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.