Lamotrigine-associated SJS/TEN overlap during valproate co-therapy managed with rhTNFR-Fc and therapeutic plasma exchange

Rationale: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, life-threatening severe cutaneous adverse reaction. Evidence for escalation therapy in relapsing disease remains limited. Patient concerns: A 49-year-old man developed fever and a rapidly progressive generalized erythematous maculopapular eruption after lamotrigine was initiated directly at 50 mg once daily during concomitant valproate therapy. Diagnoses: At admission on August 3, 2023, no epidermal detachment was observed and SJS/TEN was not clinically recognized. On August 9 (hospital day 7), epidermal fragility, small blisters, and a positive Nikolsky sign led to recognition of the SJS/TEN spectrum, with detachment below 10%. Severity-of-illness score for toxic epidermal necrolysis was 1 at that time; age > 40 years was the only positive criterion. By day 12, detachment reached approximately 17% of the body surface area, supporting SJS/TEN overlap. The algorithm of drug causality for epidermal necrolysis score for lamotrigine was 5 (probable). Skin biopsy was declined. Interventions: During the initial diagnostic uncertainty on hospital days 1 and 2, lamotrigine was continued; it was discontinued on day 3 when a severe drug eruption was suspected. Intravenous immunoglobulin and intravenous methylprednisolone produced transient improvement. New epidermal detachment prompted methylprednisolone escalation and recombinant human tumor necrosis factor receptor-Fc fusion protein treatment. Relapse during corticosteroid tapering prompted 3 therapeutic plasma exchange sessions while corticosteroid therapy continued. Outcomes: Three therapeutic plasma exchange sessions were subsequently administered with continued corticosteroid therapy, after which the eruption cleared. The patient was discharged on hospital day 33 and had no relapse or reported sequelae at 3-month follow-up. Lessons: This case illustrates the evolution from a severe drug eruption to SJS/TEN overlap, reinforces the importance of reduced lamotrigine starting doses and slow titration during valproate co-therapy, and provides a clinical example of stepwise multidisciplinary rescue management in relapsing disease.