Can Vemurafenib Induce Vitiligo in Metastatic Melanoma Patients?

Abstract

Melanoma is a mucocutaneous or ocular, sporadic or familial, neoplasm that is associated with a range of genetic factors. Environmental predisposing factors include the exposure to intense sunlight associated with sunburn, as well as a type II phototype. Between 1.5% and 20% of patients with melanoma may have vitiligo-like lesions. From a clinical point of view, the latter may be classified as: a) lesions adjacent to the primary melanoma or metastatic regression; b) development of a melanocytic nevi nevus halo on pre-existing nevi; or c) vitiliginous lesions at sites distant to the melanoma, whether isolated or associated with the ocular findings of Vogt-KoyanagiHarada syndrome. We report this relationship of vitiligo-like lesions in a patient with a metastatic melanoma who attended our Unit for treatment with vemurafenib.A 56 year-old male, with no past medical history, was referred to our outpatient clinic complaining about a cutaneous lesion on his back, which had developed abnormal changes for 2 years. With a clinical diagnosis of typical nevi, the patient had the lesion excised. Histological examination revealed superficial spreading melanoma (SSM), absence of ulceration, a 1.9 mm Breslow Depth Index, and a Clark IV Level with positive sentinel node.An elective lymph node dissection was required, and the presence of micrometastases was observed in three nodes (Stage IIIA). BRAF (Serine Threonine kinase B raf) V600E mutation in primary tumor and lymph node were analyzed, with a positive result in both cases. After evaluation of the case by our Hospital Oncological Committee, treatment with 960 mg Vemurafenib (Roche; Basel, Switzerland) twice daily was started.Eight weeks later, vitiligo-like depigmented macules developed on the patient's neckline (Figure 1). The examination with a Wood's lamp revealed similar lesions on the periocular and perioral area. A skin biopsy was then performed, showing a loss of melanocytes on the basal layer in the excised area.After ten months of treatment, the patient remains tumorfree, according to the imaging tests performed, and is under periodic follow-ups by the Units of Dermatology and Oncology. Ethics committee approved the presentation of this case report with academic and research purpose under signed of the informed consent by our patient.

Panniculitis and vitiligo occurring during BRAF and MEK inhibitors combination in advanced melanoma patients: Potential predictive role of treatment efficacy

“…Dermatologic complications, such as rash, dry skin, photosensitivity, squamo-proliferative growth, hand-foot skin reactions have been frequently observed during the administration of BRAF and MEK inhibitors [6]. More recently, two additional cutaneous side effects have been described: panniculitis and vitiligo-like lesions [7,8,9]. The pathogenesis of these cutaneous reactions is not fully elucidated, although an immune-mediated mechanism is advocated [10].…”

“…Panniculitis during combination therapy was reportedly rare [7, 11]. Vitiligo-like lesions were observed during BRAF inhibitor mono-therapy but they were rarely reported during the combination of BRAF and MEK inhibitors [8,9,12].…”