What should be done for a patient taking lamotrigine (antiepileptic medication) who develops a burning sensation in the mouth, conjunctivitis, a blister on the roof of the mouth, and fever?

Immediate Discontinuation of Lamotrigine and Emergency Evaluation Required

This patient is presenting with classic features of Stevens-Johnson Syndrome (SJS) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) secondary to lamotrigine, which requires immediate drug cessation and urgent medical intervention. 1, 2

Critical Recognition

The constellation of symptoms—burning mouth sensation, conjunctivitis, oral blisters, and fever—represents a severe cutaneous adverse reaction (SCAR) to lamotrigine. These are hallmark features of SJS/toxic epidermal necrolysis (TEN), which carries significant mortality risk if not managed promptly. 1, 2

• Mucosal involvement (oral blisters, conjunctivitis) distinguishes SJS from simple drug eruptions and indicates severe disease 1
• Fever combined with mucocutaneous lesions suggests systemic inflammatory response 2, 3
• Timing typically occurs 2-6 weeks after drug initiation or dose escalation 1, 3

Immediate Management Steps

1. Stop Lamotrigine Immediately

Discontinue lamotrigine permanently—do not attempt rechallenge at any dose or rate. 1, 2, 4

• Even after symptom resolution, rechallenge is contraindicated as this represents a severe systemic hypersensitivity reaction 5
• Document this as a drug allergy in all medical records to prevent future re-exposure 6

2. Emergency Assessment

Evaluate for progression to life-threatening complications:

• Assess body surface area involvement: >10% suggests SJS; >30% indicates TEN 1
• Check vital signs: hypotension and tachycardia indicate systemic involvement 6, 5
• Evaluate respiratory status: dyspnea or stridor suggests airway compromise requiring immediate intervention 6
• Calculate SCORTEN: predicts mortality risk in SJS/TEN based on age, malignancy, heart rate, body surface area involvement, serum urea, glucose, and bicarbonate 1

3. Acute Pharmacologic Treatment

Administer combination therapy with antihistamines and corticosteroids for optimal symptom control: 6, 5

• Diphenhydramine 25-50 mg IV for immediate symptomatic management 6, 5
• Methylprednisolone 100 mg IV for aggressive control of the allergic reaction 6, 5, 2
• Continue antihistamines every 6 hours for 24-48 hours until symptoms resolve 6
• Implement corticosteroid taper over several days for moderate to severe reactions 6, 2

Critical pitfall: Never use corticosteroids alone without antihistamines—combination therapy is essential. 6, 5

4. Supportive Care

• Intravenous fluids for hydration and hemodynamic support 2
• Antibacterial therapy to prevent secondary infection of denuded skin 2
• Cool compresses to affected areas for symptomatic relief 6
• Ophthalmology consultation for conjunctival involvement to prevent permanent ocular sequelae 1

5. Laboratory Monitoring

Obtain baseline and serial measurements:

• Complete blood count: assess for eosinophilia (suggests DRESS syndrome) 3, 4
• Liver function tests: hepatitis is common in hypersensitivity syndrome and can progress to fulminant hepatic failure 3, 4
• Renal function: acute renal failure may develop 3
• Inflammatory markers: elevated in systemic reactions 1

Hospitalization Criteria

Admit to intensive care unit if: 2

• Body surface area involvement >10% 1
• Hemodynamic instability (hypotension, tachycardia) 6
• Respiratory compromise 6
• Evidence of hepatic or renal dysfunction 3, 4
• SCORTEN score indicating high mortality risk 1

Ongoing Monitoring

• Observe for 30-60 minutes after initiating treatment to ensure reaction is not progressing 6
• Monitor for delayed reactions over 24-48 hours, as some hypersensitivity reactions have delayed components 6
• Watch for organ involvement: hepatitis, nephritis, or hematologic abnormalities may develop days after initial presentation 3, 4
• Psychiatric symptoms may emerge unexpectedly after severe cutaneous reactions 7

Alternative Seizure Management

If lamotrigine was prescribed for epilepsy:

• Levetiracetam is preferred as first-line alternative due to efficacy and good tolerability profile 8
• Avoid enzyme-inducing anticonvulsants (phenytoin, carbamazepine, phenobarbital) which also carry high risk of severe cutaneous reactions 8
• Valproic acid should be used cautiously, as concomitant use with lamotrigine increases risk of SJS/DRESS 2, 7

Key Clinical Pitfalls

• Delaying treatment: Hypersensitivity reactions can rapidly progress to anaphylaxis with cardiovascular collapse 6, 5
• Attempting dose reduction or rechallenge: This represents a severe systemic reaction requiring permanent discontinuation 5
• Misdiagnosing as viral infection: The clinical similarity to infectious illnesses may delay recognition 3
• Continuing polytherapy: Multiple antiepileptic drugs increase frequency of adverse effects 2