann Rheum Dis 77:1107–1117. https://doi.org/10.1136/annrheumdis-2018-213131
Leinonen S, Immonen I, Kotaniemi K (2018) Fluocinolone acetonide intravitreal implant (Retisert((R))) in the treatment of sight threatening macular oedema of juvenile idiopathic arthritis-related uveitis. Acta Ophthalmol. https://doi.org/10.1111/aos.13744
Pichi F, Nucci P, Baynes K, Lowder CY, Srivastava SK (2017) Sustained-release dexamethasone intravitreal implant in juvenile idiopathic arthritis-related uveitis. Int Ophthalmol 37:221–228. https://doi.org/10.1007/s10792-016-0265-9
Ravelli A, Grom AA, Behrens EM, Cron RQ (2012) Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun 13:289–298. https://doi.org/10.1038/gene.2012.3
Boom V, Anton J, Lahdenne P, Quartier P, Ravelli A, Wulffraat NM, Vastert SJ (2015) Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Pediatr Rheumatol Online J 13:55. https://doi.org/10.1186/s12969-015-0055-3
Aytac S, Batu ED, Unal S, Bilginer Y, Cetin M, Tuncer M, Gumruk F, Ozen S (2016) Macrophage activation syndrome in children with systemic juvenile idiopathic arthritis and systemic lupus erythematosus. Rheumatol Int 36:1421–1429. https://doi.org/10.1007/s00296-016-3545-9
Nakagishi Y, Shimizu M, Kasai K, Miyoshi M, Yachie A (2016) Successful therapy of macrophage activation syndrome with dexamethasone palmitate. Mod Rheumatol 26:617–620. https://doi.org/10.3109/14397595.2014.906053
Minoia F, Davi S, Horne A, Demirkaya E, Bovis F, Li C, Lehmberg K, Weitzman S, Insalaco A, Wouters C, Shenoi S, Espada G, Ozen S, Anton J, Khubchandani R, Russo R, Pal P, Kasapcopur O, Miettunen P, Maritsi D, Merino R, Shakoory B, Alessio M, Chasnyk V, Sanner H, Gao YJ, Huasong Z, Kitoh T, Avcin T, Fischbach M, Frosch M, Grom A, Huber A, Jelusic M, Sawhney S, Uziel Y, Ruperto N, Martini A, Cron RQ, Ravelli A, Pediatric Rheumatology International Trials O, Childhood A, Rheumatology Research A, Pediatric Rheumatology Collaborative Study G, Histiocyte S (2014) Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol 66:3160–3169. https://doi.org/10.1002/art.38802
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Batu, E.D. Glucocorticoid treatment in juvenile idiopathic arthritis. Rheumatol Int 39, 13–27 (2019). https://doi.org/10.1007/s00296-018-4168-0
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DOI: https://doi.org/10.1007/s00296-018-4168-0