Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs

Young Min Ye; Suh Young Lee; Young Hee Nam; Young Il Koh; Sae Hoon Kim; Sujeong Kim; Hye Ryun Kang; Min Hye Kim; Jun Gyu Lee; Jung Won Park; Hye Kyung Park; Hyen O. La; Mi Yeong Kim; Seong Ju Park; Yong Eun Kwon; Jae Woo Jung; Sang Hyon Kim; Cheol Woo Kim; Min Seok Yang; Min Gyu Kang; Jin Yong Lee; Joo Hee Kim; Sang Heon Kim; Gyu Young Hur; Young Koo Jee; Hyun Jung Jin; Chan Sun Park; Yi Yeong Jeong

doi:10.4168/aair.2019.11.2.212

Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs

Young Min Ye, Suh Young Lee, Young Hee Nam, Young Il Koh, Sae Hoon Kim, Sujeong Kim, Hye Ryun Kang, Min Hye Kim, Jun Gyu Lee, Jung Won Park, Hye Kyung Park, Hyen O. La, Mi Yeong Kim, Seong Ju Park, Yong Eun Kwon, Jae Woo Jung, Sang Hyon Kim, Cheol Woo Kim, Min Seok Yang, Min Gyu KangJin Yong Lee, Joo Hee Kim, Sang Heon Kim, Gyu Young Hur, Young Koo Jee, Hyun Jung Jin, Chan Sun Park, Yi Yeong Jeong

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

Abstract

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. Methods: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. Results: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. Conclusions: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

Original language	English
Pages (from-to)	212-221
Number of pages	10
Journal	Allergy, Asthma and Immunology Research
Volume	11
Issue number	2
DOIs	https://doi.org/10.4168/aair.2019.11.2.212
Publication status	Published - 2019 Mar 1

Bibliographical note

Funding Information:
This study was supported by a grant from the Ministry of Food and Drug Safety and the Korean Institute of Drug Safety and Risk Management for operation of the regional pharmacovigilance center in 2018 and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0970).

Publisher Copyright:
Copyright © 2019 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology
Pulmonary and Respiratory Medicine

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10.4168/aair.2019.11.2.212

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Ye, Y. M., Lee, S. Y., Nam, Y. H., Koh, Y. I., Kim, S. H., Kim, S., Kang, H. R., Kim, M. H., Lee, J. G., Park, J. W., Park, H. K., La, H. O., Kim, M. Y., Park, S. J., Kwon, Y. E., Jung, J. W., Kim, S. H., Kim, C. W., Yang, M. S., ... Jeong, Y. Y. (2019). Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs. Allergy, Asthma and Immunology Research, 11(2), 212-221. https://doi.org/10.4168/aair.2019.11.2.212

@article{cee3a017815f4306b93ab26fcd2ec1e5,

title = "Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs",

abstract = "Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. Methods: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. Results: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. Conclusions: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.",

author = "Ye, {Young Min} and Lee, {Suh Young} and Nam, {Young Hee} and Koh, {Young Il} and Kim, {Sae Hoon} and Sujeong Kim and Kang, {Hye Ryun} and Kim, {Min Hye} and Lee, {Jun Gyu} and Park, {Jung Won} and Park, {Hye Kyung} and La, {Hyen O.} and Kim, {Mi Yeong} and Park, {Seong Ju} and Kwon, {Yong Eun} and Jung, {Jae Woo} and Kim, {Sang Hyon} and Kim, {Cheol Woo} and Yang, {Min Seok} and Kang, {Min Gyu} and Lee, {Jin Yong} and Kim, {Joo Hee} and Kim, {Sang Heon} and Hur, {Gyu Young} and Jee, {Young Koo} and Jin, {Hyun Jung} and Park, {Chan Sun} and Jeong, {Yi Yeong}",

note = "Funding Information: This study was supported by a grant from the Ministry of Food and Drug Safety and the Korean Institute of Drug Safety and Risk Management for operation of the regional pharmacovigilance center in 2018 and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0970). Publisher Copyright: Copyright {\textcopyright} 2019 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease",

year = "2019",

month = mar,

day = "1",

doi = "10.4168/aair.2019.11.2.212",

language = "English",

volume = "11",

pages = "212--221",

journal = "Allergy, Asthma and Immunology Research",

issn = "2092-7355",

publisher = "Korean Academy of Asthma, Allergy and Clinical Immunology",

number = "2",

}

Ye, YM, Lee, SY, Nam, YH, Koh, YI, Kim, SH, Kim, S, Kang, HR, Kim, MH, Lee, JG, Park, JW, Park, HK, La, HO, Kim, MY, Park, SJ, Kwon, YE, Jung, JW, Kim, SH, Kim, CW, Yang, MS, Kang, MG, Lee, JY, Kim, JH, Kim, SH, Hur, GY, Jee, YK, Jin, HJ, Park, CS & Jeong, YY 2019, 'Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs', Allergy, Asthma and Immunology Research, vol. 11, no. 2, pp. 212-221. https://doi.org/10.4168/aair.2019.11.2.212

TY - JOUR

T1 - Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs

AU - Ye, Young Min

AU - Lee, Suh Young

AU - Nam, Young Hee

AU - Koh, Young Il

AU - Kim, Sae Hoon

AU - Kim, Sujeong

AU - Kang, Hye Ryun

AU - Kim, Min Hye

AU - Lee, Jun Gyu

AU - Park, Jung Won

AU - Park, Hye Kyung

AU - La, Hyen O.

AU - Kim, Mi Yeong

AU - Park, Seong Ju

AU - Kwon, Yong Eun

AU - Jung, Jae Woo

AU - Kim, Sang Hyon

AU - Kim, Cheol Woo

AU - Yang, Min Seok

AU - Kang, Min Gyu

AU - Lee, Jin Yong

AU - Kim, Joo Hee

AU - Kim, Sang Heon

AU - Hur, Gyu Young

AU - Jee, Young Koo

AU - Jin, Hyun Jung

AU - Park, Chan Sun

AU - Jeong, Yi Yeong

N1 - Funding Information: This study was supported by a grant from the Ministry of Food and Drug Safety and the Korean Institute of Drug Safety and Risk Management for operation of the regional pharmacovigilance center in 2018 and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0970). Publisher Copyright: Copyright © 2019 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. Methods: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. Results: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. Conclusions: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

AB - Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. Methods: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. Results: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. Conclusions: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

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Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs

Abstract

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