Patients’ perceived allergy to contrast agents should not sidetrack important imaging studies
By Nicole R. Wulf, PharmD, and Joan Kapusnik-Uner, PharmD, FASHP, FCSHP
Hippocrates, the father of modern medicine, was one of the first early thinkers to suggest that human disease likely comes from our environment or our bodies instead of magic or curses from the gods. With his inspiration, medical science throughout the centuries has studied our physiology and illnesses, in part, to help separate fact from popular myth. One such myth that still lingers with patients—as well as some clinicians who treat them—is the notion of important iodine allergy.
A recently published study we co-authored, however, rather definitively puts this myth to rest. In short, an allergy to iodine does not and cannot exist. We conclude that the reactions patients have had to seafood, shellfish, povidone-iodine, and iodine-based contrast agents used for imaging tests are real but are likely caused by other non-iodine component proteins or molecules.
Our literature review, published in the American Journal of Health-System Pharmacy, a peer-reviewed journal of the American Society of Health-System Pharmacists, echoes guidelines drawn from leading medical societies and conclusions in several previous studies. In fact, in the 70 years of evidence that we investigated, we could not locate one finding where a patient reaction was caused by iodine, which is a naturally occurring substance in the human thyroid gland. One allergy specialist and researcher concluded: “The term ‘iodine allergy’ should never be used in the context of radiocontrast-associated adverse reactions because it leads to poorer clinical outcomes” (Macy, 2018).
We would take it a step further and contend that we should stop using the term “iodine allergy” altogether, as it is confusing and may lead to less-than-optimal care decisions. Hopefully, our conclusion, as well as those of other researchers and radiology associations, will help educate patients and clinicians to pursue important—and even life-saving—imaging studies despite concerns over a documented allergy episode.
As of 2019, nearly 3% of adults (about 7.2 million Americans) reported a shellfish allergy and nearly 1% (2.2 million) reported a finfish allergy (Gupta et al., 2019). The origin of the association between iodine and allergic reactions to seafood is unclear and likely predates our literature review, which began with articles from 1947.
Despite the lack of evidence, questioning patients about seafood allergies prior to receiving diagnostic imaging studies is quite common. In an anonymous survey sent to 231 faculty radiologists and interventional cardiologists at six Midwest academic medical centers in 2008, 69% of respondents indicated that they inquire about a seafood allergy before radiocontrast media administration and 37.2% of respondents reported that they would withhold the agent or recommend pre-medication, such as steroids, based on a self-reported seafood allergy (Beaty et al., 2008). A survey of 100 cardiologists in the United Kingdom found similar results; 66% said they routinely ask about a previous history of shellfish/iodine allergy and 56% would pre-treat self-reported allergic patients with steroids and antihistamines (Baig et al., 2014).
Yet self-reported, unverified “iodine allergies” could be based only on a patient’s perceived prior adverse reactions to a contrast agent, or dislike or intolerance of seafood—the latter of which, as other investigators determined, is likely due to proteins, tropomyosin, or parvalbumin (Lopata et al., 2016).
Our study focused on the iodine contained in various contrast media, as well as amiodarone, povidone-iodine, and other iodine-containing compounds. A seven-year endeavor, our review focused on 81 articles that met our inclusion criteria out of the original 435 potential papers concerning allergy or hypersensitivity to iodine. Not one, however, supported the notion that iodine is an allergen or causes a verified immune-mediated reaction with symptoms such as rash, swollen tongue or face, or difficulty breathing.
This is particularly concerning considering contrast agents are important diagnostic aids for enhancing the visibility of blood vessels and organ systems to help radiologists and other physicians identify irregularities inside the body. Contrast media are vital in managing conditions such as cancer, heart disease, trauma, and many others.
An unfortunate consequence of a patient’s self-identified iodine allergy, and a clinician’s reluctance to educate and explore root causes, is that it could result in a care delay or a patient receiving unnecessary steroids before an imaging test, which could cause harm.
How should clinicians proceed?
Stop thinking that an allergy to “seafood” is essential information for making patient care decisions related to drug therapy or contrast-media imaging studies. When an adverse reaction presents in a given patient, it should be understood that the iodine is not causing the reaction. An assessment of the timing of symptoms and exact drug(s) or diagnostic agents administered should be documented. Clinicians need to determine the precise diagnostic agent or drug ingredient trigger to ensure patients receive the most appropriate imaging and care at the time of the adverse event, as well as in the future. For example, physicians and patients could determine whether the patient had an adverse reaction to a specific type or brand name of contrast media in the past and explore options to avoid that or similar ingredient formulations. They could also determine whether the reaction was due to another cause, such as an interaction with another medication or dehydration.
When a patient has no history with contrast media but professes a seafood or povidone-iodine allergy, education is warranted if the patient expresses concern. Highly targeted medication alerts at the point of ordering could support physicians and patients in understanding the patient’s risks and prompt subsequent allergy testing or an investigation into potential other causes of the allergic-type reaction.
We urge clinicians to follow published guidelines from the American College of Radiology (ACR) that state “restricting contrast medium use or premedicating solely on the basis of unrelated allergies is not recommended.” ACR guidelines also recommend that if a patient reports a history of allergic-like reactions to a contrast agent, radiologists should consider another class of agent (ACR Committee on Drugs and Contrast Media, 2021). Similarly, the American Academy of Allergy, Asthma and Immunology states: “Despite the common belief that individuals with seafood allergy have a higher risk of radiocontrast media reactions, no convincing data exist to support this, and it has no theoretical basis” (Chapman et al., 2006).
Given this growing volume of research, we hope other medical societies and the FDA consider industrywide changes to imaging protocols and prescribing guidelines, as well as educational outreach and initiatives for clinicians and patients. With such a clear consensus, improved clinical decision support at the point of ordering could help reduce care delays, shorten hospital stays, conserve imaging tests, and overall improve patient outcomes.
We believe our research, based on an exhaustive review of the prevailing literature on the topic, further supports the idea that healthcare providers who still ask patients about iodine or seafood allergies before an imaging study should reassess these protocols. In most cases, the benefits of imaging for patients with “iodine” or “seafood” allergies will far outweigh any unlikely risks. Careful observation of these patients is important as well as making changes or updating allergen history to stop perpetuating this myth.
Nicole R. Wulf, PharmD, is a clinical pharmacist and Joan Kapusnik-Uner, PharmD, FASHP, FCSHP, is vice president of clinical content, both with FDB (First Databank). FDB provides drug and medical device knowledge that helps healthcare professionals make precise decisions.
American College of Radiology Committee on Drugs and Contrast Media. (2021). ACR manual on contrast media, 2021. https://www.acr.org/-/media/ACR/files/clinical-resources/contrast_media.pdf
Baig, M., Farag, A., Sajid, J., Potluri, R., Irwin, R. B., & Khalid, H. M. I. (2014). Shellfish allergy and relation to iodinated contrast media: United Kingdom survey. World Journal of Cardiology, 6(3), 107–111. https://doi.org/10.4330/wjc.v6.i3.107
Beaty, A. D., Lieberman, P. L., & Slavin, R. G. (2008). Seafood allergy and radiocontrast media: Are physicians propagating a myth? The American Journal of Medicine, 121(2), 158.e1–158.e4. https://doi.org/10.1016/j.amjmed.2007.08.025
Chapman, J., Bernstein, I. L., Lee, R. E., Oppenheimer, J., Nicklas, R. A., Portnoy, J. M., Sicherer, S. H., Schuller, D. E., Spector, S. L., Khan, D., Lang, D., Simon, R. A., Tilles, S. A., Blessing-Moore, J., Wallace, D., & Teuber, S. S. (2006). Food allergy: A practice parameter. Annals of Allergy, Asthma & Immunology, 96, S1–S68. https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20and%20Parameters/food-allergy-2006.pdf
Gupta, R. S., Warren, C. M., Smith, B. M., Jiang, J., Blumenstock, J. A., Davis, M. M., Schleimer, R. P., & Nadeau, K. C. (2019). Prevalence and severity of food allergies among US adults. JAMA Network Open, 2(1), e185630. https://doi.org/10.1001/jamanetworkopen.2018.5630
Lopata, A. L., Kleine-Tebbe, J., Kamath, S. D. (2016). Allergens and molecular diagnostics of shellfish allergy. Allergo Journal International, 25, 210–218. https://doi.org/10.1007/s40629-016-0124-2
Macy, E. M. (2018). Current epidemiology and management of radiocontrast-associated acute- and delayed-onset hypersensitivity: A review of the literature. The Permanente Journal, 22, 17-072. https://doi.org/10.7812/TPP/17-072