Optimizing investigation of suspected allergy to polyethylene glycols

Abstract

Background: Polyethylene glycols (PEGs) are polymers of varying molecular weight (MW) used widely as excipients in drugs and other products, including the mRNA vaccines against coronavirus disease 2019. Allergy to PEGs is rare. Skin testing and graded challenge carries a high risk of inducing systemic reactions. Objective: We evaluated skin prick test (SPT) results and in vitro reactivity over time to different MW PEGs and assessed cross-sensitization patterns in PEG allergy. Methods: Ten patients with previously diagnosed PEG allergy underwent SPT twice with PEGs 26 months apart. Lower MW (PEG 300, 3000, 6000) were tested, followed by PEG 20,000, in stepwise, increasing concentrations. Cross-sensitization to polysorbate 80 and poloxamer 407 was assessed. SPT was performed in 16 healthy controls. In vitro basophil histamine release (HR) test and passive sensitization HR test were performed in patients and controls. Results: Patients previously testing positive on SPT to PEG 3000 and/or 6000 also tested positive to PEG 20,000. Patients with a longer interval since diagnosis tested negative to lower MW PEGs and positive mainly to higher concentrations of PEG 20,000. Three patients developed systemic urticaria during SPT. Eight patients showed cross-sensitization to poloxamer 407 and 3 to polysorbate 80. All controls tested negative. In vitro tests showed limited usefulness. Conclusions: Skin test reactivity to PEG can decrease over time, but titrated SPT with increasing concentrations of PEG 20,000 can be diagnostic when lower MW PEGs test negative. To avoid systemic reactions, stepwise SPT is mandatory. (J Allergy Clin Immunol 2021;nnn:nnn-nnn.)

mRNA COVID-19 vaccine safety in patients with previous immediate hypersensitivity to pegaspargase

“…Therefore, patients with IgE-mediated sensitization to PEG have been shown to lose sensitization to lower-molecularweight PEG before higher-molecular-weight PEG and reactivity to lower-molecular-weight PEG can be variable. 5 The lack of evidence of any immediate reaction on either the first or second dose of the Pfizer-BioNTech COVID-19 mRNA vaccines also does not support an IgE mechanism or immunological resensitization to PEG as a result of immunization.…”

“…4 IgE-mediated PEG allergy is rare but has been demonstrated with positive skin testing and elevated specific IgE levels. [5][6][7] Interestingly, patients with immediate hypersensitivity to pegaspargase typically have subsequent tolerance to PEG3350, which is routinely used to treat constipation associated with other chemotherapeutic agents for ALL and LL. However, patients and clinicians maintain high vigilance toward the possibility of cross-reactivity reactions to higher-molecular-weight PEG-containing products.…”

Janssen COVID-19 vaccine tolerated in 10 patients with confirmed polyethylene glycol allergy

“…[3][4][5] Although patients with immediate hypersensitivity to PEGs may show crosssensitization to polysorbates, the clinical relevance of this sensitization is not clear. 6,7 The mRNA coronavirus disease 2019 (COVID-19) vaccine from Pfizer-BioNTech is now licensed in the United States and Europe (Comirnaty), and Moderna COVID-19 mRNA vaccine under emergency use authorization in the United States is now licensed in Europe (Spikevax). The rollout of the mRNA vaccines in December 2020 was associated with cases of anaphylaxis that sparked new interest in the cross-sensitizing potential between PEGs and polysorbates.…”

“…The rollout of the mRNA vaccines in December 2020 was associated with cases of anaphylaxis that sparked new interest in the cross-sensitizing potential between PEGs and polysorbates. 6,7 The liponanoparticles of the mRNA COVID-19 vaccines are stabilized by a PEG 2000-lipid. The single-dose adenoviral vector COVID-19 vaccine available in the United States (Janssen; Johnson&Johnson) and the 2-dose adenoviral vector vaccine used in the United Kingdom, Europe, Australia, and Canada (ChAdOx1 [AZD1222, Vaxrevia]) contain polysorbate 80 as a stabilizer.…”

“…Clinical details, not related to COVID-19 vaccination of 4 patients, have been published previously. 6,9 All patients had been diagnosed with PEG allergy 1.5 months to 9 years before COVID-19 vaccination, with 8 of 10 patients reporting anaphylaxis (World Allergy Organization grade 3-5) 8 following documented PEG exposure. No patient had a history of previous adverse reactions to any vaccine, and none had experienced a clinical reaction to polysorbate 80econtaining products.…”