Hypersensitivity reactions to �Non-Steroidal Anti-Inflammatory Drugs: Single versus multiple reactors

Ana Reis Ferreira, Natacha Santos, Carmen Botelho , Eunice Castro, Josefina R. Cernadas

Serviço de Imunoalergologia, Hospital de São João, EPE, Porto, Portugal

Background •  Non-­‐Steroidal  Anti-­‐Inflammatory  Drugs  (NSAIDs)  

COX-­‐2  COX-­‐1  

Prostaglandins  /  Thromboxanes  

NSAIDs  

Non-­‐selective  COX  inhibitors  –   Acetylsalicylic  acid  (ASA)  –   Diclofenac  –   Ibuprofen  Weak  COX-­‐1  inhibitor  –   Paracetamol  

COX-­‐2  preferencial  inhibitors  –   Nimesulide  –   Meloxicam  

COX-­‐2  selective  inhibitors  –   Coxibes  

Background

•  NSAID  hypersensitivity  reactions  (HSR)  prevalence  in  the  general  populaGon  –  0.6%  to  2.5%  

   

•  COX-­‐1  inhibition  responsible  for  HSR  to  NSAIDs?  

Stevenson  et  al.  Ann  Allergy  Asthma  Immunol.  2001  Sep;87(3):177-­‐80.  

Single  vs  

Multiple  reactors  

Aim

To  characterize  clinical  data  of  the  patients  referred  to  our  

Drug  Allergy  Unit  for  NSAID  hypersensitivity  reactions:  

–  Demographical  data  

–  Type  of  reaction  

–  Suspected  drug(s)    

  •  Single  versus  Multiple  reactors  

•  Tolerance  to  weak    COX  –  1  inhibitors  

Methods

•  Clinical  data  from  the  records  of  the  patients  referred  in  the  last  10  years  for  NSAID  hypersensitivity  

•  Patients  grouped  according  to  symptoms:  

–  Cutaneous  symptoms  (Urticaria  and/or  angioedema)  

–  Aspirin-­‐Exacerbated  Respiratory  Disease  (AERD)  

–  Anaphylaxis  

•  Fisher’s   exact   test   was   used   to   compare   frequencies  

(significance  level  of  5%).  

 

 

Results

•  204  patients,  143♀:♂61  

•  16-­‐81  years-­‐old  (47.3±13.7)  

•  36.8%  were  atopic  

•  29.4%  had  a  previous  medical  diagnosis  of  asthma  

•  Mean  age  for  1st  reaction  was  37.4  ±  14.1  years  

•  Symptoms  occurred  in  the  1st  hour  after  exposure  in  45.6%  

Results

Number  of    implicated  NSAIDs  

46,6%  

23,5%  

19,1%  

8,3%   2,5%  

1  2  3  4  ≥5  

Results

Most  implicated  drugs:    

–  Acetilsalicilic  acid  (ASA)  –  63.2%  of  the  patients  

–  Ibuprofen  –  30.9%  of  the  patients  

–  Paracetamol  –  29.9%  of  the  patients  

Results

Cutaneous  symptoms  (urticaria  and/or  angioedema)    

•  154  patients  (75.5%)  

•  Reaction  to  1  NSAID  in  42.2%  of  the  patients.  

•  Most  implicated  drugs:  

–  ASA  -­‐  63%    

–  Paracetamol  -­‐  35.1%    

–  Ibuprofen  -­‐  33.8%  

Results

Aspirin-­‐Exacerbated  Respiratory  Disease  (AERD)    

•  18  patients  (8.8%)  -­‐  4  without  previous  asthma  diagnosis  

•  Reaction  to  1  NSAID  in  44.4%  of  the  patients.    

•  Most  implicated  drugs  

–  ASA    -­‐  77.8%  

–  Ibuprofen  -­‐  38.9%    

–  Diclofenac  -­‐  27.8%  

Results

Anaphylaxis    

•  21  patients  (10.3%)  

•  All  these  patients  referred  HR  to  only  1  NSAID  

•  8  to  ASA,  6  to  diclofenac  and  the  others  to  different  NSAIDs  

   

Eleven   patients   presented   different   types   of   reactions   to   NSAIDs  

and  were  not  included  in  the  previous  groups.  

Results Suspected  NSAIDs  according  to  symptoms  (single  vs  multiple)  

0%  

20%  

40%  

60%  

80%  

100%  

Cutaneous   AERD  

Single  

Multiple  

Single  

Multiple  

Single  

Multiple  

Single  

Multiple  

ASA  

Paracetamol  

Ibuprofeno  

Diclofenac  

Results Tolerance  to  ASA  and  weak  COX-­‐1  inhibitors  when  asked  

Cutaneous   AERD  

2%   0%  

54%  

93%  

24%  

75%  

ASA  

Paracetamol  

Nimesulide  

Results

Cutaneous   AERD  

52,6%  

16,7%  

p=0.0051  

HSR  to  weak  COX-­‐1  inhibitors  (paracetamol  and  nimesulide)  

Conclusion

•  ASA  was  the  most  frequently  implicated  drug.  

•  Almost   half   the   patients   reported   HR   to   only   one  NSAID.    

•  Urticaria   and/or   angioedema  were   the  most   common  symptoms,  with  AERD  and  anaphylaxis  occurring  each  in  approximately  10%  of  the  patients.  

•  HR   to   weak   COX-­‐1   inhibitors   was   more   frequent   in    patients  with  cutaneous  symptoms.  

Comments    

•  This   may   suggest   that   COX-­‐1   inhibition   plays   a   less  important   role   in   patients   with   cutaneous   symptoms  than  in  those  with  AERD.  

•  Drug   challenges   with   NSAIDs   with   different   COX-­‐1  inhibition   patterns   may   provide   a   more   accurate  diagnosis  of  NSAID  HRS  and  confirm  this  hypotesis.