Transcript DESEANSIBILIZACION A ASA

Desensitization in non-steroidal
anti-inflammatory drugs (NSAID)
hypersensitivity
Ricardo Cardona Villa, M.D.
MSc in Immunology - Allergist
Chief of Clinical Allergology Service
IPS Universitaria - Clínica León XIII
Medical School
Universidad de Antioquia
Acetylsalycilic acid (ASA)
A model of NSAID
The End of Suffering
http://goyotovar.lasideas.es/wp-content/imagenes/aspirina.jpg
Acetylsalycilic acid is extracted from the tree
"Salix alba", called salicin, discovered in 1827
History
1899 The product was registered as
Aspirin by Felix Hoffman
1980 Stevenson et al described
two patients with previous
ASA induced asthmatic
reactions
The creator of Aspirin, Felix Hoffmann
and a package circa 1900.
Chemical classification of NSAIDs
Chemical group
Drugs
Alkanones
Nabumetone
Anthranilic acids (fenamates)
Meclofenamic acid, mefenamic acid
Arylpropionic acids
Fenoprofen, Flurbiprofen, Ibuprofen, Ketoprofen,
Naproxen, Oxaprozín
Enolic acids
Oxicams (Piroxicam, Tenoxicam, Meloxicam),
Pyrazolidinediones
(Oxyphenthatrazone, Phenylbutazone)
Heteroaryl acetic acids
Diclofenac, Ketorolac, Tolmetin
Indole and indene acetic acids
Etodolac, Indomethacin, Sulindac
Para-aminophenol derivatives
Acetaminophen (paracetamol)
Pyrazol derivatives
Aminopyrine, Antipyrine, Dipyrone
Salicylic acid derivatives
Aspirin, choline magnesium trisalicylate,
diflunisal, Olsalazine, Salicylsalicylic, Salsalate,
Salicylate, Sulfasalazine
Mario Sánchez-Borges. WAO Journal 2008; 1: 29-33
Terminology
Selectivity: agents that inhibit more one enzyme than
the other, but can inhibit both of them (Meloxicam,
Nimesulide)
Specificity: agents that inhibit only one enzyme at
doses that produce maximum clinical efficacy
(Celecoxib - Etoricoxib - Lumiracoxib)
Classification of some NSAIDs
Selectivity
Weak COX inhibitors
Drugs
Acetaminophen, Salsalate, Salicylamide,
sodium salicylate, choline-magnesium
trisalicylate
COX-1 / COX-2 inhibitors
Piroxicam, Indomethacin, Sulindac, Tolmetin,
Ibuprofen, Naproxen, Fenoprofen,
Meclofenamate, Mefenamic acid, Diflunisal,
Ketoprofen, Diclofenac, Ketorolac, Etodolac,
Nabumetone, Oxaprozin, Flurbiprofen
COX-2 preferential inhibitors
Nimesulide, Meloxicam
COX-2 selective inhibitors
Celecoxib, Rofecoxib, Valdecoxib, Parecoxib,
Etoricoxib, Lumiracoxib
Mario Sánchez-Borges. WAO Journal 2008; 1: 29-33
Concept COX
Membrane phospholipids
(–)
glucocorticoids
(–)
arachidonic acid
COX-1
Endotoxins
cytokines
mitogens
(+)
(–)
(–)
Stomach: PGE2/PGI2
Kidney: PGE2/PGI2
Platelets: TxA2
Endothelium: PGI2
Physiological effects
(–)
COX-2
"Classic
NSAIDs"
Inflammation:
macrophages
synoviocytes
Inflammatory mediators
Selective
inhibitors of
COX-2
Meloxicam
Celecoxib
Rofecoxib
COX-1 / COX-2 comparison
PARAMETER
COX-1
COX-2
HOMOLOGY
Similar to COX-2
( 60%*- 75%)
Similar to COX-1
( 60%*- 75%)
REGULATION
Constitutive
Inducible
TISSUE
EXPRESSION
Most tissues, but
particularly
platelets, stomach
and kidney
Inflammatory stimuli and
mitogens in
macrophages/monocytes,
synoviocytes, chondrocytes,
fibroblasts, endothelial cells.
Constitutive in CNS and
kidney
COX-1 and COX-2 structure
COX-1
COX-2
C-terminal
active site
C-terminal
active site
Hydrophobic
Channel
Hydrophobic
Channel
Isoleucine
at 523,
closes the
hydrophilic
pocket
N-terminal
Valin at
523 allows
the access
to the
hydrophilic
pocket
Hydrophilic
pocket
N-terminal
Arginin
At 120
Kurumbail R G, Stevens A M, Gierse J K, McDonald J J, et al.
Nature. 1996;384:644–648
Arginin
at 120
Membrane phospholipids
Arachidonic acid
Lipoxygenase pathway
Cyclooxygenase pathway
5-Lipoxygenase (5-LO)
Cyclooxygenase
Shunt from COX –
towards the
LO-pathway
LT-A4
LTA4 hydrolase
LT-B4
COX-1
ASA/
NSAID
LTC4 synthase
Cys-leucotriene
LTC4,
LTD4, LTE4
PG-E2
Reduced
inhibition
COX-2
Change of
the COX-2
structure
Generation of products
of the LO-pathway
Claudia Jenneck, Uwe Juergens, Markus Buecheler, and Natalija Novak Ann Allergy Asthma Immunol. 2007;99:13–21.
Using the classification proposed by the
Committee of the World Allergy Organization,
the following types of hypersensitivity
reactions should be considered:
Allergic hypersensitivity
Non-allergic hypersensitivity
Johansson SGO, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global use: report of the Nomenclature
Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol.2004;113:832-836.
Mario Sánchez-Borges
WAO Journal 2008;1:29 - 33
Clinical Manifestations
1. Allergic hypersensitivity
1.1 Immediate reactions
1.1.1 Urticaria and
Angioedema
1.1.2 Allergic Anaphylaxis
Sànchez Borges, M. Clinical management of non steroidal antiinflammatory drug hypersensitivity.
2008;1:29-33. WAO Journal.
Clinical Manifestations
1. Allergic hypersensitivity
1.1 Immediate reactions
1.1.1 Urticaria and
Angioedema
1.1.2 Allergic Anaphylaxis
1.2 Late reactions
1.2.1 Skin diseases
1.2.2 Pneumonitis
1.2.3 Aseptic meningitis
1.2.4 Nephritis
1.2.5 Hepatitis
Sànchez Borges, M. Clinical management of non steroidal antiinflammatory drug hypersensitivity.
2008;1:29-33. WAO Journal.
Clinical Manifestations
1. Allergic hypersensitivity
1.1 Immediate reactions
1.1.1 Urticaria and
Angioedema
1.1.2 Allergic Anaphylaxis
1.2 Late reactions
1.2.1 Skin diseases
1.2.2 Pneumonitis
1.2.3 Aseptic meningitis
1.2.4 Nephritis
1.2.5 Hepatitis
2. Nonallergic hypersensitivity
2.1 Respiratory
Hypersensitivity
2.2 Skin Hypersensitivity
2.3 Non-allergic anaphylaxis
Sànchez Borges, M. Clinical management of non steroidal antiinflammatory drug hypersensitivity.
2008;1:29-33. WAO Journal.
Classification:
Respiratory pattern
Includes respiratory disease exacerbated by ASA,
the Tetrad of Samter (nasal polyposis, rhinosinusitis, asthma
and intolerance to ASA) and ASA-induced asthma.
Andrzej Szczeklik and Marek Sanak
European Journal of Pharmacology 533 (2006) 145–155
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca
J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Skin Pattern
Including urticaria and angioedema
induced by NSAIDs
urticaria and angioedema induced
by multiple drugs and
urticaria and angioedema induced
by a single drug.
Mario Sánchez-Borges
WAO Journal 2008;1:29Y33
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca
J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Mixed Pattern
It presents with skin and respiratory symptoms
including urticaria and angioedema associated with
cough, breathlessness, runny nose, wheezing,
tearing or conjunctival irritation
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca
J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Mario Sánchez-Borges
WAO Journal 2008;1:29-33
Systemic Pattern
Anaphylactic reactions are type I hypersensitivity,
usually observed in simple reactors who tolerate other
chemically unrelated NSAIDs IgE antibodies specific for
the allergen.
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca
J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Mario Sánchez-Borges
WAO Journal 2008;1:29-33
Management
The management of patients with intolerance to
NSAIDs depends on their medical history.
The patient should be classified as simple reactor
or cross reactor and according to the type of
reaction either cutaneous or systemic.
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca
J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Mario Sánchez-Borges
WAO Journal 2008;1:29-33
When the patient is a simple reactor, oral provocation
testing with an NSAID of a different chemical group
involved is recommended.
If the test is negative, the patient may receive
treatment with NSAIDs testing and avoid the
suspected medication.
If the test is positive, the patient should be handled as
a cross reactor.
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca
J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Mario Sánchez-Borges
WAO Journal 2008;1:29-33
When the patient is classified as a cross reactor, an oral
challenge test can be performed with a weak COX-1
inhibitor or preferential COX-2, or
with a specific COX-2 inhibitor.
If the test is negative, it can be administered to the
patient and if positive try oral challenge with another
COX-2 specific inhibitor.
If the latter (previous) test is positive, avoid all NSAIDs
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca
J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Mario Sánchez-Borges
WAO Journal 2008;1:29-33
Algorithm for clinical management
of skin NSAID-induced reactions
Weak COX-1
Inhibitors
Acethaminofen
Salsalate
Another
COX-2
Desensitization
Mario Sánchez-Borges, Arnaldo Capriles-Hulett and Fernan Caballero-Fonseca
Am J Clin Dermatol 2002; 3 (9): 599-607
Medical history
Cutaneous
single-reactor
Cutaneous
cross reactor
Oral challenge with
unrelated NSAID
Alternative
medication
Negative
Avoid COX-1 inhibitors,
oral challenge
with COX-2 inhibitors
Oral challenge
With COX-2 inhibitor
Weak COX-1 Inhibitors
Acethaminofen
Salsalate
Treatment
Single drug
anaphylaxis
Negative
*
Positive
Negative
Treatment
Positive
Positive
Another
COX-2
Algorithm for clinical management
of skin NSAID-induced reactions
Modificated of Mario Sánchez-Borges, Arnaldo Capriles-Hulett and Fernan Caballero-Fonseca
Am J Clin Dermatol 2002; 3 (9): 599-607
Treatment
*
Positive
Avoidance
NSAID
Desensitization
NSAID
avoidance
*
Position paper
The indications for drug provocation testing can be
divided into 4 groups that are intertwined:
1. To exclude hypersensitivity – in history not suggestive of
hypersensitivity to the drug and in patients with nonspecific
symptoms, such as vagal symptoms by local anesthesia
W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez,
K. Brockow, W. J. Pichler, P. Demoly
Allergy 2003: 58: 854–863
Position paper
2. To provide safety – pharmacology and / or structural unrelated
drugs as proven hypersensitivity to other antibiotics in
patients allergic to beta-lactams. This can also be helpful in
anxious people who could reject the drug recommended
without tolerance tests
W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez,
K. Brockow, W. J. Pichler, P. Demoly
Allergy 2003: 58: 854–863
Position paper
3. To exclude cross-reactivity of related drugs in proven
hypersensitivity, such as a cephalosporin in a patient allergic
to penicillin or an alternative to NSAIDs in asthmatic patients
sensitive to ASA
W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez,
K. Brockow, W. J. Pichler, P. Demoly
Allergy 2003: 58: 854–863
Position paper
4. To establish a firm diagnosis in history suggestive of drug
hypersensitivity to allergic tests negative, inconclusive or
unavailable, such as a maculopapular rash during treatment
with Aminopenicillin with negative allergy tests
W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez,
K. Brockow, W. J. Pichler, P. Demoly
Allergy 2003: 58: 854–863
A drug provocation test is the controlled
administration of a drug in order to
diagnose hypersensitivity reactions
The challenge test should be done under medical supervision
for an alternative drug, structurally or pharmacologically
related to the suspect medicine.
The provocation test drug is also known as challenge or
controlled re-challenge, drug challenge, incremental
challenge, re-challenge or test of tolerance.
W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez,
K. Brockow, W. J. Pichler, P. Demoly
Allergy 2003: 58: 854–863
Regarding the limitations of drug provocation test,
consider the "gold standard“ to establish or refute
the diagnosis of hypersensitivity to a substance.
Although allergic symptoms can be reproduced, so
can the adverse reaction by another mechanism
W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez,
K. Brockow, W. J. Pichler, P. Demoly
Allergy 2003: 58: 854–863
After provocation test, it is desirable to keep the
patient under observation for 24 hours, but local
restrictions may affect this ideal
W. Aberer, A. Bircher, A. Romano, M. Blanca, P. Campi, J. Fernandez,
K. Brockow, W. J. Pichler, P. Demoly
Allergy 2003: 58: 854–863
Protocol of nasal aspirin
challenge
Basal nasal symptoms, nasal inspiratory flows and volumes
are recorded during the first 30 minutes every 10 minutes.
Then for the evaluation of specific nasal hyperreactivity, are
challenged with 0.9% NaCl (80 ul) instilled into each nostril
with an Eppendorf pipette.
E. Nizankowska-Mogilnicka, G. Bochenek, L. Mastalerz, M. S´wierczynska, C. Picado, et al.
Allergy 2007: 62: 1111–1118
Protocol of nasal aspirin
challenge
Nasal symptoms, nasal inspiratory flow and volume are
measured within 30 minutes every 10 minutes. If there is a
change from 20% in the values recorded upper airway is
hyperreactive and therefore the challenge can not be done.
Finally, 80 ul of L-ASA are instilled into each nostril (total
aspirin dose: 16 mg)
E. Nizankowska-Mogilnicka, G. Bochenek, L. Mastalerz, M. S´wierczynska, C. Picado, et al.
Allergy 2007: 62: 1111–1118
Nasal provocation tests may be the first
choice in the diagnosis of NSAID
intolerance
Instillation: Syringe
MILEWSKI M, MASTALERZ L, NIZANKOWSKA E, SZCZEKLIK A. Nasal
provocation test with lysine-aspirin for diagnosis of aspirin-sensitive asthma.
J Allergy Clin Immunol 1998;101:581–586.
CASADEVALL J, VENTURA PJ, MULLOL J, PICADO C. Intranasal challenge with
aspirin in the diagnosis of aspirin intolerance asthma: evaluation of nasal
response by acoustic rhinometry. horax 2000;55:921–924.
Control of peak nasal inspiratory flow is an
objective measure of response, which has
high specificity
Inspiratory flow meter
S. JIMENEZ-TIMON J., VIGARA Y.M., CIMARRA C., MARTINEZ CERA. Nasal challenge in patients allergic to
Alternaria. Allergy 1997, 52. 37, 208–209.
HOLMSTROM M., SCADDING G.K., LUND V.J., DARBY Y.C., . Assessment of nasal
obstruction. A comparison between rhinomanometry and nasal inspiratory
peak flow. Rhinology 1990;28:191–196.
KRAYENBUHL M.C., HUDSPITH B.N. SCADDING G.K., BROSTOFF J. Nasal response to allergen and hyper-osmolar
challenge. Clin Allergy 1988;18:157–164.
In conclusion, a history of previous reaction after
ingestion of aspirin is not a reliable guide to the
diagnosis of aspirin hypersensitivity (AH). Since
there is no other in vitro test of AH, the challenge
of aspirin is the only diagnostic tool available
L. J. Cormican, S. Farooque, D. R. Altmannw and T. H. Lee
Clin Exp Allergy 2005; 35:717–722
Management of patients with
Aspirin-Exacerbated Respiratory
Disease (AERD)
M. Sánchez-Borges, A. Capriles-Hulett, F. Caballero-Fonseca J Invest Allergol Clin Immunol 2004; Vol. 14(4): 329-334
Desensitization is a
term used in a broad
sense, refers to the
elimination of reactions
to ASA by repeated
exposure and increasing
doses of medication
M. Pilar Berges-Gimeno and Donald D. Stevenson
JOURNAL OF ASTHMA Vol. 41, No. 4, pp. 375–384, 2004
Tips
•During the desensitization with ASA, there is a continuous
inhibition of COX-1 and of phospholipase A2. This leads to a
decrease in the synthesis of LTs and prostanoids.
•Recipients (patients) cysLT1 are "down regulated“, then there is
a "leveling" of the effects of the LTs. Studies have shown that
during acute desensitization there is a slight decrease in TXB2
and LTB4.
•During chronic desensitization, the synthesis of LTB4
substantially decreases
Ferreri NR, Howland WC, Stevenson DD, Spiegelberg HL. Release of leukotrienes, prostaglandins, and histamine into nasal secretions of
aspirin-sensitive asthmatics during reactions to aspirin. Am Rev Respir Dis 1988;137:847–854.
Juergens UR, Christiansen SC, Stevenson DD, Zuraw BL. Inhibition of monocyte leukotriene B4 production after aspirin desensitization. J
Allergy Clin Immunol 1995;96:148–156.
General requirements for aspirin
desensitization
ASA desensitization should be performed in a place capable of
providing advanced cardiac care, ventilator support and
continuous monitoring by qualified personnel.
The supervising physician must be available immediately to the
bedside of the patient after the drug is first applied, and
recognize early warning signs. This is when the most severe and
unpredictable reactions almost always occur
Eric Macy, MD Jonathan A. Bernstein, MD; Mariana C. Castells, MD, Ph; Sandra M. Gawchik, DO; Tak H. Lee, MD, ScD, FRCPath, FRCP; Russell A. Settipane,
MD¶; Ronald A. Simon, MD; Jeffrey Wald, MD; and Katharine M. Woessner, MD;
for the Aspirin Desensitization Joint Task Force
Ann Allergy Asthma Immunol. 2007;98:172–174.
Candidates for ASA
desensitization
1. AERD* patients who have no concomitant
respiratory disease but who have moderate or severe
asthma, nasal congestion intractable or both on the
basis of REIA. These patients should be considered for
aspirin desensitization after treatment failure with
topical corticosteroids, LTR1A, and 5-LO INH.
* AERD: Aspirin-Exacerbated Respiratory Disease
Donald D. Stevenson and Ronald A. Simon
J Allergy Clin Immunol 2006;118:801-4.
Candidates for ASA
desensitization
2. AERD patients with concomitant respiratory diseases
which are under aggressive therapy but have not
responded
to
treatment,
including
topical
corticosteroids, LTR1A and 5-LO INH.
3. AERD patients with a history of multiple polyps.
Donald D. Stevenson and Ronald A. Simon
J Allergy Clin Immunol 2006;118:801-4.
Candidates for ASA
desensitization
4. Patients requiring systemic corticosteroids to control
AERD.
5. AERD patients who require aspirin for other
diseases.
Donald D. Stevenson and Ronald A. Simon
J Allergy Clin Immunol 2006;118:801-4.
Candidates for ASA
desensitization
6. Others…...
In a long-term study of 65 patients with ASA intolerance
who underwent desensitization, there was a significant
decrease in the number of infectious sinusitis and the use
of prednisone with improvement in smell and symptoms of
asthma and rhinitis. The need for sinus surgery decreased
from one every 3 years to once every 9 years. This study
demonstrated the beneficial effect of long-term
desensitization to ASA over a period of 6 years
Stevenson DD, Hankammer MA, Mathison DA. Aspirin desensitization treatment of aspirin sensitive patients with
rhinosinusitis asthma: long term outcomes. J Allergy Clin Immunol. 1996;98:751-758.
A subsequent study by Berges-Gimeno and colleagues with
172 patients demonstrated a percentage improvement of
67% patients at 6 months of treatment, which persisted for
1 to 5 years with reduction in the occurrence of purulent
sinusitis about 5 episodes per year to less than half
Berges-Gimeno, P, Simon RA, Stevenson DD.
Long term treatment with aspirin desensitization in asthmatic patients with
aspirin exacerbated respiratory disease. J Allergy Clin Immunol 2003;111:180-186.
The traditional model of desensitization to ASA have been
administered for 3 days, increasing doses of the drug until
the patient tolerated 650 mg without adverse effects. The
patient should continue receiving a daily dose of 650 mg
every 12 hours
Oliver P. and Ludger K. Aspirin desensitization in aspirin intolerance: update on
current standars and recent improvements. Current Opinion in Allergy and Clinical
immunology. 2006;6:161-166
Scripps Clinic ASA Oral challenge
Protocol
TIME
DAY 1
DAY 2
DAY 3
8 AM
Placebo
15-30 mg
150 mg
11 AM
Placebo
45-60 mg
325 mg
2 PM
Placebo
100 mg
650 mg
FEV1 every hour for 3 hours after each dose.
Placebo day: FEV1 baseline or first AM value >70% predicted.
First, AM FEV1 value should be within ±5% from placebo.
FEV1 values should not change (i.e. <15%) during 9-hour placebo
challenges.
Jennifer Altamura Namaz y and Ronald A. Simon
Ann Allergy Asthma Immunol 2002;89:542–550.
Protocol
One to 7 days before challenge, determine airway stability.
1.
2.
3.
4.
5.
FEV1 >60% of predicted value (>1.5 L absolute).
FEV1 every hour x 3 hours – <10% variability.
Start or continue montelukast, 10 mg every day.
Start or continue ICSs/LABs.
Start SCS burst for low FEV1 or any bronchial
instability.
6. Discontinue antihistamines 48 hours before
challenge.
Donald D. Stevenson and Ronald A. Simon
J Allergy Clin Immunol 2006;118:801-4.
Rapid desensitization
There is a rapid desensitization protocol in 7 hours based on
the controlled administration of increasing doses of ASA 90minute intervals until the patient can tolerate a dose of 650
mg, measuring lung function using FEV1 and considering
significant a decrease of over 20 % from the baseline.
Castells, M. Desensitization for drug allergy.
Current Opinion in Allergy and Clinical Immunology.2006;6:476-481.
White AA, Stevenson DD, Simon RA. The blocking effect of essential controller medications during aspirin challenges in patients with
aspirine xacerbated respiratory disease. Ann Allergy Asthma Immunol 2005; 95:330–335.
Desensitization to aspirin in a
patient with asthma
TIME
DOSE (mg)
0
4
90
40
180
81
240
162
330
325
420
650
Aspirin to be continued at 650 mg orally, twice a day.
Mariana Castells
Curr Opin Allergy Clin Immunol 6:476–481. 2006
White AA, Stevenson DD, Simon RA. The blocking effect of essential controller medications during aspirin challenges in patients with
aspirinexacerbated respiratory disease. Ann Allergy Asthma Immunol 2005; 95:330–335.
A clinical case
• 37 year old female patient
• Cronic sinusitis
• Serious Asthma
• 5 nasal polyps operations
• NSAIDs intolerance
(Anaphilaxis by ASA)
A clinical case
• Stable condition
• FEV1 - 71%
• Progressive doses: up to 81 mgs
• Adverse symptoms occur
• Systolic blood pressure fell by 20%
• FEV1 - 40% drop
• …stopped and postponed!
A clinical case
• Next day…
• FEV1 - 73%
• Beginning at 81 mg until 650 mg.
• Acumulated doses: 1343 mg
• One year with a 650 mg dose
every 12 hours of ASA.
• Today: patient discontinued treatment
due to severe stomach problems
P
1
Age
46
G
Diagnosis
Outcome
F
AERD
1343
650 bid
1262
650 bid
Good tolerance
1343
650 bid
Good tolerance
Oral challenge
(875 mg). Next
day single dose
650 mg
650 bid
Sinus and nasal
symptoms
improvement
100
100 daily
Good tolerance
1343
650 bid
Good tolerance
2*
51
F
3*
37
F
-AERD
- Anaphylaxis with ASA
35
Maintenance
dose (mg)
Good tolerance, no
polyps in the follow
up
- AERD
-ASA induced angioedema
- Anaphylaxis with ibuprofen and
diclofenac
4
Cumulated
Dose (mg)
F
AERD
Cardiologist prescription of ASA.
Patient with history of ASA
induced urticaria and angioedema
5*
63
F
6
35
M AERD
*Cardona R., Ramírez R.R., Reina Z., Escobar M.F., Morales E. Alergia e intolerancia a antiinflamatorios no esteroideos:
desensibilización exitosa en tres casos y revisión de literatura. Biomédica. 2009. 29(2) 181-190
Others…...
ASA desensitization can be considered as a therapeutic
alternative with good clinical efficacy and very cost-effective
in patients who:
• Remain intolerant of NSAIDs and chronic pain
• Require ASA for prophylaxis cardiovascular and
thromboembolic disease
• In patients with asthma and recurrent polyposis which
can not be controlled with polypectomies or sinus
surgery
• In women with antiphospholipid syndrome during
pregnancy
Gollapudi RR, Teirstein PS, Stevenson DD, Simon RA.
Aspirin sensitivity: implications for patients with coronary artery disease. JAMA.2004;292:3017-3023.
Castells, M. Desensitization for drug allergy.
Current Opinion in Allergy and Clinical Immunology.2006;6:476-481.
Thanks !!