key: cord-1031925-sni1e160
authors: Sellaturay, Priya; Nasser, Shuaib; Islam, Sabita; Gurugama, Padmalal; Ewan, Pamela W.
title: Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID‐19 vaccine
date: 2021-04-09
journal: Clin Exp Allergy
DOI: 10.1111/cea.13874
sha: 01b98dbb1174280f0795d5f8ae1d619ee7ecbfa5
doc_id: 1031925
cord_uid: sni1e160

On the first day of the UK vaccination campaign with the coronavirus disease 2019 (COVID-19) vaccine there were reports of 2 cases of anaphylaxis within minutes of administration of the Pfizer/BioNTech messenger RNA (mRNA) vaccine and a third case of an allergic reaction not requiring adrenaline (epinephrine). This was alarming, as anaphylaxis to vaccines is rare; in the order of 1 case per million doses (1), and therefore likely to injure public confidence. The UK Medicines and Healthcare products Regulatory Agency (MHRA) issued precautionary advice restricting access to the vaccine (2), which was subsequently relaxed in line with the Summary of Product Characteristics. The cause of these vaccine anaphylaxis cases is unclear, but polyethylene glycol (PEG) is a candidate allergen (3,4). Here we demonstrate for the first time that allergy to PEG can cause anaphylaxis to the Pfizer/BioNTech vaccine.

issued precautionary advice restricting access to the vaccine, 2 which was subsequently relaxed in line with the summary of product characteristics. The cause of these vaccine anaphylaxis cases is unclear, but polyethylene glycol (PEG) is a candidate allergen. 3, 4 Here, we demonstrate for the first time that allergy to PEG can cause anaphylaxis to the Pfizer/BioNTech vaccine.

Allergy to PEG is rare, 5,6 but reactions can be severe or even fatal. 7 PEG is an excipient of many drugs, but hypersensitivity depends on its molecular weight (MW). She gave a history of allergic reactions to multiple products including drug anaphylaxis. Three years ago, after a first dose of azithromycin containing PEG 6000, she developed facial swelling, widespread urticaria and wheezing. Adrenaline was administered, and she was taken to hospital. She described urticaria with shampoos, conditioners, shower gels containing PEG and immediate burning of the mouth with toothpastes and mouthwash containing PEG. She had never received products such as laxatives, depoprogesterone or depo-methylprednisolone containing PEG 3500.

She was investigated in our drug allergy clinic 15 days after vaccination. She was not known to be PEG allergic prior to vaccination, but due to the severity of her reaction and previous history we suspected PEG allergy.

Skin prick testing was undertaken to PEG 400, 600, 2000, 3350, 4000, 6000, 8000 and 20,000 at 0.1% and 1% (w/v in Coca's solution) and polysorbate 80 at 10% and 20% (Thermo Fisher Scientific).

We also tested the Pfizer/BioNTech vaccine, excipients of the vac- vaccines such as influenza) and as a food additive and is thus widely tolerated.

To our knowledge, this is the first demonstration that anaphylaxis to the Pfizer/BioNTech vaccine can be due to PEG allergy. The case had a large positive skin prick test to PEG 4000 and systemic reaction on skin prick testing, confirming a reproducible response to PEG. Mast cell tryptase level did not increase in the index reaction or in the skin test-induced anaphylaxis. This might be because the severe features of the skin test reaction were predominantly respiratory as in food anaphylaxis where tryptase is often within the normal range, but does not explain the vaccine reaction. 11

Diagnosis of PEG allergy is challenging, with most PEG-allergic patients presenting with severe anaphylaxis to multiple unrelated drugs. 6 Our patient's history of multiple drug allergic reactions with sudden-onset anaphylaxis supported a diagnosis of PEG allergy. She also reacted to PEG in shower gels, shampoos, toothpaste and mouthwash.

It was unusual that skin prick tests were positive only to PEG 4000 and not at higher molecular weights. PEG skin prick tests may become positive slightly later from 10-30 minutes. 5 Undiagnosed PEG-allergic patients are at risk of anaphylaxis to mRNA vaccines containing PEG, so should be identified before vaccination. We suggest a guide to detecting PEG allergy based on our clinical experience and review of the literature in Table 1 

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