Changing Spectrum of Suspected Drugs of Epidermal Necrolysis

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• Using the WHO global database of individual case safety reports (VigiBase), the authors compared the most common culprit drugs in toxic epidermal necrolysis (TEN) over two periods: 1997–2001 and 2016–2020. Overall, 67 new drugs were newly associated with TEN in the second period. The most striking change was the rise of anti-cancer therapies, including mogamulizumab, pembrolizumab, vemurafenib, and cobimetinib. An additional 11 anti-epileptics, 2 NSAIDs, 11 anti-infectives, and 10 cardiovascular drugs were also seen.

• This study demonstrates the striking therapeutic progress seen over the past 2 decades and the increasing variety of drugs reported to cause TEN over this time. New antiepileptic drugs and anti-cancer therapies seem to carry a high risk and should be added to the spectrum of drugs known to commonly cause TEN.

– Margaret Hammond, MD

Written by

 

 

Lindy Fox MD

Using VigiBase, the WHO global database of individual case safety reports that houses over 20 million reports of adverse medication reactions, this group aimed to identify the medications most commonly associated with toxic epidermal necrolysis (TEN) and how the most frequent offenders might have changed over time. The authors divided the cases of TEN into 2 groups (labeled period 1 and 2): January 1, 1997– December 31, 2001, and January 1, 2016–January 15, 2020.

This study found that the most common causes of TEN in period 1 were allopurinol, aromatic anticonvulsants, lamotrigine, sulfonamides, and nevirapine. Importantly, the period 1 dates correspond to those of the EuroScar study, which, to date, serves as the gold standard of drugs implicated in severe cutaneous adverse reactions and can, in the current report, be thought of as validating the findings for period 1 of this study.

These same medications were also associated with TEN in period 2; but, of note, more recently introduced medications, also stood out. These included zonisamide, nimesulide (an NSAID withdrawn from the market in the United States and some European countries), coxibs, levetiracetam, and anticancer agents, including mogamalizumab, vemurafinib, and cobimetinib.

The strength of this report is its worldwide application. The significance of this report is 3-fold. First, it reinforces that drugs that are well-established culprits should still be considered so, and their ranks have not changed much over time. Secondly, physicians must be vigilant and consider newer agents as well, especially other classes of NSAIDs, anticonvulsants, and cancer therapies as potential causes of TEN. Finally, we are reminded that although some things stay the same, we must constantly reassess as medical therapeutics advance today and in the future.

Abstract 

Epidermal Necrolysis (EN), including Stevens Johnson syndrome and toxic epidermal necrolysis, is a rare life-threatening disease characterised by a diffuse skin and mucosal detachment.1From 70 to 90% of the cases are due to drugs. Prompt identification and discontinuation of the suspected drug(s) are vital.1,2 To assess the changing spectrum of drugs associated with EN, we performed a multicentre retrospective study using VigiBase, the WHO global database of individual case safety reports (Appendix).3

Journal of the American Academy of Dermatology

Changing Spectrum of Suspected Drugs of Epidermal Necrolysis: An WHO Pharmacovigilance Database Analysis From 1997 to 2020

J Am Acad Dermatol 2020 Nov 17;[EPub Ahead of Print], T Bettuzzi, S Ingen-Housz Oro, C Chinchilla Purtillo, L Le Cleach, P Maison, N de Prost, P Wolkenstein, B Lebrun-Vignes, E Sbidian 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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