Chronic urticaria exacerbated by the

antioxidant food preservatives, butylated

hydroxyanisole (BHA) and butylated
hydroxytoluene (BHT)
D. L. Goodman, MD, LTC, MC, USA, J. T. McDonnell, MD,
H. S. Nelson, MD, T. R. Vaughan, MD, MAJ, MC, USA, and
R. W. Weber, MD Aurora, Colo.

Two patients with chronic idiopathic urticaria in whom remissions were achieved with dye- and
preservative-elimination diet had exacerbations of their urticaria when they were challenged
under double-blind, placebo-controlled conditions with butylated hydroxyanisole and butylated
hydroxytoluene. After elimination of butylated hydroxyanisole and butylated hydroxytoluene from
their diets, there was marked abatement of the frequency, severity, and duration of their
urticaria. These antioxidants appear capable of aggravating symptoms in certain patients with
chronic urticaria. (J ALLERGYCL1NIMMUNOL1990;86:570-5.)

The rate of successful identification of etiologic fac-

tors in most studies of chronic urticaria does not ex-
ceed 20%. 1-3 Numerous investigators have examined
the possible role o f ingested dyes and benzoate pre-
servatives in chronic urticaria. Juhlin 4 has estimated
that 30% of patients with chronic urticaria will have
whealing produced by food additives.
We report in this study the evaluation of two patients
with chronic urticaria in whom routine evaluation re-
vealed no obvious etiology. Each patient noted marked
improvement in frequency, severity, and duration of
urticarial episodes with the institution of a dye-
and preservative-free diet. Once the patients were
stabilized, they underwent double-blind, placebo-
controlled, oral challenges with a series of food ad-
Abbreviations used
BHA: Butylated hydroxyanisole
BHT: Butylated hydroxytoluene
NaB: Sodium benzoate
OHBA: Parahydroxybenzoic acid
PGE2, PGF:~: Prostaglandins E: and F~
FD&C: Food, drugs, and cosmetics
ditives. Both patients had exacerbations of their ur-
ticaria after challenge with B H A and BHT. Sub-
sequent avoidance of ingestants containing these
antioxidants resulted in sustained diminution in their
urticarial episodes. Long-term follow-up revealed ur-
ticarial flairs after dietary indiscretion but an otherwise
quiescent disease.

From the Allergy-Clinical Immunology Service, Fitzsimons Army
Medical Center.
The opinions or assertions contained herein are the private views
of the authors and are not to be construed as official or as re-
flecting the views of the Department of the Army or the De-
partment of Defense. The protocol under which this study was
conducted was approved by the Clinical Research and Human
Use Committee of Fitzsimons Army Medical Center and the
Office of the Surgeon General of the United States Army.
Received for publication April 24, 1990.
Revised June 14, 1990.
Accepted for publication June 20, 1990.
Reprint requests: David L. Goodman, MD, LTC, MC, Allergy-
Clinical Immunology Service, Fitzsimons Army Medical Center,
Aurora, CO 80045-5001.
1/1/23343
CASE REPORTS
Patient No. 1
A 32-year-old white male army pediatrician was referred
to the Fitzsimons Allergy-ClinicalImmunology Service with
a 4-year history of daily urticaria, noticeably worse during
the morning hours. He had experienced two episodes of
severe generalized urticaria and angioedema after ingestion
of 650 mg of aspirin, and one such episode after ingestion
of 650 mg of acetaminophen. He had a history of childhood
asthma and allergic rhinitis that had remitted during ado-
lescence. He had consulted several physicians for evaluation
of his urticaria and had progressively restricted his diet. At
the time of admission, he was eating only fresh beef obtained
daily from a butcher, asparagus, broccoli, one ounce of
oatmeal with 2 ounces of milk each morning, and deionized

570
VOLUME86
NUMBER 4, PART 1
water. He had lost 31 pounds while he was receiving this
diet.
Laboratory evaluation demonstrated an elevated IgE of
1650 IU / ml and a persistent low-grade cryoglobulinemia of
mixed, predominantly IgM type. Skin biopsy specimens of
an early, as well as an older, lesion revealed no leukocy-
toclastic angiitis. Normal studies included complete blood
count with differential, serum protein electrophoresis, an-
tinuclear antibody, serum IgG, IgA, and IgM, C3 and C4,
urinalysis, and chest x-ray. A hepatitis B antigen screen was
negative. Pulmonary function testing revealed normal val-
ues. Prick skin tests for 23 foods were negative, but skin
tests for aeroallergens revealed multiple positive reactions
to pollens, corroborating the patient's rhinitis history.
Patient No. 2
A 42-year-old white male Army helicopter pilot was re-
ferred to the Allergy-Clinical Immunology Service with a
3-year history of urticaria occurring four to five times
weekly. He associated the onset of the hives with undergoing
a vasectomy. He occasionally noticed angioedema of the
lips after meals, but could not associate these occurrences
with any particular food. There was an occasional pressure-
induced component, and both emotional stress and sexual
intercourse exacerbated his symptoms. There were no per-
sonal nor family history of atopy, no associated diseases,
and no obvious environmental exposures.
Severe episodes were refractory to antihistaminic treat-
ment and required brief courses of oral corticosteroid ther-
apy to induce remission. Although a dye- and preservative-
free diet (Table I)s greatly improved his symptoms, he had
lost 20 pounds during a 2-month period. He found the diet
poorly palatable and could only tolerate it for brief periods
of time.
Laboratory evaluation revealed normal complete blood
count with differential, serum protein electrophoresis, an-
tinuclear antibody, C3 and C4, serum IgG, IgA, IgM, and
IgE, urinalysis, and chest x-ray. Food prick skin testing was
uniformly negative, as was a panel of prick skin tests to
aeroallergens.
MATERIAL AND METHODS
Both patients were admitted to hospital and placed on a
rigid dye-free and preservative-free diet, with an elemental
diet formula (Vivonex/Tolerex, Norwich-Eaton Pharma-
ceuticals, Norwich, N.Y.). Both patients were observed for
a 5- to 7-day period before the institution of the challenges
to establish an estimate of baseline activity. The patients
were asked to rate pruritus on a scale of 0 to 4 + , from
absent to severe enough to warrant use of a colloidal sus-
pension bath to relieve symptoms. Lesions were graded in
the following manner: 0, absent; 1 + , sparse maculopapular
lesions or solitary wheals; 2 + , generalized maculopapular
lesions; 3 + , wheals confined to one or two extremities or
body areas; and 4 + , wheals generalized over entire body.
A positive response was judged as a 3 + or 4 + objective
reaction, occurring within 12 hours of ingestion. Reactions
occurring after 24 hours from ingestion were considered as
not caused by the challenge, and reactions occurring be-
Chronic urticaria exacerbated by BHA/BHT 571
TABLE I. Dye- and preservative-free diet*
Foods allowed
Meats: lamb, chicken, beef, veal, turkey (fresh or
frozen)
Fish (fresh or frozen)
Vegetables: potatoes, lettuce, carrots, parsley,
mushrooms
Cereal grains: rice
Fruits: pears (fresh, canned, nectar)
Cooking oils: safflower without preservatives
Condiments: sugar, honey, salt, pepper, gelatin
(plain)
Beverages: (unflavored) coffee, tea, pear nectar,
water
Optional foods
Preservative-free bread, spaghetti, matzo (plain),
eggs, milk, butter, cottage cheese
Foods not allowed
Cheese, margarines, prepared salad dressings, pick-
les, prepared sauces, breakfast cereals, cakes,
mayonnaise, chocolate, instant foods, sweets,
packaged meals, bread (unless marked
preservative-free), bananas, licorice, rhubarb,
grapes, apples, wine, beer, fruit juices (except
pear nectar), instant coffee, preserves, marma-
lade, jam.
*Modified from reference 5.
tween 12 and 24 hours as equivocal. The patients' pruritus
assessment did not enter into the judgment of determining
a positive or negative response. The physician evaluating
the clinical response was blinded to the contents of the
challenges, and the code was not broken until the entire
sequence of challenges was completed.
Challenge substances were provided for patient No. 1 in
clear gelatin capsules (Eli Lilly & Co., Indianapolis, Ind.)
filled with dextrose to mask the white crystalline additives,
or in the case of the dyes, in 2 ounces of preservative-free
grape juice. For patient No. 2, all challenge powders were
provided in grey opaque gelatin capsules (Dura Foods,
E1 Paso, Texas). The dyes and preservatives were obtained
from Sigma Chemical Co., St. Louis, Mo., Allied Chemical
Co., Morristown, N.J., and Kodak Scientific Chemical Co.,
Rochester, N.Y. All dyes and preservatives were assayed
at -->98.5% purity.
After a minimum 6-hour overnight fast, the patients in-
gested the first challenge dose. This dose was followed by
the second, larger dose 2 to 4 hours later, assuming that no
major exacerbation o f symptoms had occurred in this time
frame. Challenges proceeded on daily intervals unless there
was a positive reaction; in that case, 24 to 48 hours was
allowed to elapse before the next challenge to allow the
reaction to return to baseline and to avoid false negatives
caused by a refractory period, as reported for aspirin chal-
lenges. 6
572 Goodman et al.
TABLE II. Dye- and preservative-challenge doses
BHA, BHT .: 125,250 mg each
Azo dye mix* 5, 20 mg each
Na benzoate 125, 250 rng each
p-hydroxybenzoic acid 125, 250 nag
Na salicylate 325 mg
Acetaminophen 325 mg
Tartrazine 5, 20 mg each
*Azo dye mix, amaranth, FDC red No. 2; ponceau, FDC red No.
4; and sunset yellow, FDC yellow No. 6.
Doses used in the challenges are presented in Table II.
These doses were derived from a challenge regimen used
by Weber et al. 7 in evaluating dye and preservative sensi-
tivity in subjects with asthma. BHA and BHT were admin-
istered simultaneously, with the initial dose including 125
mg of each and the second dose including 250 mg of each.
NaB and OHBA were administered in similar doses; patient
No. 1 received these compounds on separate challenge days,
whereas patient No. 2 received these compounds simulta-
neously. Tartrazine was administered in doses of 5 mg and
20 mg. The other azo dyes, amaranth (FD&C red No. 2),
ponceau (FD&C red No. 4), and sunset yellow (FD&C
yellow No. 6) were administered in similar doses as indi-
vidual challenges to patient No. 1 and as a mix to patient
No. 2. Because of his past history, patient No. 1 was also
challenged with sodium salicylate, 325 mg, and acetamin-
ophen, 325 mg. Placebo challenges were either dextrose or
lactose powder. Patient No. 1 had an additional placebo of
unadulterated grape juice as well. The challenge sequence
was randomized to eliminate any order bias.
In addition to the clinical assessment, patient No. 1 had
serial plasma determinations throughout the challenge pe-
riod for hemolytic complement 50, activated C3 and factor
B, histamine, and PGE2, PGF2~, and dihydroxy-keto-PGF2,.
Blood was drawn at baseline and half-hour intervals after
the first dose until 2 hours, and then hourly intervals until
6 hours after the second dose.
After the initial challenges were completed on patient
No. 1 and the code was broken, the patient, as well as two
normal control subjects, underwent an additional double-
blind session with BHA, 250 mg, and placebo. This
procedure was done to evaluate the predictive value of
the sequential vascular response test of Fisherman and
Cohen?' 9This test is basically an earlobe bleeding time but
has been advanced to diagnostic in adverse reactions to
BHA/BHT, as well as aspirin and other chemicals. Prick
skin tests with serial dilutions of BHA, BHT, sodium sa-
licylate, and OHBA were performed on patient No. 1.
The protocol was approved by the Fitzsimons Army Med-
ical Center Institutional Review Committee, and all subjects
signed an informed consent.
RESULTS
Subjective symptoms of pruritus, as well as urti-
carial lesions, decreased within 48 hours to a lower
baseline, while patients were receiving the restricted
J. ALLERGYCLIN.IMMUNOL.
OCTOBER 1990
TABLE IlL Double-blind challenge results
Patient No. 1 Patient No. 2
(No. of (No. of
Substance challenges) challenges)
BHA/BHT Positive (3) Positive (2)
Placebo Negative (3) Negative (3)
Tartrazine/azo dyes Negative (2) Negative (1)
Benzoates Negative (2) Negative (3)
Na salicylate Positive (1) ND
Acetaminophen Positive (1) ND
ND, Not done.
diet, but did not clear entirely. Urticarial activity was
stable throughout the remainder o f the prechallenge
observation period. For both patients, all positive re-
actions occurred between 1 and 6 hours after the chal-
lenge doses. There were no delayed reactions, and
there were no noncutaneous reactions (e.g., drowsi-
ness, headache, rhinitis, or wheezing). All positive
reactions were graded as 4 + by the blinded observer
and as producing 4 + pruritus in the patients. During
the prechallenge period, as well as placebo-challenge
days, pruritus ranged from 0 to 2 + , but lesions were
graded as no higher than 1 + . Lesion severity was
therefore markedly increased over baseline with a pos-
itive challenge, with no equivocal events. The chal-
lenge results are outlined in Table III.
Patient No. 1 reacted to all three of the mixed
B H A / B H T challenges, as well as the single B H A
challenge. He had strong reactions to both sodium
salicylate and acetaminophen. He was not challenged
to aspirin. He was consistently negative to the ben-
zoates, tartrazine, and placebo. H e complained of 2 +
pruritus with the sunset yellow ( F D & C yellow No.
6), but lesional activity was 1 + . Patient No. 2 was
positive to both B H A / B H T challenges and negative
to all N a B / O H B A , azo dye mix, and placebo chal-
lenges.
Serial complement and prostaglandin determina-
tions during the challenges in patient No. 1 were unre-
warding. Hemolytic complement 50 was observed to
decrease 30% to 35% randomly on both p l a c e b o -
challenge day and days when an active compound was
administered. Activated C3 and factor B were spo-
radically elevated on four occasions, twice with pla-
cebo and once during the prechallenge baseline pe-
riod. The histamine assay was subsequently found to
be unreliable and is not reported. The prostaglandin
levels all decreased as the day progressed, regardless
of whether placebo or active compound was admin-
istered. Serial earlobe bleeding times were all un-
changed with both placebo and B H A in the patient
and control subjects. Patient No. 1 had a brisk urti-
carial response to the BHA. Neither control subject
VOLUME86
NUMBER 4, PART 1
developed urticarial lesions after ingestion of BHA.
Prick skin tests with BHA, BHT, sodium salicylate,
and OHBA were negative.
The oatmeal that patient No. 1 had been routinely
ingesting for breakfast contained BHA and BHT. Both
patients started receiving diets specifically avoiding
BHA and BHT. These diets resulted in sustained dim-
inution in frequency and severity of urticaria for both
patients. Patient No. 1, at 7-year follow-up, continued
to rigidly adhere to his diet and noted exacerbations
of his urticaria when unexpected exposures occurred.
Patient No. 2, at 1-year follow-up, also continued to
follow his diet, noting only two minor exacerbations,
again after ingesting foods containing BHA and BHT.
These two episodes lasted < 12 hours and required no
medication. Each patient returned to his preillness
weight and was able to resume his normal occupation.
Neither patient has undergone blinded rechallenge
with BHA/BHT.
DISCUSSION
BHA and BHT were originally developed as an-
tioxidants for petroleum and rubber products but were
discovered to be effective antioxidants for animal fats
in the mid 1950s. lo These compounds are now added
to various foods, cosmetics, and pharmaceuticals to
prevent oxidation of unsaturated fatty acids9 The U.S.
average daily intake per person of BHT alone was
estimated as 2 mg in 1970.1~ With the greater present
reliance of the American diet on processed and pack-
aged foods, currently daily intake of BHA and BHT
may be substantially larger. Despite a wealth of animal
toxicology literature on these antioxidants, there are
only rare reports of adverse reactions to BHA and
BHT in humans9
In 1973, Fisherman and Cohen 8 reported that seven
patients with either asthma or rhinitis were intolerant
to BHA and BHT. These findings were identified by
a doubling 6f their earlobe bleeding times, There were
no clinical details provided, nor were there indications
as to why B H A and BHT were suspected to cause
difficulty9 No rationale for the reported effect on the
bleeding time was listed. The following year, per-
forming a similar study, Cloninger and Novey 11 re-
futed these findings.
Roed-Petersen and Hjorth 12found four patients with
eczematous dermatitis who had positive patch tests to
BHA and BHT. Dietary avoidance of the antioxidants
resulted in remissions in two patients. When both
patients were challenged with ingestion of 10 to 40
mg of BHA or BHT, these patients had exacerbations
of their dermatitis. Osmundsen 13 reported a case of
contact urticaria apparently caused by BHT contained
in plastic folders; the patient had positive wheal-and-
flare responses to 1% BHA and BHT in ethanol. Re-
Chronic urticaria exacerbated by BHA/BHT 573
cently, a case of acute urticarial vasculitis caused by
BHT in chewing gum was reported. 14
In 1975, Thune and Granholt 15 reported on 100
patients with recurrent urticaria evaluated with pro-
vocative food-additive challenges. Sixty-two patients
had positive challenges, with two thirds reacting
to multiple substances9 Positivity rates for individ-
ual dyes, preservatives, or anti-inflammatory drugs
ranged from 10% to 30%. Most reactions occurred
within 1 to 2 hours, with a number occurring between
12 and 20 plus hours. Six of 47 patients tested to BHA
reacted, and six of 43 patients reacted to BHT. It is
unclear whether these were the same six patients9 Test
doses were administered in two to three increments
with the cumulative dose of BHA and BHT totalling
17 mg. The provocative challenges were not blinded,
nor do the authors state criteria for a positive chal-
lenge9
Juhlin 16 used a 15-day, single-blind challenge bat-
tery of dyes, preservatives, and placebo to evaluate
330 patients with recurrent urticaria. Antihistamines
were withheld from 4 to 5 days before the commence-
ment of the challenge sequence. Testing was accom-
plished when patients had "no or slight symptoms."
Tests were judged positive if "clear signs of urticaria
or angioedema" occurred within 24 hours. Slightly
less than half of the 330 patients (156) received a
B H A / B H T challenge with cumulative doses of 111
mg administered during four doses. Fifteen percent
of the patients had positive reactions. Lactose placebo
was administered in two doses on days 1, 3, 9, and
12, although modifications in the order did occur.
Active substances were administered in single to six
divided doses at hourly intervals. Most patients did
not undergo the entire challenge schedule; one third
of the patients did not receive a placebo challenge.
The studies of Roed-Petersen and Hjorth 12 and
Osmundsen 13 suggest that adverse reactions to BHA
and BHT m a y be mediated through immunologic
mechanisms. The role of these antioxidants in causing
or aggravating chronic urticaria has been less clear.
Identification of provokers in a disease of waxing and
waning nature may be difficult. Are reactions truly
causally related or only spontaneous exacerbations of
the process? This is especially an issue when a back-
ground of urticarial activity persists during challenges9
A sharp definition of what constitutes a positive re-
action is necessary. Additionally, the observer rating
the severity of the reaction must be blinded as well
as the subject, since he is just as susceptible to ex-
pectation bias. The studies of Thune and Granholt 15
and Juhlin 16 fail on both counts. The 13% to 15%
incidence of B H A / B H T reactions reported is most
likely an overestimate. The importance of double
blinding in such studies has been pointed out by Weber
574 Goodman et al.
et al. 7 and reenforced by Stevenson et al. 17 In the
former study of 15 patients who reacted to dyes or
preservatives on open challenge, only three patients
responded under repeat double-blind conditions.
This study constitutes the first double-blind,
placebo-controlled, multiple challenge protocol doc-
umenting the link of BHA and BHT with chronic
urticaria. The demonstration of symptom aggravation
did not rest on single challenges. Despite the extensive
evaluation in patient No. 1, the mechanism of action
is uncertain. An immunologic process is not supported
by the inconsistent changes in complement compo-
nents, negative immediate skin tests, and lack of vas-
culitis in biopsy specimens. The low-grade cryoglob-
ulinemia is perplexing, but 7 years of follow-up have
failed to reveal evidence for a connective tissue dis-
order.
Positive reactions to the BHA/BHT challenge
doses occurred in our patients between 1 and 6 hours
after ingestion. Although this temporal sequence is
not inconsistent with that observed with adverse (e.g.,
urticarial) reactions to ingested foods, the longer in-
terval to symptom onset would possibly diminish
awareness of potential causality in a patient unsus-
pecting of the source of the exacerbant. The diet con-
tent of BHA/BHT may, as above noted, be less than
the amounts used in our challenge sequence. It may
be reasonably expected that "natural" dietary expo-
sures to the additives at these lower levels might not
be as readily perceived by the patient as being poten-
tially related to exacerbations of their urticaria. Thus,
the lack of historical association by patients between
ingestion of food additives and exacerbation of their
urticaria may be roughly analogous to that often-noted
lack of perceived association by cat-allergic individ-
uals between chronic exposure and chronic symptom-
atology.
A dose-response effect to BHA/BHT in these pa-
tients was suggested, since their peak clinical urti-
carial responses occurred after, but within 2 hours of,
the ingestion of the second dose of the incremental
challenge with the antioxidants. However, on subse-
quent analysis of the blinded graders' observations on
the positive challenge days, it was readily apparent
that urticarial responses were developing as soon as
15 to 90 minutes after ingestion of the first dose, but
they simply did not reach "positivity," as defined by
our rating scale, until after ingestion of the second
dose. Consequently, in this descriptive study, we have
elected to indicate a potentially broad range of tem-
poral response (within the stated study time limits) to
prevent inappropriate attention focused on any more
circumscribed interval of observation.
Rather than focus on dose-response determinations,
we chose to use larger doses to discriminate more
clearly positive and negative challenges. We then re-
J. ALLERGY CLIN, IMMUNOL.
OCTOBER 1990
lied on specific elimination of BHA/BHT from the
patients' diets to ascertain clinical relevance. Imple-
mentation of a titrated dosage schedule in subsequent
challenges might be useful in determining a more spe-
cific threshold for particular patients.
Patient No. 1, after completion of the double-blind
challenges, underwent an additional double-blind
challenge with BHA, 250 mg, and with placebo. He
(in contrast to two normal control subjects) responded
to the BHA challenge with a significant exacerbation
of urticaria. We did not, however, further define the
specificity of the reactions with respect to BHA versus
BHT in either of the two patients. Practically speak-
ing, both agents are most often used in combination
in their antioxidant roles, and thus, clinical avoidance
would entail avoidance of both agents.
The strict elimination diets did not toally ablate
lesions in either patient. It may be that the antioxidants
acted as potentiators of an underlying unrelated pro-
cess, similar to the action of aspirin in chronic urti-
caria. 18In distinction to their lack of effect in asthma,
nonacetylated salicylates, as with patient No. 1, have
been reported to exacerbate urticaria. 18 The pre-
sumed route of action of these agents is through
the arachidonic acid cascades and might thus explain
the apparently concomitant predilection to urticar-
ial responses to both aspirin/acetaminophen and
BHA/BHT of patient No. 1. We could not, however,
demonstrate any changes with positive challenges in
the levels of the prostaglandins that we measured.
Although both of our patients were certainly ex-
posed to other potential antioxidants in their dietary
intake, neither patient presented a history of adverse
reactions to vitamins nor snlfites. They were not chal'-
lenged to those agents. It should be emphasized that.,
of the multiple dyes and preservatives with which they
were challenged (which, by virtue of their ranking
among the most common additives in our food supply,
make them reasonable potential precipitants of urti-
caria), they mounted urticarial responses only to
BHA/BHT.
The schedule used in this study was a truncated
incremental challenge. The doses used may be con-
sidered large and certainly far exceed an average daily
intake. However, such doses are more likely to provide
a definitive reaction. Clinical relevance can then be
ascertained by elimination of the incriminated agent
from the diet. It must be noted that such doses, al-
though they are appropriate for urticaria evaluations,
could be dangerous if potential asthmatic responses
were being examined.
The true incidence of antioxidant sensitivity in
chronic urticaria is presently unknown. High reaction
rates of adverse reactions to food additives have not
been substantiated by carefully done, double-blind
studies.7, 17 We have reviewed our experiences with
VOLUME 86
NUMBER 4, PART 1
271 consecutively referred patients with chronic
urticaria evaluated at Fitzsimons Army Medical Cen-
ter during the time interval encompassed by this
study. In those subjects in whom an underlying etiol-
ogy of chronic urticaria was not identified, dye- and
preservative-free diets were used. In eleven (4%) of
these patients, such elimination diets produced sig-
nificant diminutions in the frequency, severity, and
duration of urticarial episodes, and they were subse-
quently subjected to double-blind challenge sequences
as described herein. The two reported patients (com-
prising 0.74% of the total group of patients with
chronic urticaria evaluated) were the only patients in
this group who responded with exacerbations of their
disease on ingestion of BHA/BHT. One other patient
from this group responded, on double-blind challenge,
to ingestion of NaB with a significant exacerbation of
urticaria. The other eight patients manifested no sig-
nificant urticarial responses on double-blind challenge
with the dye and preservative panel.
In those patients in whom a thorough evaluation
has failed to reveal a recognizable cause of chronic
urticaria, a dye- and preservative-free diet should be
considered. Patients with chronic urticaria benefiting
from intervention warrant further investigation to de-
termine the specific offending additive(s) or preser-
vative(s). Open, single-blind, and /or double-blind
challenges may be used to further authenticate sen-
sitivity.
We consider the evaluation schema for chronic ur-
ticaria described in this study to be analogous to that
used in food-hypersensitivity diagnosis. Properly used
dietary manipulations, combined with open or single-
blind and subsequent double-blind challenge se-
quences may allow specific avoidance recommenda-
tions that result in amelioration of urticarial episodes
while the need to invoke extreme dietary elimination
measures is alleviated.
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