Betül Özdel ÖZTÜRK, Nilay Orak AKBAY, Sevim BAVBEK, Elif Er GÜLBEZER, Francesca NENCİNİ, Alessandra VULTAGGİO

Üç TNF-α İnhibitörü ile Lokal ve Tosilizumab ile Lokal/Sistemik Aşırı Duyarlılık Reaksiyonu Gelişen Bir Hasta: Tosilizumab ile Desensitizasyon

Tümör nekroz faktör-alfa (TNF-α) inhibitörleri, kronik enflamatuvar hastalıklar için etkili alternatiflerdir. Genellikle iyi tolere edilirler, ancak erken/geç tip lokal veya sistemik aşırı duyarlılık reaksiyonlarına (ADR) yol açabilirler. Tosilizumab, interlökin-6 reseptörlerine karşı bir monoklonal antikordur. Hem intravenöz (İV) hem de subkütan (SK) yolla verilir ve sınırlı sayıda çalışmada tosilizumab ilişkili enjeksiyon ve/veya infüzyon reaksiyon oranının %7-8 olduğu bildirilmiştir. TNF-α inhibitörleri veya tosilizumab arasında çapraz reaktivite beklenmemektedir. Ancak biz burada olağan dışı bir olgu olan üç TNF-α inhibitörü, adalimumab, etanersept ve golimumab, ile lokal enjeksiyon yeri reaksiyonu gelişen bir hasta sunduk. Hastada daha sonra SK ve İV tosilizumab ile sırasıyla lokal enjeksiyon yeri reaksiyonu ve anafilaksi gelişti. Tüm biyolojik ajanlarla yapılan deri prick testleri negatif, intradermal testlerin erken okumaları pozitifti. Bununla birlikte tosilizumab hızlı ilaç desensitizasyon yoluyla başarıyla uygulandı.

A Patient with Local Hypersensitivity Reactions to Three TNF-α Inhibitors and Local/Systemic Hypersensitivity Reactions to Tocilizumab: Desensitization to Tocilizumab

Tumor necrosis factor-alpha (TNF-α) inhibitors are effective alternatives for chronic inflammatory diseases. They are generally well tolerated; however, they may lead to the immediate/delayed local or systemic hypersensitivity reactions (HSR). Tocilizumab is a monoclonal antibody against interleukin 6 receptors. It is given both via intravenous (IV) and subcutaneous (SC) routes and there are limited data reporting that the overall injection and/or infusion reaction rate to tocilizumab is estimated as 7-8%. Cross-reactivity between either TNF-α inhibitors or tocilizumab is not expected. However, we herein present an unusual case of a patient who reacted with local injection site reactions (ISRs) to three TNF-α inhibitors, adalimumab, etanercept, and golimumab. The patient then reacted with ISR and anaphylaxis to SC and IV tocilizumab, respectively. Skin prick tests with all biologicals were negative but positive in early readings of intradermal testing. After all, tocilizumab was successfully administered via rapid drug desensitization.

PDF

___

Aaltonen KJ, Virkki LM, Malmivaara A, et al. Systematic review and meta analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis. PLoS One. 2012;7:e30275.
Bavbek S, Lee MJ. Subcutaneous Injectable Drugs Hypersensitivity and Desensitization: Insulin and Monoclonal Antibodies. Immunol Allergy Clin North Am. 2017;37:761-771.
Puxeddu I, Giori L, Rocchi V, et al. Hypersensitivity reactions during treatment with infliximab, etanercept, and adalimumab. Ann Allergy Asthma Immunol. 2012;108:123-124.
Rocchi V, Puxeddu I, Cataldo G, et al. Hypersensitivity reactions to tocilizumab: role of skin tests in diagnosis. Rheumatology (Oxford). 2014;53:1527-1529.
Soyer O, Demir S, Bilginer Y, et al. Severe hypersensitivity reactions to biological drugs in children with rheumatic diseases. Pediatr Allergy Immunol. 2019;30:833-840.
Zeltser R, Valle L, Tanck C, et al. Clinical, histological, and immunophenotypic characteristics of injection site reactions associated with etanercept: a recombinant tumor necrosis factor alpha receptor: Fc fusion protein. Arch Dermatol. 2001;137:893-899.
Justet A, Neukirch C, Poubeau P, et al. Successful rapid tocilizumab desensitization in a patient with Still disease. J Allergy Clin Immunol Pract. 2014;2:631-632.
Cansever M, Şahin N, Dursun I, et al. Successful Slow Desensitization to Tocilizumab in a 15-Year-Old Patient. J Investig Allergol Clin Immunol. 2018;28:436-438.
Vultaggio A, Matucci A, Nencini F, et al. Hypersensitivity Reactions to Biologicals: True Allergy? Curr Treat Options Allergy. 2016;3:147-157.
Bavbek S, Kendirlinan R, Çerçi P, et al. Rapid Drug Desensitization with Biologics: A Single-Center Experience with Four Biologics. Int Arch Allergy Immunol. 2016;171:227-233.