title: Dupuytren's contractures associated with the BRAF inhibitor vemurafenib: a case report.
abstract: BACKGROUND
  Two previous cases of the development of Dupuytren's contractures were reported in association with BRAF inhibitor treatment for BRAF V600E mutation-positive metastatic melanoma and metastatic papillary thyroid carcinoma. We reported on a third case with a slower onset of presentation.
  
  
  METHODS
  A 66-year-old white man was diagnosed with a BRAF V600E mutated metastatic cutaneous melanoma. He was commenced on oral vemurafenib 960 mg twice daily. A marked response was achieved for his metastatic disease. He noticed a change of his hair characteristics and a feeling of "lumps" in both palms by 6 months. By 9 months, classical Dupuytren's contracture was apparent.
  
  
  CONCLUSIONS
  Dupuytren's contracture is not a known side effect of BRAF inhibitor treatment. The timeline for the development of Dupuytren's contracture on BRAF inhibitor treatment is not well defined. Although the etiology of Dupuytren's contracture is unknown, an increase in tumor necrosis factor has been demonstrated to be a possible mechanism. BRAF inhibition has been shown to increase immune reaction in the tumor microenvironment and is associated with high serum tumor necrosis factor level. We propose that an increased level of tumor necrosis factor associated with BRAF inhibition may increase the risk of the development of Dupuytren's contractures.
authors.affiliation: Sandton Oncology Centre, 159 Rivonia Road, Morningside, Sandton, Johannesburg, Gauteng, 2199, South Africa. dr.szewai.chan@gmail.com.
authors.forename: Sze Wai
authors.initials: SW
authors.lastname: Chan
authors.affiliation: Sandton Oncology Centre, 159 Rivonia Road, Morningside, Sandton, Johannesburg, Gauteng, 2199, South Africa. voro@global.co.za.
authors.forename: Daniel Alberto
authors.initials: DA
authors.lastname: Vorobiof
mesh_terms: D000368:Aged; D004387:Dupuytren Contracture / Q000139:chemically induced*; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use; D000077484:Vemurafenib; D000096142:Cutaneous Malignant Melanoma
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf