title: Sarcoidosis in Patients Treated with Vemurafenib for Metastatic Melanoma: A Paradoxical Autoimmune Activation.
abstract: BACKGROUND
  Vemurafenib, a BRAF inhibitor, is a first-line treatment for inoperable melanoma. Sarcoidosis has never been reported in patients on vemurafenib.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  BRAF inhibitors probably have immune system-enhancing effects and should therefore be recognized as potential inducers of sarcoidosis.
authors.affiliation: Service de Dermatologie, Hx00F4;pital Cochin, Assistance Publique - Hx00F4;pitaux de Paris (APHP), Paris, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Lheure
authors.forename: Nora
authors.initials: N
authors.lastname: Kramkimel
authors.forename: Nathalie
authors.initials: N
authors.lastname: Franck
authors.forename: Sara
authors.initials: S
authors.lastname: Laurent-Roussel
authors.forename: Agnès
authors.initials: A
authors.lastname: Carlotti
authors.forename: Astrid
authors.initials: A
authors.lastname: Queant
authors.forename: François
authors.initials: F
authors.lastname: Goldwasser
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupin
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D003875:Drug Eruptions / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012507:Sarcoidosis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000009:adverse effects* / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced*; D000077484:Vemurafenib
chemical_list: D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D007703:Peptidyl-Dipeptidase A