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Erythema multiforme, epidermal type — Clinical Guidelines

Overview

Toxic epidermal necrolysis (TEN), also known as the epidermal type of erythema multiforme, is a severe, potentially fatal mucocutaneous reaction characterized by extensive skin and mucosal detachment resembling scalded skin. It often arises as an adverse drug reaction but can also be triggered by infections and other causes 1 16 18 19.

Diagnosis

Clinical Presentation: Full-thickness epidermal necrosis with widespread skin detachment, typically >30% of body surface area 1 16.

Histological Features: Separation of epidermis from dermis without significant dermal inflammation 16.

SCORTEN Score: Used to predict mortality and guide management intensity 7 (Evidence: Moderate).

Differential Diagnosis: Important to rule out other causes like staphylococcal scalded skin syndrome and other severe drug reactions 14 (Evidence: Moderate).

Management

First-Line Treatments:

- Supportive Care: Aggressive fluid and electrolyte management, wound care, and barrier maintenance 7 17. - Immunomodulatory Therapy: Intravenous immunoglobulin (IVIG) 8 (Evidence: Weak).

Adjunctive Treatments:

- Extracorporeal Therapies: Therapeutic plasma exchange (TPE) and continuous hemofiltration (CHF) in severe cases 2 (Evidence: Weak). - Antibiotics: Prophylactic or therapeutic use to prevent or manage sepsis 17 (Evidence: Weak).

Special Populations

Pediatrics: Extracorporeal therapies like TPE and CHF can be considered in severe cases with multiple organ dysfunction 2 (Evidence: Weak).

Elderly: Higher risk of complications and mortality; close monitoring and multidisciplinary care essential 11 (Evidence: Moderate).

Comorbidities: Patients with underlying conditions like bone marrow transplantation may have increased susceptibility and severity 5 (Evidence: Weak).

Key Recommendations

Early Recognition and Aggressive Supportive Care: Initiate prompt supportive care including fluid resuscitation and wound management to prevent complications 7 17 (Evidence: Moderate).

Consider Immunomodulatory Therapies: Use IVIG in severe cases to potentially reduce mortality 8 (Evidence: Weak).

Utilize Extracorporeal Therapies for Severe Cases: Employ TPE and CHF in patients with extensive skin detachment and organ dysfunction 2 (Evidence: Weak).

Monitor for and Manage Sepsis: Given the high risk of wound sepsis, prophylactic and therapeutic antibiotics may be necessary 17 (Evidence: Weak).

SCORTEN Score for Risk Stratification: Use SCORTEN to assess prognosis and guide intensity of care 7 (Evidence: Moderate).

References

1 Li X, Yan Z, Chen S, Wu Y, Qiu G, Hu F. Potential drugs associated with toxic epidermal necrolysis: a disproportionality analysis based on the FAERS database (2004-2024). Archives of dermatological research 2025. link 2 Cui Y, Shi J, Wang C, Zhou Y, Wang F, Miao H et al.. Sequential Blood Purification for Pediatric Fatal Toxic Epidermal Necrolysis: A Case Series. Blood purification 2022. link 3 Bettuzzi T, Ingen-Housz-Oro S, Maison P, de Prost N, Wolkenstein P, Lebrun-Vignes B et al.. Biases associated with epidermal necrolysis reporting in pharmacovigilance: An exploratory analysis using World Health Organization VigiBase. Pharmacoepidemiology and drug safety 2022. link 4 Harris B, Bitner B, Thomas L. Differin. Journal of cosmetic dermatology 2019. link 5 Asai C, Watanabe Y, Mukaijo J, Takamura N, Okawa T, Yamaguchi Y et al.. Case of toxic epidermal necrolysis occurring after bone marrow transplantation accompanied by engraftment failure. The Journal of dermatology 2019. link 6 Brown CS, Defazio JR, An G, O'Connor A, Whitcomb E, Hart J et al.. Toxic Epidermal Necrolysis with Gastrointestinal Involvement: A Case Report and Review of the Literature. Journal of burn care & research : official publication of the American Burn Association 2017. link 7 Zhang F, Zhou J. Toxic epidermal necrolysis: 13 years of experience in the management at a Department of Dermatology in China. Cutaneous and ocular toxicology 2017. link 8 Rodgers BK, Kumar AB. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation. American journal of therapeutics 2016. link 9 Islam S, Singer M, Kulhanjian JA. Toxic epidermal necrolysis in a neonate receiving fluconazole. Journal of perinatology : official journal of the California Perinatal Association 2014. link 10 Wu ML, Deng JF. Toxic epidermal necrolysis after extensive dermal use of realgar-containing (arsenic sulfide) herbal ointment. Clinical toxicology (Philadelphia, Pa.) 2013. link 11 Ventura F, Fracasso T, Leoncini A, Gentile R, de Stefano F. Death caused by toxic epidermal necrolysis (Lyell syndrome). Journal of forensic sciences 2010. link 12 Katsuta Y, Iida T, Hasegawa K, Inomata S, Denda M. Function of oleic acid on epidermal barrier and calcium influx into keratinocytes is associated with N-methyl D-aspartate-type glutamate receptors. The British journal of dermatology 2009. link 13 Mittmann N, Knowles SR, Gomez M, Fish JS, Cartotto R, Shear NH. Evaluation of the extent of under-reporting of serious adverse drug reactions: the case of toxic epidermal necrolysis. Drug safety 2004. link 14 Zakrzewski JL, Lentini G, Such U, Duerr A, Tran V, Guenzelmann S et al.. Toxic epidermal necrolysis: differential diagnosis of an epidermolytic dermopathy in a hematopoietic stem cell transplant recipient. Bone marrow transplantation 2002. link 15 Freeman MS. Microdermabrasion. Facial plastic surgery clinics of North America 2001. link 16 Adornato MC. Toxic epidermal necrolysis associated with quinidine administration. The New York state dental journal 2000. link 17 Harnar TJ, Dobke M, Simoni J, Ninnemann JL. Toxic epidermal necrolysis complicated by severe wound sepsis: a case study. The Journal of burn care & rehabilitation 1987. link 18 de Groot R, Oranje AP, Vuzevski VD, Mettau JW. Toxic epidermal necrolysis probably due to Klebsiella pneumoniae sepsis. Dermatologica 1984. link 19 O'Sullivan M, Hanly JG, Molloy M. A case of toxic epidermal necrolysis secondary to indomethacin. British journal of rheumatology 1983. link

Erythema multiforme, epidermal type