Anaphylaxis following ingestion of docusate
Question:
1/12/2023
I have a 73-year-old women who developed hypotension (60/40), hives, emesis and near LOC 15 minutes after docusate ingestions. No additional exposures, exercise or stings. Ingredients include red dye 40, yellow dye 6, gelatin, glycerin, mannitol, pharmaceutical ink, PEG 400, propylene glycol, Sorbian, sorbitol, H20. ImmunoCap negative for red dye, gelatin, alpha gal, and normal tryptase at baseline. I did SPT for PEG using MiraLAX (PEG3350) at 1:100,1:10,1:1, all negative. IDs to depomedrol negative. I am apprehensive to do an oral challenge to MiraLAX until I have a good source her reaction. Is there additional testing you would recommend first? Is oral ingestion of PEG different then negative SPT? Does SPT for docusate exist? Is polysorbate 80 testing of any benefit given similar structure to PEG? She is due for a colonoscopy this spring.
Answer:
Regarding PEG. Low molecular weight PEG is primarily associated with contact hypersensitivity, and high molecular weight (>1000) associated with generalized, systemic reactions. (1) A very good review of PEG allergy reports data addressing threshold tolerance, though these data concern high and very high molecular weight PEG. (2) Testing with intradermal serial titration testing with Depo-Medrol and skin prick titration with MiraLAX were both negative. For completeness, it is reasonable to testing with triamcinolone acetonide to assess Polysorbate 80. However, with the exposure being a low molecular weight PEG excipient and negative skin testing, proceeding with controlled oral challenge would be appropriate. Otherwise, will you commit the patient to avoidance of all PEG?
I was unable to find any reference detailing a test for dioctyl sodium sulfosuccinate (docusate), nor reports of allergy or anaphylaxis. As with most package inserts, there are mentions of the potential risk of allergic reactions, including anaphylaxis.
Consider skin prick test with Pedia-Lax Liquid (docusate 10mg/mL). Serial titration with 1:100, 1:10, then 1:1. You should also have two or three volunteers for controls to assess for irritant effect.
Alternatively, lactulose is a good bowel cleansing agent, matching the quality of the polyethylene glycol solution. In one study lactulose was preferred by both patients and gastroenterologists. (3)
Another very good reference regarding PEG testing from Kim Blumenthal’s group. (4)
1) Stone CA Jr, Liu Y, Relling MV, et al. 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.
2) Sellaturay P, Nasser S, Ewan P. Polyethylene Glycol-Induced Systemic Allergic Reactions (Anaphylaxis). J Allergy Clin Immunol Pract. 2021 Feb;9(2):670-675.
3) Li CX, Guo Y, Zhu YJ, et al. Comparison of Polyethylene Glycol versus Lactulose Oral Solution for Bowel Preparation prior to Colonoscopy. Gastroenterol Res Pract. 2019 Apr 11;2019:2651450. doi: 10.1155/2019/2651450. PMID: 31097959; PMCID: PMC6487087.
4) Banerji A, Wickner PG, Saff R, Stone CA Jr, Robinson LB, Long AA, Wolfson AR, Williams P, Khan DA, Phillips E, Blumenthal KG. mRNA Vaccines to Prevent COVID-19 Disease and Reported Allergic Reactions: Current Evidence and Suggested Approach. J Allergy Clin Immunol Pract. 2021 Apr;9(4):1423-1437.
Jeffrey G. Demain, MD, FAAAAI