What are the risks and management strategies for Stevens-Johnson syndrome in patients taking Lamictal (lamotrigine)?

Lamotrigine-Associated Stevens-Johnson Syndrome: Risk and Management

Critical First Action

Discontinue lamotrigine immediately upon any suspicion of Stevens-Johnson syndrome, as this single intervention is the most critical factor determining survival. 1, 2, 3

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Risk Factors and Prevention

Incidence and High-Risk Scenarios

• Lamotrigine is one of the most common antiepileptic drugs causing SJS/TEN, with cutaneous reactions occurring in 3-10% of patients 4, 5
• Concomitant use with valproic acid dramatically increases SJS risk and should be avoided whenever possible 4, 5, 6
• Polytherapy with multiple antiepileptic drugs increases adverse effect frequency 4

Genetic Susceptibility

• HLA-B*15:02 genotype in Chinese and Southeast Asian populations increases susceptibility to lamotrigine-induced SJS 7
• Japanese patients with HLA-B31:01 and Korean patients with HLA-B44:03 are at increased risk 7
• The FDA recommends HLA subtype testing prior to starting lamotrigine in at-risk populations 7

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Recognition and Diagnosis

Clinical Presentation

• Prodromal symptoms include fever, painful rash, and mucosal involvement (oral, ocular, genital) 3, 4
• Look for target lesions, purpuric macules, blisters, and areas of epidermal detachment 3
• Document the exact date of rash onset and progression pattern 3

Diagnostic Workup

• Obtain skin biopsy showing confluent epidermal necrosis with subepidermal vesicle formation 8, 3
• Calculate SCORTEN within 24 hours to predict mortality risk (scores 0-7) 1, 2, 3
• Laboratory tests: CBC, CRP, electrolytes, liver function, coagulation studies, glucose, magnesium, phosphate 2, 3

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Immediate Management Algorithm

Step 1: Drug Discontinuation and Transfer

• Stop lamotrigine immediately - this is non-negotiable 1, 2, 3
• Document all medications taken in the previous 2 months with exact start dates 2, 3
• Transfer patients with >10% body surface area involvement to a specialized burn unit or ICU within hours, not days 1, 2, 3

Step 2: Supportive Care Framework

Fluid Management:

• Establish IV access and initiate fluid resuscitation guided by urine output 2, 3
• Avoid overaggressive fluids that cause pulmonary, cutaneous, and intestinal edema 1, 3
• Monitor vital signs, urine output, and electrolytes regularly 1, 2

Wound Care:

• Handle skin gently to minimize shearing forces and further detachment 1, 3
• Irrigate wounds with warmed sterile water, saline, or chlorhexidine (1:5000) 1, 3
• Apply greasy emollient (50% white soft paraffin with 50% liquid paraffin) over entire epidermis 1, 3
• Use nonadherent dressings (Mepitel or Telfa) on denuded dermis with secondary foam dressings 1, 3

Infection Prevention:

• Do NOT use prophylactic antibiotics - they increase colonization with resistant organisms, particularly Candida 1, 2, 3
• Monitor for clinical signs of infection (confusion, hypotension, reduced urine output, decreased oxygen saturation) 3
• Institute targeted antimicrobial therapy only when infection is clinically evident 1, 3

Step 3: Systemic Immunomodulation (Within 72 Hours)

First-Line Options:

• IV methylprednisolone 0.5-1 mg/kg if started within 72 hours of onset, then convert to oral with tapering over at least 4 weeks 1, 2
• OR Cyclosporine 3 mg/kg daily for 10 days, tapered over 1 month - has shown reduced mortality compared to predicted rates 1, 2

Step 4: Mucosal Management

Ophthalmology (MANDATORY within 24 hours):

• Apply preservative-free lubricant eye drops every 2 hours throughout acute illness 1, 2
• Daily examination by ophthalmologist to remove inflammatory debris and break down conjunctival adhesions 1, 2
• Consider amniotic membrane transplantation for better visual outcomes 1
• Use topical antibiotics when corneal fluorescein staining or ulceration present 8, 1

Oral Care:

• Apply white soft paraffin ointment to lips immediately, then every 2 hours 8, 1
• Benzydamine hydrochloride oral rinse every 3 hours, particularly before eating 8, 1
• Antiseptic oral rinse (1.5% hydrogen peroxide or 0.2% chlorhexidine) twice daily 8, 1
• Viscous lidocaine 2% or cocaine mouthwashes 2-5% for severe oral discomfort 8, 1

Urogenital Care:

• Apply white soft paraffin ointment to urogenital skin and mucosae every 4 hours 1
• Consider vaginal dilators or tampons wrapped in Mepitel to prevent vaginal synechiae 1

Step 5: Nutritional Support

• Provide continuous enteral nutrition: 20-25 kcal/kg daily during catabolic phase, 25-30 kcal/kg during recovery 1, 2
• Use nasogastric feeding when oral intake precluded by buccal mucositis 1

Step 6: Pain Management

• Adequate background simple analgesia with opioid infusions for breakthrough pain 1, 3
• Consider patient-controlled analgesia where appropriate 3
• Consider sedation or general anesthesia for dressing changes 3

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Environmental and Adjunctive Measures

• Barrier nursing in temperature-controlled room (25-28°C) on pressure-relieving mattress 1, 3
• Low molecular weight heparin for VTE prophylaxis in immobile patients 2
• Proton pump inhibitor if enteral nutrition cannot be established 2

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Multidisciplinary Team Coordination

• Lead by dermatologist or plastic surgeon with skin failure expertise 2, 3
• Include intensive care physicians, ophthalmologists, specialist skincare nurses 1, 2, 3
• Additional specialists as needed: respiratory medicine, gastroenterology, gynecology, urology, oral medicine, microbiology, pain team, dietetics, physiotherapy, pharmacy 3

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Discharge Planning and Long-Term Follow-Up

• Provide written documentation that patient must permanently avoid lamotrigine and all potentially cross-reactive medications 1, 2
• Encourage MedicAlert bracelet with lamotrigine listed 1, 2
• Document drug allergy in all medical records and inform all healthcare providers 1, 2
• Report adverse drug reaction to pharmacovigilance authorities 1, 2
• Arrange dermatology follow-up within weeks of discharge 2
• Schedule ophthalmology follow-up to monitor for chronic ocular complications 2
• Inform patients about potential fatigue and lethargy for several weeks requiring convalescence 1

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Special Considerations for Pediatric Patients

• Up to 50% of pediatric SJS/TEN cases are infection-related (HSV, Mycoplasma pneumoniae) 8
• Test for infective triggers and consult infectious disease team in all pediatric cases 8, 3
• Manage in age-appropriate specialist units with pediatric intensivists 8, 3

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Critical Pitfalls to Avoid

• Delayed transfer to specialized care significantly increases mortality - transfer within hours, not days 1, 2, 3
• Failure to involve ophthalmology within 24 hours leads to permanent visual impairment 1, 2
• Indiscriminate prophylactic antibiotics increase resistant organism colonization 1, 2, 3
• Overaggressive fluid resuscitation causes pulmonary and intestinal edema 1, 3
• Continuing lamotrigine or delaying discontinuation worsens condition and increases mortality 1
• Overlooking valproic acid co-administration as a major risk factor 4, 5, 6

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Regarding Lamotrigine Re-challenge

• SJS is not an absolute contraindication to lamotrigine reintroduction 7
• Prime re-challenge candidates: mild initial rash that occurred >4 weeks prior 7
• Manufacturers have developed strict re-challenge dosing regimens 7
• However, given the life-threatening nature of SJS/TEN, re-challenge should only be attempted under exceptional circumstances with specialist supervision and informed consent