IgE-mediated reaction to a banana-flavored drug additive
Maria Baeza2000, Journal of Allergy and Clinical Immunology
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were obtained before challenge as the baseline and serially for 60 minutes after the challenge testing. In addition, all patients' conditions were observed, and FEV 1 was measured every 60 minutes until 8 hours after challenge to detect the late asthmatic response.
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of leukotrienes. Among such antileukotriene drugs, specific receptor antagonists of the Background -Leukotriene receptor antagonists significantly blunt allergen-in-cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) have been found to inhibit asthmatic reac-duced bronchoconstriction in asthmatic subjects. Inhibitors of leukotriene syn-tions induced by allergens, 3-6 exercise, 7-9 and aspirin. 10 11 thesis should theoretically provide similar protection, but conflicting results have Another class of antileukotriene drugs is represented by compounds which inhibit the bio-been obtained when synthesis inhibitors have been tested in allergen challenge. synthesis of leukotrienes by inhibition of the 5-lipoxygenase or its activation. BAYx 1005 BAYx 1005, a new inhibitor of leukotriene synthesis, was therefore evaluated in an inhibits the production of leukotrienes 12 by antagonism of the 5-lipoxygenase activating pro-allergen bronchoprovocation study. Methods -Ten men with mild allergic tein (FLAP) 13 which has a pivotal role in the stimulation-evoked synthesis of leukotrienes asthma and bronchial hyperresponsiveness to histamine were recruited. On two from arachidonic acid. Consistent with this mode of action, BAYx 1005 has been found to different occasions each subject inhaled a single dose of allergen, previously de-inhibit IgE-dependent leukotriene formation in human lung in vitro, as well as the allergen-termined to cause at least a 20% fall in forced expiratory volume in one second induced reactions in isolated human bronchi and animal models of asthma. 14-16
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1202 Letters to the Editor
J ALLERGY CLIN IMMUNOL
DECEMBER 2000
TABLE I. Patient data
PC20-sulpyrine
(mg/mL)
Patient
No.
Sex Age (y)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
M
M
M
M
M
M
M
M
F
F
F
F
F
F
F
F
F
29
42
35
39
40
45
33
56
38
42
29
38
46
30
50
42
47
Duration
(y)
3
8
5
16
7
11
4
29
2
9
25
3
15
5
6
9
10
Atopy
HD, Gr
Cd
HD, C, Gr
None
None
Cd
None
None
None
Gr, HD
C
None
Cd
None
None
HD, Cd
None
Nasal
polyp
FEV1
(% predicted)
–
+
–
+
–
+
–
+
–
+
+
–
+
–
+
+
+
76
70
87
84
72
76
86
71
88
70
76
70
69
88
70
74
68
FVC
Eosinophils
IgE
(% predicted)
(%)
(RIST) (U/mL)
97
96
103
94
96
99
97
89
88
97
89
91
101
88
97
118
82
9
4
7
5
3
8
7
9
3
5
4
6
4
4
6
8
10
466
132
475
151
54
260
123
19
48
133
37
116
245
89
63
340
77
Placebo
Celecoxib
10
10
10
20
20
10
10
20
100
10
20
10
20
250
10
20
4
10
10
10
20
20
10
10
20
100
10
20
10
20
250
10
20
4
All patients used metered-dose inhalers of β-stimulants to control their asthma.
RIST, Radioimmunosolvent test; FVC, forced vital capacity; HD, house dust; C, cat; Gr, grass; Cd, Candida.
were obtained before challenge as the baseline and serially for 60
minutes after the challenge testing. In addition, all patients’ conditions were observed, and FEV1 was measured every 60 minutes until
8 hours after challenge to detect the late asthmatic response.
Significant decreases in FEV1 were not reproducible after the
treatment with either celecoxib or placebo, even 8 hours after challenge testing. None of the subjects reported any adverse effect after
celecoxib administration, nor could they discriminate between celecoxib and placebo.
Our results revealed that a specific COX-2 inhibitor, celecoxib,
is safely available for patients with AIA. Furthermore, inhibition of
COX-1 may play an important role in the pathogenesis of AIA,
whereas COX-2 might not. However, inhaled sulpyrine is a relatively weak stimulus compared with oral or inhaled acetylsalicylic
acid challenge. The difference between inhalation challenge with
sulpyrine and challenge with a full therapeutic dose (650 mg) of
acetylsalicylic acid should be made clear. Also, to determine the
exact relationship between celecoxib and leukotriene production or
release in AIA, additional studies will be required.
This is the first clinical report that the selective inhibition of
COX-2 would not be involved in the mechanism of bronchoconstriction in AIA.
Satoshi Yoshida, MD, FAAAAI
Yuko Ishizaki, MD
Kazuya Onuma, MD
Department of Medicine
Harvard Medical School
Boston, MA
Tatsuhiro Shoji, MD, FACG
Hiroshi Nakagawa, DDS, BSc,
Hideaki Amayasu, MD, FACAAI
AOKI International Medical Center and
Hirosaki University School of Medicine
Hirosaki Japan
REFERENCES
1. Spector SL, Wangaard CH, Farr RS. Aspirin and concomitant idiosyncrasies in adult asthmatic patients. J Allergy Clin Immunol 1979;64:500-6.
2. American Thoracic Society. Standards for the diagnosis and care of
patients with chronic obstructive pulmonary diseases (COPD) and asthma. Am Rev Respir Dis 1987;136:225-44.
1/8/110926
doi:10.1067/mai.2000.110926
IgE-mediated reaction to a banana-flavored
drug additive
To the Editor:
Potential drug allergens in IgE-mediated penicillin-adverse reactions include polymers, hapten-protein conjugates, impurities, and
additives. However, true hypersensitivity to additives such as dyes,
preservatives, and antiseptics has rarely been proved.
We describe an 8-year-old girl in whom oral itching with wheals
developed over her face and trunk and angioedema developed on
both eyelids within 1 hour of receiving her first oral dose of 250 mg
of Penilevel (Laboratorios ERN SA, Barcelona, Spain) containing
phenoxy-methyl-penicillin and banana essence as a flavoring additive. Symptoms resolved within 24 hours after treatment with antihistamines. She had tolerated 2 previous doses of intramuscular
injections of Penilevel containing only the active ingredient. She
had previously been found to have hay fever and oral allergy syndrome to several vegetables (celery and carrot) and fruits (banana,
peach, melon, and watermelon).
After a washout period, prick and intradermal skin tests with benzylpenicilloyl polylysine, minor determinant mixture, penicillin G,
and phenoxy-methyl-penicillin yielded negative results. A commercial
skin prick test with banana yielded negative results, but a prick-prick
test with fresh fruit elicited a positive wheal reaction (11 × 7 mm). The
total IgE level was 71.7 kU/L. The specific IgE response to penicillin
J ALLERGY CLIN IMMUNOL
VOLUME 106, NUMBER 6
G, penicillin V, and amoxicillin was negative and to banana was 1.25
kU/L (class II, CAP system; Pharmacia & Upjohn Diagnostics AB,
Uppsala, Sweden). After parental informed consent was obtained, oral
open challenge with active principle, phenoxy-methyl-penicillin, in
increasing amounts to therapeutic dose, was well tolerated.
Pure banana essence and banana extract were purified by a gelfiltration and desalting column with a polyacrylamide column (BioGel P-6DG columns; BioRad Laboratories, Hercules, Calif). Total
protein concentrations of 0.2 mg/mL of each were used for SDSPAGE and immunoblotting with serum of the patient. Results are
presented in Fig 1.
We present a case of urticaria and angioedema by sensitization to
a flavoring excipient contained in a pediatric drug. A type I hypersensitivity to essence was strongly suggested by the results of SDSPAGE immunoblotting. Allergic reactions to hidden allergens,
although infrequent, are increasingly being reported. Some studies
reveal that as much as the 30% of the anaphylactic shock episodes
are due to a hidden or inadvertently consumed allergen. In addition,
10.2% of anaphylactic shocks are considered idiopathic, raising the
hypothesis of allergy to masked food allergens.1 It is also known that
some proteins usually contained in vaccines of live attenuated virus,
which have been cultured in chicken embryo fibroblasts, potentially
may be dangerous, and caution must be exercised in children allergic to egg protein.2 More recently, several cases of IgE-mediated
reactions to gelatin as hidden allergen in vaccines3 or foods,4 as well
as hyaluronidase in pediatric oncologic drugs,5 have been reported.
Natural and artificial fruit essences such as strawberry, banana,
or peach are commonly used as flavoring agents in drugs in the
pediatric pharmacopoeia, like some antibiotics, nonsteroidal antiinflammatory drugs, anticonvulsants, or antihistamines. Natural
fruit components may be also present in essences or syrups.
In vitro studies with fruits and some other extracts that contain
high amounts of carbohydrates are difficult. For that reason we
processed our extracts through a desalting gel-filtration column to
improve the resolution of the studies, and we were able to disclose
the allergenic proteins present in the banana essence. We could
demonstrate that those proteins were also present in the banana fruit
to which the patient was allergic. Besides coincidental reactions, the
possibility of an iatrogenic adverse effect caused by excipient sensitization should be considered in atopic patients with food allergy.
The inclusion of the excipients in the allergologic study could
exclude the responsibility of the β-lactamic component in the reaction of this patient. We believe that the study of food additives in
drug allergy should always be considered.
Victor Matheu, MD
Lydia Zapatero, MD, PhD
Mercedes Alcázar, MD
María Isabel Martínez-Molero, MD
Maria L. Baeza, MD
Hospital General Universitario
Gregorio Marañón
Madrid, Spain
REFERENCES
1. Moneret-Vautrin DA, Kanny G. Food-induced anaphylaxis. A newFrench multicenter study. Bull Acad Natl Med 1995;179:161-72.
2. Trotter AC, Stone BD, Laszlo DJ, Georgitis JW. Measles, mumps, rubella vaccine administration in egg-sensitive children: systemic reactions
during vaccine desensitization. Ann Allergy 1994;72:25-8.
3. Kelso JM, Jones RT, Yunginger JW. Anaphylaxis to measles, mumps, and
rubella vaccine mediated by IgE gelatin. J Allergy Clin Immunol
1993;91:867-72.
4. Nakayama T, Aizawa C, Kuno-Sakai H. A clinical analysis of gelatin
allergy and determination of its causal relationship to the previous administration of gelatin-containing acellular pertussis vaccine combined with
diphtheria and tetanus toxoids. J Allergy Clin Immunol 1999;103:321-5.
Letters to the Editor 1203
FIG 1. Immunoblotting experiment. Lane A, Immunoblot with
processed banana extract demonstrating serum-specific IgE
against proteins ranging from 14 to 97 kd. Lane B, Immunoblotting with processed banana essence showing IgE-binding proteins ranging 30 to 66 kd. Lane B1, Banana essence inhibited by
banana fruit showing that antigenic components were homologous in both extracts. Lane B2, Banana essence inhibited by
banana essence. MW, Molecular weight.
5. Szepfalusi Z, Nentwich I, Dobner M, Pillwein K, Urbanek R. IgE-mediated allergic reaction to hyaluronidase in paediatric oncological patients.
Eur J Pediatr 1997;156:199-203.
1/8/111239
doi:10.1067/mai.2000.111239
Contact allergy to polidocanol, 1992 to 1999
To the Editor:
Previous small studies1 have indicated that polidocanol (CAS
9002-92-0) can be a relevant contact allergen in patients with chronic dermatitis. To assess the current prevalence of and risk factors for
polidocanol contact sensitivity in a clinical patch test population,
we analyzed data from 8739 patients tested with a topical drugs
patch test series in 30 centers of the Information Network of Departments of Dermatology (IVDK; http://www.ivdk.gwdg.de2) in Germany and Austria from January 1992 to December 1999. Test substances were supplied by Hermal/Trolab (Reinbek, Germany).
Results were based on readings at 72 hours.
In total, 3186 patients were tested with 0.5% polidocanol in
water, resulting in the following reactions: 0.94% questionable (erythematous), 0.88% slightly irritating, 0.97% weakly positive, and
0.25% strongly positive. In total, 6202 were tested with 3.0% polidocanol in petrolatum, resulting in the following reactions: 1.79%
questionable, 0.48% irritating, 1.77% weakly positive, and 0.34%
strongly positive. Among those 649 patients tested synchronously
with both preparations, concordance was moderate (Cohen’s simple
κ, 0.53; 95% CI, 0.29-0.76). Current or previous clinical relevance
was documented for 53% of patients with positive reactions, based
on probable or certain deterioration of pre-existing dermatitis by
application of polidocanol-containing topical drugs.3 The propor-
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