BI02 Toxic epidermal necrolysis in an immunosuppressed patient on tumour necrosis factor-α inhibition: a role for interleukin-6 targeting

Abstract

Immune checkpoint inhibitors (ICIs) are associated with immune-related cutaneous adverse events, which may rarely progress to toxic epidermal necrolysis (TEN). Development of TEN in patients already receiving tumour necrosis factor (TNF)-α inhibition is highly unusual, particularly as infliximab is included in the treatment algorithm for grade 4 immune-mediated cutaneous toxicity. We describe a case of TEN occurring despite established TNF-α blockade and highlight the clinical response to interleukin-6 inhibition. Clinical presentation and drug exposures were reviewed. Treatment followed European Society of Medical Oncology (ESMO) guidance for severe immune-related adverse events. A 60-year-old man with metastatic melanoma treated with ipilimumab had a background of ulcerative colitis managed with long-term azathioprine and infliximab. He developed a persistent low-grade immune-mediated rash following ICI initiation. Piperacillin–tazobactam was prescribed for sepsis of unknown origin, stopped after 6 days, and reintroduced 2 weeks later. Shortly after re-exposure, he developed a rapidly progressive blistering eruption with epidermal detachment and oral and genital mucosal involvement, affecting 47% of his body surface area. Grade 4 immune-related cutaneous toxicity consistent with toxic epidermal necrolysis was diagnosed, necessitating admission to a specialist burns unit. High-dose intravenous methylprednisolone (up to 4 mg kg−1) failed to control disease progression. A single dose of tocilizumab was administered, concurrently for ICI-related pneumonitis, resulting in rapid clinical improvement with arrest of epidermal loss and stabilization of cutaneous disease. TEN was likely triggered by piperacillin–­tazobactam in the context of ICI-mediated immune priming, with its occurrence despite infliximab therapy, recommended by ESMO for grade 4 toxicity, being unusual. Long-term TNF-α inhibition prior to ICI exposure may have altered immune signalling, shifting inflammatory dominance towards alternative cytokine pathways. The rapid response to a single dose of tocilizumab supports an interleukin-6-driven process and consideration of targeted cytokine inhibition in refractory cases, highlighting the need for UK-specific guidance.