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Drug Allergy
Penicillin, Aspirin and Sulfa Drugs
Diagnosis and Treatment
Adverse Reactions to Drugs
Can be categorized as follows:
 (1) Drug intolerance --- predictable side
effect at low to therapeutic doses due to
altered drug metabolism or end organ
hyperacuity
 (2) Idiosyncratic drug reactions
 (3) Immunologic drug reactions (AKA drug
allergy)

Adverse Drug Reactions
Type
Drug intolerance
Idiosyncrasy
Immunologic drug
reactions
Example
Tinnitus after a single
ASA tablet
Glucose 6-phosphate
deficiency: anemia
after antioxidant drugs
Anaphylaxis from
betalactam antibiotics
Types of Allergic Reactions
 Type
I (immediate)
 Type II (cytolytic)
 Type III (immune-complex associated)
 Type IV (delayed)
Types of Allergic Reactions
Type
I
II
III
IV
Mechanism
Examples
Anaphylactic (IgE-mediated) Acute anaphylaxis,
urticaria
Complement dependent
Hemolytic anemias,
cytolysis (IgG/IgM)
thrombocytopenias,
interstitial nephritis
Immune complex damage
Serum sickness, drug
fever, some cutaneous
eruptions, vasculitis
“Delayed” or Cellular
Contact dermatitis,
Hypersensitivity
?morbilliform dermatitis
Symptoms of allergic drug reactions




Skin reactions (80%)
Anaphylaxis (9 - 15%)
Respiratory symptoms
(6 - 9%)
Drug fever (2 - 6%)
Anaphylaxis versus Anaphylactoid
Reactions
Anaphylaxis refers to a systemic, immediate
hypersensitivity reaction due to the IgEmediated release of mediators from mast
cells and basophils.
 Anaphylactoid reactions refer to clinically
similar events as anaphylaxis but are not
mediated by IgE. They cause, via an
unknown mechanism, the degranulation of
mast cells and/or basophils.

Multivalency



Generally, an antigen must be presented to the
immune system in a multivalent form to elicit a
specific immune response.
Valency refers to the number of binding sites
available to bind antibody.
Multivalency is necessary to ensure cross-linking
of receptors on the surface of cells, which then
causes transduction of the signal within the cell
and the initiation of an immune response.
Multivalency
Drugs alone are poor stimulators of immune
responses due to their simple structure and
low molecular weight.
 Drugs can fulfill the requirement for
multivalency and elicit an immune response
in two ways: (1) form hapten-carrier
complexes and (2) be converted into
reactive intermediates.

Haptenization


A hapten in this case
would be a particular
drug, which would be
immunogenic in
protein-conjugated but
not free form.
An example would be
penicillins and other
betalactams that bind
covalently to proteins.
Conversion into reactive intermediates
This may occur via drug metabolism in the
liver or elsewhere.
 This is the case with sulfonamides, which
are acetylated and oxidated to yield the
predominant N4-sulfonamidoyl hapten.

Factors that Increase the Risk of Allergic Reactions


Chronic diseases that require continuous or frequent
courses of therapy with the same or cross-reactive drugs
Some allergic reactions are more likely to occur with
certain infections
–
–



e.g. Aminopenicillins with EBV infection,
Sulfonamides with AIDS patients
Atopy, a genetically determined state of hypersensitivity,
manifested as asthma, hay fever, and atopic dermatitis
History of other drug allergy
Family history of allergic drug reactions
Evaluation of Drug Allergy
First, obtain a complete drug reaction
history, atopic history, complete medication
list, and chronology of all symptoms and
signs.
 Second, narrow the list of medications
suspected based on the temporal association
between starts and stops and changes in
dose.

Evaluation of Drug Allergy

Third, stop and/or substitute all drugs with
known allergic potential begun on the day
of or several days prior to the reaction. If
the suspected drug cannot be substituted,
skin testing can be used to assess IgE
response. Currently skin testing is
accepted to test only for penicillin allergy.
Radioallergosorbent testing can also be used
to evaluate for drug allergy.
RAST Testing

In RAST testing, a given
allergen is bound to
polydextran bead. Serum
is then added and antigenspecific IgE will bind to
the immobilized antigen.
Radiolabeled anti IgE is
then added. The amount of
bead-bound radioactivity
is proportional to the
concentration of antigenspecific IgE in the serum.
Disadvantages of RAST testing
Skin testing is preferred since it correlates
better with clinical symptoms. A positive
RAST test may occur in asymptomatic
individuals.
 Expensive
 Limited range of antigens available

Evaluation of drug allergy



Finally, in skin test negative patients, readminister the
suspected drug if necessary with gradual escalation of the
dose or desensitize. Another option, of course, would be
choose another drug.
Rechallenge should generally begin at 1% of the desired
therapeutic dose and increased incrementally (3-fold) at
intervals determined by the half life of the drug and the
patient’s prior experiences with it
No rechallenge of drug should be done in patients with
Stevens-Johnson syndrome, toxic epidermal necrolysis, or
with any mucous membrane involvement.
Drug Desensitization
Effective in the treatment of type I allergic
reactions and may be effective for other
reactions that are delayed in onset but are
not IgE-mediated
 Antigen-specific mast cell desensitization
appears to be responsible for the tolerant
state
 Specific mast cell desensitization is poorly
understood

Drug Desensitization

Successful antibiotic
desensitizations

Penicillins
Sulfonamides
Aminoglycosides
Clindamycin
Cephalosporins
Vancomycin
Pentamidine
Anti-tubercular agents








Successful
desensitizations to other
agents

Chemotherapeutics
Heterologous sera
Deferoxamine
Measles vaccine
Tetanus toxoid
D-penicillamine
Corticotropin
Carbamazepine







Antivenoms
Insulin
LHRH
Heparin
Desensitization
The starting dose for the drug can be
determined by performing intradermal skin
tests with the native drug at a dose that does
not cause a non-specific irritant reaction.
 For example, if a 0.02 ml intradermal
injection of a drug at 1 mg/ml concentration
does not cause a local or systemic reaction,
oral desensitization may be started at the
dose injected (i.e. the tolerated dose, 20 µg).

Desensitization
Parenteral desensitization should be using
1/10 or 1/100 of the dose that was
administered intradermally.
 Desensitization is a REVERSIBLE process
that is dependent on the continued presence
of the drug.
 It is also drug-dose dependent in that a
substantial dose increase may result in
breakthrough allergic symptoms.

Desensitization


Sullivan et al48
30 patients with histories of allergic reactions to PCN,
positive skin tests, and life threatening infections (bacterial
endocarditis, Pseudomonas sepsis or pneumonia) were
desensitized. Skin test reactions disappeared or diminished
in all 23 subjects who were retested after desensitization.
Full courses of antibiotic therapy and cure of the infections
were accomplished in 30 of 30 patients.No deaths,
anaphylaxis, or severe acute allergic reactions occurred.
Pruritic cutaneous eruptions appeared in 9 patients (30%) 6
to 48 hrs after the onset of therapy. One patient developed
reversible nephritis 3 weeks into therapy with PCN G.
I
Kiss you!!
Penicillins
The reported history of penicillin allergy
ranges from 0.7% to 10%.
 There are four classes of betalactam
antibiotics: penicillins, cephalosporins,
carbapenems, and monobactams.
 The first three all have bicyclic nuclei in
contrast to monobactams (aztreonam),
which lacks a second ring adjacent to the
betalactam nucleus.

Major and minor determinants

The betalactam ring is
unstable and readily
acylates lysine
residues in proteins.
The penicilloyl
epitope is produced,
which is called the
“major determinant”
since over 75% of all
IgE mediated reactions
are directed against
this epitope.
Minor Determinants
Beta lactams can also haptenize covalently
through carboxyl and thiol groups, which
results in a variety of less dominant or
“minor” determinants.
 Minor determinant IgE responses have been
associated with anaphylaxis, while
penicilloyl IgE responses are usually
associated with urticarial reactions.

Signs and symptoms



Allergic symptoms
commonly include:
an erythematous,
maculopapular and
usually pruritic rash
urticaria

Less common
symptoms include
angioedema, serum
sickness, arthralgias,
bronchospasm,
laryngeal edema, and
anaphylaxis
Signs and Symptoms
An example of a delayed reaction would be
maculopapular or morbilliform rashes
associated with treatment with
aminopenicillins, particularly ampicillin.
 The incidence of rash associated with
ampicillin has been estimated at 9.5%.
 Since the rash typically appears 2-3 days or
more after drug administration, it is thought
to represent type IV (delayed)
hypersensitivity.

Skin testing
More than 80% of history-positive patients
will have negative skin tests.
 Allergic reactions observed in the
retreatment of history-positive, skin testnegative patients have virtually all been
mild and self-limited; no life-threatening
false-negative reactions have been reported.

Sogn et al

A prospective study using patients with infectious
diseases for which penicillin or related compounds
was the drug of choice. Patients were skin tested
with major and minor determinant antigens. Only
if skin tests were negative, patients were given
penicillin or a semisynthetic penicillin. 9 skin test
positive patients were accidentally given
penicillin and 2 had allergic reactions. The allergic
reactions noted in the table that follows were
urticaria, generalized erythema, and pruritis.
Sogn et al
Patients with a
history of
penicillin allergy
Patients without
a history of
penicillin allergy
Skin test
positive
Skin test
negative
Allergic
reactions
139
566
7/566 (1.2%)
25
568
0/568 (0.0%)
Skin testing
Up to 67% of patients with positive skin
tests have experienced clinical allergic
reactions when given therapeutic doses of
penicillin.
 For patients with a history of rash with the
aminopenicillins, skin testing with extended
observation for late reactions and also patch
testing is recommended.

Skin Testing

Since recurrent rather than continuous
therapy can resensitize patients to penicillin,
skin tests should be repeated before
subsequent courses of therapy.
Cephalosporins

It has been reported that there is an 8.1%
incidence of allergic reactions to various
cephalosporins in patients with histories of
penicillin allergy compared to a reaction
rate of 1.9% in patients without such
histories.
Cephalosporins
The overall incidence of cephalosporin
allergy in the general population is about
4%, so the 8% incidence of reactions in the
PCN-allergic group is only a 2-fold
increase.
 When PCN-allergic patients receive ANY
drug, the incidence of adverse drug
reactions is 3 times higher compared to
those with no history of PCN allergy.

Skin testing with Cephalosporins
Currently there are no reliable
cephalosporin allergens available for skin
testing.
 Allergic reactions to cephalosporins do not
appear to correlate with positive penicillin
test reactions.

Summary of Studies of Cephalosporin to Patients with
Histories of Penicillin Allergy and Penicillin Skin Test
Evaluations
Sulfa Drugs
Co-trimazole, or sulfamethoxazoletrimethoprim, is used extensively in the
HIV population as prophylaxis against
Pneumocystis carinii pneumonia.
 It is estimated that the overall prevalence of
sulfa hypersensitivity in the general
population is approximately 3.3%, while in
the HIV population it is in the range of 1720%.

Sulfa Drugs
Up to 80% of these reactions has been
reported in HIV-positive patients compared
to less than 5% in HIV-negative patients.
 The incidence of adverse events to
cotrimazole is greater than 50% in patients
receiving the medication for treatment for
active PCP.

Sulfa Drugs and HIV
A recent retrospective case-control study
found an association between the number of
opportunistic infections and the occurrence
of TMP/SMX hypersensitivity reactions
 Hennessy et al, however, found no
correlation between low CD4 counts and an
increased risk of hypersensitivity reactions
to sulfa

Hennessy et al

A retrospective cohort
study involving
patients in an
outpatient HIV clinic
and universityaffiliated IM and ID
practices receiving
cotrimazole for
primary PCP
prophylaxis.

The outcome
measured was the
occurrence of a
cutaneous
hypersensitivity
reaction (rash, fever,
or pruritis) per chart
review that resulted in
discontinuation of
cotrimazole.
Hennessy et al
CD4 Count
Number of Subjects
Relative Rate (95%
Confidence Interval)
<80
50
1.00 (ref)
81-160
41
0.74 (0.30-0.77)
161-250
54
0.26 (0.09-0.74)
>250
54
0.76 (0.35-1.64)
Signs and Symptoms



The most common adverse reactions to sulfa drugs
in AIDS patients include rash, nausea and
vomiting.
The rash is usually a generalized exanthema,
which may or may not be pruritic and often is
accompanied by fever.
The majority of patients can be treated with
antihistamines and the rash in over 65% of cases
will resolve without further sequelae despite
continuation of cotrimazole.
History of Rash and Rechallenge


A history of rash is not necessarily a
contraindication to retreatment as less than 20%
may have a recurrence on rechallenge.
Shafer et al
–
34 homosexual men given IV cotrimazole for PCP with
development of hypersensitivity reactions in 21 of these
patients (erythematous macular or maculopapular
rashes, fever). All 31 survivors were started on oral
cotrimazole for PCP prophylaxis but only 4 developed
reactions which necessitated discontinuation of the drug
(desquamative rash, fever, etc..)
Sulfonamide Hypersensitivity Reaction

Multiorgan, systemic disease characterized
by fever, skin rash, and toxicity in one or
more internal organs starting 7 to 14 days
after initiation of therapy.
–
–
Incidence of life-threatening reactions is less
than 1/1000
skin reactions occur in 1.5 - 3% given sulfa
drugs
Sulfonamide Hypersensitivity Reaction


Maculopapular eruptions and urticarial rash occur
most frequently within the first 1-3 days after
administration, are usually not accompanied by
fever, and resolve spontaneously on withdrawal.
Other disease states associated with the
hypersensitivity reaction include: hepatotoxicity,
eosinophilic pneumonitis, aseptic meningitis, AIN,
serum sickness, polyarthritis, and blood
dyscrasias.
Stevens Johnson syndrome and TEN
with sulfa drugs



Non-urticarial drug
eruptions (StevensJohnson syndrome, TEN)
typically occur 7-14 days
after initiation of
treatment
Incidence is between
1/1000 and 1/3000
Any patients with either
disease should be removed
from the drug and
rechallenge avoided
Mechanism

The mechanism of hypersensitivity to cotrimazole
is poorly understood. Several hypotheses have
been put forward to explain the predominance of
reactions in HIV patients:
– (1) slow acetylation in HIV patients
– (2) polypharmacy with drugs such as INH and
rifampin that compete for metabolism in the
liver
– (3) reduced availability of cellular glutathione
Sulfa Drug Metabolism

Sulfa drugs are metabolized in the liver by two
pathways: oxidative metabolism by the
cytochrome p450 system and acetylation by Nacetyltransferase.
Sulfa drug Metabolism

Sulfamethoxazole is predominantly cleared
by acetylation and excreted by active
tubular excretion. The alternative pathway
yields a reactive metabolite,
sulfamethoxazole hydroxylamine, which
can generate an immune response.
–
Generally, slow acetylators develop more
adverse reactions, whereas rapid acetylators are
more prone to show an inadequate response to a
standard dose.
Slow acetylation

The ratio of rapid versus slow acetylators
varies widely among ethnic groups
throughout the world.
–
For example, approximately 50% of Caucasians
and African-Americans are “slow” acetylators
while this is rare among Asians.
Slow Acetylation in AIDS patients

Lee et al investigated the prevalence of slow
acetylation in AIDS patients
Group
AIDS-ill
Prevalence of Slow
Acetylation
27/29 (93%)
AIDS-stable
19/29 (66%)
HIV positive
10/18 (56%)
Control (HIV negative)
18/29 (62%)
Slow acetylation in AIDS patients
The cause of the increased prevalence of
slow acetylation in acutely ill AIDS patients
is not known.
 Due to slow acetylation, more of the drug is
shunted to alternative oxidative pathways.

–
These pathways form toxic metabolites which
are normally detoxified by scavengers, such as
glutathione. A few studies have reported
decreased levels of GSH in HIV patients but
this has not been confirmed in other studies.
Slow acetylation in AIDS patients

The accumulated metabolites can then cause
cellular injury which may be expressed
clinically as an adverse reaction.
Skin Testing
Some investigators have reported positive
skin tests in approximately 25% of patients
with immediate hypersensitivity reactions to
SMX, but others have not found it useful in
predicting the recurrence of SMX related
adverse events.
 Currently, skin testing cannot be
recommended.

Desensitization
The earlier reports of desensitization to
sulfonamides had limited success rates,
ranging from 45 to 82%.
 The success rates of desensitization have
improved significantly over the years.

Desensitization


Kalanadhabhatta et al39
A prospective study with 13 patients with AIDS
(CD4<200) with PCP and allergy to sulfonamides who
failed alternative therapy (dapsone, pentamidine). The
allergic reactions noted were a generalized, pruritic
maculopapular rash, urticaria, angioedema, and pruritis.
All patients had tolerated oral desensitization to
cotrimazole without any adverse reaction including three
patients who were critically ill and on mechanical
ventilation. Total follow up ranged from 4 to 84 weeks.
Mahir at Burke Street Pub
NSAIDS
In 1922, the association of ASA sensitivity,
asthma, and nasal polyposis was described
by Widal et al and was subsequently coined
as the “aspirin triad.”
 Aspirin-induced asthma (AIA) affects 10%
of adults with asthma.

–
After ingestion of ASA or an NSAID, an acute
asthma attack occurs within 3 hrs, usually
accompanied by profuse rhinorrhea,
conjunctival injection, and periorbital edema.
NSAID Intolerance (NI)
NI prevalence in asthma and nasal
polyposis or rhinosinusitis is 30-40%.
 In chronic urticaria, the prevalence of
NSAID intolerance is 20-30%.

Mechanisms
The search for an underlying antigen antibody mechanism has not been
successful.
 Skin tests with ASA-lysine have been
negative, and numerous attempts to
demonstrate specific antibodies against
ASA or its derivatives have been
unsuccessful.

Mechanisms

In patients with AIA, asthmatic attacks can
be caused by ASA and other NSAIDS.
After desensitization, cross desensitization
to other NSAIDS that inhibit
cyclooxygenase (COX) also occurs.
–
Szczeklik et al reported in 1975 that drug crossreactivity could be predicted on the basis of
each NSAID’s in vitro inhibition of COX. This
has been consistently reaffirmed over the years.
Mechanisms

During inflammatory
respiratory disease,
leukotrienes, histamine,
and eosinophilic cationic
protein are formed and
released with subsequent
increase in vascular
permeability, mucus
secretion, and bronchial
hyperreactivity.
Mechanisms

Three hypothesis have been proposed to
explain AIA:
–
–
–
(1) cyclooxygenase inhibition
(2) overproduction of leukotrienes
(3) chronic inflammation of the airways
COX Inhibition
5-lipoxygenase and COX catalyze the
production of leukotrienes and
prostaglandins, respectively.
 Prostaglandin E2 has several
immunoregulatory effects, including
inhibition of 5-lipoxygenase and preventing
the release of mediators from mast cells.

COX Inhibition



When ASA is given, COX-1 and COX-2 are disabled,
PGE2 synthesis stops and its modulating effects on mast
cells and 5-LO are removed, and mediators are released or
synthesized.
Leukotrienes are continuously and aggressively
synthesized in patients with AIA before any exposure to
NSAIDS/ASA, and during ASA-induced reactions, marked
acceleration of synthesis occurs.
It is not known why interruption of PGE2 synthesis does
not induce respiratory reactions in all humans.
Chronic inflammation of the airways
Eosinophil infiltration of the airways
appears to be a central feature of AIA.
 The large numbers of eosinophils, loaded
with leukotriene enzymes, may be
responsible for the overproduction of
leukotrienes.

Delayed reactions to NSAIDS

Appear to have an immunologic basis since
they recur on re-exposure with a shorter
latency after re-exposure.
Signs and Symptoms



Urticaria, angioedema, rhinoconjunctivitis,
bronchial asthma, and occasionally anaphylactoid
reactions.
Stevens Johnson syndrome and TEN have been
associated with NSAIDS in 14% and 19% of
cases, respectively.
The most frequent delayed cutaneous reaction is a
morbilliform exanthem, which usually occurs 1
week after therapy is begun and can last 2 weeks.
Testing
Numerous attempts to demonstrate specific
antibodies against ASA or its derivatives
have been unsuccessful. Skin test responses
with ASA-lysine have been negative.
 Currently, the only way to test for NSAID
intolerance is with provocation tests.

–
–
There are three types of provocation tests: oral
(most common), inhaled, and nasal.
Only oral ASA challenges are available in the
US.
Oral ASA Challenge
A standard 3 day protocol is described
below.
Time Day 1
Day 2
Day 3
8 AM Placebo ASA, 30 mg ASA, 150 mg
11 AM Placebo ASA, 60 mg ASA, 325 mg
2 AM Placebo ASA, 100 mg ASA, 650 mg

Oral ASA Challenge



Patients with a history of severe or very rapid ASA
or NSAID-induced reactions may be started with a
dose lower than 30 mg.
As soon as signs and symptoms of reactions occur
(20% decrease in FEV1, rhinorrhea, ocular
injection, periorbital edema, stridor, and rarely
flushing, urticaria, cramps, or explosive diarrhea),
the ASA challenge is stopped.
Oral challenges to detect anaphylaxis should not
be done; history of anaphylaxis should be relied
upon instead.
Prevention and Treatment


Patients should avoid ASA and other analgesics
that inhibit COX.
NSAIDS that cross react with ASA in respiratory
and cutaneous reactions:
–
–
–
–
–
–
–
piroxicam
ketoprofen
ketorolac
indomethacin
tolmetin
naproxen
diflunisal
mefenamic acid
meclofenemate
etodolac
oxaprozin
zomepirac
naproxen sodium
flurbiprofen
diclofenac
nabutemone
sulindac
ibuprofen
fenoprofen
Prevention and Treatment

Acetaminophen is usually safe for these
patients to take. However, high dose
acetaminophen (1000 mg followed by 1500
mg) has been shown to have a crossreaction prevalence of 34%.
–
Animal models have demonstrated that
acetaminophen may have COX inhibitory
activity.
Prevention and Treatment

Patients can also take the following drugs,
which are all without anti-COX activity or
are weak anti-COX 2 inhibitors:
–
sodium salicylate, salicylamide, choline
magnesium trisalicylate, benzydamine,
chloroquine, azapropazone, and
dextropropoxyphene
COX-2 Inhibitors
Selective inhibitors of COX-2, in theory,
should be safe in patients with AIA due to
continued synthesis of the protective
prostanoid, PGE2, by COX-1.
 However, COX-2 inhibitors have not yet
been studied in patients with AIA and are
currently contraindicated.

Desensitization



NSAID allergic patients can also be desensitized.
Small incremental doses of ASA are taken over 2
to 3 days until 400 to 650 mg of ASA is tolerated.
ASA should then be given daily, with doses
ranging from 80 to 325 mg to maintain
desensitization.
After each dose of ASA, there is a refractory
period of 2 to 5 days, during which ASA and other
COX inhibitors can be given without any risk of
an allergic reaction.
Desensitization

The patient most likely to benefit from
desensitization is one with AIA who has just
had sinus/polyp surgery.
–

ASA desensitization has been shown to delay
recurrence of nasal polyp formation by an
average of 6 years.
The mechanism behind desensitization is
poorly understood but may be associated
with downregulation of leukotriene
receptors.
Stevenson et al

Between 1988 and 1994, 78 patients with asthma and
documented ASA sensitivity per oral challenge (decrease
of 20% or more in FEV1 and/or naso-ocular reactions
within 3 hours of incremental oral challenges) were
enrolled in a prospective study investigating ASA
desensitization. 10 patients discontinued ASA
desensitization treatment due to gastritis. 3 patients were
lost to follow up. After desensitization, all patients began a
treatment program of 650 mg of ASA twice daily, which
was continued from 1 to 6 years (mean 3.1 years). Data
was compared for 65 patients from the year prior to ASA
desensitization and one year before re-evaluation (January
to March 1995)
Stevenson et al
Stevenson et al
Conclusion


Patients with a history of penicillin allergy should
be skin tested. More than 80% of patients with a
history of penicillin allergy will have negative skin
tests.
Allergic reactions observed in the re-treatment of
history-positive, skin-test negative patients have
virtually all been mild and self-limited; no life
threatening false-negative reactions have been
reported.
Conclusion

Up to 67% of patients with positive skin tests have
had allergic reactions when given therapeutic
doses of penicillin. There are no skin tests
available to evaluate for cephalosporins. Positive
penicillin skin tests do not predict allergic
reactions to cephalosporins. If no other
alternatives are available, cephalosporins can be
administered cautiously to patients with a history
of penicillin allergy.
Conclusion

There is an increased frequency of adverse
reactions to sulfa drugs in HIV patients; the
reason for which is not known at this time.
A history of rash is not necessarily a
contraindication to retreatment since less
than 20% may have a recurrence on
rechallenge. Skin testing cannot be
recommended to evaluate sulfa allergy.
Desensitization to sulfa drugs has had
variable success.
Conclusion

NSAID intolerance prevalence in asthma and
nasal polyposis or rhinosinusitis is 30-40%.
Aspirin-induced asthma affects 10% of adults with
asthma. The only way to test for NSAID
intolerance in the US is with an oral provocation
test. High dose acetaminophen has been shown to
have a cross-reaction prevalence of 34%. After
ASA desensitization, cross desensitization to other
NSAIDS than inhibit cyclooxygenase also occurs.
The patient most likely to benefit from
desensitization is one with AIA who has just had
sinus/polyp surgery.
Thanks

I would like to thank Andrew Namen,
Donnie Dunagan, Ryan Secan, Melissa
Matulis, and Steve Cochran for their
assistance.