Aspirin Allergy In a High Risk VA Population and Potential Benefit From Aspirin Desensitization

J ALLERGY CLIN IMMUNOL

VOLUME 133, NUMBER 2

Abstracts AB265

UESDAY

913 Non-Steroidal Antiinflammatory Drugs (NSAIDs)-InducedAcute Urticaria: A Genome-Wide Association Study In TheSpanish Population

Dr. Jose A. Cornejo-Garcia, PhD1, Dr. Mike Lee2, Dr. Natalia Blanca-

L�opez, MD, PhD3, Dr. Lieh-Bang Liou4, Dr. Chien-Hsiun Chen5,

Dr. Inmaculada Do~na, MD, PhD6, Veronique Godineau1, Dr. Jose Julio

Laguna7, Dr. F. Javier Fernandez, MD, PhD8, Dr. Pedro Ayuso

Parejo, PhD3, Mrs. Maria del Carmen Plaza-Ser�on, Bsc3, Dr. Gabriela

Canto, MD, PhD3, Dr. Miguel Blanca, MD, PhD6; 1Research Laboratory,

Carlos Haya Hospital, Malaga, Spain, 2Laboratory for International Alli-

ance on Genomic Research, RIKEN Center for Integrative Medical Sci-

ences, Yokohama Kanagawa, Japan, 3Allergy Service, Infanta Leonor

Hospital, Madrid, Spain, 4Division of Rheumatology, Allergy and Immu-

nology, Chang Gung Memorial Hospital at Lin-kou, Kwei-san, Tao-yuan,

Taiwan, 5Institute of Biomedical Sciences, Academia Sinica, Taipei,

Taiwan, 6Allergy Service, Carlos Haya Hospital, M�alaga, Spain, 7HospitalDe La Cruz Roja, Madrid, Spain, 8UMH Alicante G.University Hospital -

Allergy Sect., Alicante, Spain.

RATIONALE: The most important group of medicaments responsible for

hypersensitivity drug reactions (HDRs) is NSAIDs, with acute urticaria/

angioedema (AUA) induced by cross-intolerance themost frequent clinical

entity. Most of the genetic studies carried out have focused in the study of

single nucleotide polymorphisms in genes related with prostaglandins and

leukotrienes synthesis. In order to identify new genetic variants potentially

involved in NSAIDs-induced AUA we conducted a GWAS in a Spanish

population.

METHODS: Patients and controls were recruited in clinical centers

integrated in the Spanish Network for Allergic Diseases. All patients

experienced more than 2 episodes with at least 2 different unrelated

NSAIDs, and those with airways or chronic urticaria were excluded.

Whole-genome scan was conducted using Axiom Genome-Wide CEU

Array chip on 308 NSAIDs-induced AUA patients and 144 NSAIDs

tolerant age, sex-matched controls.

RESULTS: Although no SNPs reached genomewide p-value after

Bonferroni correction, our results revealed 32 SNPs with suggestive

significant associations (10-8<p<10-5) with NSAIDs-induced AUA. The

lowest p values corresponded to polymorphisms located on chromosome

17; rs7225428 in GOSR2 (p51.11x10-6), rs197111 (p57.68x10-6), and

rs1071682 in EFTUD2 (p51.77x10-5).

CONCLUSIONS: The identification of new variants potentially associ-

ated with NSAIDs-induced AUA opens up new clues for understanding the

mechanisms underlying this disease, the most important clinical entity

induced by HRs.

914 Tolerance To COX-2 Inhibitors In Children With MultipleHypersensitivity To Non- Steroidal Anti-Inflammatory Drugs

Dr. Jose Luis Corzo Higueras, MD1, Dr. Maria Angeles Zambonino2,

Dr. Candelaria Mu~noz1, Dr. Cristobalina Mayorga, PhD3, Dr. Gloria

Requena1, Dr. Antonio Urda1, Dr. Miguel Blanca, MD, PhD4, Dr. Maria

J. Torres, MD, PhD4; 1Pediatric Service, Carlos Haya Hospital, M�alaga,Spain, 2Allergy Service, Carlos Haya Hospital, M�alaga, Spain, M�alaga,

Spain, 3Research Laboratory for Allergic Diseases, Hospital Regional

Universitario de Malaga - FIMABIS-IBIMA, Malaga, Spain, 4Allergy

Service, Carlos Haya Hospital, M�alaga, Spain.RATIONALE: Multiple hypersensitivity to non-steroidal anti-inflamma-

tory drugs (NSAIDs) can affect children, with the mechanism proposed

being inhibition of the cyclooxygenase enzyme-1 (COX-1). In these

patients non-chemically related NSAIDs, even COX-2 inhibitors, can

induce the reaction, hampering treatment of fever and inflammatory

processes. We have retrospectively analyzed tolerance to etoricoxib, a

selective COX-2 inhibitor, and to meloxicam, a preferential COX-2

inhibitor, in children diagnosed of multiple hypersensitivity to NSAIDs,

confirmed by drug provocation tests (DPT).

METHODS: We analyzed the clinical records of all children (aged 1-14

years) diagnosedwith multiple hypersensitivity reactions to NSAIDs in the

Pediatric Allergy Unit during the period January 2006 to January 2013. In

all cases tolerance to paracetamol, etoricoxib and meloxicam was also

assessed.

RESULTS: The study included 41 children with a diagnosis confirmed by

a DPT with acetyl salicylic acid and the culprit NSAID. DPT with

paracetamol and etoricoxib was negative in all children. However 2 (4.9%)

children developed a reaction after the administration of meloxicam, one

developed lip angioedema two hours after its administration and the other

lip and eye angioedema one hour after.

CONCLUSIONS: These data indicate that both etoricoxib and melox-

icam are good alternatives for treatment in older children with multiple

hypersensitivity to NSAIDs. More studies with larger populations need to

be conducted.

915 Aspirin Allergy In a High Risk VA Population and PotentialBenefit From Aspirin Desensitization

Bhavisha Patel, MD1,2, Joseph Karls2, Sandra Tompkins2, Dawn

Nyland2, Jo Ann Clough2, Jane Ludwig2, Sameer K. Mathur, MD, PhD,

FAAAAI1,2; 1University of Wisconsin School of Medicine and

Public Health, Madison, WI, 2William S. Middleton Veterans Hospital,

Madison, WI.

RATIONALE: There is strong evidence for the use of aspirin as part of

anti-platelet therapy in patients with cardiovascular disease. However,

there is a population of patients who are unable to take aspirin due to a

listed allergy to aspirin. In order to improve the utilization of aspirin, we

sought to better understand the prevalence and nature of aspirin allergies.

METHODS: In an IRB-approved protocol (HS-2012-0685), the medical

records of all veterans admitted to the William S. Middleton Veterans

Hospital from 1999 to 2004 were accessed. We used discharge codes to

identify the group admitted with cardiovascular diagnoses and cross-

referenced pharmacy allergy records to identify the subset with aspirin

allergy listed.

RESULTS: There were 20,476 patient discharge records analyzed. Of

those, 1609 (7.86%) were discharged with a cardiovascular diagnosis

including cerebrovascular event, transient ischemic attack, coronary

bypass, percutaneous cardiovascular procedure, acute myocardial infarc-

tion, cardiac arrest, angina, or chest pain. Of these 1609 patients, 28

patients (1.74%) had an aspirin allergy. We estimate an overall prevalence

of aspirin allergy in the VA population of 1.76%.

CONCLUSIONS: The prevalence of aspirin allergy in the VA patients

with cardiovascular disease is 1.74%. This group of patients is currently not

gaining the benefits of secondary prevention from aspirin utilization and

represents a target group of candidates for aspirin desensitization.

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