Polysorbate immediate-type hypersensitivity
Question:
3/11/2019
I have a patient who experienced anaphylaxis to Xolair, anaphylactoid reaction to Fasenra and diffuse pruritus with Nucala. Given her history of severe persistent asthma and inability to tolerate ANY form of steroids due to central serous chorioretinopathy, Dupixent was tried. She tolerated Dupixent and her asthma is now well controlled. After reviewing all ingredients of above named biologic agents, it seems as though polysorbate 20 may be the culprit. I was able to find a skin test protocol for polysorbate 80 (irritating dose of 1:10) but I could not find anything in the literature for polysorbate 20. I was wondering if there was a skin test that might help?
Answer:
The polysorbates used in the formulation of biopharmaceuticals are mixtures of different fatty acid esters with the monolaurate fraction of polysorbate 20 making up only 40-60% of the mixture and the monooleate fraction of polysorbate 80 typically making up >58% of the mixture. Polysorbates include oleic acid (Polysorbate-80), lauric acid (Polysorbate-20), and stearic acid (Polysorbate-60). These all appear to be immunologically cross reactive with polyethylene gylcols. The Stone and coworkers article noted below has the skin testing methodology well described. Immediate-type hypersensitivity to all of the polysorbates can be skin tested for using the same dilutions. Tolerance of dupilumab has essentially already answered your question.
Stone CA Jr, Liu Y, Relling MV, Krantz MS, Pratt AL, Abreo A, Hemler JA, Phillips EJ. Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized. J Allergy Clin Immunol Pract. 2018 Dec 14. pii: S2213-2198(18)30823-7. doi: 10.1016/j.jaip.2018.12.003.
Palacios Castaño MI, Venturini Díaz M, Lobera Labairu T, González Mahave I, Del Pozo Gil MD, Blasco Sarramián A. Anaphylaxis Due to the Excipient Polysorbate 80. J Investig Allergol Clin Immunol. 2016;26(6):394-396.
Kerwin BA. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways. J Pharm Sci. 2008 Aug;97(8):2924-35.
I hope this information is of help to you and your patient.
Regards,
Eric Macy, MD, MS, FAAAAI