Cutaneous granulomatous eruption and successful response to potent topical steroids in patients undergoing targeted BRAF inhibitor treatment for metastatic melanoma

JAMA Dermatol. 2014 Mar;150(3):307-11. doi: 10.1001/jamadermatol.2013.7919.

Abstract

Importance: 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.

Observations: 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 and relevance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Aged
  • Aged, 80 and over
  • Biopsy, Needle
  • Clobetasol / therapeutic use
  • Disease Progression
  • Drug Eruptions / drug therapy
  • Drug Eruptions / etiology*
  • Drug Eruptions / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / therapeutic use
  • Immunohistochemistry
  • Lower Extremity
  • Male
  • Melanoma / pathology*
  • Melanoma / surgery
  • Molecular Targeted Therapy / methods
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Oximes / adverse effects
  • Oximes / therapeutic use
  • Proto-Oncogene Proteins B-raf / adverse effects
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Pyridones / adverse effects
  • Pyridones / therapeutic use
  • Pyrimidinones / adverse effects
  • Pyrimidinones / therapeutic use
  • Risk Assessment
  • Sampling Studies
  • Sentinel Lymph Node Biopsy / methods
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / surgery
  • Survival Rate
  • Treatment Outcome

Substances

  • Imidazoles
  • Oximes
  • Pyridones
  • Pyrimidinones
  • trametinib
  • Clobetasol
  • Proto-Oncogene Proteins B-raf
  • dabrafenib