Abstract

Severe cutaneous manifestations are commonly seen in drug hypersensitivity reactions which can present as pustular and bullous skin eruption. This can further progress and deteriorate into Steven- Johnsons syndrome or Toxic Epidermal Necrolysis syndrome (TENs) which require hospitalization. We report the case of a woman in her early fifties with metastatic melanoma who developed SJS and TENs 11 days following administration of Dabrafenib and Trametinib. Interestingly our patient had previously undergone 4 cycles of dual immunotherapy followed by single infusion of Nivolumab prior to this. Nivolumab had to be stopped due to grade 3 toxicity (hepatitis and hypoadrenalism). We believe this primed her immune system for potentially any hypersensitive reaction, in addition to attacking cancerous cells. Dabrafenib and Trametinib was commenced 18 days after discontinuation of immunotherapy. Our patient developed symptoms consistent with SJS and TEN, which was later confirmed on skin biopsy. She recovered well and following ITU admission and step down to oncology inpatient ward was discharged home. To our knowledge there are no links between Dabrafenib and SJS and TEN, although this has been reported in other BRAF inhibitors such as Vemurafenib. We changed her treatment to a third type of BRAF inhibitor, Encorafenib and Binimetinib (MEKtovi) which resulted in good Complete response control of her Melanoma for 6 months, to date.

Keywords: Skin side effects with Melanoma treatment; Dabrafenib and trametinib; Steven-Johnsons Syndrome (SJS); Toxic Epidermal Necrolysis syndrome (TENs); Encorafenib and binimetinib; Vemurafenib; Complete response; Prior immunotherapy before BRAF inhibitors

Abbreviations: TEN: Toxic Epidermal Necrolysis; SJS: Steven-Johnsons Syndrome; (BRAF/MEKi): BRAF and MEK inhibitor biologic tablets