PEG Allergy and How to Test: A Guide for Clinicians and Patients Too!
Polyethylene glycols (PEGs) also known as macrogols, are hydrophilic polymers.
You’ll find them everywhere: medications, cosmetics, even food!
As an Allergist/Immunologist, I’ve had moments where I’m scratching my head—”Why did my patient react to a ‘harmless’ colonoscopy prep or depot steroid injection?” 🤔 Two seemingly unrelated reactions, but one hidden culprit…
PEG—the ninja excipient.
But Wait, There’s More! 🥷
Not all PEG-allergic patients will react to every exposure.
We’re learning that molecular weight matters—the bigger the PEG, the higher the risk of anaphylaxis.
And dose counts too: small exposures may fly under the immune radar, while large doses can light the fire.
⚠️ Bonus twist: Polysorbate (PEG’s structural cousin) can trigger cross-reactivity—you may be chasing two villains in the same disguise.
Why PEG Allergy Deserves Attention
Rare but severe: Over 7 years in 4 major UK hospitals, only 42 patients were identified—but reactions? Some were life-threatening.
Master of disguise: PEG hides in bowel preps, depot injections, tablet coatings, cosmetics, even vaccines. Many patients with “multiple drug allergy” may be reacting to PEG’s many forms.
Vaccine nuance: While PEG in COVID vaccines made headlines, the broader issue is this—many vaccines and injectables contain PEG or polysorbate.
PEG’s Hideouts: Where to Look
Here’s your clinician cheat sheet:
Oral: Bowel preps (PEG 3350), laxatives, some coated tablets.
Injectables: Depot steroids (e.g., Depo-Medrol™), contraceptives (e.g., Depo-Provera™), PEGylated biologics, contrast agents.
Vaccines: Some newer formulations contain PEG or polysorbate 80.
Topicals: Creams, lotions—small doses, but ask if history is suspicious.
💡 Pro tip: Same drug name ≠ same formulation. PEG may sneak into one version, but not another. Always check excipient lists—or phone a pharmacist!
Why Is PEG Everywhere?
PEG is the Swiss Army knife of excipients:
Solubility & stability: Keeps tricky drugs dissolved and stable. Without it, many compounds would clump or degrade.
Depot release: Controls slow-release in injections (e.g., steroids).
Biologics booster: “PEGylation” improves half-life of proteins.
Nanoparticle shield: PEG coats lipid nanoparticles in some vaccines.
Osmotic action: In bowel preps, it draws water into the gut.
Tablet & Topical stealth mode: As a binder or moisturizer, PEG hides in coatings and creams.
In a nutshell: PEG’s magic is solving formulation puzzles – making drugs dissolve, stay stable, or release slowly. That’s why it’s everywhere. And that’s why, when allergy strikes, it can seem like the culprit is hiding in plain sight.
The Immune Plot: How PEG Sparks Reactions
PEG isn’t a protein—but it can still stir up the immune system. Here’s how:
1. IgE-Mediated Reaction
Some patients form anti-PEG IgE. The next exposure? 🎯 Boom—mast cell degranulation: hives, angioedema, anaphylaxis. Skin tests may pick this up – if done properly.
2. Complement Activation (CARPA)
Anti-PEG IgG/IgM latch onto PEG clusters → complement activation → pseudoanaphylaxis. Feels like classic allergy, but not IgE. Skin tests? Hit or miss.
3. Dose & Molecular Weight Threshold
High-MW PEGs (e.g., PEG 3350) are more likely to cause reactions. Tiny PEG-300? Often tolerated. Big size + big dose = bigger risk.
4. Other Pathways
Direct mast cell activation? Possibly. If history screams allergy but tests are negative, keep this on your radar.
When to Suspect PEG Allergy: Clinic Detective Work 🕵️♀️
“Doc, I got hives after a Depo shot years ago. Last month, a steroid injection made me swell up and wheeze. Are they related?”
Yup. If both products contain high-MW PEG, they might be.
Red flags to look for:
Multiple immediate reactions to unrelated meds.
‘Multiple drug allergy’ that doesn’t fit pharmacologically.
Severe symptoms: hypotension, lip/tongue swelling, respiratory distress.
Reactions to PEG-rich meds: laxatives, depot shots, PEGylated drugs.
Ask smart questions: “Ever had a reaction to colonoscopy prep? Depot steroids? PEG-containing vaccines?”
Diagnosing PEG Allergy: Skin Testing (How we do it)
There’s no commercial test. No quick blood panel. So we MacGyver it.
Key principles:🔍
1. Start low & slow
Begin with dilute PEG solutions.
2. Use known products:
- SPT with PEG 3350 solution.
- IDT with Depo-Medrol (PEG) and Triamcinolone (PS80).
3. Controls:
Always use histamine (+) and saline (–).
4. Escalate stepwise:
- Start with skin prick test.
- If negative but suspicion is high, proceed to intradermal (1:100 → 1:10).
- Observe ≥30 minutes between each step (Reports of delayed systemic reactions)
⚠️ Warning: Intradermal testing can trigger systemic reactions. Epinephrine must be ready.
Interpretation: Wheal ≥3 mm above negative control = positive.
Bonus tip: Don’t forget polysorbate—test it if history suggests cross-reactivity.
If tests are inconclusive? Consider a graded challenge under controlled conditions.
Vaccination in PEG-Allergic Patients: Can It Be Done Safely? Yes.
The truth? Even PEG-allergic patients can tolerate vaccines with PEG—if done thoughtfully.
✅ General Approach:
1. Risk Stratify
- No PEG/polysorbate history? Proceed with routine vaccination.
- Past reaction? Refer to an allergist.
2.Skin Testing
Optional but helpful. Positive = confirm allergy. Negative = not a free pass, but lower risk.
3.Informed Consent & Planning
Explain graded dosing under supervision is often successful.
4.Graded Dosing Protocol
- Start with 10% of the dose → wait 30–60 mins.
- If no reaction, give remaining 90% → observe again.
- Some high-risk patients get 3–4 step splits.
5.Choose Alternatives
If PEG-free vaccines exist, consider switching (watch for polysorbate too).
6.Document & Educate
- Update EMR allergy list and give patient information about PEG allergy.
- Recommend a medical alert ID.
- Discuss about Epinephrine auto-injector for patients with history of anaphylaxis as PEG is found in many types of medications.
PEG in Food: Should You Worry? 🍽️
You might ask, “Wait—PEG in my patient’s ice cream? Could that spark allergy?”
Yes, PEG hides in foods (it wears the code E‑1521). You’ll spot it in:
- Dietary supplements (capsule/tablet coatings & binders).
- Processed snacks (chewing gum, candies) as an emulsifier or anti-caking agent.
- Beverages as an anti-foaming or lubricant.
- Sauces & dressings for stabilization or thickness.
But here’s the good news: clinical reactions from food-grade PEG are virtually nonexistent. Why?
- Tiny doses: Food exposure is usually a few mg/kg/day—way below the levels that trigger allergy.
- Low molecular weight: Food PEGs tend to be small (e.g., PEG-400 to 600 Da), which is much less likely to rile the immune system.
- Oral route advantage: Ingestion is gentler; systemic anaphylaxis from eating PEG is extremely rare (so far, no reported cases!).
Bottom line: For PEG-allergic patients, focus on the big players—high-dose, high-MW exposures like bowel preps, depot injections, PEGylated biologics, and certain vaccines. Food-grade PEG? Generally safe and low risk.
✅ Final Takeaway
PEG allergy is sneaky but manageable.
Recognize the red flags.
Test thoughtfully.
Vaccinate safely.
And I always ask my patients to bring something for entertainment (book,tablet,music) … for the prolonged observation period during testing.
📌 Once a person is tested positive to PEG, give them a list of common medications containing PEG.
The Allergy Immunology Clinic stands ready to help evaluate patients with PEG allergy. Please contact us to arrange for an appointment
References
Kennard L, Rutkowski K, Mirakian R, Wagner A. Polyethylene glycol: Not Just a Harmless Excipient. J Allergy Clin Immunol Pract. 2018.
Banerji A, Wickner PG, et al. Evaluation of PEG and Polysorbate Allergy in Vaccines. J Allergy Clin Immunol Pract. 2021.
Kelso JM. Polyethylene glycol allergy… for real this time! Ann Allergy Asthma Immunol. 2024.
- Sellaturay P, Nasser S, Ewan P. Polyethylene Glycol-Induced Systemic Allergic Reactions (Anaphylaxis). J Allergy Clin Immunol Pract. 2021.
