What is an "iodine allergy"?

Are you allergic to iodine?

Everyone ingests iodine in their diet, and not just that found in iodized salt. Iodine is an essential element for life, and is used principally in the production of thyroid hormones. A lack of iodine leads to the formation of a goiter, and can cause hypothyroidism.

So why do we speak of an iodine allergy? Mostly through ignorance. Especially in radiology, one is often asked are you allergic to iodine or to seafood. What is the true story?

Radiocontrast materials (RCM)

RCM's are molecules containing several carbon atoms, and also hydrogen, oxygen, nitrogen and in general 3 and sometimes 6 atoms of iodine. The carbon content of these molecules is a lot more substantial than the iodine content, so why don't we speak of an allergy to carbon?

Immediate reactions to RCM's

Immediate reactions (anaphylactic) to RCM's occur in approximately 2% of patients receiving an ionic RCM (older products), and in approximately 0.5% of patients receiving non-ionic materials (more recent production). Very severe anaphylactic reactions occur in approximately 0.2% of patients receiving an ionic material, and 0.04% of patients receiving a non-ionic material. Death from a reaction to these products occurs on the order of 1-2 per 100,000 procedures, more with ionic than non-ionic products.

Risk factors associated with these reactions include: female gender, asthma (especially if poorly controlled while during the test), and a previous history of a reaction to RCM. Taking medication called beta-blockers, or the presence of significant cardiac disease are not associated with a greater incidence of reaction, but with a more severe reaction. An allergy to fish or seafood is not associated with a greater incidence of reaction to RCM and vice-versa.

The mechanism of these reactions is most often due to a direct effect by the RCM molecule (and not by the iodine atoms) on mastocytes (cells implicated in the allergic response) leading to their degranulation (liberation of diverse substances including histamine, which causes an allergic reaction): often described as a pseudo-allergy. However in Europe, several recent studies have demonstrated a that a large number of patients having had such reactions have positive skin tests to the RCM in question, suggesting a real allergic mechanism mediated by the allergic antibodies known as IgE (or "IgE-mediated").

When a patient known to have had a reaction to RCM requires an additional procedure involving RCM exposure, the approach is as follows:

1. Determine if the radiological procedure is absolutely necessary
2. Explain the risks to the patient
3. Ensure adequate hydration before the procedure
4. Use a non-ionic and iso-osmolar RCM, particularly in patients at higher risk (asthma, patients on a beta-blocker, patients with cardiac pathology)
5. Use a pre-treatment regimen involving cortisone and antihistamines: this pre-treatment is effective in preventing the majority of reactions, but is less effective in preventing the recurrence of very severe reactions.

Late reactions to RCM

About 2% of patients receiving RCM present with a late reaction, occurring from 1 hour to 1 week after having received the RCM: it mostly involves a cutaneous eruption (mediated by white blood cells, lymphocytes) of light to moderate intensity which evolves over several days.

Seafood

An allergy to seafood is also a relatively frequent problem, but is not associated with a higher incidence of reactions to RCM: it involves an IgE mediated reaction to a protein found in the seafood, and once again the iodine atom is not involved.

Given the relatively high incidence of immediate reactions to RCM and of allergies to seafood, it may happen that a patient presents with both problems at once, but they remain two very distinct problems.

Iodinated soaps (Proviodine, Betadine)

Reactions to iodinated soaps are rare: they involve a late reaction (mediated by lymphocytes) to the proviodone molecule, and not to the iodine atom.

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André Caron, MD FRCPC
(translation: Andrew Moore, MD FRCPC)