Hypersensitivity to polyethylene glycol in adults and children: An emerging challenge: Hypersensitivity to polyethylene glycol

Annamaria  Bianchi; Paolo Bottau; Elisabetta Calamelli; Silvia  Caimmi; Giuseppe  Crisafulli; Fabrizio  Franceschini; Lucia  Liotti; Francesca  Mori; Claudia  Paglialunga; Francesca  Saretta; Mariangela  Tosca; Fabio  Cardinale; Amelia  Licari; Michele  Miraglia Del Giudice; Carlo Caffarelli

doi:10.23750/abm.v92iS7.12384

Hypersensitivity to polyethylene glycol in adults and children: An emerging challenge

Hypersensitivity to polyethylene glycol

Authors

Annamaria Bianchi UOC Pediatria, Azienda Ospedaliera San Camillo Forlanini, Circonvallazione Gianicolense 87, Roma, 00152 Italy
Paolo Bottau Pediatric and Neonatology Unit, Imola Hospital, Imola (BO), Italy
Elisabetta Calamelli Pediatric and Neonatology Unit, Imola Hospital, Imola (BO), Italy
Silvia Caimmi Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
Giuseppe Crisafulli UOC di Pediatria. Dipartimento Materno-Infantile, Università di Messina, Messina, Italy
Fabrizio Franceschini UOC Pediatria, Azienda Ospedaliero-Universitaria "Ospedali Riuniti", Ancona, Italy
Lucia Liotti UOC Pediatria, Azienda Ospedaliero-Universitaria "Ospedali Riuniti", Ancona, Italy
Francesca Mori Allergy Unit, Meyer Children's Hospital, 50139, Florence, Italy
Claudia Paglialunga UOC di Pediatria, Azienda Ospedaliera-Universitaria "Consorziale-Policlinico", Ospedale Pediatrico Giovanni XXIII, 70123 Bari, Italy
Francesca Saretta SC Pediatria, Ospedale Latisana-Palmanova, Dipartimento Materno-Infantile Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
Mariangela Tosca Allergy Centre, IRCCS G. Gaslini Pediatric Hospital, Genova, Italy
Fabio Cardinale Department of Pediatrics, Giovanni XXIII Pediatric Hospital, University of Bari, Bari, Italy
Amelia Licari Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy
Michele Miraglia Del Giudice Department of Woman, Child and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
Carlo Caffarelli Pediatric Clinic, Department of Medicine and Surgery, Unversity of Parma, Parma, Italy

DOI: https://doi.org/10.23750/abm.v92iS7.12384

Keywords:

Polyethylene glycol hypersensitivity, PEG allergy, vaccine allergy, Drug allergy

Abstract

Hypersensitivity reactions to polyethylene glycol (PEG) is an emerging challenge and the interest about this disease is growing since PEG is considered one of the possible causes of coronavirus disease 2019 (COVID 19) vaccine-associated anaphylaxis. PEG is used in a wide variety of pharmaceutical, medical, industrial, cosmetic, and food products and can be an active ingredient or used as an excipient. PEG is present in several medications, and it may or may not be present in different formulations and dosages of the same drug. Lack of standardization nomenclature, inadequate labelling of products and lack of knowledge about PEG involvement in hypersensitivity reactions expose patients at risk of presenting multiple reactions before a diagnosis could be made. In this review we describe the main cases published in literature and propose an allergy work-up and management.

References

Wolfson AR, Robinson LB, Li L, et al. First-dose mRNA COVID-19 vaccine allergic reactions: limited role for excipient skin testing. J Allergy Clin Immunol Pract 2021:9:3308-3320.e3.

Sellaturay P, Nasser SM, Islam S et al. Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID-19 vaccine. Clin Exp Allergy 2021;51:861-863.

Liotti L, Bianchi A, Bottau P, et al. COVID-19 Vaccines in children with cow’s milk and food allergies. Nutrients 2021;13:2637.

Cardinale F, Ciprandi G, Barberi S, et al. Consensus statement of the Italian society of pediatric allergy and immunology for the pragmatic management of children and adolescents with allergic or immunological diseases during the COVID-19 pandemic. Ital J Pediatr. 2020;46:84.

Wenande E, Garvey LH. Immediate-type hypersensitivity to polyethylene glycols: a review. Clin Exp Allergy 2016;46:907–22.

Caballero ML, Krantz MS, Quirce S, Phillips EJ, Stone CA Jr. Hidden dangers: Recognizing excipients as potential causes of drug and vaccine hypersensitivity reactions. J Allergy Clin Immunol Pract 2021: :S2213-2198(21)00302-0.

Banerji A, Wickner PG, Saff R, et al. mRNA Vaccines to Prevent COVID-19 Disease and reported allergic reactions: Current evidence and suggested approach. J Allergy Clin Immunol Pract 2021;9:1423-1437.

Duncan R, Veronese FM. PEGylated protein conjugates: a new class of therapeutics for 21st century. In: Verones FM, editor. PEGylated protein drugs: Basic science and clinical applications. Basel: Birkhäuser; 2009.

Knop K, Hoogenboom R, Fischer D, Schubert US. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed Engl 2010;49:6288–308.

Roseingrave L. Verdict of medical misadventure in case of fatal allergic reaction. The Irish Times. Available at https://www.irishtimes.com/news/crime-and-law/courts/coroner-scourt/verdict-ofmedicalmisadventure-in-case-of-fatal-allergic-reaction-1.3324937. Accessed on 12 December 2017.

Berndt K, Kuske M, Beissert S, Spornraft-Ragaller P, Bauer A. Non-IgE-dependent hypersensitivity to macrogol 6000. J Dtsch Dermatol Ges 2018;16:479-481.

Giangrande N, García-Menaya JM, Marcos-Fernández M, Cámara-Hijón C, Bobadilla-González P. Anaphylaxis due to macrogol in a laxative solution with a positive basophil activation test. Ann Allergy Asthma Immunol 2019;123:302-304.

Jover Cerdá V, Rodríguez Pacheco R, Doménech Witek J, Marco de la Calle FM, de la Sen Fernández ML. Immediate hypersensitivity to polyethylene glycols in unrelated products: when standardization in the nomenclature of the components of drugs, cosmetics, and food becomes necessary. Allergy Asthma Clin Immunol 2019;15:9.

Stone CA Jr, Liu Y, Relling MV, et al. Immediate hypersensitivity to polyethylene glycols and polysorbates: more common than we have recognized. J Allergy Clin Immunol Pract 2019;7:1533-1540.e8.

Sellaturay P, Nasser S, Ewan P. Polyethylene glycol-induced systemic allergic reactions (Anaphylaxis). J Allergy Clin Immunol Pract 2021;9:670-675.

Cox F, Khalib K, Conlon N. PEG That Reaction: A Case series of allergy to polyethylene glycol. J Clin Pharmacol 2021;61:832-835.

Bruusgaard-Mouritsen MA, Johansen JD, Garvey LH. Clinical manifestations and impact on daily life of allergy to polyethylene glycol (PEG) in ten patients. Clin Exp Allergy 2021;51:463-470.

Hamano S, Nishima D, Satake M, Kudo K, Yanagita K, Tezuka J. Recurrent immediate type hypersensitivity reaction induced by macrogol in a 3-year-old boy. J Investig Allergol Clin Immunol 2020;30:72-73.

Sari Gökay S, Çelik T, Yusuf Sari M, Ekinci F, Dinçer Yildizdaş R, Levent Yilmaz H. Urticaria as a rare side effect of polyethylene glycol-3350 in a child: Case report. Acta Clin Croat 2018; 57:187-189.

Chan A, Shih V, Tham Chee Kian. Liposomal doxorubicin-associated acute hypersensitivity despite appropriate preventive measures. J Oncol Pharm Pract 2007;13:105-7.

McCabe E, Tormey V, Doran JP. Polyethylene glycol: an underrecognized compound in certolizumab pegol and Movicol that may cause anaphylaxis. Rheumatology (Oxford) 2020;59:908-910.

Fernandez CA, Stewart E, Panetta JC et al. Successful challenges using native E. coli asparaginase after hypersensitivity reactions to PEGylated E. coli asparaginase. Cancer Chemother Pharmacol 2014;73:1307–1313.

Krantz MS, Liu Y, Phillips EJ, Stone CA Jr. Anaphylaxis to PEGylated liposomal echocardiogram contrast in a patient with IgE-mediated macrogol allergy. J Allergy Clin Immunol Pract 2020;8:1416-1419.

Oh Y, Niijima H, Kawahara Y, et al. An immediate hypersensitivity reaction induced by PEGylated recombinant factor VIII. Haemophilia 2020;26:36-9.

Kozma G, Shimizu T, Ishida T, Szebeni J. Anti-PEG antibodies: properties, formation, testing and role in adverse immune reactions to PEGylated nanobiopharmaceuticals. Adv Drug Deliv Rev 2020;154-155:163-75.

Hesselbach C, Bohning W, Wettengel R. [Anaphylactic shock after sucking on a throat lozenge]. Dtsch Med Wochenschr 1990; 15:1397–9.

Ohnishi A, Hashimoto K, Ozono E, et al. Anaphylaxis to carboxymethylcellulose: add food additives to the list of elicitors. Pediatrics 2019;143:e20181180.

AAIITO-SIAAIC. Linee di indirizzo per la gestione da parte degli allergologi dei pazienti a rischio di reazioni allergiche ai vaccini per COVID-19. Versione 15/02/2021. Available at

https://www.aaiito.it/go/chisiamo/351/Emergenza COVID-19. Accessed on 1 May 2021.

M.A. Bruusgaard-Mouritsen, Margrethe Jensen B., Poulsen L.K. et al. Optimizing investigation of suspected allergy to polyethylene glycols. J Allergy Clin Immunol Published online: May 27, 2021.

Franceschini F, Bottau P, Caimmi S, et al. Evaluating children with suspected allergic reactions to vaccines for infectious diseases. Allergy Asthma Proc 2018;39:177-183.

Zhou ZH, Stone CA Jr, Jakubovic B, et al. Anti- PEG IgE in anaphylaxis associated with polyethylene glycol. J Allergy Clin Immunol Pract 2021;9:1718-20.

Wenande EC, Skov PS, Mosbech H, Poulsen LK, Garvey LH. Inhibition of polyethylene glycol-induced histamine release by monomeric ethylene and diethylene glycol: a case of probable polyethylene glycol allergy. J Allergy Clin Immunol 2013; 31:1425–7.

Bommarito L, Mietta S, Nebiolo F, Geuna M, Rolla G. Macrogol hypersensitivity in multiple drug allergy. Ann Allergy Asthma Immunol 2011;107:542–3.

Restivo V, Candore G, Barrale M. et al. Allergy to polyethilenglicole of anti-SARS CoV2 vaccine recipient: a case report of young adult recipient and the management of future exposure to SARS-CoV2. Vaccines 2021;9:412.

Baretto RL, Beck S, Heslegrave J et al. Validation of international consensus equation for acute serum total tryptase in mast cell activation: A perioperative perspective. Allergy 2017;72:2031-2034.

Caffarelli C, Franceschini F, Caimmi D, et al. SIAIP position paper: provocation challenge to antibiotics and non-steroidal anti-inflammatory drugs in children. Ital J Pediatr 2018;44:147.

Mirakian R, Ewan PW, Durham SR, et al. BSACI guidelines for the management of drug allergy. Clin Exp Allergy 2009;39:43-61.

Dworzynski K, Ardern-Jones M, Nasser S. Diagnosis and management of drug allergy in adults, children and young people: summary of NICE guidance. BMJ 2014;349:4852.