title: Cutaneous granulomatous eruption and successful response to potent topical steroids in patients undergoing targeted BRAF inhibitor treatment for metastatic melanoma.
abstract: OBJECTIVE
  Targeted BRAF inhibitor therapy (vemurafenib, dabrafenib) is an effective, novel treatment for patients with metastatic melanoma with the V600E BRAF mutation. This therapy is associated with squamous cell carcinomas and keratoacanthomas. Granulomatous eruptions have not been previously reported.
  
  
  METHODS
  Two patients with melanoma developed cutaneous granulomatous eruptions during targeted BRAF inhibitor therapy. In case 1, after 2 months of treatment with dabrafenib and trametinib (MEK inhibitor), a papular eruption concerning for progression of disease prompted cessation of treatment. After the histopathologic diagnosis of granulomas, the patient was treated with clobetasol ointment with resolution within days and resumption of therapy. In case 2, after 5 months of vemurafenib treatment, the patient developed a granulomatous eruption, which resolved 3 weeks after cessation of therapy.
  
  
  CONCLUSIONS
  We report 2 cases of cutaneous granulomatous eruptions on treatment with targeted BRAF inhibitors, a previously unreported association. Although additional investigations are necessary to better elucidate the pathogenic mechanisms, our report includes a treatment plan that prevents unnecessary discontinuation of therapy. Given the Food and Drug Administration approval of vemurafenib for metastatic melanoma, clinicians should be aware of this possible cutaneous reaction and treatment option to optimize patient management.
authors.affiliation: University of Illinois College of Medicine, Chicago.
authors.forename: June J
authors.initials: JJ
authors.lastname: Park
authors.affiliation: Department of Dermatology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Hawryluk
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Tahan
authors.affiliation: Massachusetts General Hospital Cancer Center, Division of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: Keith
authors.initials: K
authors.lastname: Flaherty
authors.affiliation: Pigmented Lesion Clinic, Department of Dermatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts6Cutaneous Oncology Program, Department of Dermatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Bo.
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Kim
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D002990:Clobetasol / Q000627:therapeutic use; D018450:Disease Progression; D003875:Drug Eruptions / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D007150:Immunohistochemistry; D035002:Lower Extremity; D008297:Male; D008545:Melanoma / Q000473:pathology* / Q000601:surgery; D058990:Molecular Targeted Therapy / Q000379:methods; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D010091:Oximes / Q000009:adverse effects / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use; D011744:Pyrimidinones / Q000009:adverse effects / Q000627:therapeutic use; D018570:Risk Assessment; D012494:Sampling Studies; D021701:Sentinel Lymph Node Biopsy / Q000379:methods; D012878:Skin Neoplasms / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D007093:Imidazoles; D010091:Oximes; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; D002990:Clobetasol; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib