ARTICLE
Auteur(s) : Amale Hassani1, Claude Ponvert2,
Chantal Karila2, Muriel Le Bourgeois2,
Jacques De Blic2, Pierre Scheinmann2
1Pediatric Service: Military Hospital Mohamed V,
Rabat-Salé, Morocco
2Paris V University: Department of Pediatrics,
Pulmonology & Allergy Unit, Sick Children’s Hospital: 149 rue
de Sèvres, 75015, Paris, France
accepté le 2 Avril 2008
Three to 15% of hospitalized and outpatients report suspected
hypersensitivity (HS) to drugs and biological substances [1, 2].
The most frequently suspected drugs are anti-infectious drugs
(40-70%) and cyclooxygenase (COX) inhibitors (non-opioid
analgesics, antipyretics and nonsteroidal anti-inflammatory drugs)
(≈ 20%) [1, 3]. According to the revised nomenclature for
allergy [4], these reactions should be called hypersensitivity
reactions, either allergic when they involve specific antibodies
and/or T cells, or non allergic when specific immunological
mechanisms are not involved or cannot be proven.
Although COX inhibitors are widely used in clinical practice,
the prevalence of suspected HS to these drugs is low (0.3-1%) in
the general population [5, 6]. Patients with chronic urticaria or
asthma and atopic patients [5-8] are at higher risk for non
allergic HS to COX inhibitors than other patients. Hypersensitivity
to these drugs is probably less frequent in children than in
adults. In the randomized prospective study of Lesko et al. [9], in
27,000 children younger than two years old, all the children
tolerated prolonged treatments with paracetamol (acetaminophen) and
ibuprofen. In the study of Martin-Munoz et al. [10], only 10% of
the children with suspected drug HS reported reactions to COX
inhibitors. In another study, HS to COX inhibitors was suspected in
only 2% of 754 adverse reactions to drugs occurring in hospitalized
children [11].
The most frequently reported reactions are cutaneous, especially
urticaria and/or angioedema, rhinitis and/or asthma. Anaphylaxis
and potentially severe toxicodermas are rare. In 260 children and
adults with suspected HS to COX inhibitors, 61.5% of the patients
reported urticaria and/or angioedema, and 24.2% rhinitis and/or
asthma. Unidentified skin reactions were reported by 10.8% of the
patients, and anaphylaxis accounted for only 3.5% of the reactions
[12]. Thirty-five per cent of 17 children with suspected HS to COX
inhibitors reported urticaria and/or angioedema (facial oedema
especially), 35.3% pruritus and/or unidentified skin reactions,
23.5% asthma, and 5.9% anaphylaxis [11]. Finally, in another study,
all the children with proven non allergic HS to COX inhibitors
reported facial oedema, 38% generalized urticaria, and 42%
respiratory symptoms [13].
In studies based on skin tests, in vitro tests and challenge
tests, 13 to 50% of the patients with suspected HS to COX
inhibitors were diagnosed as hypersensitive to these drugs [10, 12,
14, 15]. Hypersensitivity to COX inhibitors was diagnosed more
frequently in patients with anaphylactic and/or immediate reactions
than in the other patients [15]. In a few patients, the reactions
may result from immediate or non immediate allergic HS, with
positive responses in in vivo and/or in vitro tests to a specific
family and tolerance to other families of COX inhibitors [16-21].
However, most reactions result from a non-allergic HS, as suggested
by a high degree (25-100%) of cross-reactivity between the various
structurally unrelated families of NSAIDs, and 2-83% of
cross-reactivity with drugs with a low COX-1 inhibitory activity,
such as paracetamol, nimesulide and coxibs [13, 15, 22-25].
Only a few studies have been performed selectively in children
with suspected or proven HS to COX inhibitors [10-13, 22-24]. We
studied 164 children reporting suspected HS to commonly used COX
inhibitors (paracetamol, ibuprofen and acetylsalicylic acid). The
aims of this study performed in the pediatric pulmonology and
allergy service of the Sick Children’s Hospital (Paris, France)
were to determine the clinical characteristics and risk factors for
HS to these drugs in children.
Patients and methods
Patients
We studied 164 children (102 M + 62 F), mean age 7.2 ± 4.2 years
(range: 7 mths-17.3 yrs), reporting 213 reactions to COX inhibitors
between 1993 and 2004. The demographic characteristics of the
children are indicated in table 1.
The initially suspected drugs were acetylsalicylic acid (ASA, n
= 106), ibuprofen (n = 64), and paracetamol (n = 43). Fourty-nine
(29.8%) children reported several reactions to a single or several
drugs. A previous known exposure to the suspected drug(s) was
reported in only 23 (14%) of the children. Other drugs or
biological substances (antibiotics, vaccines, etc.) were also
suspected to be a possible cause of the reaction in 79 cases.
The reactions (table 2) were
classified according to their nature, severity and chronology. The
reactions occurring less than 1h, between 1 and 48 h, and more
than 48 h after the beginning of the treatment were classified
as immediate, accelerated and delayed, respectively [26]. Most
children reported immediate and accelerated reactions, and most
reactions were cutaneous, either isolated (n = 129, 61%) or
associated with respiratory symptoms (n = 33, 15.6%) and shock (n =
24, 11.4%). Isolated respiratory symptoms (rhinitis, cough, asthma)
and conjunctivitis were exceedingly rare. Children reporting
several reactions were classified on the basis of their more severe
and/or rapid reaction.
Table 1 Demographic characteristics of 164 children
with suspected hypersensitivity to COX inhibitors
|
Number and sex
|
164 (102 M, 62 F)
|
|
Age
|
Mean = 7.2 yrs (range: 7 mths-17.3 yrs)
|
|
Time between the (last) reaction and work-up
|
Mean = 8 mths (range: 4-20 mths)
|
|
Familial history of atopy
|
85 (52%)
|
|
Personal atopy
|
102 (62%)
|
|
Previous known exposure to the suspected drug
|
23 (14%)
|
|
Suspected allergic reactions to other drugs
|
60 (37%)
|
Table 2 Clinical characteristics of 213 suspected
allergic reactions to COX inhibitors reported by 164 children
|
Type and chronology of the reactions
|
Immediate (≤ 2 h)
|
Accelerated (≤ 48 h)
|
Delayed (> 48 h)
|
Total: n (%)
|
|
Isolated urticaria and/or angioedema
|
45
|
69
|
15
|
129 (61%)
|
|
Cutaneous + respiratory symptoms
|
16
|
7
|
10
|
33 (15.6%)
|
|
Anaphylactic shock (± skin and/or respiratory symptoms)
|
18
|
6
|
0
|
24 (11.4%)
|
|
Isolated rash
|
6
|
7
|
3
|
16 (7.5%)
|
|
Isolated respiratory symptoms (rhinitis, cough, asthma)
|
0
|
10
|
0
|
10 (4.3%)
|
|
Isolated conjunctivitis
|
0
|
1
|
0
|
1 (0.5%)
|
|
Total
|
85 (40.1%)
|
100 (46.7%)
|
28 (13.2%)
|
213 (100%)
|
Diagnosis
Diagnosis was based on a convincing clinical history (recurrent
and/or anaphylactic or immediate or accelerated reactions to
isolated administrations of COX inhibitors) or on positive response
to oral challenge (OC) with the suspected drug(s). OC tests were
performed in the hospital under strict supervision, during
24 h (immediate reactions) or 48-72 h (non-immediate
reactions), after informed consent of the parents. Children
received a first dose of 1 or 10 mg of the drug, based on
the severity of the reaction. The dose was increased gradually,
with a 20 mn interval between each dose, until the appropriate
cumulative dose per day for age and weight was reached. The second
and third days, the children received half the therapeutic dose at
9 A.M. and 12, and were supervised for a possible reaction
until 17-18 h. OC were performed at least with another one COX
inhibitor in children with a convincing clinical history of HS or a
positive OC to a single drug (i.e. paracetamol in children reacting
to ibuprofen and/or ASA, or ASA and/or ibuprofen in children
reacting to paracetamol), except for the children with a known
tolerance to these drugs since their suspected allergic reaction.
One hundred and thirty-nine OC were performed (ASA: 83, ibuprofen:
44, and paracetamol: 12). Challenges were classified as positive if
an objective adverse reaction (e.g. urticaria and/or angioedema,
conjunctivitis, rhinitis and/or asthma) occurred during or within
24 to 48 hours of the end of the challenge.
Diagnosis of HS to other drugs or biological substances was
based on positive immediate, semi-late or late responses in skin
tests (betalactams, vaccines) and challenge with the suspected
drugs or biological substances, as previously reported [27, 28].
Familial and personal atopy was determined by means of anamnesis
(known history of atopic dermatitis, food allergy, allergic
rhinitis/rhinoconjunctivitis and asthma) and/or prick-tests with
common aeroallergens and/or foods, and serum specific IgE
determinations.
Statistical analysis
The differences for quantitative data were assessed by the
Student’s t test, and the differences for qualitative data were
assessed by the Chi 2 test or by the Fisher’s test when
the number of cases was low. A p value < 0.05 was considered
significant.
Results
The mean time between the (last) suspected allergic reaction and
the allergological work-up was 8 mths (range: 4-20 mths). Two
children reporting accelerated urticaria and/or angioedema to ASA
and/or ibuprofen were initially diagnosed tolerant to COX
inhibitors based on negative responses in a one-day OC. However,
these children reported relapses during subsequent treatments with
the initially suspected drugs and were diagnosed intolerant to COX
inhibitors based on positive responses in a 2-day OC performed in
the hospital. Thus, HS to one or several COX inhibitors was
diagnosed in 81 children (49.4%, 55 M + 26 F), based on a
convincing clinical history (n = 36/81, 44.4%) or positive
responses in OC tests (n = 45/81, 55.6%).
ASA hypersensitivity was diagnosed in 64 of the 106 (60%)
children with suspected HS to this drug, based on a convincing
clinical history (n = 42/64, 65.6%) or on a positive response in OC
(n = 22, 34.4%). Ibuprofen HS was diagnosed in 49 (76.5%) of the 64
children reporting reactions to this drug, based on clinical
history (n = 40/49, 81.6%) or OC (n = 9, 18.4%). Paracetamol HS was
diagnosed in 10 of the 43 children (23.2%) with suspected HS to
this drug, based on clinical history (n = 8/10, 80%) or OC (n = 2,
20%). In OC, the mean reactogenic dose was 9 mg/kg (range:
0.9-21.8) with ASA, 9.7 mg/kg (range: 1.7-18.2) with
ibuprofen, and 19.4 mg/kg (range: 3.4-37.5) with paracetamol.
The mean time between the beginning of the OC and the reaction was
190 mn (range: 15 mn-24 h) with ASA, 60 mn (range:
20 mn-2 h) with ibuprofen, and 35 mn (range: 15 mn-2 h)
with paracetamol.
Among the 64 children with ASA hypersensitivity, 39 (61%)
cross-reacted with ibuprofen (5 based on response in OC, and 34 on
clinical history) and 8 (12.5%) with paracetamol (1 in OC, and 7
based on clinical history). Thirty-nine of the 49 children with
ibuprofen HS (79.6%) cross-reacted with ASA (20 in OC, and 19 based
on clinical history) and 4 (8%) with paracetamol (1 in OC, and 3
based on clinical history). Thus, cross-reactivity between ASA and
ibuprofen was frequent (78/113 = 69.1% vs. 35/113 = 30.9% of
children with selective reactions to ASA or ibuprofen, p <
0.0001). In contrast, only 12/113 (10.6%) of the children with ASA
and/or ibuprofen hypersensitivity were intolerant to paracetamol,
but all the children with paracetamol HS (10/10 = 100%) were
intolerant to ASA and/or ibuprofen (3 based on response in OC, and
7 on clinical history, p < 0.001).
Potential risk factors for HS to COX inhibitors were anaphylaxis
(83.3% vs. 40.4% for other reactions, p = 0.002) and immediate and
accelerated reactions (55.4% vs. 32.1% for delayed reactions, p =
0.02), personal atopy (75.3% vs. 49.3% in the tolerant children, p
< 0.001), and older age (mean age = 8.2 ± 4.1 vs. 6.2 ± 4.0 yrs
in the tolerant children, p = 0.003). Chronic/recurrent urticaria
was reported in 11/81 (13.6%) children intolerant to COX
inhibitors, ASA and/or ibuprofen especially, and 4/83 (4.8%)
children tolerant to these drugs. However, the difference was not
statistically significant (p = 0.061). Sex was not a risk factor.
Cross-reactivity between COX inhibitors was more frequent in
children with anaphylaxis than in the other children (50% vs. 20%,
p < 002).
Finally, 12 (14.4%) of the 83 children diagnosed tolerant to COX
inhibitors were differentially diagnosed as having allergic or non
allergic HS to antibiotics (n = 7), DTP vaccine (n = 1) and
miscellaneous drugs (n = 4).
Discussion
To our knowledge, we report the largest study performed in children
with suspected HS to commonly used COX inhibitors. Most reactions
were cutaneous (urticaria and/or angioedema especially), either
isolated or associated with respiratory symptoms and/or
anaphylaxis. Diagnosis was based on a convincing clinical history
or on positive responses in OC tests. Immediate-reading skin tests
and in vitro tests (specific IgE determination, histamine and
leukotriene release tests, basophil activation test) were not
performed because these tests are not standardized and because
their diagnostic and predictive values are controversial [10,
16-18, 21, 29, 30]. Theoretically, several children may have been
misdiagnosed as having paracetamol, ibuprofen or ASA
hypersensitivity by means of clinical history only. However,
according to the international guidelines, challenge tests are
contra-indicated in patients with a suggestive clinical history
and/or in whom the challenge may induce a severe reaction.
Alternatively, challenge with other COX inhibitors are indicated to
evaluate the tolerance of the COX inhibitor-sensitive patients to
these alternative drugs [31, 32]. Moreover, numerous children
diagnosed as having HS to a single suspected drug, based on
clinical history, also reacted to one or several other COX
inhibitors, based on their clinical history or on challenge tests.
These results strongly suggest that the children were also
sensitive to the initially suspected drug.
In this study, HS to paracetamol, ibuprofen and ASA was frequent
(49.4%) in a selected population of children with suspected HS to
these drugs, consistent with the results of other studies showing
that 13 to 50% of patients with suspected HS to COX inhibitors have
allergic or non allergic HS to these drugs [10, 12, 13, 15]. We
confirm and extend the results of Kvedariene et al. [15], showing
that severe and/or immediate and accelerated reactions are risk
factors for HS to COX inhibitors. In their study, 9 of 13 (69.2%)
patients with paracetamol HS reported immediate, and 5 (38.5%)
anaphylactic reactions. In our study, atopy was also diagnosed as a
significant risk factor for HS to COX inhibitors, consistent with
the results of other studies [7, 8, 13, 24]. In the study of
Sanchez-Borges et al. [24], in 50 adults and children with HS to
COX inhibitors, 41 patients (82%) had a personal history of atopy
versus 7 (14.5%) of the control subjects. This relation betwen
atopy and non allergic HS to COX inhibitors may result from a non
specific hyperreactivity of preactivated basophils, mast cells and
eosinophils, as reported in patients intolerant to ionic and
hyperosmolar radiocontrast media [33]. Although the difference was
not statistically significant, chronic/recurrent urticaria was also
more frequent in the children intolerant to COX inhibitors than in
the children tolerant to these drugs, consistent with the results
of previous studies performed in adult patients [5-7]. Finally,
mean age was significantly higher in the sensitive children than in
the children tolerant to COX inhibitors, in agreement with the
results of other studies [34].
The anti-inflammatory properties of non opioid analgesics,
antipyretics and NSAIDs are related to their inhibitory activity on
the cyclo-oxygenase enzymes COX-1 and COX-2. Classical NSAIDs, such
as ASA and ibuprofen, are strong inhibitors of the COX-1 and weak
inhibitors of the COX-2. In contrast, paracetamol, nimesulide and
coxibs have low COX-1 and high COX-2 inhibitory activities [35,
36]. Most patients with NSAID hypersensitivity cross-react with
other COX inhibitors, including drugs with a weak COX-1 inhibitory
activity [13, 15, 22-25]. Cross-reactivity is dependent on the
COX-1 inhibitory activity and the dose of the drugs. In patients
with NSAID intolerance, drugs with a low COX-1 inhibitory activity
may be tolerated when given at low doses, but may induce a reaction
when given at higher doses [25]. In our study, two children
tolerated the low doses of NSAIDs given in a one-day OC, but were
intolerant to a higher cumulative dose administered in a 2-day
challenge. We also showed a high degree of cross-reactivity between
ASA and ibuprofen, and a 100% degree of cross-reactivity with
NSAIDs in the children with paracetamol HS. Finally, only 14% of
the children with suspected HS to paracetamol, ibuprofen and/or ASA
had been previously treated with the suspected drug. Thus, most
children had not been previously « sensitized », and
their reactions could not result from allergic HS. Thus, our
results strongly suggest that, in children as in adults, most HS
reactions to COX inhibitors result from a non allergic HS linked to
the COX-1 inhibitory activity of these drugs. However, in a few
children, HS reactions may result from allergic HS to selective
(families of) drugs, without cross-reactivity with structurally
unrelated COX inhibitors, as previously reported [16-21].
Conclusion
We show that HS to commonly used COX inhibitors is frequent in
children with suspected HS to these drugs. In most cases, the
reactions are cutaneous (urticaria and/or angioedema especially),
either isolated or associated with respiratory symptoms and/or
anaphylaxis. We also show that the risk of HS to these drugs is
significantly increased in children reporting severe and/or
immediate and accelerated reactions, in children reporting
reactions to NSAIDs (ASA, ibuprofen), and in older and atopic
children than in other children. Finally, our results show a high
degree of cross-reactivity between the various families of COX
inhibitors, and suggest that, in children as in adults, most HS
reactions to COX inhibitors result from a non allergic HS linked to
the COX-1 inhibitory activity of these drugs. In those children,
« selective » COX-2 inhibitors, such as coxibs and
nimesulide, could be interesting alternative drugs. Unfortunately,
at the moment, these anti-inflammatory drugs are contra-indicated
in children under the age of 12 years in most European countries.
Acknowledgements
Financial support: none. Conflict of interest: none.
References
1 Haddi E, Charpin M, Tafforeau M, Kulling G,
Lanteaume A, Kleisbauer JP, et al. Atopy and
systemic reactions to drugs. Allergy 1990; 45: 236-9.
2 Rebelo Gomes E, Demoly P. Epidemiology of drug
hypersensitivity reactions. Curr Opin Allergy Clin Immunol 2005; 5:
309-16.
3 Hunziker T, Kunzi EP, Braunschweig S,
Zehnder D, Hoigné R. Comprehensive drug monitoring
(CHDM): adverse skin reactions, a 20-year study. Allergy 1997; 52:
388-93.
4 Johansson SGO, Hourihane JO B, Bousquet J,
Bruijnzeel-Koomen C, Dreborg S, Haahtela T,
et al. A revised nomenclature for allergy: an EAACI position
statement from the EAACI nomenclature task force. Allergy 2001; 56:
813-24.
5 Botey J, Ibero M, Malet A, Marin A,
Eseverri JL. Aspirin-induced recurrent urticaria and recurrent
angioedema in non atopic children. Ann Allergy 1984; 53: 265-7.
6 Settipane RA. Aspirin and allergic diseases: a review. Am
J Med 1983; 74: 102-9.
7 Bochenek G, Nizankowska E, Szczeklik A. Testing
for aspirin hypersensitivity. Allergy 2002; 57: 562-5.
8 Kalyoncu AF, Karakaya G, Sahin AA,
Baris YI. Occurrence of allergic conditions in asthmatics with
analgesic intolerance. Allergy 1999; 54: 428-35.
9 Lesko SM, Mitchell AA. The safety of acetaminophen
and ibuprofen among children younger than two years old. Pediatrics
1999; 104: e39-e44.
10 Martin-Munoz F, Moreno-Ancillo A,
Dominguez-Noce C, Diaz-Pena JM, Garcia Ara C,
Boyano T, et al. Evaluation of drug-related
hypersensitivity reactions in children. Invest Allergol Clin
Immunol 1999; 9: 172-7.
11 Titchen T, Cranswick N, Beggs S. Adverse
reactions to nonsteroidal anti-inflammatory drugs, COX-2 inhibitors
and paracetamol in a pediatric hospital. Br J Clin Pharmacol 2005;
59: 718-23.
12 Schubert B, Grosse Perdekamp MT, Pfeuffer P,
Raith P, Bröcker EB, Trautmann A. Nonsteroidal
anti-inflammatory drug hypersensitivity: fable or reality? Eur J
Dermatol 2005; 15: 164-7.
13 Kidon MI, Kang LW, Chin CW, Hoon LS,
See Y, Goh A, et al. Early presentation with
angioedema and urticaria in cross-reactive hypersensitivity to
nonsteroidal anti-inflammatory drugs among young, asian, atopic
children. Pediatrics 2005; 16: e675-e680.
14 Asero R. Oral aspirin challenges in patients with a
history of intolerance to single nonsteroidal anti-inflammatory
drugs. Clin Exp Allergy 2005; 35: 713-6.
15 Kvedariene V, Bencherioua AM, Messaad D,
Godard P, Bousquet J, Demoly P. The accuracy of the
diagnosis of suspected paracetamol (acetaminophen)
hypersensitivity: results of a single-blinded trial. Clin Exp
Allergy 2002; 32: 1366-9.
16 Gala G, Blanco R, Quirce S, Perez-Camo I,
Alvarez-Fernandez JA, Diez-Gomez ML. Diclofenac-induced
urticaria with aspirin tolerance. Allergy 1998; 53: 623-4.
17 Gamboa PM, Sanz ML, Caballero MR,
Antépara I, Urrutia I, Jauregui I, et al. Use
of CD63 expression as a marker of in vitro basophil activation and
leukotriene determination in metamizol-allergic patients. Allergy
2003; 58: 312-7.
18 Grob M, Pichler WJ, Wüthrich B. Anaphylaxis to
celecoxib. Allergy 2002; 57: 264-5.
19 Mendizabal S, Diez-Gomez ML. Paracetamol
sensitivity without aspirin intolerance. Allergy 1998; 53:
457-8.
20 Romano A, Pietrantonio F. Delayed hypersensitivity
to flurbiprofen. J Intern Med 1997; 241: 81-3.
21 Zhu DX, Zhao L, Mo L, Li HL.
Identification and characterization of IgE reactivities to aspirin
and related coumpounds. J Invest Allergol Clin Immunol 1997:
160-8.
22 Boussetta K, Ponvert C, Karila C, Le
Bourgeois M, de Blic J, Scheinmann P.
Hypersensitivity reactions to paracetamol in children. Allergy
2005; 60: 1174-7.
23 Kidon MI, Kang LW, Chin CW, Hoon LS,
Goh A, Poh Lin JT, et al. Hypersensitivity to
paracetamol in NSAID-sensitive Asian children. Int Arch Allergy
Immunol 2007; 144: 51-6.
24 Sanchez-Borges M, Capriles-Behrens E,
Caballero-Fonseca F. Hypersensitivity to nonsteroidal
anti-inflammatory drugs in childhood. Pediatr Allergy Immunol 2004;
15: 376-80.
25 Settipane RA, Stevenson DD. Cross-reactivity with
acetaminophen in aspirin-sensitive subjects with asthma. J Allergy
Clin Immunol 1989; 84: 26-33.
26 Levine BB. Immunological mechanisms of penicillin
allergy: a haptenic model system for the study of allergic diseases
in man. N Engl J Med 1966; 275: 1115-25.
27 Ponvert C, de Blic J, Le Clainche L,
Paupe J, Scheinmann P. Allergy to betalactam antibiotics
in child. Pediatrics 1999; 104: e45-e54.
28 Ponvert C, Karila C, Bakondé VB, de
Blic J, Le Bourgeois M, Scheinmann P. Allergy to
multivalent vaccines in children: a study of 30 cases using
immediate, semi-late and late responses in skin tests, specific
antibody determinations, and challenge with monovalent and bivalent
vaccines. Rev Fr Allergol Immunol Clin 2001; 41: 701-11.
29 Lebel B, Messaad D, Kvedariene K,
Rougier M, Bousquet J, Demoly P.
Cysteinyl-leukotriene release test (CAST) in the diagnosis of
immediate drug reactions. Allergy 2001; 56: 688-92.
30 Sanz ML, Gamboa P, de Weck AL. A new combined
test with flow cytometric basophil activation and determination of
sulfidoleukotrienes is useful for in vitro diagnosis of
hypersensitivity to aspirin and other nonsteroidal
anti-inflammatory drugs. Int Arch Allergy Immunol 2005; 136:
58-72.
31 Nizankowska-Mogilnicka E, Bochenek G,
Mastarlerz L, Swierzynska M, Picado C,
Scadding G, et al. EAACI/GA2LEN guideline: aspirin
provocation tests for diagnosis of aspirin hypersensitivity.
Allergy 2007; 62: 1111-8.
32 Ispano M, Fontana A, Scibilia J,
Ortolani C. Oral challenge with alternative nonsteroidal
anti-inflammatory drugs and paracetamol in patients intolerant to
these agents. Drugs 1993; 46: 253-6.
33 Katayama H, Yamaguchi K, Kozuka T,
Takashima T, Seez P, Matsuura K. Adverse reactions
to ionic and non-ionic contrast media: a report from the Japanese
Committee on the safety of contrast media. Radiology 1990; 175:
621-8.
34 Adkinson NF. Drug allergy. In:
Adkinson Jr. NF, Yunginger JW, Busse WW,
et al., eds. Middlen’s allergy: principles and practice, 6th
edn. Philadelphia, USA: Mosby, 2003: 1679-94.
35 Cryer B, Feldman M. Cyclooxygenase-1 and
cyclooxygenase-2 selectivity of widely used nonsteroidal
anti-inflammatory drugs. Am J Med 1998; 104: 413-21.
36 Kato M, Nishida S, Kitasato H, Sakata N,
Kawai S. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of
nonsteroidal anti-inflammatory drugs: investigation using human
peripheral monocytes. J Pharm Pharmacol 2001; 53: 1679-85.
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