Cross hypersensitivity

of NSAIDs
.

OUTLINE
Introduction to NSAIDs
Cross reactivity of NSAIDs in
immediated type
yp hypersensitivity
yp
y

Cross reactivity
y of NSAIDs in
delayed type hypersensitivity of NSAIDs

Conclusions

I t d ti
Introduction
to
t NSAIDs
NSAID


NSAIDs
Immediated type

Delayedtype
y
yp

Urticaria,
Angioedema, Anaphylaxis

MP rash, Fixed drug eruption,

DRESS, Drug hypersensitivity syndrome, SJS, TEN

Pseudoallergy

True allergy

True allergy

NSAIDs
Immediated type
salicylates
NSAIDs

True allergy urticaria, angioedema

anaphylaxis
Pseudoallergy


IgE

 Pseudoallergy True allergy Immediated type

Pseudoallergy

True allergy

Urticaria,
Angioedema, Anaphylaxis

Urticaria,
Angioedema, Anaphylaxis

Cox I (PGE2 )

(IgE)

Cox I

NSAIDs
Cox I

NSAIDs /

 NSAIDs
1. Salicylicacids

Cardiprin 100

Aggrenox

B-aspirin

Ascot

 NSAIDs
2.Indol
.
andindeneaceticacids

Indomethacin

Indomed

Sulindac

Clinoril

 NSAIDs
3.Heteroaceticacids
.

Voltaren

Voltaren SR

Dosanac

Diclofenac

Ketorolac

Voltaren

 NSAIDs
4.Arilpropionic
.
acids

Heidi 200 mg

Heidi 400 mg

Ketoprofen

Ibuprofen

Naproxen

Loxoprofen

Nurofen

Synflex
Napxen,Napxen

Loxonin

 NSAIDs
5. Fenamates

Mefenamic acid

Ponstan

Floctafenine

Idarac

 NSAIDs
6. Oxicams

Piroxicam

Meloxicam

Tenoxicam

Lomoxicam

Tilcotil ,Seftil

Feldene,
Flamic

Feldene-D

Mobic,
Melcam

 NSAIDs
7. Cox II inhibitor
Celecoxib

Rofecoxib

Valdecoxib

Parecoxib

Celebrex

Etoricoxib

Dynastat
Lumiracoxib

Nimesulide

Arcoxia


NSAIDs
Immediated type

Delayedtype
y
yp

Urticaria,
Angioedema, Anaphylaxis

MP rash, Fixed drug eruption,

DRESS, Drug hypersensitivity syndrome, SJS, TEN

Pseudoallergy

True allergy

True allergy

 NSAIDs Pseudoallergy
: Urticaria, Angioedema, Anaphylaxis, Asthma
Cox I

PGE2 (PGE2
Mast cell
stabilizer) Histamine mediators
Cox I

Cox I

 NSAIDs Cox
1. CoxI

2. Cox I
CoxI

Cox I
dose

3. CoxII

CoxI
Cox I
dose

CoxII

4.

NSAIDs
Cox

C I

Cox I
dose

dose

C I
Cox

Cox
I

Aspirin
Ibuprofen
Naproxen
Ketorolac
I d
Indomethacin
th i
Diclofenac
Piroxicam
Sulindac
Mefenamic acid
Floctafenine

Paracetamol
<1000
mg/dose
( Paracetamol
>1000mg/dose
> 1000 mg/dose

Nimesulide
Meloxicam

Celecoxib
Etoricoxib
Parecoxib

Anaphylaxis
NSAIDs

Rachel U. Lee,1 Donald D. Stevenson2Aspirin-Exacerbated Respiratory Disease:

Evaluation and ManagementAllergy Asthma Immunol Res. 2011 January;3(1):3-10.

 Pseudoallergy
.. 18 Ibuprofen 1
30


Diclofenac ,Piroxicam
Piroxicam
Sulindac

 Pseudoallergy

NSAIDs

. Paracetamol
. Meloxicam
Celecoxib
.
. Aspirin

 NSAIDs Cox
1. CoxI

2. Cox I
CoxI

Cox I
dose

3. CoxII

CoxI
Cox I
dose

CoxII

4.

NSAIDs
Cox

C I

Cox I
dose

dose

C I
Cox

Cox
I

Aspirin
Ibuprofen
Naproxen
Ketorolac
I d
Indomethacin
th i
Diclofenac
Piroxicam
Sulindac
Mefenamic acid
Floctafenine

Paracetamol
<1000
mg/dose
( Paracetamol
>1000mg/dose
> 1000 mg/dose

Nimesulide
Meloxicam

Celecoxib
Etoricoxib
Parecoxib

Anaphylaxis
NSAIDs

Rachel U. Lee,1 Donald D. Stevenson2Aspirin-Exacerbated Respiratory Disease:

Evaluation and ManagementAllergy Asthma Immunol Res. 2011 January;3(1):3-10.

 NSAIDs Psuedoallergy

/ CIU

NSAIDs
1

NSAIDs

anaphylaxis

NSAIDs
> 1

Cross Reactivity
NSAIDs
NSAIDs
NSAIDs

 NSAIDs True allergy

: Urticaria, Angioedema, Anaphylaxis, Asthma
(IgE)

1
> 1

 NSAIDs
NSAIDs
COX II

NSAIDs COX I
1.Salicylic acids

Ascot,
B-aspirin
Cardiprin,
Aggrenox
(Aspirin)

2. Indol and
Indene
acetic acids
Indomed
(Indomethacin)

Clinoril
(Sulindac)

3. Heteroacetic 4.Arilpropionic
acids
acids

5.Fenamates

6.Oxicams

7.Cox-2
inhibitors

Voltaren,
Dosanac
(Diclofenac)

Nurofen,
Heidi
(Ibuprofen)

Ponstan
(Mefenamic
acid)

Feldene,
Flamic
(Piroxicam)

Celebrex
(Celecoxib)

Ketalac
(Ketorolac)

Synflex
(Naproxen)

Idarac
(Floctafenine)

Tilcotil, Seftil
(Tenoxicam)

Dynastat
(Peracoxib)

Mobic, Melox
(Meloxicam)

Arcoxia
(Etoricoxib)

Anaphylaxis
NSAIDs

Loxonin
(Loxoprofen)

 True allergy
.. 18 Ibuprofen 1
30


Naproxen

Piroxicam Mefenamic acid

 True allergy

NSAIDs

. Diclofenac
. Indomethacin
Piroxcicam
.
. Aspirin

 NSAIDs
NSAIDs
COX II

NSAIDs COX I
1.Salicylic acids

Ascot,
B-aspirin
Cardiprin,
Aggrenox
(Aspirin)

2. Indol and
Indene
acetic acids
Indomed
(Indomethacin)

Clinoril
(Sulindac)

3. Heteroacetic 4.Arilpropionic
acids
acids

5.Fenamates

6.Oxicams

7.Cox-2
inhibitors

Voltaren,
Dosanac
(Diclofenac)

Nurofen,
Heidi
(Ibuprofen)

Ponstan
(Mefenamic
acid)

Feldene,
Flamic
(Piroxicam)

Celebrex
(Celecoxib)

Ketalac
(Ketorolac)

Synflex
(Naproxen)

Idarac
(Floctafenine)

Tilcotil, Seftil
(Tenoxicam)

Dynastat
(Peracoxib)

Mobic, Melox
(Meloxicam)

Arcoxia
(Etoricoxib)

Loxonin
(Loxoprofen)

 NSAIDs True allergy

NSAIDsCrossReactivity
/ CIU

NSAIDs
1

NSAIDs

NSAIDs
Cross Reactivity
> 1
NSAIDs

anaphylaxis
NSAIDs


NSAIDs
Immediated type

Delayedtype
y
yp

Urticaria,
Angioedema, Anaphylaxis

MP rash, Fixed drug eruption,

DRESS, Drug hypersensitivity syndrome, SJS, TEN

Pseudoallergy

True allergy

True allergy



NSAIDs Deleyed type reaction1

-
True allergy (
( T cell)5
-
( Fixed drug eruption Oxicams) 6
SJS/TEN

NSAIDs

NSAIDs

- NSAIDs

- Desensitization 1

CONCLUSIONS

NSAIDs hypersensitivity Immediated Deleyed type

Immediated type
NSAIDs

True
Pseudo allergy

CONCLUSIONS

NSAIDs > 1
Pseudoallergy

NSAIDs
Cox I

Cox II inhibitor
Cox I Cox II (
4%)

CONCLUSIONS

NSAIDs 1 > 1
True allergy

NSAIDs
NSAID

CONCLUSIONS

Delayed type True allergy

NSAIDs

REFERENCE
1. Cuerda Galindo E, Goday Bujn JJ, Garca Silva JM, Martnez W, Verea Hernando M, Fonseca E. Fixed drug eruption from piroxicam.J Eur Acad Dermatol
Venereol. 2004 Sep;18(5):586-7.
2. Kowalski ML, Makowska JS, Blanca M, Bavbek S, Bochenek G, Bousquet J, Bousquet P, Celik G, Demoly P, Gomes ER, Niankowska-Mogilnicka E,
Romano A, Sanchez-Borges M, Sanz M, Torres MJ, De Weck A, Szczeklik A, Brockow K. Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs)
- classification, diagnosis and management: review of the EAACI/ENDA(#) and GA2LEN/HANNA*. Allergy. 2011 Jul;66(7):818-29. doi: 10.1111/j.13989995.2011.02557.x. Epub 2011 Feb 14.
3 Knowles
3.
K l SR,
SR Drucker
D k AM,
AM Weber
W b EA,
EA Shear
Sh NH
NH. M
Managementt options
ti for
f patients
ti t with
ith aspirin
i i andd nonsteroidal
t id l antiinflammatory
tii fl
t drug
d sensitivity.
iti it
Ann Pharmacother. 2007 Jul;41(7):1191-200. Epub 2007 Jul 3. Review.
4. Posadas SJ, Pichler WJ. Delayed drug hypersensitivity reactions - new concepts. Clin Exp Allergy. 2007 Jul;37(7):989-99.
g M,, Capriles-Hulett
p
A,, Caballero-Fonseca F,, Prez CR. Tolerabilityy to new COX-2 inhibitors in NSAID-sensitive ppatients with cutaneous
5. Snchez Borges
reactions. Ann Allergy Asthma Immunol. 2001 Sep;87(3):201-4.
6. Snchez Borges M, Capriles-Hulett A, Caballero-Fonseca F, Gonzalez- Aveledo L. Hypersensitivity reaction to Non steroidal Anti-inflammatory drugs : An
update. Pharmaceutical. 2010 Jan ; 3:10-18.
7. Szczeklik A, Sanak M. The broken balance in aspirin hypersensitivity. Eur J Pharmacol. 2006 Mar 8;533(1-3):145-55. Epub 2006 Feb 7.
Asero R. Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders. Ann Allergy Asthma Immunol. 1999
Jun;82(6):554-8.