Some food for thought on the nature of contrast allergies... The following is copied from the URL below:
http://www.radiology.ucsf.edu/instruction/abdominal/ab_handbook/04-IodineAllergy.html.
IODINE ALLERGY AND CONTRAST ADMINISTRATION
Patients are frequently asked about iodine or seafood allergy before IV
contrast material is administered because of a commonly held belief among
radiologists and others in the medical community of a specific cross-
reactivity between iodinated radiographic contrast material and other iodine-
rich substances. "Iodine allergy" is often used as a collective term for
adverse reactions to these agents. Patients commonly provide positive or
ambiguous responses to such questions; such responses are likely to become
more common with the increasing consumption of seafood and the increasing
prevalence of allergies in the general population. Our purpose is to show
that iodine does not confer a specific cross-reactivity between iodine-rich
substances, that the cross-reactivity that does exist is nonspecific, and
that the concept of iodine allergy is fallacious and may result in the
inappropriate nonuse of IV contrast material in patients intolerant of
antiseptics or seafood that contain iodine.
Background Physiology and Immunology
Iodine is an essential trace mineral, required for the synthesis of thyroid
hormones. Ingested iodine is converted to iodide, the ionized form of
iodine, in the gut. Dietary sources include fish, iodized salt, and iodates
used as bread preservatives. Fish is a good source of iodine because, over
the millennia, iodine has been leached from the soil and washed into the
oceans. Iodine in fish may be free, as a substituent for chlorine, or bound
to protein.
To briefly review, the immune system consists of nonspecific and specific
responses. Mediators of nonspecific responses include phagocytes,
complement, and interferon. Specific immune responses, which require an
antigen-antibody interaction, are mediated by B and T lymphocytes. Simple
atoms or molecules such as iodine or contrast material do not have the
complexity required for antigenicity, although theoretically they might act
as haptens. Haptens are agents that are too small to act as antigens by
themselves but that, by binding to larger carrier molecules, provoke an
antibody response to the hapten-carrier complex. Allergy, or
hypersensitivity, is a specific, excessive immune response to an antigen and
results in damage to the host. The most common type is immunoglobulin E-
mediated and is known as anaphylactic or immediate hypersensitivity.
Iodine and Contrast Material Reactions
Contrast materials are triiodinated benzoic acid derivatives that, in
solution, contain a small amount of free iodide. Adverse reactions to these
substances may be classified as idiosyncratic or nonidiosyncratic.
The mechanism of idiosyncratic reactions is unknown. Among the theories for
such reactions is the allergy theory, which proposes that either contrast
material or iodine acts as a hapten, thus, provoking a specific immune
response. An antigen-antibody reaction then occurs when the patient is
subsequently re-exposed to contrast material. Contrast materials can cause
the formation of antigenic iodoproteins in vitro [1]. However, the same
group of investigators subsequently failed to show a significant
relationship between contrast sensitivity and the presence of lymphocytes
specifically reactive to either contrast material or iodide [2].
Additionally, attempts to induce antibody formation in vivo using an animal
model have been unsuccessful, despite optimal conditions [3]. The mechanism
of idiosyncratic contrast reactions is therefore unlikely to be a specific
immune response (i.e., true allergy) and is more likely due to activation of
complement or other mediators of the nonspecific immune system.
Consequently, idiosyncratic contrast reactions are best
termed "anaphylactoid," "allergy-like," or "pseudoallergic," rather
than "allergic." Additionally, the activation is almost certainly a function
of the contrast molecule as a whole rather than free iodide. For example,
none of 23 patients with documented contrast sensitivity reacted to
subcutaneous sodium iodide [4].
Nonidiosyncratic reactions are due to direct toxic or osmolar effects. The
only adverse effect of contrast material that can convincingly be ascribed
to free iodide is iodide mumps and other manifestations of iodism. "Iodide
mumps" refers to swelling of the submandibular, sublingual, and parotid
salivary glands after the administration of intravascular contrast material.
It is part of a continuum of nonidiosyncratic reactions that are due to
overload of normal physiologic pathways of iodide metabolism. This continuum
is known as iodism; it also includes lacrimal gland swelling, coryza, and
skin rashes. Most cases occur in patients with renal impairment, presumably
because reduced renal excretion results in a higher in vivo iodide
concentration.
Iodine and Seafood Intolerance
"Food intolerance" is a general term that includes all exaggerated or
abnormal reactions to food, whether caused by immune or nonimmune
mechanisms. For example, food-borne illness caused by fish and shellfish may
be due to allergy, transmittal of infection, or the presence of toxins.
These different mechanisms are of largely academic interest to the
radiologist, because they may not be distinguishable in a patient with a
history of illness after seafood ingestion. Nonetheless, accurate use of
terminology suggests that such patients are best described as seafood-
intolerant rather than seafood-allergic.
Hypersensitivity reactions to seafood almost always commence within 2 hr of
exposure [4]. Symptoms include pruritus, urticaria, angioedema,
bronchospasm, rhinitis, vomiting, diarrhea, and shock. The manifestations
may be life threatening, even if initial symptoms are minimal (e.g.,
tingling in the mouth or throat). The reactions are true allergies and are
probably immunoglobulin E-mediated. For example, 85% of patients with
shellfish sensitivity have positive skin-prick tests to shrimp extract, the
method of choice for revealing tissue immunoglobulin E. The responsible
seafood antigen is at least partially characterized as the fish equivalent
of the muscle protein tropomyosin [4]. No evidence exists that the iodine
content of seafood is related to these reactions.
Iodine and Antiseptics
The active agent in many commercially available antiseptics is
polyvinylpyrrolidone-iodine. Examples include Betadine (Purdue Frederick,
Norwalk, CT) and Povidine (Alpharma, Baltimore, MD). Polyvinylpyrrolidone
(povidone) is a polymer similar to dextran. It acts as a carrier that
delivers complexed diatomic iodine directly to the bacterial cell surface.
Diatomic iodine is bactericidal, apparently because of inactivation of
essential bacterial enzymes. Adverse cutaneous reactions to the compound are
rare; only two reactions were recorded in 5000 applications. It is likely
that many such reactions are due to skin irritation rather than allergy, and
in any case the iodine component is probably not involved. None of five
patients with a history of contact dermatitis after povidone-iodine reacted
to patch testing with potassium iodide solution, whereas all reacted to
povidone-iodine [5]. Systemic side effects are extremely rare.
Transcutaneous absorption of iodide in neonates and in bum patients can
result in iodism. One case of a systemic anaphylactoid reaction due to
vaginal use of povidone-iodine has been reported [6].
Cross-Reactivity and Iodine Allergy
Evidence exists of a nonspecific cross-reactivity between contrast material
sensitivity and allergy to seafood, as well as other foods. In a large
review, 5% of 112,003 cases of intravascular ionic contrast administration
resulted in a reaction. The relative risk of a reaction in patients with
seafood allergy (diagnostic criteria unspecified) was 3.0, compared with 2.9
for those with allergy to eggs, milk, or chocolate; 2.6 for those with
allergy to fruit and strawberries; and 2.2 for those with asthma [7]. In
other words, a seafood allergy increases the risk of a contrast reaction by
about the same factor, as does any other allergy. Additionally, these
figures suggest that at least 85% of patients with seafood allergy receiving
IV contrast material will not have an adverse reaction. This risk-benefit
profile should be considered before patients with seafood allergy are denied
IV contrast material or recommended for corticosteroid premedication. We are
unaware of any investigation of contrast reactivity in patients intolerant
of povidone-iodine.
The likely mechanisms of idiosyncratic contrast reactions, seafood
allergies, and povidone-iodine dermatitis are distinct; they are activation
of nonspecific immune mediators by the contrast molecule, immunoglobulin E-
mediated hypersensitivity to fish muscle protein, and irritant contact
dermatitis, respectively. Little evidence exists that elemental iodine or
iodide is responsible for idiosyncratic contrast reactions or povidone-
iodine dermatitis, and no evidence exists that it is involved in seafood
allergy. The notion that iodine confers a specific cross-reactivity between
these agents is unfounded. The term "iodine allergy" is therefore
unfortunate, because it perpetuates muddled thinking and unsubstantiated
beliefs. It should be abandoned and replaced by more neutral descriptive
terms such as "contrast material sensitivity," "seafood intolerance,"
and "povidone-iodine dermatitis."
Clinical Implications
Patients reporting iodine or seafood allergy should be questioned as to the
exact nature and severity of the reaction. If possible, seafood allergy
should be distinguished from other causes of seafood intolerance. The
presence of a seafood allergy places the patient at a threefold risk of an
adverse reaction to contrast material. As with any other allergy, the nature
and severity of the reaction should be considered when choosing the type of
contrast material and when determining the need for a premedication regimen.
Seafood allergy should not of itself be regarded as an absolute
contraindication to the administration of IV contrast material. There is no
reason to believe that iodine allergy based on skin reactions to topical
antiseptics is of any specific relevance to the administration of IV
contrast material.
References
1. Nilsson R, Ehrenberg L, Fedorcsak I. Formation of potential antigens
from radiographic contrast media. Acta Radiol 1987; 28:473-77
2. Stejkal V, Nilson R, Grepe A. Immunologic basis for adverse
reactions to radiographic contrast media. Acta Radial 1990; 31:605-612
3. Can- DH, Walker AC. Contrast media reactions: experimental evidence
against the allergy theory. Br J Radiol 1984;57: 469-173
4. Daul CB, Morgan JE, Lehrer SB. Hypersensitivity reactions to
Crustacea and mollusks. Clin Rev Allergy 1993,11:201-222
5. Van Ketel WG, van den Berg WHHW. Sensitization to povidone-iodine.
Dermatol din 1990;8: 107-109
6. Waran KD, Munsick RA. Anaphylaxis from povidone-iodine (letter).
Lancet 1995;345: 1506
7. Shehadi WH. Adverse reactions to intravascularly administered
contrast media. AJR 1975;24: 145-152
