Discussion
Hypersensitivity Reaction (HSR) is common in cancer patients. Although this can potentially happen with any therapeutic agent, such reactions are common with platinum compounds, L-asparaginase, epipodophyllotoxins, methotrexate, procarbazine and taxanes at a rate of approximately 6% of infusions. (1,2) HSR to plasticizing agents like phthalates and triphenyl phosphite that are used in combination with polyvinyl chloride (PVC) have also been well studied in the past. Phtahalates specifically have been found to be a triggering factor for asthma and contact dermatitis. (3) Additionally, triphenyl phosphite has been reported to cause HSR in a case series involving 5 patients with reactions varying from urticarial, angioedema to anaphylaxis. (4) Direct allergic reactions to PVC are rare but several studies have suggested allergic reactions to different components of PVC. (5-6) Because of this reported hypersensitivity to PVC, many hospitals have now switched to PVC free tubing systems. As in our case, the low sorb tubing system was used, which is PVC free and has a polyethylene lining which provides an inert surface to most chemicals and helps prevent absorption of drugs into the matrix of the tubing material. Polyethylene compounds such as Polyethylene glycol has been reported previously to cause HSR as part of the PEGylated L-asparaginase or oral agents used for bowel regimen. (7-9)
The HSR rate and severity depends on the administration route of allergen. For example, pooled HSR rates using PEG-asparaginase in children with acute lymphoblastic leukemia were between 23.5% and 8.7% for IV and intramuscular (IM) administration, respectively (10). However, Burke et al reported higher rates of PEG asparaginase associated HSR with IM route (11).
Although HSR in pediatric cancer patients is not rare, for patients with negative allergy history, the HSR differential diagnosis should include autoimmune/rheumatologic disorders, hereditary angioedema, some immunodeficiency disorders and mast cell disorders. As in our patient, she was diagnosed with Hashimoto Thyroiditis during her work up. High concordance of allergic disorders with Hashimoto disease (up to 23%) has previously been reported, which could be an added factor for the severe reaction in our patient. (12) HSR management options include use of an alternative drug, giving the same drug with premedication, or performing desensitization. Switching agents, especially chemotherapy can have a negative impact on patients’ outcome when the culprit agent is essential or is the best treatment option.
Skin tests can be used in the evaluation of IgE-mediated drug reactions, but standardized testing dose for testing is only available for a few drugs. The unclear mechanisms responsible for reactions to certain drugs, and possible toxicity of testing reagents restrict the use of this testing approach.
Furthermore, referral to allergist/immunologist is warranted for patients with negative allergy history and multiple and/or severe HSR.
Up to date, no HSR to low sorb tubing has been reported in the published literature. This case highlights the importance of targeted work up and referral to an allergist in cancer patients with negative allergy history, as switching cancer specific management may affect patient outcomes.
Authorship Contributions: Amber Gibson has contributed to the manuscript by leading the project and writing of the manuscript; Usman Baig and contributed to the manuscript by revising the manuscript and providing the table; Sana Mohiuddin has contributed to the manuscript by editing the manuscript and providing the figure, Wafik Zaky has contributed to the manuscript by serving as a senior author and final revision of the manuscript.
Disclosure of Conflicts of Interest: There are no conflicts of interest to disclose by any author.