{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T15:45:33Z","timestamp":1764603933316,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Juvenile idiopathic arthritis (JIA) is one of the most frequent diseases in the practice of pediatric rheumatology. JIA treatments have been modified and improved with the use of biological drugs along with technological innovations. However, different types of hypersensitivity reactions to biological drugs have also been reported. Anaphylaxis and infusion reactions occurring during the intravenous infusion require a critical approach in the acute period. On the other hand, the detection of drug-related late-type reactions and the development of antibodies to the agent highlight the need for an understanding of the drug-induced etiology to prevent the patient from continuing the treatment with the culprit drug. The chronic disease process, concomitant immune dysregulation, and multiple drug use may result in these hypersensitivity reactions. In this review, the hypersensitivity reactions to the biological treatments used in patients with juvenile idiopathic arthritis and the management of these conditions are discussed.<\/jats:p>","DOI":"10.3390\/jcm11247291","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T03:23:49Z","timestamp":1670556229000},"page":"7291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hypersensitivity to Biological Treatments in Juvenile Idiopathic Arthritis: How Should It Be Managed?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-8894","authenticated-orcid":false,"given":"Muserref","family":"Kasap Cuceoglu","sequence":"first","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University, Ankara 06100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8534-0930","authenticated-orcid":false,"given":"Ozge","family":"Basaran","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University, Ankara 06100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7444-251X","authenticated-orcid":false,"given":"Ozge","family":"Soyer","sequence":"additional","affiliation":[{"name":"Division of Allergy, Department of Pediatrics, Hacettepe University, Ankara 06100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seza","family":"Ozen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Hacettepe University, Ankara 06100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","unstructured":"Brunner, H.I., and Ruperto, N. (2021). 14\u2014Therapeutics: Biologics and Small Molecules, Elsevier Inc.. [8th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rider, P., Carmi, Y., and Cohen, I. (2016). Biologics for Targeting Inflammatory Cytokines, Clinical Uses, and Limitations. Int. J. Cell Biol., 2016.","DOI":"10.1155\/2016\/9259646"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100","DOI":"10.4103\/0019-5154.53175","article-title":"Biologics: Target-specific treatment of systemic and cutaneous autoimmune diseases","volume":"54","author":"Raychaudhuri","year":"2009","journal-title":"Indian J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/all.14984","article-title":"Hypersensitivity reactions to biologicals: An EAACI position paper","volume":"77","author":"Bavbek","year":"2022","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Makurvet, F.D. (2021). Biologics vs. small molecules: Drug costs and patient access. Med. Drug Discov., 9.","DOI":"10.1016\/j.medidd.2020.100075"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/all.12350","article-title":"International Consensus on drug allergy","volume":"69","author":"Demoly","year":"2014","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s40629-020-00126-6","article-title":"Hypersensitivity reactions to biologics (part I): Allergy as an important differential diagnosis in complex immune-derived adverse events","volume":"29","author":"Wedi","year":"2020","journal-title":"Allergo J. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.iac.2017.01.012","article-title":"Adverse Reactions to Biologic Therapy","volume":"37","author":"Patel","year":"2017","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jaci.2018.02.018","article-title":"Hypersensitivity reactions to therapeutic monoclonal antibodies: Phenotypes and endotypes","volume":"142","author":"Isabwe","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.1038\/cti.2015.14","article-title":"Clinical development methodology for infusion-related reactions with monoclonal antibodies","volume":"4","author":"Doessegger","year":"2015","journal-title":"Clin. Transl. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s10620-018-5319-6","article-title":"Incidence and Management of Infusion Reactions to Infliximab in an Alternate Care Setting","volume":"64","author":"Checkley","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"ref_12","first-page":"134","article-title":"Serious infusion-related reaction after rituximab, abatacept and tocilizumab in rheumatoid arthritis: Prospective registry data","volume":"57","author":"Salmon","year":"2018","journal-title":"Rheumatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Subklewe","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_14","first-page":"705","article-title":"Spotlight on tocilizumab in the treatment of car-t-cell-induced cytokine release syndrome: Clinical evidence to date","volume":"16","author":"Si","year":"2020","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/intimm\/dxab011","article-title":"IL-6: From arthritis to CAR-T-cell therapy and COVID-19","volume":"33","author":"Kishimoto","year":"2021","journal-title":"Int. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/RHU.0b013e318285f1e9","article-title":"Anaphylaxis to etanercept in two children with juvenile idiopathic arthritis","volume":"19","author":"Crayne","year":"2013","journal-title":"J. Clin. Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1111\/pai.13114","article-title":"Severe hypersensitivity reactions to biological drugs in children with rheumatic diseases","volume":"30","author":"Soyer","year":"2019","journal-title":"Pediatr. Allergy Immunol."},{"key":"ref_18","first-page":"552","article-title":"Desensitisation overcomes rituximab- and tocilizumab-related immediate hypersensitivity in childhood","volume":"38","author":"Demir","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/j.jaip.2017.04.044","article-title":"First-dose anaphylaxis to infliximab: A case of mammalian meat allergy","volume":"5","author":"Chitnavis","year":"2017","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.1111\/all.14432","article-title":"Medical algorithm: Diagnosis and treatment of drug hypersensitivity reactions to biologicals","volume":"75","author":"Yang","year":"2020","journal-title":"Allergy Eur. J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1007\/s10067-015-2889-y","article-title":"Anaphylaxis to anakinra in a pediatric patient with systemic juvenile idiopathic arthritis successfully treated with canakinumab: A case-based review","volume":"34","author":"Aguiar","year":"2015","journal-title":"Clin. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s40521-020-00242-2","article-title":"Hypersensitivity Reactions to Biologicals: From Bench to Bedside","volume":"7","author":"Akarsu","year":"2020","journal-title":"Curr. Treat. Options Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12016-021-08879-w","article-title":"Hypersensitivity and Immune-related Adverse Events in Biologic Therapy","volume":"62","author":"Waldron","year":"2022","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_24","first-page":"31","article-title":"Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome","volume":"6","author":"Choudhary","year":"2013","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1136\/annrheumdis-2021-220578","article-title":"Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles","volume":"81","author":"Saper","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hollenbach, J.A., Ombrello, M.J., Tremoulet, A.H., Montero-Martin, G., Prahalad, S., Canna, S., Shimizu, C., Deutsch, G., Tan, S., and Remmers, E.F. IL-1 and IL-6 inhibitor hypersensitivity link to common HLA-DRB1*15 alleles. medRxiv, 2021.","DOI":"10.1101\/2020.08.10.20172338"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.jdcr.2019.07.004","article-title":"Drug-induced hypersensitivity syndrome with myocardial involvement treated with tofacitinib","volume":"5","author":"Damsky","year":"2019","journal-title":"JAAD Case Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41591-019-0733-7","article-title":"Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: A case report","volume":"26","author":"Kim","year":"2020","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1007\/s10067-018-4095-1","article-title":"Anakinra treatment in macrophage activation syndrome: A single center experience and systemic review of literature","volume":"37","author":"Demir","year":"2018","journal-title":"Clin. Rheumatol."},{"key":"ref_30","first-page":"125","article-title":"Update on the management of systemic juvenile idiopathic arthritis and role of IL-1 and IL-6 inhibition","volume":"8","author":"Grevich","year":"2017","journal-title":"Adolesc. Health. Med. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/acr.21625","article-title":"Consensus treatment plans for new-onset systemic juvenile idiopathic arthritis","volume":"64","author":"Dewitt","year":"2012","journal-title":"Arthritis Care Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12969-015-0055-3","article-title":"Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis","volume":"13","author":"Boom","year":"2015","journal-title":"Pediatr. Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mannion, M.L., and Cron, R.Q. (2022). Therapeutic strategies for treating juvenile idiopathic arthritis. Curr. Opin. Pharmacol., 64.","DOI":"10.1016\/j.coph.2022.102226"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/gene.2012.3","article-title":"Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: Diagnosis, genetics, pathophysiology and treatment","volume":"13","author":"Ravelli","year":"2012","journal-title":"Genes Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1684\/ejd.2010.0932","article-title":"Acute generalized exanthematous pustulosis: An overview of the clinical, immunological and diagnostic concepts","volume":"20","author":"Speeckaert","year":"2010","journal-title":"Eur. J. Dermatol."},{"key":"ref_36","first-page":"601412","article-title":"Acute generalized exanthematous pustulosis induced by etanercept: Another dermatologic adverse effect","volume":"2013","author":"Kavala","year":"2013","journal-title":"Case Rep. Dermatol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1111\/j.1365-4632.2011.05002.x","article-title":"Varicella-like generalized pustulosis induced by adalimumab","volume":"52","author":"Suga","year":"2013","journal-title":"Int. J. Dermatol."},{"key":"ref_38","first-page":"8","article-title":"Acute Generalized Exanthematous Pustulosis Induced by Cetuximab","volume":"13","author":"Masood","year":"2021","journal-title":"Cureus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3389\/fmed.2021.758354","article-title":"Case Report: Successful Treatment of Acute Generalized Exanthematous Pustulosis With Secukinumab","volume":"8","author":"Zhang","year":"2021","journal-title":"Front. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.jid.2017.01.003","article-title":"Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Associations, Outcomes, and Pathobiology-Thirty Years of Progress but Still Much to Be Done","volume":"137","author":"Stern","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.2147\/CMAR.S163391","article-title":"Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies","volume":"10","author":"Chen","year":"2018","journal-title":"Cancer Manag. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/24\/7291\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:32Z","timestamp":1760146592000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/24\/7291"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":41,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["jcm11247291"],"URL":"https:\/\/doi.org\/10.3390\/jcm11247291","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2022,12,8]]}}}