INTRODUCTION
Nivolumab is a human immunoglobulin monoclonal antibody IgG4 that binds to and thus blocks the programmed death (PD-1) receptor, and ipilimumab is a monoclonal antibody against CTL antigen 4 (CTLA-4). The medications have been approved for the treatment of metastatic melanoma. The development of immune checkpoint inhibitors (ICI) such as nivolumab and ipilimumab have improved survival outcomes for malignancies, but they are associated with higher risk for cutaneous toxicities.1,2 Cutaneous immunerelated adverse events (irAEs) vary from maculopapular rash to Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).
SJS and TEN are rare but life-threatening delayed hypersensitivity reactions due to T-lymphocyte cytotoxicity resulting in apoptosis of epithelial keratinocytes.3 Patients classically present with maculopapular rash that rapidly progresses to blister formation and epidermal desquamation with positive Nikolsky sign. The amount of body surface area involvement differs for SJS and TEN. SJS involves less than 10% of body surface area (BSA), whereas TEN involves more than 30% BSA. Mucous membrane manifestations affecting ocular, respiratory, or genital areas as well as systemic symptoms are common.
SJS and TEN are rare but life-threatening delayed hypersensitivity reactions due to T-lymphocyte cytotoxicity resulting in apoptosis of epithelial keratinocytes.3 Patients classically present with maculopapular rash that rapidly progresses to blister formation and epidermal desquamation with positive Nikolsky sign. The amount of body surface area involvement differs for SJS and TEN. SJS involves less than 10% of body surface area (BSA), whereas TEN involves more than 30% BSA. Mucous membrane manifestations affecting ocular, respiratory, or genital areas as well as systemic symptoms are common.
CASE 1
We describe the case of a 62-year-old Caucasian male with stage 4 metastatic melanoma with brain metastasis who was directly transferred to the intensive care unit from an outside hospital for management of acute widespread rash on day 17 after the last cycle of ipilimumab and nivolumab. Of note, he developed eczema on his limb after the first cycle approximately 5 months prior, which resolved with corticosteroids. On initial examination, the patient was hemodynamically stable and had diffuse erythema and desquamation on the neck, chest, back, abdomen, upper extremities, and face with periocular hemorrhagic crusting. Scattered bullae and erosions were noted on abdomen, distal upper extremities, proximal thighs, genitalia, and distal lower extremities with positive Nikolsky sign. There were fissures of the lips without oral cavity involvement. Labs were significant for elevated blood urea nitrogen. The diagnosis of toxic epidermal necrolysis was supported by a skin biopsy of the right hand demonstrating full thickness necrosis and lichenoid interface dermatitis with frequent necrotic keratinocytes. A single dose of Etanercept was administered but repeat dosing was not possible due to MRSA bacteremia. The
