What is polyethylene glycol (PEG) allergy?

The short answer

PEG allergy refers to an allergy to polyethylene glycol (PEG). A polymer you can find in several substances that you may use every day. It is a serious problem that sometimes may be fatal. This article illustrates what are PEG, PEG-containing products, and PEG allergy.

Key Facts:

Polyethylene glycol (PEG) or macrogol and its derivatives are a widely used polymer that is commonly used in the preparation of cosmetics, household products, and many other daily used products.
PEG is also commonly used in the pharmaceutical field to prepare different pharmaceutical formulations such as the anticancer agent Doxil.
The administration of PEG-containing medications (PEGylated therapeutics) was found to induce your body to produce anti-PEG antibodies.
The daily used cosmetic products containing PEG or PEG derivatives were also found to induce your body to produce anti-PEG antibodies. These antibodies are known as pre-existing anti-PEG antibodies that could be found in healthy populations.
The presence of anti-PEG antibodies in your blood increases your risk of developing a hypersensitivity reaction when you take medications or use products containing PEG molecules.
The circulating anti-PEG antibodies could recognize and interact with PEG molecules in your medications or other PEG-containing products you use daily. This could lead to hypersensitivity reactions.
An intradermal skin test could be helpful in confirming PEG allergy

What is PEG:

PEG means polyethylene glycol polymer. It is also known as macrogol. It is also known as polyethylene oxide as it is composed of repeated units of ethylene oxide.

PEG is an inert synthetic hydrophilic polymer with broad-spectrum applications (Ref.).

PEG is Generally Recognized as Safe by the FDA (Ref).

You will find PEG labeled on the market products as PEG-X while the abbreviation PEG means polyethylene glycol while X is a number that represents the average molecular weight of PEG.

For example, PEG-300 means polyethylene glycol with an average molecular weight of 300 g

PEG-4000 means polyethylene glycol with an average molecular weight of 4000 g.

For cosmetic products, the numerical value refers to the average number of ethylene oxide units.

What is PEG allergy:

PEG allergy is a potentially life-threatening hypersensitivity reaction that could result from a hidden molecule present in many of your daily used products. The anaphylaxis reaction to PEG is rarely reported, however, during the last few decades, reports of the hypersensitivity reaction against PEG molecules have significantly increased. This is attributed to the fact that nowadays, PEG commonly exists in a wide range of cosmetics and skin and hair care products.

PEG allergy may be mild and localized when it results from topical or oral administration of PEG-containing products. It may be limited just to dermatological symptoms and can be easily controlled. However, allergy to PEG is problematic when it results after intravenously or intramuscularly administered drugs. The symptoms are rapidly worsening and anaphylaxis could result.

A review of the FDA adverse events reports from 2005 to 2017 about 4 cases of anaphylaxis to PEG per year (Ref).

How does PEG allergy occur?

Many researchers reported that the administration of PEGylated therapeutics (medications that contain PEG molecules) such as vaccines or anticancer agents induces the formation of antibodies against PEG commonly known as anti-PEG antibodies.

Also, using cosmetics products containing PEG in normal daily life leads to the formation of antibodies against PEG.

Your body reacts with PEG as an antigen, hence anti-PEG antibody is formed commonly anti-PEG IgM antibodies (Ref).

When you administer medications containing PEG molecules which are commonly present in numerous pharmaceutical products, the anti-PEG antibodies that were previously formed within your body can recognize and react with PEG molecules in your medications leading to a hypersensitivity reaction (Ref). This is simply illustrated in the figure below:

**Graphical illustration of how PEG allergy occurs**

This hypersensitivity allergic reaction to PEG could be a life-threatening allergy.

A reported death case following PEG-induced anaphylaxis. An Ireland man 24 years old developed urticaria after an injection of glucocorticoid containing PEG. One year later, he was given a second glucocorticoid injection and died from anaphylaxis (Ref).

Moreover, the anti-PEG antibodies formed when you take medication containing PEG or when you use cosmetics or any products containing PEG, these antibodies were found to affect the therapeutic effect of some medications.

There is a large body of research confirming that anti-PEG antibodies lead to a rapid clearance of certain medications from your body.

When your body has circulating anti-PEG antibodies and then you take medications also containing PEG, this medication is rapidly removed from your body, as a result, you lose the effect and the action of this medication. This phenomenon is commonly referred to as the Accelerated Blood Clearance ABC phenomenon

Symptoms of PEG allergy:

Symptoms of PEG allergy are similar to those recorded with any allergic reactions. Moreover, symptoms associated with PEG allergy may be expressed at a higher intensity and could develop an anaphylaxis reaction.

These symptoms include (Ref):

Cardiopulmonary distress symptoms such as tachycardia and dyspnea
Chest pain
Breathlessness
Flushing
Fever
Rash

In severe cases of PEG allergy symptoms may develop into:

Pulmonary hypertension.
Systemic hypo/hypertension
Hematological changes such as thrombocytopenia

A recent study reported a case of hypersensitivity reaction to PEG.

A female 20-year-old showed a hypersensitivity reaction after administration of the Pfizer/BioNTech COVID-19 vaccine.
Symptoms appeared as headache and elevated heart rate. 5 minutes later, she had angioedema, cramping and abdominal pain.
She was admitted to the emergency department.
The history of this patient showed a previous PEG allergy to food and other products containing PEG molecules.
Thus, her body had an anti-PEG antibody, when she administered this type of vaccine which contains PEG, an anaphylaxis reaction occurred within a few minutes.

A 2013 study published in the Journal of Nature Reviews Nephrology examined the safety of OEGinestide for patients with chronic kidney disease.

PEGinesatede was approved by the FDA in 2011 for the treatment of patients with chronic kidney stones suffering from anemia.
Fetal hypersensitivity reactions were reported for 0.02 % of treated patients rapidly within 30 minutes of administration.
The hypersensitivity reaction occurred during the first exposure to the drug.
This medication was withdrawn from the market in 2013 due to this hypersensitivity reaction.

A 2015 study reported a case of 39 39-year-old male who was referred to the emergency room for loss of consciousness and dyspnea after taking Colyte®(o containing PEG-3350).

The patient received Colyte® before the colonoscopy
He arrived at the Emergency Department with a blood pressure of 80/66 mmHg, and severe respiratory distress with wheezing sounds in whole lung fields.

How to test PEG allergy:

A skin test can be helpful for the identification of PEG allergy before its occurrence. It has been successfully used to confirm suspected allergy to PEG-containing products.

This test is best performed on those with previous sensitivity to PEG products and those at high risk of developing PEG allergies.

An intradermal test was performed with a diluted solution of PEG and noticed the skin results. In the case of PEG allergy existence, swelling, edema, and an allergic reaction occur.

For example, the intradermal skin test for PEG 3350 (MiraLAX) testing was performed using sequential skin pricks at 1.7 mg/mL, 17 mg/ml, and 170 mg/mL. Methylprednisolone acetate (PEG-containing), methylprednisolone sodium (control)

PEG-containing products:

Medications (Pharmaceutical products):

It is commonly used in pharmaceutical formulations (medications) as a solubilizing agent and surfactant. You can find PEG in the following (Ref):

Pharmaceutical products
- Tablets containing antihistaminic drugs such as Telfast, cetirizine, loratadine
- Laxatives such as Miralax and Clearlax
- Injection such as Doxil for breast cancer therapy and Depo-Provera for contraception.
- Vaccines such as Pfizer/BioNTech COVID-19 vaccine
Cosmetics:

PEG is widely used in cosmetics and personal care products, it is used as penetration enhancers for topical cosmetics as skin and hair care products. Also, it acts as a surfactant, and skin conditioning

Cosmetics containing PEG:
- Lotions such as Bioderma lotion
- Cream such as Zarasyl cream
- Shampo such as Dial Kids for body and hair wash.
- Toothpaste such as Sensodyne
Foods and drinks:

Also, you can find PEG as an additive in your foods and drinks

Foods and drinks containing PEG:
- Soft drinks
- Popcorn
- Dairy products
- Bread
- Fast foods
- Coloring agents in foods