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.

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.

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.

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.

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.