Allergy Asthma Immunol Res.  2019 Mar;11(2):212-221. 10.4168/aair.2019.11.2.212.

Phenotypes of Severe Cutaneous Adverse Reactions Caused by Nonsteroidal Anti-inflammatory Drugs

• 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
• Ye YM

• KMID: 2431853
• DOI: http://doi.org/10.4168/aair.2019.11.2.212

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.

Keyword

Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Stevens-Johnson Syndrome

MeSH Terms

Acetaminophen
Acetates
Acetic Acid
Anti-Inflammatory Agents, Non-Steroidal
Cicatrix
Classification
Cyclooxygenase 2 Inhibitors
Diethylpropion
Drug Hypersensitivity
Drug Hypersensitivity Syndrome
Hospitals, University
Incidence
Korea
Phenotype*
Propionates
Prospective Studies
Retrospective Studies
Salicylates
Salicylic Acid
Stevens-Johnson Syndrome
Acetaminophen
Acetates
Acetic Acid
Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase 2 Inhibitors
Diethylpropion
Propionates
Salicylates
Salicylic Acid

Figure

• 

  Fig. 1 Distribution of subjects according to culprit NSAID class (A) and the proportions of SCAR phenotypes according to NSAID class (B). NSAID, nonsteroidal anti-inflammatory drug; SCAR, severe cutaneous adverse reaction; UC, unclassified.

• 

  Fig. 2 Proportions of culprit NSAIDs according to SCAR phenotype. NSAID, nonsteroidal anti-inflammatory drug; SCAR, severe cutaneous adverse reaction; UC, unclassified; DRESS, drug reaction with eosinophilia and systemic symptoms; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis.

• 

  Fig. 3 Time interval between initiation of drug and onset of symptoms according to culprit NSAID. NSAID, nonsteroidal anti-inflammatory drug; UC, unclassified; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis; DRESS, drug reaction with eosinophilia and systemic symptoms; AAP, acetaminophen; AA, acetic acid; PA, propionic acid; SA, salicylic acid.

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