A blistering eruption after starting a new anticonvulsant
A 34-year-old woman with epilepsy, recently started on lamotrigine 25 mg daily and titrated to 100 mg daily over 10 days, presents with a 4-day history of fever (38.9 °C), sore mouth and eyes, and a widespread painful eruption. She has dusky erythematous macules coalescing into targetoid lesions over the trunk and face, with Nikolsky sign positive in areas of erythema. Mucosal examination shows haemorrhagic crusting of the lips, erosions on the buccal mucosa, and conjunctival injection with pseudomembrane formation. Body surface area of epidermal detachment is estimated at 12%. She is tachycardic at 118 bpm and her urine output has fallen. She is on no other new medications and has no prior drug allergies.
1. How do you distinguish Stevens–Johnson syndrome from toxic epidermal necrolysis in this patient, and what does the distinction change in management?
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Classification is by the percentage of body surface area with epidermal detachment (blistering plus Nikolsky-positive skin that peels with lateral pressure), not by the total area of erythema:
- SJS: <10% detachment.
- SJS/TEN overlap: 10–30%.
- TEN: >30%.
At an estimated 12%, this patient falls into the SJS/TEN overlap category. The distinction matters for prognosis (mortality rises steeply with increasing detachment - roughly 10% for SJS, 30% for overlap, and up to 50% for TEN), for triage (TEN and overlap warrant burn-unit or ICU-level care), and for the intensity of supportive management. It does not change the two immediate priorities, which are identical: stop the culprit drug and provide aggressive supportive care.
Immediate actions
- Stop lamotrigine now. Lamotrigine is a well-recognised cause, especially with rapid titration; do not restart it or any aromatic anticonvulsant (carbamazepine, phenytoin, phenobarbital, oxcarbazepine) because of cross-reactivity.
- Fluid and electrolyte resuscitation guided by urine output and insensible losses from denuded skin.
- Wound care with non-adherent dressings; avoid silver sulfadiazine if there is sulfonamide concern; maintain temperature and analgesia.
- Ophthalmology review urgently - daily examination, topical steroids, and symblepharon prevention; this is the highest-yield intervention for long-term morbidity.
- Mucosal care - oral rinses, analgesia, and consideration of a urinary catheter if genital erosions impair voiding.
- SCORTEN calculation (age, malignancy, tachycardia, initial detachment, urea, bicarbonate, glucose) to guide prognosis and level of care.
- Infection surveillance with cultures, but not routine prophylactic systemic antibiotics.
- Anticonvulsant replacement - liaise with neurology; consider a non-aromatic agent such as levetiracetam or valproate.
- Specific immunomodulation - evidence is limited; IVIG and cyclosporine are used in some centres, and short-course systemic corticosteroids remain controversial. The decision should be made by a multidisciplinary team, and the strongest evidence-based interventions remain withdrawal of the drug and supportive care.
2. The patient asks whether she will have long-term eye and skin problems, and her family asks about 'genetic testing' for drug allergy. How do you counsel them and what follow-up do you arrange?
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Long-term sequelae counselling
- Ocular: Conjunctival scarring, symblepharon, dry eye, trichiasis, corneal neovascularisation, and visual loss are the most feared chronic complications. Risk is reduced by early and sustained ophthalmological involvement. Arrange ophthalmology follow-up for at least 12 months, with lubricants and monitoring for lid and conjunctival scarring.
- Cutaneous: Post-inflammatory hyperpigmentation is common and expected, particularly in darker skin. Scarring is uncommon but can occur. Nail dystrophy or shedding may follow. Warn about photosensitivity and the need for sun protection.
- Mucosal: Vaginal and oral synechiae can occur; genital examination and, where relevant, gynaecology referral are appropriate.
- Psychological: Body image and anxiety are common; offer support.
Genetic counselling and 'testing'
- There is no routine clinical genetic test that predicts SJS/TEN for lamotrigine in this patient's context. HLA-B*15:02 is associated with carbamazepine-induced SJS/TEN in certain Southeast Asian populations and is a licensed pre-prescription test in some settings; HLA-B*57:01 predicts abacavir hypersensitivity. Neither applies to lamotrigine.
- Explain that the most important preventive measure is documentation of the allergy and avoidance of aromatic anticonvulsants because of cross-reactivity. Provide a written allergy card and advise her to tell every prescriber and pharmacist.
- If future anticonvulsant therapy is needed, involve neurology and consider agents with low risk (e.g., levetiracetam, valproate, gabapentin) with careful counselling.
Follow-up plan
- Dermatology clinic at 2 weeks, then 3 months, then annually as needed.
- Ophthalmology at 1 week, 1 month, 3 months, and 12 months.
- Monitor for late ocular and mucosal complications.
- Document the reaction in the medical record with the specific drug and reaction type, and notify the patient's epilepsy team and primary care physician.