Regression of nevi, vitiligo-like depigmentation and halo phenomenon may indicate response to immunotherapy and targeted therapy in melanoma

We present two patients with stage IV melanoma, the first with BRAF wild-type melanoma with multiple visceral metastases treated with immunotherapy (pembrolizumab) and the second with BRAFV600E melanoma with subcutaneous and lymph nodes metastasis treated with BRAF and MEK-inhibitors (dabrafenib/trametinib). Already after the second cycle of immunotherapy, the first patient developed a diffuse regression of nevi, perceptible only with the use of dermoscopy and 3 months later a clinically evident poliosis of the eyebrows. The second patient, treated with dabrafenib/trametinib, developed small areas of leukoderma on his chest and white halos around nevi with a dermoscopic globular or structureless pattern. Both observations are suggestive for an immune reaction against melanocytic cells, which is further supported by the complete response to systemic therapy in both patients. It has been demonstrated that the development of vitiligo-like depigmentation during immunotherapy is associated with a better prognosis; in our patient, the phenomenon of poliosis appeared much later than the dermoscopic presence of regression among his nevi, suggesting that the latter may be an early sign (along with vitiligo-like phenomena) of good response to immunotherapy. On the other hand, the development of halo nevi and leukoderma during treatment with BRAF/MEK-inhibitors, suggests that not only immunotherapy but also targeted therapy may induce an immunologic response against melanoma and nevi, again indicative of a favorable prognosis. More data are needed to confirm these findings; however, they indicate that dermatologists should be involved in the follow-up of patients with melanoma, both in studies and clinical practice.