The most common immediate hypersensitivity to macrogols is associated with PEG 3350, however the epidemiology, mechanisms and cross-reactivity are poorly understood. Thousands of medications contain either PEGs or structurally similar polysorbates.
Skin testing and oral challenges with PEG and polysorbate-containing agents were employed to determine clinical reactivity and cross-reactivity between the two allergens.
Skin and provocation testing demonstrated symptomatic reactivity in both cases to PEG 3350 and polysorbate 80… [and] increased directly proportional to the molecular weight of PEG tested.
Immediate hypersensitivity to PEG 3350 with cross-reactive polysorbate 80 hypersensitivity may be under recognized in clinical practice and can be detected with clinical skin testing.
Macrogols, including polyethylene glycols (PEG) and the structurally related polysorbates, are compounds whose primary feature includes polyether groups. They have wide ranging use in medical and commercial settings, with molecular weights (MW) that range from 200 to 35,000g/mol.
[Patient 1]… 5 years prior to presentation, he noted that while preparing for a colonoscopy, taking oral Colyte® brand colonoscopy preparation (active ingredient PEG 335023) he developed severe itching of his palate and throat…
Two years prior to presentation, he underwent injection of methylprednisolone acetate (excipient PEG 335024) into his neck as treatment of radicular pain from a bulging disk. Within seconds of receiving this medication, he developed urticaria [rash], burning all over the body, throat tightness, wheezing, and hypotension.
One year prior to presentation, he was scheduled for routine follow up of his initial colonoscopy. During his first few sips of Moviprep® brand colonoscopy preparation (active ingredient PEG 335025) he developed severe itching of his palate and throat, along with diffuse urticaria.
Three months prior to presentation, he attempted once again to undergo colonoscopy, using oral GavilyteTM-G generic preparation (active ingredient PEG 335026). He consumed approximately 10–12 ounces and subsequently developed itching, burning urticarial rash…
[H]e experienced syncope and fell, knocking a hole in the drywall with his head. Upon hearing the fall, his son, a nurse, arrived and checked his father’s blood pressure, which was 60/20…
[Patient 2] was a 51 year old with an occupational history as a mechanic exposed to glycol containing hydraulic fluids… One month prior to presentation, he began to develop a reaction just prior to a scheduled colonoscopy after use of a polyethylene glycol 3350 colonoscopy preparation.
Both patients subsequently underwent prick and intradermal skin tests…
Patient 1 was subsequently demonstrated to have skin test positivity [allergic reaction] to other polysorbate 80 containing products, including eye drops and conjugated pneumococcal vaccine…
While Patient 2 had negative prick testing to PEG 3350 containing products… he did have positive testing to triamcinolone acetonide containing polysorbate 80.
Upon challenge with PEG 3350 he developed diffuse urticaria, respiratory distress and hypotension requiring epinephrine and emergency department transfer.
The most commonly known clinical use of macrogols such as PEG 3350 is in colonoscopy preparation or constipation treatment.
However, a review of common products and the literature demonstrates that polyethylene glycol and structurally similar polysorbate compounds can be found in vascular graft materials, surgical gels, PEGylated medications, household and industrial compounds, and as an excipient in a multitude of other medications both injectable and oral. In these settings, PEGs and polysorbates are not consistently described in ingredient lists.
High molecular weight polyethylene glycols are common excipients in a wide variety of medications, household products and industrial products which may provide a vehicle for sensitization in a subset of susceptible individuals.
Allergists should be aware that cross-reactive immediate hypersensitivity to polyether containing compounds such as macrogols/ PEGs and polysorbates can occur, that they may occur via a Type I hypersensitivity mechanism, and that they may be underrecognized.