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 or to simplify things: it's easier to ask if you're allergic to iodine than to ask if you've ever had a reaction to iodinated contrast media (ICM). Especially in radiology, one is often asked are you allergic to iodine or to seafood. What is the true story?

Iodinated Contrast Media (ICM)

ICM 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? We should no longer use the phrase "alleric to iodine" but rather "hypersensibility to ICM". The iodine atom contained in the ICM is no more responsible for the reaction than the carbon atom: it is the entire molecule that is responsible for the reaction.

Immediate reactions to ICM

Immediate reactions (anaphylactic) to ICM's occur in approximately 2% of patients receiving an ionic ICM (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.

There exist several molecules of non-ionic ICM on the market, for example: iopidamol (Isovue), iohexol (Omnipaque), ioversol (Optiray), iopromide (Ultravist), and iodixanol (Visipaque).

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 ICM. 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 ICM and vice-versa.

The mechanism of these reactions is most often due to a direct effect by the ICM 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 ICM in question, suggesting a real allergic mechanism mediated by the allergic antibodies known as IgE (or "IgE-mediated").

What to do in a patient requiring the use of an ICM and who has already had an immediate adverse reaction:

When a patient known to have had a reaction to ICM requires an additional procedure involving ICM 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 ICM, particularly in patients at higher risk (asthma, patients on a beta-blocker, patients with cardiac pathology). One should use a different ICM than was used previously.
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.
6. Always be prepared to treat a possible hypersensitivity reaction when using ICM.

Late reactions to ICM

About 2% of patients receiving ICM present with a late reaction, occurring from 1 hour to 1 week after having received the ICM: it mostly involves a cutaneous eruption (mediated by white blood cells, lymphocytes) of light to moderate intensity which evolves over several days. Rarely, it may involve a very severe rash, known as a SCAR (severe cutaneous adverse reaction).

What to do in a patient requiring the use of an ICM and who has already had a delayed adverse reaction:

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

1. For a reaction such as a mild to moderate maculopapular rash, the risk/benefit must be carefully assessed before proceeding. A different ICM should also be used than the one used for the previous reaction: if an allergic evaluation has already been done, a ICM that tested negative on the late reading should be used. Clinical follow-up (which may include your blood tests) is important to treat any delayed reaction.
2. For a severe reaction (SCAR: such as a DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), a Stevens-Johnson/TEN (Toxic Epidermal Necrolysis), an AGEP (Acute Generalized Exanthematous Pustulosis), vasculitis), the use of an ICM should be avoided: these reactions constitute an almost absolute contraindication to the reuse of a ICM.

Recommended approach after a reaction to ICM

A global change in the approach to adverse reactions to ICM should be seriously considered.

Given the frequency and occasional severity of these reactions, and the uncertain and controversial effect of prednisone/antihistamine premedication, we recommend:

1. That the name of the ICM used (Isovue, Optiray, Omnipaque, Visipaque, other) be written in the radiology report, as well as the description of the reaction and treatment given in the event of such a reaction.
2. Patients with a moderate to severe adverse reaction should be referred to an allergist for evaluation, if possible within 1 to 6 months after the reaction.
3. That a brief report of the reaction be given to the patient upon leaving radiology, including the name of the product used, a brief description of the reaction and the treatment given. A report of a reaction to ICM should not say that the patient had a "reaction to iodine".

Other idodinated products

Seafood

An allergy to seafood is also a relatively frequent problem, but is not associated with a higher incidence of reactions to ICM: 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 ICM 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 (Povidone, Betadine, Dovadine)

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

References

1. Sánchez-Borges M , Aberer W, Brockow K, Celik GE, Cernadas J, Greenberger PA, et al. Controversies in drug allergy: Radiographic contrast media. J Allergy Clin Immunol Pract 2019;7:61-65.
2. Torres MJ, Trautmann A, Böhm I, Scherer K, Barbaud A, Bavbek S, et al. Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity. Allergy. 2021;76:1325-1339.

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

Updated 11/2024