What is the diagnosis of a 2-5 mm blister in the mouth potentially caused by Lamotrigine?

Lamotrigine-Induced Oral Mucosal Hypersensitivity Reaction

A 2-5 mm blister in the mouth in a patient taking lamotrigine represents a drug-induced hypersensitivity reaction and requires immediate discontinuation of lamotrigine to prevent progression to Stevens-Johnson syndrome or toxic epidermal necrolysis.

Clinical Diagnosis

This presentation is consistent with lamotrigine-associated mucocutaneous hypersensitivity reaction, which manifests as:

• Oral mucosal lesions including blisters, ulcers, or erosions 1
• Early warning sign of potentially life-threatening severe cutaneous adverse reactions 1
• Can progress to Stevens-Johnson syndrome (SJS) with fever, generalized rash, and multi-site mucosal involvement 1

Immediate Management

Discontinue lamotrigine immediately upon appearance of any oral lesions or rash 1, 2:

• The incidence of allergic skin reactions in adults is 5.1%, with 3.9% requiring drug withdrawal 2
• Stevens-Johnson syndrome occurs in approximately 0.4% of patients 2
• Oral ulcers can appear weeks after initiation, particularly following changes in concomitant medications 3

Risk Factors Present

The following factors increase risk of mucocutaneous reactions:

• Concomitant valproic acid use increases risk to 9.1% versus 2.8% with enzyme-inducing medications 2
• Rapid dose escalation or higher initial doses 2
• Recent discontinuation of enzyme-inducing drugs (carbamazepine, oxcarbazepine) can cause delayed lamotrigine toxicity manifesting as oral ulcers 22-39 days later 3

Critical Pitfalls to Avoid

Do not continue lamotrigine even if lesions appear minor:

• Polytherapy with antiepileptic drugs increases adverse effect frequency 1
• Treatment must be discontinued if any rash or mucosal lesion appears 1
• Oral ulcers may indicate rising lamotrigine levels from drug interactions 3

Monitoring for Progression

Assess for features of Stevens-Johnson syndrome:

• Fever and systemic symptoms 1
• Genital mucosal involvement 1
• Generalized cutaneous rash 1
• Constitutional symptoms (weakness, malaise) 1

If SJS is suspected, hospitalize immediately for intensive supportive care including intravenous fluids, antibacterial therapy, and corticosteroids 1.

Rechallenge Considerations

Lamotrigine is contraindicated in patients with previous lamotrigine-induced rash 4. However, in select cases with mild reactions:

• Three patients successfully continued lamotrigine with anti-allergic medications 2
• Three patients tolerated rechallenge at ≤12.5 mg/day without recurrence 2
• This approach carries significant risk and should only be attempted under close supervision 2