A. Case study
B. More information
C. Editors' comments
E. CPD questions (South Africa, Australia)
A. Case study
A 7-year-old boy
was referred to a dietitian to determine the cause of recurring episodes
of generalized urticaria, as the ailment was thought to be food-related.
The clinical history revealed that he had experienced episodes of slight
urticaria infrequently (about twice per year) since early childhood.
In the previous 6 months, the severity of the episodes of urticaria
had become greater. Most of the more severe reactions occurred during
friends' birthday parties or on vacation.
to a drug: The mother was questioned about her son's use of pharmaceuticals,
including over-the-counter medications, vitamins, "naturopathic"
supplements and other herbal remedies. The mother related an episode
from when her son was 4 years old. He experienced a severe reaction
after taking cough syrup. The doctor suspected a drug allergy, and the
medication was never prescribed after that.
What can cause urticaria? There are many causes (see also the March
Educational Newsletter's case study):
to a food or food additive: Because the child developed reactions mostly
while at parties, some substance found in typical party food could be
a cause. The mother said that she kept "party food" (such
as sweets, chips and soft drinks) for treats and special occasions,
so that her son did not have them often. He might therefore eat more
of these types of foods at parties than he is used to.
Because he experienced
the symptoms in a different environment than he is used to, environmental
allergens (e.g., house dust mite, fungi, pollen, trees, pets or a chemical
present in a toy or used in a hobby) needed to be considered. But no
correlation could be found.
contact sensitivity, hypersensitivity to insect stings or bites, collagen
vascular disease, chronic idiopathic/auto-immune urticaria and infectious
diseases were excluded as possible causes.
additives was suspected, as it can be present in both cough syrup
and "party foods". Cough syrups often contain a coloring
agent to make them more appealing to children. Tartrazine is often
How does one test
for a sensitivity to additives?There are no skin
prick tests or serum-specific IgE tests for additives, as reactions
to them are not thought to be IgE-mediated.
Blood CAST (Cellular
Allergen Stimulation Tests) tests can be done for certain additives,
although they do not have a high level of sensitivity compared to serum-specific
diet can be done, but was not practical in this case, because it was
already known that the child reacted to foods that contain additives.
challenges can be done. A doctor colleague of the dietitian was asked
to assist in performing the challenges. The child reacted to a dose
of 10mg of tartrazine. The diagnosis was made.
|TIP for Allergy
More details on tartrazine can be accessed in Allergy Advisor.
To assist in the management of a tartrazine sensitive patient
such as the above, Allergy Advisor contains a diet sheet for
a tartrazine-free diet. The diet sheet lists the foods that
are allowed and those that could contain and therefore should
be avoided. The diet sheet can be modified by the health professional,
if required, to make the diet sheet more individual. In addition,
an information sheet on tartrazine sensitivity can be printed
from Allergy Advisor for patients to take home with them.
Together with the diet sheet, this sheet helps the patient
understand the condition better and helps ensuring that the
patient will stay symptom-free in the long-term.
B. More information:
Tartrazine is a water-soluble
synthetic dye that is commercially available in the form of a sodium
salt. Tartrazine is also available as the water-insoluble Aluminium
Lake. Tartrazine is a monoazo dye, derived from coal tar. Azo dyes are
a large category of colorings used in food and cosmetics and include
Quinoline Yellow, Yellow 2G, Sunset Yellow FCF, Carmoisine, Amaranth,
Ponceau, Erythrosine, Red 2G, Patent Blue V, Indigo Carmine, Brilliant
Blue FCF, Green S, Black PN, Brown FK, Chocolate Brown, Pigment Rubine,
Acid Yellow, Azodisalicylate, Chicago Sky Blue, Congo Red, Direct Black
38, Direct Blue 6, Direct Blue 15, Direct Brown 95, Fast Yellow, Lithol
Red, Methyl Orange, Methyl Red, Methyl Yellow, Naphthalene Fast Orange
2G, Neoprontosil, New Coccine, Orange II, Phenylazo-2-naphthol, Ponceau
3R, Ponceau SX, Red 2G, Red 10B, Salicylazosulphapyridine, Sunset Yellow,
and Trypan Blue.
Tartrazine is used
to give foods a lemon-yellow color, particularly those foods with lemon
and lime flavours. It is generally used in combination with other colors,
such as blue (to yield various shades of green). It appears reddish
at alkaline pH.1 Tartrazine is stable to heat and light and has an
ADI (Adequate Daily Intake) of 7.5 mg/kg body weight.
comment by FACTS's food scientist, Maritza
Tartrazine is approved and certified by the Food and Drug Administration
(FDA) as FD&C Yellow no. 5 and is also known as E 102. It
is listed as a color that may be used in a wide range of foodstuffs,
subject to specific quantitative limits. The use of tartrazine
is, however, prohibited in some countries such as Austria and
colors such as tartrazine are used more frequently in the food
industry because they are less expensive than natural colorants,
uniform, and extremely potent (i.e., less can be used to gain
the same effect); and remain stable in high processing temperatures,
acids, carbon dioxide, storage and light.
Where is tartrazine
Tartrazine is widely used for coloring drinks, foods, drugs and cosmetics,
for identification purposes and to produce an attractive appearance.
The content of tartrazine in one tablet may vary from 0.02 to 2.5mg,
while 250ml of soft drink may contain from 0.8 to 8.0mg tartrazine.1,2
High concentrations are used in, for example, snack foods such as sweets
to create bright colors to make them more acceptable to children.
Foods: The foods
in which tartrazine is typically used include baked goods, cereals,
soft drinks (particularly orange and lime drinks), canned foods; ice
cream and other frozen desserts; other desserts, sweets and confectionery;
pickles, sauces and seasonings.1
Drugs: The dye is
added to drugs in both solid and liquid preparations, including commonly
prescribed drugs as well as non-prescription drugs. Examples of these
are nutritional supplements, antihistamines, antibiotics, analgesics,
antidepressants, oral contraceptives, sedatives, hypnotics and corticosteroids.1,3
Azo dyes are also
widely used in the textile, printing and paper manufacturing industries,4
as well as in laboratories as either biological stains or pH indicators.5
According to the Codex Alimentarius Commission standards, additives
used as ingredients to perform specific functions in pre-packaged foods
must be declared on the label by the appropriate category name, e.g.,
colorant, followed by the approved name or serial number. No foodstuff
containing tartrazine may be sold unless the word "tartrazine"
appears in the list of ingredients.
However, if tartrazine
occurs in a food within a food (e.g., in jam within a packaged cake),
it does not have to appear on the list of ingredients,6 unless it
contributes to more than 2% of the product's weight.
Some experts suggest that additives (including tartrazine) do not cause
ANY adverse reactions. Studies that do report adverse reactions to tartrazine
are noted below. Some of the suggested effects of tartrazine are controversial.
This is mainly because of the limited number of studies done and the
variation in the methodology used.
suggests that tartrazine does not induce an IgE-mediated response, although
allergic mechanisms have been suspected. The exact mechanism of reaction
has not been established thus far. Adverse reactions to tartrazine are
considered to be due to an intolerance or sensitivity. The amount of
tartrazine required to produce sensitivity in susceptible persons varies
from 0.85ug to 25mg. It is estimated that the average daily consumption
of dyes is 15mg, about 85% of which is tartrazine.1
The most common
manifestation of tartrazine sensitivity is urticaria and, to a lesser
extent, angioedema. Evidence also suggests that chronic urticaria may
be caused by tartrazine.1
a. Skin manifestations:
Acute and/or chronic urticaria7,8,9,10,11,12,13
One published case report suggests that food-additive intolerance should
always be considered in patients who experience repeated episodes of
urticaria/angiodema after the ingestion of commercial food products,
even if these are considered free of additives.10
Various types of purpura1,16,17,18,19,20
Recurrent fixed drug eruption (a distinctive eruption characterized
by recurrences of one or more circumscribed lesions in the same site,
or sites, when the causative "drug", in this case tartrazine,
b. Systemic reactions:
Inhibition of platelet aggregation26
Tartrazine has been implicated in hyperactivity (also referred to as
hyperkinesis or overactivity), concentration difficulties and learning
difficulties in children.25 Whether this is true is controversial
and is yet to be proven. There have been many conflicting results in
studies. This can be partly explained by methodological variations in
trial design such as the use of placebos, the number of double-blind
challenges, and challenge doses.27
Some studies show that parents' reports of their child's adverse behavioral
changes after ingestion of tartrazine could not be validated objectively
when double-blind challenges were done. This does not exclude the possibility
that there are children who experience behavioral changes upon the ingestion
of additives such as tartrazine. However, it does show that parents'
beliefs in the behavioral effects of tartrazine are often groundless
and unreliable. This is in contrast to the situation of children with
atopic disease, where tartrazine may act as a trigger for asthma and
eczema. Improved control of the disease (including the exclusion of
tartrazine) is often accompanied by a significant improvement in behavior
Parents should be
informed of the range of factors that are known to influence behavior,
as well as the limited amount of evidence that exists for the role of
food additives and foods in causing behavior disturbances. Many health
professionals do not believe that azo dyes cause hyperkinesis. Many
families are unaware that clinical and educational psychologists, family
therapy and other facilities can assist in treating behavioral problems
As suggested above,
conditions such as uncontrolled eczema and perennial hayfever should
also be considered as causes of "hyperactivity" in children.
Itching from eczema and severe nasal obstruction from hay fever may
lead to sleep deprivation or disturbed sleep, causing fatigue or paradoxically,
hyperactivity (restless movement subconsciously aimed at generating
the stimulus for staying awake) the next day. In the case of these underlying
conditions, which can indirectly cause hyperactivity, a sensitivity
to additives may be falsely blamed.
Asthma has been linked to tartrazine sensitivity in many studies7,8,9,13,29,
but not all studies confirm this30. More recent and well designed
studies are fairly conclusive in showing that tartrazine may present
a significant problem for asthmatics.1 Routine tartrazine exclusion
will not benefit most asthmatics, only those very few individuals with
intolerance can induce cutaneous and/or respiratory reactions.32
It has been suggested that aspirin-sensitive individuals are more
prone to be sensitive to tartrazine as well, and that tartrazine
will exacerbate asthma in aspirin-sensitive individuals. Various
studies report the frequency of adverse reactions to tartrazine
among aspirin-intolerant patients with asthma to vary widely, ranging
from 0 to 44%.2 Settipane33 reported that 15% of aspirin-sensitive
asthmatics reacted to tartrazine doses of 0.22 to 0.44mg, whereas
Samter reported an 8% incidence of tartrazine sensitivity in aspirin-intolerant
patients. Another study found that approximately 2.4% of aspirin-allergic
individuals cross-react to tartrazine.2,9 Rosenhall found that
8% of 1868 patients with rhinitis or asthma reacted to a challenge
of tartrazine, although the loose criteria for positive challenges
has been commented on.
However, some studies
have found negative results. Weber34 found that a 16% tartrazine reaction
rate in 44 patients with perennial asthma could not be replicated with
a double-blind challenge. None of the patients reacted. One article
(with a review of studies on this subject) came to the conclusion that
asthmatics or patients with urticaria, whether aspirin-sensitive or
-insensitive, have no reason to avoid tartrazine, unless it is specifically
demonstrated that tartrazine provokes an adverse reaction during controlled
ingestion challenges.30 The difference between the various studies
in the literature may be due to the variation in interpretation of the
reactions and in the methodologies used.1
individuals, various drugs, most of which are prostaglandin inhibitors,
have been found to also cross-react with aspirin. These include (in
decreasing order of frequency) indomethacin (100%), ibuprofen, mefenamic
acid, phenylbutazone, sodium benzoate and acetaminophen (5%).33 It
is not clear whether the cross-reactivity between these drugs and aspirin
is similar to that between tartrazine and aspirin.
with other azo dyes:
Few adverse reactions have been reported to other azo dyes (see list
above). It is not clear whether the attention given to tartrazine is
because it is a more commonly used than other azo dyes, or because the
others cause fewer reactions in proportion to their use. Tartrazine
is, however, structurally unique as it contains a sulfanil group in
addition to its pyrazolone structure, but the clinical significance
is not known.1
Azo dyes can cross-react with permanent hair dyes containing p-phenylenediamine.
||compiled by Karen du Plessis
Food & Allergy Consulting & Testing Services (FACTS)
PO Box 565
Comments by our editor
Even though there is no conclusive evidence that tartrazine
causes hyperactivity in children, there are many parents and even
health professionals that believe this. There are so many holes
in the methodology used in the various studies done that one cannot
rule out that tartrazine can cause hyperactivity or not. And this
is the case with many other types of adverse reactions. It is
important to consider all aspects of a patient's history before
ruling out a diagnosis - no matter if it has not been confirmed
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. Dipalma JR. Tartrazine
sensitivity. Am Fam Physician 1990;42(5):1347-1350.
2. Virchow C, Szczeklik A, Bianco S, et al. Intolerance to tartrazine
in aspirin-induced asthma: results of a multicenter study. Respiration
3. Bhatia MS. Allergy to tartrazine in alprazolam. Indian J Med Sci
4. Chung KT, Stevens SE Jr, Cerniglia CE. The reduction of azo dyes
by the intestinal microflora. Crit Rev Microbiol. 1992;18(3):175-90.
5. Chung KT. The significance of azo-reduction in the mutagenesis and
carcinogenesis of azo dyes. Mutat Res. 1983 Apr;114(3):269-81.
6. Orchard DC, Varigos GA. Fixed drug eruption to tartrazine. Australas
J Dermatol 1997;38(4):212-214.
7. Settipane GA, Chafee FH, Postman M, et al. Significance of tartrazine
sensitivity in chronic urticaria of unknown aetiology. J Allergy Clin
8. Stenius BSM, Lemola M. Hypersensitivity to acetylsalicylic acid (ASA)
and tartrazine in patients with asthma. Clin Allergy 1976;6:119-128.
9. Morales MC, Basomba A, Pelaez A, et al. Challenge tests with tartrazine
in patients with asthma associated with intolerance to analgesics (ASA-triad):
a comparative study with placebo. Clin Allergy 1985;15:55-59.
10. Asero R. A strange case of "tuna allergy". Allergy 1998;53:816-817.
11. Jimenez-Aranda GS, Flores-Sandoval G, et al. Prevalence of chronic
urticaria following the ingestion of food additives in a third tier
hospital. Rev Alerg Mex 1996;43(6):152-156.
12. Montano Garcia ML, Orea M. Frequency of urticaria and angioedema
induced by food additives. Rev Alerg Mex 1989;36(1):15-8.
13. Collins-Williams C. Clinical spectrum of adverse reactions to tartrazine.
J Asthma. 1985;22(3):139-43.
14. Worm M, Vieth W, Ehlers I, Sterry W, Zuberbier T. Increased leukotriene
production by food additives in patients with atopic dermatitis and
proven food intolerance. Clin Exp Allergy 2001;31(2):265-73.
15. Van Bever HP, Docx M, Stevens WJ. Food and food additives in severe
atopic dermatitis. Allergy 1989;44(8):588-594.
16. Criep LH. Allergic vascular purpura. J Allergy 1971;48:7-12.
17. Michaelson G, Pettersson L, Juhlin L. Purpura caused by food and
drug additives. Arch Dermatol 1974;109:49-52.
18. Wüthrich B. Adverse reactions to food additives. Ann Allergy
19. Kubba R, Champion RH. Anaphylactoid purpura caused by tartrazine
and benzoates. Br J Derm 1975;Suppl2:61-2.
20. Kalinke DU, Wüthrich B. Purpura pigmentosa progressiva in type
III cryoglobulinemia and tartrazine intolerance. A follow-up over 20
years. Hautarzt 1999;50(1):47-51.
21. Bell RT, Fishman S. Eosinophilia from food dye added to enteral
feeding. N Engl J Med 1990;322:1822.
22. Trautlein JJ, Mann WJ. Anaphylactic shock caused by yellow dye in
an enema (case report). Ann Allergy 1978;41:28-29.
23. Pohl R, Balon R, Berchou R, Yeragani VK. Allergy to tartrazine in
antidepressants. Am J Psychiatry 1987;144:237-238.
24. Desmond RE, Trautlein JJ. Tartrazine (FD&C yellow #5) anaphylaxis:
a case report. Ann Allergy 1981;46:81-2.
25. Novembre E, Dini L, Bernardini R, Resti M, Vierucci A. Unusual reactions
to food additives. Pediatria Medica e Chirurgica 1992;14(1):39-42.
26. Gallagher JS, Splansky GL, Bernstein IL. Inhibition of platelet
aggregation by tartrazine and a pyrazolone analogue in normal and allergic
individuals. Clin Allergy 1980;10:683-90.
27. Pollock I, Warner JO. Effect of artificial food colours on childhood
behaviour. Arch Dis Child 1990;65:74-77.
28. David TJ. Reactions to dietary tartrazine. Arch Dis Child 1987;62(2):119-122.
29. Chafee FH, Settipane GA. Asthma caused by FD&C approved dyes.
J Allergy 1967;40:65-72.
30. Stevenson DD, Simon RA, Lumry WR, Mathison DA. Adverse reactions
to tartrazine. J Allergy Clin Immunol 1986;78(1 Pt 2):182-191.
31. Ardern KD, Ram FS. Tartrazine exclusion for allergic asthma. Cochrane
Database Syst Rev. 2001;(4):CD000460.
32. Moneret-Vautrin DA, Wayoff M, Bonne C. [Mechanisms of aspirin intolerance]
Ann Otolaryngol Chir Cervicofac. 1985;102(5):357-63.
33. Settipane GA. Aspirin and allergic diseases: a review. Am J Med.
1983 Jun 14;74(6A):102-9.
34. Weber RW, Hoffman M, Raine DA, Nelson HS. Incidence of bronchoconstriction
due to aspirin, azo dyes, non-azo dyes and preservatives in a population
of perennial asthmatics. J Allergy Clin Immunol 1979;64:32-37.
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: DT03/3/074/13
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
do not reach us.
6. Cut and paste the area indicated below into a e-mail message
and e-mail it to email@example.com
to be received no later than 31 August 2003. Answer sheets received
after this date will not be processed.
ALL THE QUESTIONS
(There is only
one correct answer per question.)
1. In which of the
following would one not expect tartrazine to be present?
(a.) Soft drinks
(b.) Soda water
2. Which of the
following are reasons why synthetic colorants are used more frequently
in the food industry?
(a.) They are less expensive than natural colorants.
(b.) Less can be used to gain the same effect.
(c.) They remain stable under high processing temperatures.
(d.) All of the above.
3. What is the main
reason for the use of tartrazine in drinks, foods, drugs and cosmetics?
(a.) Identification purposes and to create an attractive appearance
(b.) To reduce the price of the product
(c.) To increase the shelf life of the product
4. Which of the
following is true regarding the mechanism of reaction to tartrazine?
(a.) It is IgE-mediated.
(b.) It is an allergic mechanism.
(c.) It is a toxic reaction.
(d.) The exact mechanism of reaction has not been established thus far.
5. What is the most
common manifestation of tartrazine sensitivity?
(d.) Inhibition of platelet aggregation
6. True or false:
Whether tartrazine causes hyperactivity is controversial and is yet
to be proven.
7. True or false:
Routine tartrazine exclusion will benefit all asthmatic patients.
8. True or false:
Cross-reactivity with tartrazine should be considered in an aspirin-intolerant
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