QWhat is Drug Induced Epidermal Necrolysis (DEN)?

A
Nicholas Brownstone, MD

Nicholas Brownstone, MD

Assistant Professor of Dermatology
Icahn School of Medicine at Mount Sinai
New York, NY

Drug-induced epidermal necrolysis (DEN) is a new term that you may hear in the hospital or come across in the dermatology literature. While it may sound like a new disease, this term is synonymous with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). Why does the field of dermatology need an alternative term for SJS/TEN?

DEN was chosen to replace SJS/TEN mainly in the pediatric dermatology literature to clearly identify mucocutaneous eruptions that are the result of culprit medications implicated in classic cases of SJS/TEN. This is an important distinction in cases of mucocutaneous eruptions that are triggered by infection which is the case in Mycoplasma-induced rash and mucositis (MIRM) and Reactive Infectious Mucocutaneous Eruption (RIME). The distinction is extremely important because it helps to direct initial management and long-term management including counseling to avoid dangerous culprit drugs in the future.

There could be an overlap in histology between SJS/TEN and MIRM/RIME. The diagnosis of MIRM/RIME requires that there is no history of “a highly worrisome medication”. While there are exceptions, patients with MIRM/RIME have prominent mucositis involving 2 or more mucous membranes with minimal to no skin involvement. Patients with SJS/TEN or DEN have more diffuse skin involvement along with prominent mucositis.

Therefore, if a pediatric patient presents with a mucocutaneous eruption who had started lamotrigine 4 weeks earlier but also has positive Mycoplasma pneumoniae IgM and IgG antibodies, then the diagnosis is DEN and not MIRM/RIME. The patient should not take lamotrigine again and you should blame this eruption on the drug!


References:

  1. Dermatology World April 2025 Page 1. Accessed August 2, 2025. https://digitaleditions.walsworth.com/publication/?i=843693&p=3&view=issueViewer&pp=1
  2. Ramien ML, Bruckner AL. Mucocutaneous Eruptions in Acutely Ill Pediatric Patients-Think of Mycoplasma pneumoniae (and Other Infections) First. JAMA Dermatol. 2020;156(2):124-125. doi:10.1001/jamadermatol.2019.3589
  3. Vassallo C, Ruffo Di Calabria V, Isoletta E, Biscarini S, Di Filippo A, Brazzelli V. Clinical and microbiological characteristics of reactive infectious mucocutaneous eruption: A case series of 5 patients. JAAD Case Rep. 2021;17:152-156. doi:10.1016/j.jdcr.2021.09.029
  4. Mycoplasma pneumoniae induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: A systematic review https://pubmed.ncbi.nlm.nih.gov/25592340/