Shortly after emergency use authorization of COVID-19 mRNA vaccines was given, the
first reports of anaphylactic reactions emerged. While the causative agent is still
a matter of debate, allergy to the excipient polyethylene glycol (PEG) is a possible
explanation [1]. PEG is a hydrophilic polymer with variable molecular weight and also
the main constituent of many bowel cleansing agents used prior to colonoscopy. Anaphylaxis
to PEG-containing bowel cleansing preparations is exceedingly rare, with an estimated
average of four cases per year in the USA [2].
Within a timespan of 3 weeks, three patients cancelled appointments for colonoscopies
at our endoscopy department owing to anaphylactic reactions to the PEG-containing
bowel cleansing agent, which they had tolerated well for previous colonoscopies. All
patients had received vaccination with the COVID-19 mRNA vaccine made by Moderna 12–18
days before these events. Radioallergosorbent tests (RASTs) did not detect specific
anti-PEG IgE in any of the three patients. Two patients opted for inpatient allergy
testing at our hospital. Both had positive skin reactions after intradermal testing
with serial dilutions of the Moderna COVID-19 vaccine and one patient also had a positive
skin reaction to PEG 6000. Interestingly, indurated plaques developed on the Moderna
vaccine injection sites and lasted for 2 days. Detailed descriptions of symptoms and
clinical findings are provided in Table 1s (see online-only Supplementary material).
The onset of a new PEG allergy shortly after COVID-19 vaccination makes a causal relationship
likely. Possible mechanisms include a “classical” type 1 hypersensitivity by vaccine-triggered
anti-PEG IgE antibodies and an IgG/IgM-mediated hypersensitivity reaction called “complement
activation-related pseudoallergy” [1]. PEG-specific anti-IgE was not detectable in
any of the three patients, but this does not rule out an IgE-mediated type 1 allergy
owing to the sensitivity issues of RAST in general [3]. Typical skin reactions shortly
after intradermal injection of the vaccine itself (two patients) and PEG 6000 (one
patient) may support a possible type 1 allergy. However, the formation of indurated
cutaneous infiltrations after intradermal application of the vaccine could also point
to elements of a T cell-mediated delayed-type hypersensitivity.
Surprisingly, the patient who declined allergy testing received a second dose of the
Moderna COVID-19 vaccine without an allergic reaction. However, dose seems to be a
critical factor for a clinical response in patients with PEG allergy: incremental
oral challenge of a patient with known PEG allergy resulted in a systemic response
only after receiving very high doses, levels usually only reached during bowel preparation
for colonoscopy [4]. Another recent case series noted individual thresholds for dose
and/or molecular weight in patients with anaphylaxis after PEG exposure [5].
Vaccine-induced de novo formation or boosting of anti-PEG IgM/IgG causing a complement
activation-related pseudoallergy is an alternative explanation for the reactions seen
in these three patients, as this entity is usually dose-dependent. To the best of
our knowledge, this is the first publication of a possible vaccine-triggered PEG (pseudo)allergy.
Healthcare professionals should be aware of the possibility of a newly developed PEG
allergy after COVID-19 vaccination. Endoscopists particularly may see these cases
as patients typically ingest high doses of PEG during colonoscopy bowel preparation.
