A. Case study
B. More information
C. Editors' comments
E. CPD questions (South Africa, Australia)
A. Case study
A 40-year-old woman presented with a recent history of adverse reactions
to various types of shellfish. She had had a mild reaction (general
flushing and erythema) to the ingestion of a meal consisting of a large
quantity of fish and shellfish (a seafood platter). In the following
6 months, she had had 2 anaphylactic experiences: 1 almost immediately
after eating 3 oysters, and another to a pasta dish that she had not
known contained mussels. Because she had developed erythema upon the
administration of iodinated X-ray contrast media 16 years before, the
diagnosis of "iodine allergy" was made. No tests were done
to confirm this. The patient was referred to a dietitian for an iodine-free
In many cases, the diagnosis of a referral should be reassessed to make
sure that it is correct. According to the history given, could one be
absolutely sure that the diagnosis of "iodine allergy" was
correct? Questions that could be asked include:
a. Does the patient tolerate other iodine-containing foods such as fish
and iodated salt?
b. What fish did she have as part of the seafood platter? Could she
be sensitive to that species alone and not other species of fish?
c. Did the patient always react to shellfish after she ate it?
d. Could one develop an allergy for the first time at the age of 40?
a. She had always eaten fish and iodated salt without any adverse reaction.
b. She had eaten canned tuna as part of the seafood platter; she had
also eaten it after the incident without experiencing adverse reactions.
c. The patient had never reacted to any food prior to eating the seafood
platter. Thereafter, she had had only the 2 encounters with shellfish,
to which she had severe reactions.
It was therefore
clear that the patient was reacting to shellfish but not fish, but both
contain iodine: so it was unlikely that the patient was reacting to
a. What about the reaction to the iodinated contrast media? Was that
not due to an "iodine allergy"?
b. What else could have caused the reaction she experienced to the shellfish?
Do the symptoms seem like those of an allergy or an intolerance?
a. Research can thus far not prove that adverse reactions to contrast
media are due to its iodine content. It has been suggested that adverse
reactions result from the contrast molecule as a whole rather than the
elemental iodine. So it was probable that the patient's reaction to
the contrast media was not due to iodine.
b. The symptoms the patient experienced seemed more like those of an
allergy. To confirm that it was an allergy, a total IgE and a serum-specific
IgE to shellfish were done. Both the results were high: total IgE 88
(class 5) and IgE to shellfish 78 (class 5).
Using the results
of the blood tests and the history, the diagnosis of an allergy to shellfish
was made. In such a case, the diagnosis can be confirmed with an oral
challenge, unless, of course, the patient has had an anaphylactic reaction,
|TIP for Allergy
When "fish" is entered into the main search function,
"Items, Substances & Allergens", this will bring
up "iodine" under the list of "Possible additional
constituents", with a risk of 2. This indicates that
an adverse reaction to iodine is not very likely. When one
clicks on "iodine", a window will open up to show
more information on iodine: the foods that contain iodine,
and other background information on iodine, as well as the
adverse reactions to iodine that have been recorded in the
literature. Under "Substances", one can find a list
of foods with the levels of iodine they contain.
B. More information:
an essential trace element required for a number of metabolic functions,
in particular the synthesis of thyroid hormones, which are crucial for
normal growth and development.1,2 Dietary sources of iodine
include seaweed and fish, iodised salt, various medicines, and iodates
added to bread as a preservative.1,3 Oriental foods are particularly
rich in iodine: for example, 100g of dry kelp (konbu) contains as much
as 170mg of iodine, while 100g of wakame seaweed contains 10mg of iodine.1
Milk products (including butter and cheese) and eggs are also rich in
iodine. The iodine content can vary in the same food for various reasons,
such as seasonal changes. One study showed that milk samples taken during
summer contained 70 micrograms/kg, and milk during winter 370 micrograms/kg
colorant erythrosine (Food Red 14/FD&C Red no. 3), which is
widely used in foods, cosmetics, and pharmaceutical products, contains
4 molecules of iodine and could therefore be seen as a source of
reactions to iodine:
It is well known that a deficiency of or a toxicity to iodine can result
in adverse reactions such as goiter.7 This newsletter will
focus on other types of adverse reactions that have been related to
a. Adverse reactions
due to dietary sources of iodine
is very little evidence that dietary sources of iodine can result
in an allergic reaction. One article by Kubota et al., however,
discusses adverse reactions due to the iodine content of foods.
The researchers stated that several patients had developed pustular
and/or maculopapular eruptions after ingesting iodine-containing
vitamin supplements and konbu in salad. Exacerbations of acne may
also be related to iodine ingestion.1
There has been a
report of a 60-year-old Japanese woman who experienced generalized pruritus
for 30 years due to the ingestion of iodine-containing food. At age
50, she developed erythroderma from iodine-containing X-ray contrast
material. When she stopped eating iodine-containing foods, she experienced
no further eruptions or pruritus. However, after mistakenly drinking
konbu tea, she developed a burning sensation in her mouth within 30
minutes. She also experienced edematous erythema on her face, neck and
upper back, as well as bilateral conjunctival congestion 12 hours later.1
also been a report of a 4-year-old boy with an iodine sensitivity
who was put on a restricted diet and thereafter demonstrated both
short stature and hypothyroidism.1
To date no
relationship has, however, been established between a sensitivity
to iodine and seafood or fish allergy.
Adverse reactions to iodinated X-ray contrast media (ICM) have been
reported to occur in 0.5-2% of recipients8,9, and the substance
can be responsible for acute or delayed reactions.10,11 It
has been proposed that the reaction to ICM is in fact due to the contrast
molecule as a whole rather than to the iodine component.3
Some adverse reactions
to ICM are considered allergy-like, with cutaneous, cardiovascular,
respiratory, and digestive symptoms. Reactions are more frequent with
ionic than with non-ionic material8,9,12, but the frequency of deaths
(which are quite rare4) is almost identical.12
to ICM can vary from mild (flushing, nausea, arm pain, pruritis, vomiting,
headache and mild urticaria) to severe and life-threatening (severe
manifestations of those reactions mentioned, convulsions, unconsciousness,
laryngeal oedema, severe bronchospasm, pulmonary oedema, severe cardiac
dysrhythmias and arrest, and cardiovascular and pulmonary collapse).11
occur within 1 hour to 1 week after contrast medium injection. The symptoms
are usually mild and include fever, rash, flushing, dizziness, pruritis,
arthralgia, diarrhoea, nausea, vomiting, headache and occasionally hypotension.
A few cases of serious delayed reactions such as shock, hypotension,
angiodema and dyspnoea have also been reported.9,11
A seasonal variation
in the incidence of late adverse skin reactions has been reported. A
study from Finland found that most skin reactions occurred in sun-exposed
areas of the body and peaked during the months of May and June. The
authors postulated a photosensitizing effect of ICM.11
There are several
predisposing factors to contrast reactions, including previous adverse
reactions, a history of asthma or bronchospasm, a history of allergy
or atopy, cardiac disease, dehydration, haematological or metabolic
conditions, renal disease, infancy, old age, anxiety, and certain medications.
These factors increase the risk of a person having severe adverse reactions.8,11,13,14
exact pathogenesis of adverse reactions to ICM is unclear. There
is, however, increasing evidence that a significant proportion of
the reactions are not due to an allergy but are T-cell-mediated.3,8,9,13
IgE-mediated anaphylaxis is rare, but it may be one of the severe
adverse reactions to ICM.12
Povidone-iodine (polyvinylpyrrolidone-iodine, or PVP-I) solution is
an effective and generally safe disinfectant agent or antiseptic. It
is used throughout the world not only in the surgical field but also
to PVP-I are uncommon and may be due to a contact allergy or irritation
of the skin. Most skin reactions to PVP-I are in fact due to skin irritation
rather than allergy, especially after prolonged exposure to the solution.
When PVP-I is used for patch testing in the aqueous state, a false-positive
result is likely to arise due to the irritation caused. It has also
been suggested that the iodine component of the solution is not likely
to be the cause.3,15,16,17
absorption of iodide in neonates and in burn patients can result
in iodism (a mild toxic syndrome characterized by hyper-salivation,
coryza, sneezing, conjunctivitis, headache, laryngitis, bronchitis,
stomatitis, parotitis, enlargement of the submaxillary glands, skin
rashes and gastric upsets). One case of a systemic anaphylactoid
reaction due to vaginal use of povidone-iodine has been reported.3
a person who is sensitive to one form of iodine avoid all other sources
Patients are frequently asked about iodine or seafood allergy before
ICM is administered, because of a commonly held belief among health
professionals that there is cross-reactivity between an allergy to ICM
and an allergy to iodine-rich foods. However, little evidence exists
that elemental iodine or iodide is responsible for the reactions to
ICM or povidone-iodine, and no evidence exists that it is involved in
seafood allergy.3 But individuals with allergies or hypersensitivity
are more likely to experience contrast material-related anaphylactoid
reactions, compared with patients without allergies. Therefore, before
deciding between prescribing ionic versus non-ionic contrast material,
any potential risk factors, including the severity of previous reactions
to food, drugs or contrast material, should be carefully assessed.18
It has been proposed
that the only adverse effect of contrast material that can convincingly
be ascribed to free iodide is iodide mumps (swelling of the submandibular,
sublingual and parotid salivary glands) and other manifestations of
The proposed mechanisms
of a reaction to ICM, seafood allergy and povidone-iodine are distinctly
different. It is suggested that reactions to ICM are due to the activation
of non-specific immune mediators by the contrast molecule. The seafood
allergy is due to an IgE-mediated hypersensitivity to seafood protein
(see the Educational Newsletter of June 2003 on adverse reactions to
fish). The skin reactions to providone-iodine are due to an irritation.
Studies could not prove that the condition "iodine allergy"
exists or that there is any cross-reactivity between these 3 sources
of iodine.3 There are also, however, no reports in the literature that
prove that adverse reactions to elemental iodine (in whatever form)
do not occur. This indicates that iodine allergy is either very rare
or does not exist, or that the methodology used in studies examining
iodine allergy was flawed.
||compiled by Karen du Plessis
Food & Allergy Consulting & Testing Services (FACTS)
PO Box 565
Comments by our editors
M. Joneja Ph. D., RDN
This single case
study elegantly incorporates examples of a number of factors that
are often ignored or misunderstood in the diagnosis and management
of adverse reactions to foods:
Assumptions about the culprit food are made without sufficient
information, for example, in this case, that iodine "allergy"
was the cause of the patient's reaction, based solely on the fact
that in the past she had experienced an adverse reaction to an
iodinated radiocontrast dye, but had eaten fish without any adverse
Misconceptions about the nature of allergic and intolerance
reactions; in this case the probably erroneous idea that iodine
in food can trigger an anaphylactic reaction. Anaphylactic reactions
to foods are almost invariably caused by antigenic proteins that
induce allergen-specific IgE. Non-protein agents can induce IgE,
but only when they act as haptens, coupled to a protein. There
is currently no evidence that iodine is able to provoke an haptenic
IgE response via the oral route
An increasing number of examples of food allergy following initial
sensitization to the allergen via the cutaneous route are appearing
in the literature. It is very likely that this method of sensitization
has been greatly underestimated. Allergists should be alert to
the possibility that patients who have not previously demonstrated
an allergic response to foods may suddenly develop an anaphylactic
reaction to a food after exposure to the allergen after sensitization
through injection (for example, accidental puncture); contact
via abraded, inflamed skin, such as occurs in eczema, erythema,
or trauma; or even as a result of skin tests, particularly intradermal
tests. In these situations the allergen reaches immune cells directly
and by-passes the normal antigen processing barrier of the gut-associated
lymphoid tissue that occurs via the oral route.
For more information
on this subject and other allergy and intolerance related topics, visit:
To join a professional
food allergy discussion list where this subject can be discussed further,
go to http://groups.yahoo.com/group/AllergyDietitian
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1. Kubota Y, Koga T, Nakayama J. Iodine allergy induced by consumption
of iodine-containing food. Contact Dermatitis. 2000 May;42(5):286-7.
2. Beers MH, Berkow R. The Merck Manual of Diagnosis and Therapy. Seventeenth
Edition. Merck Research Laboratories, NJ, 1999.
3. Coakley FV, Panicek DM. Iodine allergy: an oyster without a pearl?
AJR Am J Roentgenol. 1997 Oct;169(4):951-2.
4. Wenlock RW, Buss DH, Moxon RE, Bunton NG. Trace nutrients. 4. Iodine
in British food. Br J Nutr 1982;47(3):381-390.
5. Poulsen E. Case study: erythrosine. Food Addit Contam. 1993 May-Jun;10(3):315-23.
6. Gardner DF, Utiger RD, Schwartz SL, Witorsch P, Meyers B, Braverman
LE, Witorsch RJ. Effects of oral erythrosine (2',4',5',7'-tetraiodofluorescein)
on thyroid function in normal men. Toxicol Appl Pharmacol. 1987 Dec;91(3):299-304.
7. Mahan LK, Escott-Stump S. Krause's Food, Nutrition & Diet Therapy.
Tenth Edition. WB Saunders Company, Pennsylvania, 2000.
8. Christiansen C, Pichler WJ, Skotland T. Delayed allergy-like reactions
to X-ray contrast media: mechanistic considerations. Eur Radiol. 2000;10(12):1965-75.
9. Webb JA, Stacul F, Thomsen HS, Morcos SK; Members Of The Contrast
Media Safety Committee Of The European Society Of Urogenital Radiology.
Late adverse reactions to intravascular iodinated contrast media. Eur
Radiol. 2003 Jan;13(1):181-4. Epub 2002 Sep 10.
10. Nicolie B. [Allergy to iodinated contrast media] Allerg Immunol
(Paris). 2002 Oct;34(8):302-4.
11. Morcos SK, Thomsen HS. Adverse reactions to iodinated contrast media.
Eur Radiol. 2001;11(7):1267-75.
12. Laroche D, Namour F, Lefrancois C, Aimone-Gastin I, Romano A, Sainte-Laudy
J, Laxenaire MC, Gueant JL. Anaphylactoid and anaphylactic reactions
to iodinated contrast material. Allergy. 1999;54 Suppl 58:13-6.
13. Moneret-Vautrin DA, Kanny G, Morisset M, Beaudouin E, Renaudin JM.
[Anaphylactoid reactions and late skin reactions to iodinated contrast
media: present state of the question--idea development] Rev Med Interne.
14. Hosoya T, Yamaguchi K, Akutsu T, Mitsuhashi Y, Kondo S, Sugai Y,
Adachi M. Delayed adverse reactions to iodinated contrast media and
their risk factors. Radiat Med. 2000 Jan-Feb;18(1):39-45.
15. Niedner R. Cytotoxicity and sensitization of povidone-iodine and
other frequently used anti-infective agents. Dermatology. 1997;195 Suppl
16. Kozuka T. Patch testing to exclude allergic contact dermatitis caused
by povidone-iodine. Dermatology. 2002;204 Suppl 1:96-8.
17. Nishioka K, Seguchi T, Yasuno H, Yamamoto T, Tominaga K. The results
of ingredient patch testing in contact dermatitis elicited by povidone-iodine
preparations. Contact Dermatitis. 2000 Feb;42(2):90-4.
18. Leder, R. How well does a history of seafood allergy predict the
likelihood of an adverse reaction to i.v. contrast material? AJR Am
J Roentgenol 1997; 169(3): 906-7.
Questions (For South African dietitians only. Australian
dietitians: where you have relevant learning goals, CPD hours related
to this resource can be included in your APD log.)
You can obtain 2 CPD points for reading
this newsletter and answering the accompanying questions. This
newsletter with questions has been accredited for dietitians.
CPD reference number: DT03/3/110/13
HOW TO EARN YOUR CPD POINTS
1. Complete your personal details below.
2. Read the newsletter and answer the questions.
3. Indicate your answers to the questions by making a "X"
in the appropriate block.
4. You will earn 2 CPD points if you answer more than 75% of the
questions correctly. If you score is between 60 and 75%, 1 CPD
point will be allocated. A score of less than 60% will unfortunately
not earn you any CPD points.
5. Make a photocopy for your own records in case your answers
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6. Cut and paste the area indicated below into a e-mail message
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to be received no later than 31 January 2004. Answer sheets received
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ALL THE QUESTIONS
(There is only
one correct answer per question.)
1. Which of the following is not a dietary source of iodine?
(b.) Milk during the summer
(d.) Iodinated X-ray contrast material
2. True or false:
There is convincing evidence that dietary sources of iodine can result
in an allergic reaction.
3. True or false:
There is convincing evidence that adverse reactions to iodinated contrast
material are due to the iodine component.
4. Which of the
following is true regarding the onset of adverse reactions to iodinated
X-ray contrast material?
(a.) It is acute.
(b.) It is delayed.
(c.) It can be acute or delayed.
5. Which of the
following is not true regarding adverse reactions to providone iodine?
(a.) They are uncommon.
(b.) Most skin reactions are due to skin irritation rather than allergy,
especially after prolonged exposure to the solution.
(c.) The cause is probably due to the iodine component of the solution.
6. True or false:
No evidence exists that elemental iodine or iodide is involved in seafood
7. What is the proposed
mechanism of a reaction to iodinated contrast material?
(a.) activation of non-specific immune mediators
(b.) IgE-mediated hypersensitivity
8. What is the proposed
mechanism for providone-iodine skin reactions?
(a.) activation of non-specific immune mediators
(b.) IgE-mediated hypersensitivity
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