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Kang, Jang, Sohn, Kang, Kim, Cho, and Kang: Optimal methods to detect DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome by electronic medical records
Original Article

Allergy Asthma Respir Dis 2018;6(3):149-154.

Published online: 5 May 2018

DOI: https://doi.org/10.4168/aard.2018.6.3.149

Optimal methods to detect DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome by electronic medical records

Dong Yoon Kang1, Dong Yeon Jang2, Kyung Hee Sohn3, Sung Yoon Kang4, Ju Young Kim5, Sang-Heon Cho1, 4, Hye-Ryun Kang1, 4

1Drug Safety Monitoring Center, Seoul National University Hospital, Seoul, Korea

2Seoul National University College of Medicine, Seoul, Korea

3Public Health Medical Service, Seoul National University Hospital, Seoul, Korea

4Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

5Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea

Correspondence to: Hye-Ryun Kang https://orcid.org/0000-0002-2317-4201 Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-0820, Fax: +82-2-742-3291, E-mail: helenmed@snu.ac.kr

• This research was supported by a grant from Ministry of Food and Drug Safety to the regional pharmacovigilance center in 2017.

Received 7 September 201713 October 2017       Accepted 8 November 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

Since drug reaction with eosinophilia and systemic symptom (DRESS) syndrome is very rare and difficult to diagnose, its exact epidemiology is still unknown. If screening tools based on laboratory results or electronic medical records are available, the occurrence of DRESS syndrome can be monitored in real time.

Methods

To screen cases with DRESS syndrome, all the results of both eosinophil and alanine transaminase (ALT) level from July 2014 to June 2015 were analyzed by 36 searching conditions for the signal detection of 7 definite DRESS cases among 199,924 patients during the study period. Those searching conditions were diverse combinations of different cutoff levels of eosinophil and ALT with or without nursing records presenting skin symptoms. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value were calculated for individual searching conditions.

Results

As cutoff levels of eosinophil and ALT for screening DRESS increased from 3% to 5% and 40 U/L to 300 U/L, respectively, the sensitivity decreased from 100% to 42.9% and the PPV increased from 0.06% to 13.0%. A combination of eosinophil >10% and ALT >300 U/L which had the highest PPV among 36 search conditions could detect DRESS syndrome by sensitivity 42.9% and PPV 13.0%. When nursing records for skin symptoms were added, PPV was augmented to 21.4%.

Conclusion

A combination of eosinophil and ALT levels is a useful search condition for the screening of DRESS syndrome. Nursing records can provide an additional increment in PPV.

Keywords: Drug hypersensitivity syndrome, Drug-related side effects and adverse reactions, Mass screening, Electronic health records

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Fig. 1.
Change of sensitivity and PPV according to search condition (eosinophil >10%, with or without nursing records). PPV, positive predictive value; ALT, alanine transaminase.
aard-6-149f1.tif
Table 1.
Clinical characteristics of the DRESS patients (n=7)
Characteristic Value
Male sex 4 (57.1)
Age (yr) 50.4±22.9 (27–85)
Initial hospital status  
 Outpatient 5 (71.4)
 Inpatient 2 (28.6)
Latency period (day)∗ 14.3±13.6 (1–38)
Clinical outcomes  
 Recovery 7 (100)
 Death 0 (0)
Causative drugs  
 Allopurinol 3 (42.9)
 Amoxicillin 1 (14.3)
 Ethambutol or isoniazid 1 (14.3)
 Piperacillin or tazobactam or vancomycin 1 (14.3)
 Meropenem or vancomycin or pantoprazole 1 (14.3)

Values are presented as number (%) or mean±standard deviation (range).

DRESS, drug reaction with eosinophilia and systemic symptoms.

∗ Time elapsed from exposure to causative drugs to the occurrence of mucocutane-ous involvement; data were available for 6 patients.

Table 2.
Diagnostic results of DRESS patients by three different criteria
DRESS syndrome patient Diagnostic criteria for DRESS syndrome
Culprit drugs Bocquet et al.9 RegiSCAR group Japaneseconsensus group
1 Amoxicillin Y Y N
2 Allopurinol N Y N
3 Allopurinol Y Y Y∗
4 Allopurinol Y Y N
5 Piperacillin/tazobactam, Vancomycin N Y N
6 Ethambutol, isoniazid Y Y N
7 Meropenem, vancomycin, pantoprazole N Y N

DRESS, drug reaction with eosinophilia and systemic symptoms; RegiSCAR, European Registry of Severe Cutaneous Adverse Reactions to drugs and collection of biological samples; Y, yes; N, no.

∗ A criteria of atypical drug-induced hypersensitivity syndrome.

Table 3.
Sensitivity, specificity, positive, and negative predictive values according to search condition
Nursing statement ALT (U/L) Eosinophil (%)
Sensitivity Specificity PPV NPV
3% 5% 10% 3% 5% 10% 3% 5% 10% 3% 5% 10%
Without nursing statement 40 100 85.7 71.4 94.07 97.50 99.57 0.06 0.12 0.57 100 100 100
80 85.7 71.4 71.4 98.39 99.30 99.87 0.19 0.36 1.90 100 100 100
100 85.7 71.4 57.1 98.94 99.55 99.92 0.28 0.55 2.41 100 100 100
150 71.4 57.1 57.1 99.50 99.78 99.96 0.49 0.92 4.44 100 100 100
200 71.4 57.1 42.9 99.70 99.87 99.98 0.83 1.52 5.77 100 100 100
300 71.4 42.9 42.9 99.85 99.94 99.99 1.66 2.42 13.00 100 100 100
With nursing statement 40 100 85.7 71.4 99.27 99.59 99.87 0.48 0.73 1.94 100 100 100
80 85.7 71.4 71.4 99.65 99.81 99.95 0.85 1.32 4.63 100 100 100
100 85.7 71.4 57.1 99.73 99.86 99.96 1.11 1.71 4.76 100 100 100
150 71.4 57.1 57.1 99.84 99.92 99.98 1.53 2.41 8.00 100 100 100
200 71.4 57.1 42.9 99.90 99.95 99.99 2.37 3.70 10.30 100 100 100
300 71.4 42.9 42.9 99.94 99.97 99.99 4.24 5.17 21.40 100 100 100

ALT, alanine transaminase; PPV, positive predictive value; NPV, negative predictive value.

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