What is the appropriate emergency department (ED) workup for a patient who developed a rash after starting lamotrigine (lamotrigine) therapy?

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From the Guidelines

The appropriate emergency department workup for a patient who developed a rash after starting lamotrigine therapy should include immediate discontinuation of the medication and a thorough evaluation for Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).

Key Considerations

  • Begin with a complete physical examination focusing on the extent and characteristics of the rash, checking for mucosal involvement (eyes, mouth, genitals), skin detachment, and systemic symptoms like fever 1.
  • Order laboratory tests including complete blood count, comprehensive metabolic panel, and liver function tests to assess for organ involvement.
  • Consider dermatology consultation for possible skin biopsy if the presentation is concerning.
  • Provide supportive care with IV fluids if needed and treat symptoms with antihistamines for itching.

Admission and Follow-Up

  • The patient should be admitted for observation if there are any concerning features such as mucosal involvement, blistering, skin detachment, or systemic symptoms.
  • Organize an outpatient clinic appointment with an ophthalmologist within a few weeks of discharge if the patient had eye involvement during the acute phase 1.
  • Organize an outpatient clinic appointment in dermatology or burns plastic surgery within a few weeks of discharge to monitor for complications in skin, mouth, urogenital tract, respiratory and gastrointestinal systems.

Patient Education and Safety

  • Encourage the patient to wear a MedicAlert bracelet or amulet bearing the name of the culprit drug.
  • Document the drug allergy in the patient’s notes and inform all doctors involved in the patient’s care, especially the GP, about the drug allergy episode and the culprit 1.
  • Warn the patient to avoid OTC medications where precise constituents are unclear and report episodes of drug-induced SJS/TEN to the national pharmacovigilance authorities. This aggressive approach is warranted because lamotrigine is known to cause serious cutaneous adverse reactions, particularly when initiated at high doses or with rapid dose escalation, as noted in the context of its administration 1. The risk is highest within the first 8 weeks of treatment, and prompt discontinuation at the first sign of rash can prevent progression to more severe reactions.

From the Research

Emergency Department Workup for Lamotrigine-Induced Rash

  • The patient should be evaluated for signs and symptoms of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), such as severe generalized skin reaction, oral mucosa erosion, and fever 2, 3, 4
  • A thorough medication history should be taken to identify the culprit medication, with lamotrigine being a common cause of SJS/TEN 2, 5, 3, 6, 4
  • Laboratory investigations, such as inflammatory markers and SCORTEN assessment, may be useful in predicting mortality risk and guiding management 4
  • The patient should be managed with immediate discontinuation of lamotrigine, systemic corticosteroids, antihistamines, and supportive care, including topical agents for symptomatic relief 2, 3, 4

Diagnostic Considerations

  • Punch biopsy may be necessary to confirm the diagnosis of SJS/TEN 2
  • The World Health Organization (WHO)-Uppsala Monitoring Centre (UMC) causality assessment scale may be used to identify the probable causative agent 4
  • Genetic testing for HLA subtypes associated with SJS/TEN may be considered, particularly in patients of certain ethnic backgrounds 6

Management and Prevention

  • Early identification and management of SJS/TEN are crucial to improve patient outcomes 2, 3, 4
  • Patients should be educated on the risks of severe cutaneous adverse reactions with lamotrigine, particularly during dose escalation 4
  • Pharmacovigilance and screening for genetic predispositions may help mitigate the risk of drug-induced SJS/TEN 6, 4
  • A strict re-challenge dosing regimen may be considered for patients who require reintroduction of lamotrigine after a previous SJS/TEN reaction 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Lamotrigine-induced Stevens-Johnson syndrome.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2007

Research

Lamotrigine and Stevens-Johnson Syndrome Prevention.

Psychopharmacology bulletin, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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