Sarcoidosis in Patients Treated with Vemurafenib for Metastatic Melanoma: A Paradoxical Autoimmune Activation

Dermatology. 2015;231(4):378-84. doi: 10.1159/000439400. Epub 2015 Oct 10.

Abstract

Background: Vemurafenib, a BRAF inhibitor, is a first-line treatment for inoperable melanoma. Sarcoidosis has never been reported in patients on vemurafenib.

Objectives: We describe 5 cases of sarcoidosis in patients treated with vemurafenib.

Methods: Seventy patients receiving vemurafenib for a BRAF-mutated inoperable stage III or IV melanoma were treated in our centre.

Results: Five patients (7.1%) developed sarcoidosis or a sarcoid-like reaction on vemurafenib; 4 patients had cutaneous signs and 3 had extracutaneous disorders (bilateral hilar lymph nodes, uveitis). Histological analysis of skin lesions revealed epithelioid granulomas without necrosis, consistent with sarcoidosis. Angiotensin-converting enzyme levels were high in 2 patients. Cutaneous and ophthalmological lesions rapidly disappeared on topical corticosteroid treatment without the cessation of vemurafenib treatment. Complete remission of melanoma was observed in 3 patients and partial remission was observed in another.

Conclusion: BRAF inhibitors probably have immune system-enhancing effects and should therefore be recognized as potential inducers of sarcoidosis.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / immunology
  • Autoimmunity / drug effects*
  • Drug Eruptions / drug therapy
  • Drug Eruptions / etiology
  • Drug Eruptions / pathology
  • Female
  • Humans
  • Indoles / adverse effects*
  • Indoles / immunology
  • Male
  • Melanoma / drug therapy*
  • Melanoma / secondary
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood
  • Sarcoidosis / chemically induced*
  • Sarcoidosis / drug therapy
  • Sarcoidosis / pathology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Sulfonamides / adverse effects*
  • Sulfonamides / immunology
  • Uveitis / chemically induced*
  • Vemurafenib

Substances

  • Adrenal Cortex Hormones
  • Antineoplastic Agents
  • Indoles
  • Sulfonamides
  • Vemurafenib
  • Peptidyl-Dipeptidase A