Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized

J Allergy Clin Immunol Pract. 2019 May-Jun;7(5):1533-1540.e8. doi: 10.1016/j.jaip.2018.12.003. Epub 2018 Dec 14.


Background: The most common immediate hypersensitivity to macrogols is associated with polyethylene glycol (PEG) 3350; however, the epidemiology, mechanisms, and cross-reactivity are poorly understood. Thousands of medications contain either PEGs or structurally similar polysorbates.

Objective: Our objective was to better understand the mechanism, cross-reactivity, and scope of PEG hypersensitivity.

Methods: Two cases with a past history of immediate hypersensitivity to PEG-containing medications were used to study potential mechanisms and cross-reactivity of immediate reactions to PEG 3350. Skin testing and oral challenges with PEG and polysorbate-containing agents were employed to determine clinical reactivity and cross-reactivity between the 2 allergens. Enzyme-linked immunosorbent assay and electrochemiluminescent immunoassay were used to detect anti-PEG specific IgG and IgE, respectively, using PEGylated protein or PEG alone as antigens in 2 cases and 6 PEG 3350 tolerant controls. We searched US Food and Drug Administration (FDA) adverse event reports for immediate reactions to PEG 3350 to determine the potential scope of this problem in the United States.

Results: Skin and provocation testing demonstrated symptomatic reactivity in both cases to PEG 3350 and polysorbate 80. Plasma samples were positive for anti-PEG specific IgE and IgG antibodies only in cases and binding increased directly proportional to the molecular weight of PEG tested. FDA adverse event reports revealed 53 additional cases of possible PEG 3350 anaphylaxis.

Conclusions: Immediate hypersensitivity to PEG 3350 with cross-reactive polysorbate 80 hypersensitivity may be underrecognized in clinical practice and can be detected with clinical skin testing. Our studies raise the possibility of an IgE-mediated type I hypersensitivity mechanism in some cases.

Keywords: Allergy; Immediate hypersensitivity; PEG; Polyethylene glycol; Polysorbate.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / adverse effects*
  • Cross Reactions
  • Humans
  • Hypersensitivity, Immediate / epidemiology
  • Hypersensitivity, Immediate / etiology*
  • Immunoglobulin E / immunology
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects*
  • Polysorbates / adverse effects*
  • Skin Tests


  • Allergens
  • Polysorbates
  • Immunoglobulin E
  • Polyethylene Glycols