Answer:
Macrogol and polyethylene glycol (PEG) adverse reactions have been discussed in prior Ask the Expert questions (see below). The issue of PEG allergy has assumed center stage during the COVID-19/SARS- CoV-2 vaccine reaction story as one hypothetical cause of reactions to the vaccines is PEG sensitivity (1). PEG is used in multiple oral and topical medications, plasticizers, solvents, surfactants, suppositories, laxatives, and personal care products. Despite this wide-spread use, sensitivity to PEG is rare but does occur. PEG is a polymer and thus may have a highly variable molecular weight, typically identified by the number following PEG. The number is either the molecular weight (medicinal products) or the number of 44 dalton-ethylene oxide units (cosmetics). The molecular weight of PEG may vary from 200 to 35 million daltons (2). Some sensitive subjects tolerate ingestion of lower molecular weight PEG containing products but react to higher molecular weight PEG products.
Investigating if PEG is responsible for multiple drug reactions could be pursued with skin testing, but this is not validated and the molecular weight of the PEG in each product may vary (2). Some physicians are using the laxative MIralax as a source of PEG for testing following reactions to COVID-19/SARS-CoV-2 vaccines (3). Again, the predictive value and utility of such testing is unknown.
I am not aware of a successful desensitization strategy for macrogols in medications injected intermittently. In general, lower molecular weight PEG and oral administration would be safer than injection. Perhaps a pharmacist could provide PEG content and molecular weight for the oral products available to treat rheumatology patients. I suggest trying products with lower PEG content and lower PEG molecular weight. Administration for the first time in a clinic with capability to treat anaphylaxis is advisable as deaths have occurred from PEG allergy (2). Daily oral administration of a PEG medication potentially would be less likely to result in future systemic reactions compared to intermittent administration by injection.
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAAI
1. Cabanillas, Beatriz, Cezmi Akdis, and Natalija Novak. "Allergic reactions to the first COVID‐19 vaccine: a potential role of Polyethylene glycol?." (2020).
2. Sellaturay P, Nasser S, Ewan P. Polyethylene glycol-induced systemic allergic reactions (anaphylaxis). J Allergy Clin Immunol Pract 2021;9:670-5.
3. Banerji A, Wickner PG, Seff R et al. mRNA vaccines to prevent COVID-19 disease and reported allergic reactions: current evidence and suggested approach. J Allergy Clin Immunol Pract 2021 (in press).
7/17/2019
Is there any data in regard to cross-reactivity between propylene glycol and macrogols?
Answer:
I asked Rachel Robison, MD for her input on your question. Her response is as follows:
"Propylene glycol (PG) and Macrogols (such as polyethylene glycols or PEGs) are synthetic substances that are used as vehicles in various cosmetic and medicinal products. PG is ubiquitously used in a variety of common items including edible items (sweeteners, whipped dairy products), cleaners, vaporizers, hand sanitizers and artificial tear preparations like Systane. It is a common cause of allergic contact dermatitis (ACD) and was named the ACD Society’s allergen of the year in 2018. In addition to causing contact dermatitis with cosmetic exposure, systemic contact dermatitis has been reported after oral ingestion. As PG is both a weak sensitizer and a cause of irritant dermatitis, patch testing interpretation can be difficult to interpret as testing results may not be robust if low concentrations are used and may lead to irritant response with higher concentrations. 1,2 There are no reports upon literature review of IgE-mediated or anaphylactic reactions to PG.
PEG is also found in multiple cosmetic and industrial products and is used quite frequently in medicine as it is found in PEGylated medications, hydrogels, tablets and lubricants. Though thought to be fairly safe, there are multiple reports of immediate type hypersensitivity reactions consistent with anaphylaxis. A 2016 systematic review, noted 37 case reports of PEG induced reactions, 80% due to oral PEG exposure.3 Some cross reactivity does appear to exist between PEG and structurally related polymers such as polysorbate 80 and poloaxmer.3
PG and PEG have dissimilar chemical structures. PG is a small, single molecule with 3 carbons and 2 OH groups ( ie a double alcohol). PEG is a multi-unit polymer with a differing molecular weight and backbone. Historically the types of reactions these agents cause are dissimilar as noted above. Few studies have looked at sensitization to both agents. A single Turkish study retrospectively looked a patch testing for both PG and PEG as a marker for nitrofurazone allergy.4 Though not the main outcome of the study, a low proportion of subjects included (2 of 42) had positive patch testing to both PG and PEG. Thus there is not sufficient literature to support cross reactivity between PG and PEG. Though I am not sure which agent your patient has reacted to in the past, given how ubiquitous both agents are it would be prudent to take a detailed history as it is likely they are already tolerating exposure to the other agent which can provide some reassurance."
References:
1. McGowan MA, Scheman A, Jacob SE. Propylene Glycol in Contact Dermatitis: A Systematic Review. Dermatitis. 2018; 29(1):6-12.
2. Lalla SC, Nguyen H, Chaudry H et al. Patch testing to propylene glycol: The Mayo experience. Dermatitis. 2018; 29(4) 200-205.
3. Wewande E and Garvey LH. Immediate-type hypersensitivity to polyethylene glycols: a review. Clin Exp Allergy. 2016; 46(7): 907-922.
4. Ozkaya E and Kilic S. Polyethylene glycol as marker for nitrofurazone allergy: 20 years of experience from Turkey. Contact Dermatitis. 2018; 78(3): 211-215.
I hope this is helpful.
Regards,
Daniel J. Jackson, MD, FAAAAI
9/25/2018: Polyethylene glycol allergy
I have a patient who came in with three episodes of anaphylaxis to three different substances/meds all containing macrogols. This was the common ingredient in all instances. First was to GoLytely, second was to miralax and the final was to possibly the lubrication used during a colonoscopy or propofol. In all three reactions, the patient had hives, throat closing, wheezing, bronchoconstriction. The episode during the colonoscopy led to intubation and hospitalization x three days. The patient does not have any known allergies or PMH. My question is how to test for a potential allergic response to macrogols/polyethylene glycol/propylene glycol. Would this be performed through skin testing? Is there any protocol in place to follow for this type of allergy?
Answer:
I asked Dr. Eric Macy for assistance with the response. He stated that Polyethylene Glycol (PEG) is a very rare allergy. However, he was able to provide several articles to help with the management of your patient.
Skin testing has been described by Wylon et al (1).
Further, a recent RCT in children by DiNardo et al (2) suggests that a non-PEG bowel prep may be a good alternative and safe approach for your patient.
1. Wylon, K., S. Dolle, and M. Worm. "Polyethylene Glycol as a Cause of Anaphylaxis." Allergy Asthma Clin Immunol 12 (2016): 67.
2. Di Nardo, G., M. Aloi, S. Cucchiara, C. Spada, C. Hassan, F. Civitelli, F. Nuti, et al. "Bowel Preparations for Colonoscopy: An Rct." Pediatrics 134, no. 2 (Aug 2014): 249-56.
I hope you find this helpful.
Best regards,
Daniel J. Jackson, MD, FAAAAI