Electrochemotherapy in the treatment of melanoma skin metastases: a report on 31 cases.

INTRODUCTION AND OBJECTIVES: Electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. MATERIAL AND METHODS: We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). RESULTS: Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. CONCLUSIONS: Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions.

Halo naevi with associated vitiligo-like depigmentations: pathogenetic hypothesis.

BACKGROUND: In analogy with melanoma-associated leucoderma, halo naevi may trigger in some patients the development of additional depigmentations which are in distribution, extent and prognosis not in accordance with classic vitiligo. OBJECTIVE: The aim of this study was to support the hypothesis that in a subset of halo naevi patients vitiligo-like lesions develop directly linked to the halo phenomenon. METHODS: Forty-one patients with halo naevi were examined for the development of depigmentations not corresponding to typical vitiligo lesions. RESULTS: We identified a subset of five halo naevi patients with additional subtle depigmentations. After the occurrence of multiple halo naevi, they developed leucoderma that showed a different disease pattern than vitiligo (variable asymmetric distribution, limited extent and lack of progression). Moreover, the characteristics of these halo naevi patients with associated leucoderma were different from classic vitiligo patients (high number of halo naevi, absence of family history for vitiligo and absence of autoimmune diseases) and the timing of occurrence of the leucoderma suggested a direct relation with the halo phenomenon. CONCLUSIONS: In this article, we describe in a limited subset of patients with multiple halo naevi discrete depigmentations at distance from halo naevi which may result from a temporary autoimmune process directly linked to the halo phenomenon. This finding illustrates the collateral damage resulting from skin immunosurveillance and may have clinical consequences as the evolution pattern in this subset of patients is less progressive compared with vitiligo. We present clinical data that support this hypothesis and suggest to call it 'halo naevi-associated leucoderma'.

Halo nevi in Turner syndrome.

Turner syndrome is a genetic disorder characterized by an abnormal or missing X-chromosome. Rarely reported cutaneous manifestations in Turner syndrome include hemangiomas, angiokeratomas, hirsutism, and halo nevi. A recent study demonstrated an increased prevalence of halo nevi in Turner syndrome when compared to vitiligo. We present a case of halo nevi with multiple melanocytic nevi in an 11-year-old patient with Turner syndrome on growth hormone.

"Halo nevi" and UV radiation.

Halo nevi, also termed Sutton nevi, are defined as benign melanocytic nevi that are surrounded by an area of depigmentation resembling a halo. Halo nevi are common in children and young adults, with a mean age at onset of 15 years. The incidence in the population is estimated to be approximately 1%. Affected individuals frequently have multiple lesions which are usually localized on the back. A familial tendency for halo nevi has been reported. The etiology of halo nevi is unknown. It is an autoimmune response and T lymphocytes are considered to play a key role in the progressive destruction of nevus cells. Halo nevi may be associated with autoimmune disorders such as vitiligo, Hashimoto thyroiditis, alopecia areata, celiac disease, atopic dermatitis and others. It has been proved that halo nevi are detected after an intense sun exposure especially after sunburns. The etiology of halo nevi, association with malignant melanoma and the role of sun exposure in the development of halo nevi are discussed.

The color of skin: white diseases of the skin, nails, and mucosa.

White diseases are a heterogenous group characterized by hypopigmentation or depigmentation. Skin and eye color are determined by the number and size of melanosomes present. Melanin is produced by melanosomes in the melanocytes present within the epidermis of the skin, uvea, and retinal pigmented epithelium (RPE). Conditions altering the number of melanocytes or concentration of melanin result in a lack of pigmentation, appearing as "white diseases" ranging from the well-known albinism and vitiligo to more esoteric white hand syndrome and Degos disease.

Type I interferon signature in the initiation of the immune response in vitiligo.

Immune-mediated responses are consistently observed in progressing vitiligo at the edge of depigmenting patches. Besides the role of the adaptive immune system, the profile of the innate immune response is now at the center of the stage. We report that plasmacytoid dendritic cells (pDC), which are the major interferon (IFN)-alpha-producing cells, are part of the infiltrate of progressive vitiligo with local production of MxA (a protein induced by IFNα). MxA was associated with expression of the type I IFN-inducible ligand CXCL9 and correlated with the recruitment of CXCR3(+) immune cells. Interestingly, strong MxA expression was observed in perilesional skin in close apposition to remaining melanocytes, surrounded by a prominent T-cell infiltrate. In contrast, MxA was not detectable in lesional skin, suggesting that IFN-α production is an early event in the progression of the disease. Our data highlight a new innate immune pathway leading to progression of vitiligo.

Vitiligo in an Italian outpatient center: a clinical and serologic study of 204 patients in Tuscany.

BACKGROUND: Vitiligo is a depigmentation disorder resulting from destruction of cutaneous melanocytes that affects 0.1-2% of the world's population, irrespective of sex and race. OBJECTIVE: To investigate the clinical and immunopathologic characteristics of a series of Italian vitiligo patients. METHODS: We examined clinical and immunopathologic data of 204 patients affected by vitiligo at a university-based dermatology outpatient hospital (second clinic) between January 1998 and March 2008. In particular, the clinical-epidemiologic characteristics of our patients, serologic parameters suggestive of immune/autoimmune activity (autoantibodies, immune complexes, complement, immunoglobulins), and the association between vitiligo and HLAs were investigated. RESULTS: Upon comparison of our results with control and literature values, the following aspects appeared to be in complete agreement: the frequency of clinical subtypes of vitiligo, an earlier onset of segmental compared with non-segmental vitiligo, the association of familial vitiligo with other autoimmune diseases, the greater association of non-segmental vitiligo than segmental vitiligo with autoimmune diseases, and some features of pediatric vitiligo. Other data were partially consistent with the literature, such as the association between vitiligo and autoimmune diseases/autoantibody activities, and the association between vitiligo and HLAs. Finally, a portion of our data did not concur with the literature, including the sex distribution and mean age of onset, the lack of association between halo nevi and autoimmune diseases, and some aspects of pediatric vitiligo. CONCLUSIONS: This study provides novel information regarding clinical features and serologic parameters in different subgroups of vitiligo, namely a significant association between active vitiligo and autoantibody activities, and significant clinical differences (i.e. activity of disease, age of onset, and coexistence of other autoimmune diseases) between vitiligo associated with autoantibodies and vitiligo negative for autoantibodies.