Salt, Seafood, and Dye: Debunking Cross-Reactivity with Radiocontrast Agents


Allergy analysis and interpretation is a fundamental component of a health-system pharmacist's day.

Allergy analysis and interpretation is a fundamental component of a health-system pharmacist’s day. Depending on a hospital’s policies and procedures, pharmacists are often asked to verify—though not necessarily dispense— radiocontrast agents for certain imaging studies.

When it’s discovered that the patient has endorsed an iodine or seafood allergy, flags are raised, alarms are sounded, and frustration overcomes any pharmacist attempting to track down a source to clarify the issue. That issue, of course, is perceived cross-reactivity with radiocontrast agents and iodine or seafood allergies.

Unfortunately, this perception is yet another product of medical myth.1 The commonly held belief that seafood allergies result from the iodine contained in the flesh just isn’t accurate.

For most fish, the parvalbumin is the allergen.2 While iodine may be found in seafood, it is not an allergen.

Iodine is also found in most table salt in the United States, and it is a necessary element for thyroid function. It is said that an individual cannot survive without iodine in the body.

Reactions with radiocontrast agents are known to cause a myriad of adverse events ranging from mild infusion reactions to acute kidney injury. Idiosyncratic reactions can also occur, but they are considered to be anaphylactoid in nature, rather than anaphylactic.1 In other words, they are not products of an allergen reacting with immunoglobulin E to produce mast cell degranulation.

The presence of iodine in contrast dye does not produce anaphylactoid reactions, but the high osmolarity of certain radiocontrast agents is thought to be the culprit. One comprehensive study found that 15% of patients who experienced an adverse reaction to high-osmolarity contrast agents had previously endorsed a seafood allergy.3

In the study, patients were just as likely to experience a reaction to the contrast dye if they had any other food allergies, asthma, or a prior contrast reaction. For some reason, however, the focus isolated the iodine content in the seafood and the contrast.

Further evidence has consistently demonstrated that a history of seafood allergy is a similar risk factor for experiencing a reaction as having any allergy, history of reaction to contrast agents, evidence of atopy, or asthma.4,5 Furthermore, the more commonly used low-osmolarity contrast agents have a far lower incidence of such anaphylactoid reactions compared with the seldom used high-osmolar agents.6

Despite the evidence, or lack thereof, radiocontrast agent adverse reactions are still associated with iodine “allergy” and seafood allergies. Over time, pharmacists could hope that the institutional protocols and alerts will be updated to reflect clinical evidence over dogma.


  • Schabelman E, Witting M. The relationship of radiocontrast, iodine, and seafood allergies: a medical myth exposed. J Emerg Med. 2010 Nov;39(5):701-707.
  • Daul CB, Morgan JE, Lehrer SB. Hypersensitivity reactions to Crustacea and mollusks. Clin Rev Allergy. 1993,1 1:201-222.
  • Shehadi WH. Adverse reactions to intravascularly administered contrast media: a comprehensive study based on a prospective survey. Am J Roentgenol Radium Ther Nucl Med. 1975 May;124(1):145-152.
  • Valls C, Andía E, Sánchez A, Moreno V. Selective use of low-osmolality contrast media in computed tomography. Eur Radiol. 2003 Aug;13(8):2000-2005.
  • Kopp AF, Mortele KJ, Cho YD, Palkowitsch P, Bettmann MA, Claussen CD. Prevalence of acute reactions to iopromide: postmarketing surveillance study of 74,717 patients. Acta Radiol. 2008 Oct;49(8):902-911.
  • Cochran ST, Bomyea K, Sayre JW. Trends in adverse events after IV administration of contrast media. AJR Am J Roentgenol. 2001 Jun;176(6):1385-1388.

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