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Noh, Yoon, Cho, Song, Park, Yu, and Hong: Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction
Original Article

Allergy Asthma Respir Dis 2018;6(1):26-33.

Published online: 5 January 2018

DOI: https://doi.org/10.4168/aard.2018.6.1.26

Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction

Soo Ran Noh1, Jisun Yoon1, 2, Hyun-Ju Cho1, 2, Seongyoon Song1, Geun-Mi Park1, Jinho Yu1, Soo-Jong Hong1, 2

1Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

2Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to: Soo-Jong Hong https://orcid.org/0000-0003-1409-2113 Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-3379, Fax: +82-2-473-3725, E-mail: sjhong@amc.seoul.kr

Received 5 June 201719 August 2017       Accepted 23 August 2017

Copyright © 2018 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Drug provocation tests (DPT) are the gold standard for confirming the diagnosis of drug hypersensitivity reactions (DHRs). However, there are little studies of DPT in children. The purpose of this study was to evaluate DPT results and safety as diagnostic methods of DHR in Korean children.

Methods

We reviewed the medical records of 39 children under 18 years of age with a suspected DHR and performed DPT between January 2010 and May 2016 at Asan Medical Center.

Results

Total 110 DPT were performed in 39 children (20 boys and 19 girls) with a history of DHR. Clinical presentation of DHR included skin rash (n=7), pruritus (n=3), urticaria (n=18), angioedema (n=19), dyspnea (n=5), hoarseness (n=1), hypothermia (n=1), and anaphylaxis (n=5). The median age at the time of DPT was 9 years. Positive DPT were observed in 21 of 39 children (53.8%) and 28 of 110 cases (25.5%). Drugs causing positive reactions were acetaminophen in 50% (9 of 18), nonsteroidal anti-inflammatory drugs in 29.2% (14 of 48), cephalosporin in 9.1% (1 of 11), trimethoprim/sulfamethoxazole in 50% (1 of 2), local anesthetics in 10% (1 of 10), and others (levodropropizine and idursulfase) in 15.4% (2 of 13). There was no statistical difference between children who had positive and negative results in sex, age, personal and parental history of allergic disease, eosinophil count, or total IgE level. Children with positive DPT did not develop anaphylaxis during the DPT procedure.

Conclusion

Drug provocation test is safe, and it can be considered in children with suspected DHRs.

Keywords: Drug hypersensitivity reaction, Drug provocation test, Child

REFERENCES

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Fig. 1.
Number of suspected and proven drug hypersensitivity reaction. DPT, drug provocation test; AAP, acetaminophen; NSAID, nonsteroidal anti-inflammatory drug; TMP/SMX, trimethoprim/sulfamethoxazole; Others, varidase, serratiopeptidase, salbutamol, ipratropium, formoterol, folic acid, Lactobacillus acidophilus, domperi-done, rebamipide, pinaverium, levodropropizine, and idursulfase.
aard-6-26f1.tif
Fig. 2.
Drug allergy card and application.
aard-6-26f2.tif
Table 1.
Baseline characteristics of study subjects
Characteristic Number (%)
Sex  
 Male 20 (51.3)
 Female 19 (48.7)
Age (yr)  
 <2 0 (0)
 2–5 9 (23.1)
 ≥6 30 (76.9)
Symptoms  
 Skin rash 7 (18.0)
 Urticaria 18 (46.2)
 Angioedema 19 (48.7)
 Pruritus 3 (7.7)
 Dyspnea 5 (12.8)
 Anaphylaxis 5 (12.8)
 Others (pale, hypothermia, hoarseness) 3 (7.7)
Personal history of allergic disease  
 Atopic dermatitis 10 (25.6)
 Allergic rhinitis 15 (41.0)
 Recurrent wheezer 3 (7.7)
 None 13 (33.3)
Parental history of allergic disease  
 Allergic rhinitis 17 (43.6)
 Asthma 2 (5.1)
 None 15 (38.5)
Table 2.
Antibiotics specific IgE (kU A/L) and drug provocation test (DPT) results
No. Amoxycilloyl Ampicilloyl PenicilloylG PnicilloylV Cefaclor DPT (+)
5 0 0     0 TMP/SMX
6 0 0 0 0 0 (–)
10 0 0 0 0 0 (–)
11 0 0 0 0 0 AAP
14 0   0 0   (–)
15 0 0 0 0 3 (2.23) (–)
16 0 0 0 0 0 (–)
22     0 0   (–)
28 0 0 0 0 0 AAP
29 2 (0.72) 2 (1.37) 1 (0.39) 2 (1.02) 2 (0.91) (–)
35 0 0 0 0 0 Cefaclor
37 0 0 0 0 0 (–)

TMP/SMX, trimethoprim/sulfamethoxazole; AAP, acetaminophen.

Table 3.
Clinical reactions of positive drug provocation tests
No. Challenge test
 Clinical reactions Timeto reaction after last dose (min) Cumulative dose to reaction (mg)
Drug tested Positive results
1 Celecoxib, aspirin Aspirin Angioedema 30 325
2 AAP, ibuprofen, celecoxib AAP, Ibuprofen Skin rash AAP unknown, ibuprofen 30 AAP 1,400, ibuprofen 277
3 AAP, Ibuprofen AAP Urticaria, dizziness 3 592
4 Celecoxib, AAP, aspirin Aspirin, AAP Urticaria, angioedema Aspirin 20, AAP 120 Aspirin 425, AAP 2,100
5 Amoxicillin, SMX/TMP SMX/TMP Urticaria, dyspnea 30 5.52
8 Aspirin, celecoxib, AAP Aspirin, AAP Urticaria Aspirin 60, AAP 1 Aspirin 450, AAP 400
11 AAP, amoxicillin/clavulanate, ibuprofen, aspirin AAP Angioedema 600 600
12 AAP, aspirin, celecoxib Aspirin Angioedema 45 175
13 Lidocaine, procaine Lidocaine Urticaria 300 22
17 Ketoprofen, diclofenac, ibuprofen Ibuprofen Angioedema, horseness, dyspnea 45 654
18 Aspirin Aspirin Angioedema, dyspnea 30 250
19 Ibuprofen, celecoxib, AAP Ibuprofen, celecoxib, AAP Urticaria Ibuprofen 10, celecoxib 50, AAP 60 Ibuprofen 85, celecoxib 100, AAP 250
23 AAP, ibuprofen, aspirin Ibuprofen Angioedema 15 362
24 AAP, aspirin Aspirin Angioedema 60 930
26 Dexibuprofen, aspirin, AAP AAP Pruritus, angioedema Unknown 475
28 AAP, aspirin, amoxicillin AAP Urticaria 30 1,125
30 Lactobacillus Acidophilus, celecoxib, AAP, aspirin, dexibrufen Dexibrufen, Aspirin Urticaria Dexibrufen 60, aspirin 60 Dexibrufen 402, aspirin 50
32 Nimesulide, aspirin, AAP AAP Skin rash 60 345
35 Cefpodoxime, cefaclor, aspirin, aceclofenac Cefaclor Angioedema, skin rash, chest tigh tness 5 180
36 Celecoxib, aspirin, levodropropizine Aspirin, levodropropizine Urticaria, angioedema Aspirin 60, levodropropizine 1 Aspirin 925, levodropropizine 9
39 Idursulfase Idursulfase Urticaria 1 1.7

AAP, acetaminophen; TMP/SMX, trimethoprim/sulfamethoxazole.

Table 4.
Comparison of characteristics between study subjects with positive and negative test results
Variable Drug provocation test results
 P-value
Positive (n=21) Negative (n=18)
Male sex (%) 52 56 0.843
Age (yr) 9 (5.5–13.0) 9 (5.8–10.8) 0.477
Personal history of allergic diseases (%) 79 50 0.065
Parental history of allergic diseases (%) 50 65 0.340
Eosinophil count (/mm3) 160.0 (95.0–285.0) 135.0 (44.5–255.0) 0.460
Total IgE (kU/L) 166.0 (83.7–383.5) 128.0 (82.3–497.0) 0.869

Values are presented as median (interquartile range) unless otherwise indicated.

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