Toxic Epidermal Necrolysis-like Reaction With Severe Satellite Cell Necrosis Associated With Nivolumab in a Patient With Ipilimumab Refractory Metastatic Melanoma

J Immunother. 2016 Apr;39(3):149-52. doi: 10.1097/CJI.0000000000000112.


Nivolumab is a fully humanized monoclonal antibody to PD-1, which has shown improved overall and progression-free survival. Across studies of nivolumab, grade 3 or 4 rash has been noted in <1% of patients. We present a case report of patient with metastatic melanoma treated with nivolumab through expanded access program, who developed toxic epidermal necrolysis. Ours is the first case report, reporting grade 4 skin toxicity associated with nivolumab. A 64-year-old female presented with widespread maculopapular skin rash with bullae and areas of skin detachment after receiving 2 doses of nivolumab for ipilimumab refractory metastatic melanoma (BRAF wild-type). She was initially treated with prednisone, which was soon changed to methyprednisone followed by immunoglobulin with minimal response to the rash. After discussion with Dermatology, she was given cyclosporine and high-dose prednisone with gradual but significant improvement in her rash. Her skin biopsy showed interface dermatitis with a lymphocytic infiltrate in the dermoepidermal junction and apoptotic keratinocytes with focal areas of complete necrosis of the epidermis with minimal infiltrate.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Fatal Outcome
  • Female
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Ipilimumab
  • Melanoma / complications*
  • Melanoma / drug therapy
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Metastasis
  • Nivolumab
  • Skin / pathology
  • Steroids / therapeutic use
  • Stevens-Johnson Syndrome / diagnosis*
  • Stevens-Johnson Syndrome / drug therapy
  • Stevens-Johnson Syndrome / etiology*


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Immunoglobulins, Intravenous
  • Ipilimumab
  • Steroids
  • Nivolumab