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During the last decade, the advent of modern sequencing methods (next generation techniques, NGS) has helped describe the composition of the human gut microbiome, enabling us to understand the main characteristics of a healthy gut microbiome and, conversely, the magnitude of its disease-related changes. This new knowledge has revealed that healthy gut microbiota allow the maintenance of several crucial physiological functions, such as the ability to regulate the innate and adaptive immune systems. Increasing evidence has pointed out a condition of dysbiosis in several autoimmune/immune mediated dermatological conditions and specific gut microbial signatures have also been reported to correlate with clinical and prognostic parameters of such diseases. Based on a literature search of relevant published articles, this review debates the current knowledge and the possible pathogenic implications of bacterial gut microbiota composition assessed through NGS techniques in systemic lupus erythematosus, atopic dermatitis, psoriasis, and alopecia areata. Evidence of a potential role of specific gut microbiota signatures in modulating the clinical course of such diseases and their main comorbidities has been also reviewed., Plain Language Summary The gut microbiota is defined as the collection of microbes (bacteria, fungi, archaea, and viruses) inhabiting the human gut. If healthy, it allows the maintenance of several crucial physiological functions, such as the ability to regulate the immune system. Accordingly, increasing evidence has pointed out a condition of imbalance in the gut microbial community (dysbiosis) in several autoimmune/immune mediated dermatological conditions. Specific gut dysbioses have also been reported to correlate with clinical and prognostic parameters of such diseases. In this review, the current knowledge and the possible pathogenic implications of bacterial gut microbiota composition assessed through advanced techniques in systemic lupus erythematosus, atopic dermatitis, psoriasis, and alopecia areata are discussed. Furthermore, evidence of a potential role of specific gut microbiota signatures affecting the clinical course and main associated diseases is also reviewed. In this scenario, an increased knowledge of gut microbiota composition and functions in autoimmune/immune mediated dermatological diseases might suggest additional treatments besides conventional therapies, and predict clinical evolution and comorbidities association.

Abstract. Reduced serum 25(OH)D levels have been largely reported in vitiligo, which is an autoimmune skin disorder characterized by the appearance of achromic macules. Since vitamin D can positively modulate immune function and stimulate melanogenesis in vitro, a possible role of sufficient vitamin D levels in promoting the stability of the disease and repigmentation process might be hypothesized in vitiligo. Hence, we conducted an observational study on medical records related to 101 vitiligo patients, in order to correlate baseline 25(OH)D levels with the baseline vitiligo activity and repigmentation of vitiligo macules on a 6-month follow-up. According to our results, at baseline we found that active vitiligo was significantly associated with 25(OH)D deficiency (≤20 ng/mL) (P = 0.036) or insufficiency (21–29 ng/mL) (P = 0.041), while stable disease was significantly associated with sufficient 25(OH)D levels (30–100 ng/mL) (P = 0.043). After 6 months, vitiligo patients with sufficient 25(OH)D levels (30–100 ng/mL) achieved a significantly higher degree of repigmentation. In conclusion, our study provides a novel evidence of a significant positive association of sufficient 25(OH)D levels with the stability of the disease and a satisfactory repigmentation process in Caucasian adult vitiligo patients and strengthen the need to assess vitamin D status in vitiligo. The correlation between sufficient vitamin D levels and a satisfactory course of the disease opens the way for future randomized controlled trials assessing a possible beneficial role of vitamin D supplementation on vitiligo.

Autism Spectrum Disorder (ASD) is a highly heterogeneous neuropsychiatric disorder with a strong genetic component. The genetic architecture is complex, consisting of a combination of common low-risk and more penetrant rare variants. Voltage-gated calcium channels (VGCCs or Ca

Summary Background The microbiome is emerging as a crucial player of the immune checkpoint in cancer. Melanoma is a highly immunogenic tumour, and the composition of the gut microbiome has been correlated to prognosis and evolution of advanced melanoma and proposed as a biomarker for immune checkpoint therapy. Objectives We investigated the gut fungal and bacterial compositions in early-stage melanoma and correlated microbial profiles with histopathological features. Methods Sequencing of bacterial 16S rRNA and the fungal internal transcribed spacer region was performed on faecal samples of patients with stage I and II melanoma, and healthy controls. A meta-analysis with gut microbiota data from patients with metastatic melanoma was also carried out. Results We found a combination of gut fungal and bacterial profiles significantly discriminating patients with melanoma from controls. In patients with melanoma, we observed an abundance of Prevotella copri and yeasts belonging to the order Saccharomycetales. We found that the bacterial and fungal community correlated to melanoma invasiveness, whereas the specific fungal profile correlated to melanoma regression. Bacteroides was identified as general marker of immunogenicity, being shared by regressive and invasive melanoma. In addition, the bacterial communities in patients with stage I and II melanoma were different in structure and richer than those from patients with metastatic melanoma. Conclusions The composition of the gut microbiota in early-stage melanoma changes along the gradient from in situ to invasive (and metastatic) melanoma. Changes in the microbiota and mycobiota are correlated to the histological features of early-stage melanoma, and to the clinical course and response to immune therapies of advanced-stage melanoma, through direct or indirect immunomodulation.

Recent studies reported the association between increased risk of nonmelanoma skin cancers (NMSCs) and the use of hydrochlorothiazide (HCTZ), one of the most commonly prescribed diuretic, antihypertensive drug, over the world. Although HCTZ is known to be photosensitizing, the mechanisms involved in its potential prophotocarcinogenic effects remain unclear. Under acute exposure, therapeutically relevant concentrations of HCTZ (70, 140, and 370 ng/mL) amplified UVA-induced double-strand breaks, oxidative DNA, and protein damage in HaCaT human keratinocytes, and this effect was associated to a defective activity of the DNA repair enzyme, OGG1. Oxidative damage to DNA, but not that to proteins, was reversible within few hours. After chronic, combined exposure to HCTZ (70 ng/mL) and UVA (10 J/cm2), for 9 weeks, keratinocytes acquired a dysplastic-like phenotype characterized by a multilayered morphology and alterations in cell size, shape, and contacts. At the ultrastructural level, several atypical and enlarged nuclei and evident nucleoli were also observed. These transformed keratinocytes were apoptosis resistant, exhibited enhanced clonogenicity capacity, increased DNA damage and inflammation, defective DNA repair ability, and increased expression of the oncogene ΔNp63α and intranuclear β-catenin accumulation (a hallmark of Wnt pathway activation), compared to those treated with UVA alone. None of these molecular, morphological, or functional effects were observed in cells treated with HCTZ alone. All these features resemble in part those of preneoplastic lesions and NMSCs and provide evidence of a biological plausibility for the association among exposure to UVA, use of HCTZ, and increased risk of NMSCs. These results are of translational relevance since we used environmentally relevant UVA doses and tested HCTZ at concentrations that reflect the plasma levels of doses used in clinical practice. This study also highlights that drug safety data should be followed by experimental evaluations to clarify the mechanistic aspects of adverse events.

Objective: The purpose of this study was to investigate the relationship between vitiligo and body mass index (BMI) to assess the possible association between vitiligo and obesity. Subjects and Methods: This was a case-control study on a total of 400 participants, i.e., 200 patients with vitiligo and 200 healthy volunteers. Medical assessments were performed by dermatologists using the modified Vitiligo European Task Force form. The height and weight of all of the participants were measured and used to calculate the BMI. Data were analyzed using multivariate logistic regression models. Adjustment for age and gender was carried out preliminarily in the case-control analysis, whereas a forward stepwise selection algorithm was used to assess which independent factors were associated with a BMI ≥30 or a BMI ≤18.5. Results: Comparison of the vitiligo and control groups revealed the absence of a significant association. The multivariate analysis of factors associated with a high BMI (≥30) in vitiligo patients showed a significant association between a high BMI and a sudden onset of vitiligo (p = 0.021; OR = 3.83; 95% CI 1.22-11.99) and the presence of inflammation and pruritus (p = 0.031; OR = 3.26; 95% CI 1.11-9.57). No significant association was observed in the analysis of factors associated with a low BMI (≤18.5) in vitiligo patients. Conclusion: In this study, vitiligo did not appear to be associated with a high BMI; obesity might not be a risk factor for vitiligo, in contrast to most autoimmune diseases which are significantly associated with obesity.

The prolonged use of drugs such as beta-blockers, acetylsalicylic acid, omeprazole, statins, oral contraceptives and hormone replacement therapy might have some role in melanocytic nevi development and be ultimately linked to melanoma risk. Aims of the study were to evaluate a possible association between the above-mentioned drugs and features such as number and atypia of melanocytic nevi in long-term users. We retrospectively looked at pharmacological, clinical and dermoscopic records of 1321 patients that attended our unit for routine mole check between January 2013 and January 2018. Patients were divided into two groups (low or high melanocytic nevi count), and multivariate analysis was performed with regards to the presence and number of melanocytic nevi and drug assumption. A positive association between the use of oral contraceptives or hormone replacement therapy (P = 0.012) and a high melanocytic nevi count was found through multivariate analysis, after adjusting for sex, age and multiple confounding factors, such as freckles, phototype and a reported history of sun exposure and sunburns. Further prospective studies are necessary to establish whether women using oral contraceptives or on hormone replacement therapy should undergo periodic monitoring of pigmented lesions.

Vitiligo is an autoimmune disease in which depigmented skin results from destruction of\ud skin melanocytes, with strong epidemiologic association with several other autoimmune\ud diseases. In previous linkage and genome-wide association studies (GWAS1, GWAS2),\ud we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We\ud carried out a third GWAS (GWAS3) of vitiligo in EUR subjects, with augmentation of\ud GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three\ud vitiligo GWAS, followed by an independent replication study. The combined analyses,\ud with 4,680 vitiligo cases and 39,586 controls, identified 23 novel replicated loci, as well as\ud 7 new suggestive loci, most encoding immune regulators, apoptotic regulators, and\ud melanocyte regulators, several of which are also associated with other autoimmune\ud diseases. Functional analyses indicate a predominance of causal regulatory variation, in\ud some cases corresponding to eQTL at these loci. Together, the identified genes provide\ud a framework for vitiligo genetic architecture and pathobiology, highlight genetic\ud relationships to other autoimmune diseases and melanoma, and offer potential targets\ud for vitiligo treatment.

The aim of the present review was to discuss recent findings on the role of beta-adrenergic system in melanoma, in order to provide information on the biological responses elicited by its activation and its potential application for melanoma treatment. A literature search was performed, and evidences regarding the involvement of stress and beta-adrenergic system in cancer and melanoma were found and discussed. Our search pointed out that beta-adrenergic system is a key regulator of important biological processes involved in the onset and progression of some solid tumors. In the last decade, functional beta-adrenoceptors have been also identified on melanoma cells, as well as on their microenvironment cells. Similarly to other common cancers too, the activation of such adrenoceptors by catecholamines, usually released under stress conditions, has been found to trigger pro-tumorigenic pathways contributing to cell proliferation and motility, immune system regulation, apoptosis, epithelial–mesenchymal transition, invasion and neoangiogenesis. The biological evidences we found clarify and sustain the clinical evidences reporting the involvement of chronic stress in melanoma onset and progression. In such scenario, it is conceivable that a therapeutic approach targeting beta-adrenergic system could constitute a novel and promising strategy for melanoma treatment.

Vitiligo is a pigmentary disorder strongly associated with autoimmune thyroid disorders (ATD). Thyroid hormones antibodies (THAb) directed toward thyroxine (T3) and triiodothyronine (T4) (T3- and T4-Ab) are rare in the general population but are increased in individuals wit ATD and extrathyroid autoimmune disorders. Because it is known that alcohol, smoke, iodine, and some thyroid disruptors can elicit the appearance of ATD, the aim of our study was to evaluate possible correlation between T3- and T4-Ab expression and past toxic exposures in vitiligo patients. Seventy vitiligo patients were examined and self-reported exposure to thyroid disruptors (4,4'-isopropylidenediphenol, perchlorates, polychlorinated biphenyls (PCBs), hexachlorobenzene, resorcinol, dichlorodiphenyltrichloroethane, alachlor/amitriole, nitrate, thiocyanate, soy isoflavones), iodine intake, smoke, and alcohol consumption were investigated through standardized questionnaires. Immunoglobulin (Ig)M-T3-Ab, IgG-T3-Ab, IgM-T4-Ab,and IgG-T4-Ab were dosed by a radioimmunoprecipitation technique. Seventy-seven (95.7 %) patients had at least one type of THAb. Most of them had contemporarily both T3- and T4-Ab (50/70). We found a significant association between PCBs and T4-IgG-Ab (P = 0.039) and between food intake containing nitrate, thiocyanate, and soy isoflavones with (IgM + IgG)-T3-Ab (P = 0.041). Our study underlines a possible influence of diet and environment in vitiligo patients in eliciting THAb. Therefore, in the event of a positive exposure to thyroid disruptors, an evaluation of thyroid function might be useful to early detect possible associated thyroid autoantibodies such as THAb.

Phyllanthus emblica, vitamin E, and caroteinods are compounds showing antioxidative, anti-inflammatory, and repigmenting effects, whose role in vitiligo treatment has not been evaluated so far. Sixty-five subjects (group A) were treated with one tablet of an oral supplement containing P. emblica (100 mg), vitamin E (10 mg), and carotenoids (4.7 mg) three times/day for 6 months and compared with a control group (group B, 65 patients), which instead was not treated with antioxidants. Both groups were simultaneously treated with a comparable topical therapy and/or phototherapy. After a 6 months follow-up, a significantly higher number of patients in group A had a mild repigmentation on the head/neck regions (p = 0.019) and on the trunk (trend, p = 0.051). The number of patients who presented no repigmentation in head/neck, trunk, upper, and lower limbs was significantly higher in group B (respectively, p = 0.009, p = 0.001, p = 0.001, p = 0.025). Moreover, group B patients showed higher signs of inflammation (p = 0.002), a more rapid growth of the lesions (p = 0.039), a higher percentage of worsening disease (p = 0.003), and more erythema (p = 0.059), whereas group A patients showed a higher percentage of steady disease (p = 0.065). Our results suggest that the supplement with antioxidants in patients with vitiligo might represent a valuable instrument to increase the effectiveness of other vitiligo treatments. [Correction added after online publication 06-Oct-2014: the dosages of vitamin E and carotenoids have been updated.]

Summary Background Autoantibodies against thyroid hormones (THAbs) directed towards triiodothyronine (T3-Ab) and/or thyroxine (T4-Ab) are very rare in the general population. They are increased in some nonthyroidal autoimmune diseases, where they seem to predict autoimmune thyroid disorders (ATDs). So far, their presence in patients with vitiligo has not been evaluated, but it might have a possible predictive role. Objectives To assess the prevalence of THAbs in a group of vitiligo patients and to correlate their presence with clinical and historical parameters. Methods In total 79 patients with nonsegmental vitiligo and 100 controls were examined. Clinical characteristics of vitiligo and family and personal medical history were evaluated. Antinuclear autoantibodies, thyroid hormones and thyroid autoantibodies were measured. IgM T3-Ab, IgG T3-Ab, IgM T4-Ab and IgG T4-Ab were assayed by a radioimmunoprecipitation technique. Fisher's test, Student's t-test and χ2-test were used for statistical analysis. Results Overall 77 of 79 patients (97%) had at least one type of THAb (11 T3-Ab, 10 T4-Ab, 56 both). In the control group, only one person (1%) had THAbs. In patients with vitiligo, T3-Abs were significantly associated with leucotrichia (IgM+IgG, P = 0·033; IgG, P = 0·039; IgM, P = 0·005) and thyroglobulin autoantibodies (IgM+IgG, P = 0·031; IgG, P = 0·058), while the absence of T3-Ab was related to personal history of cancer (IgM+IgG, P = 0·021; IgG, P = 0·039). T4-Abs were significantly associated with vitiligo activity (IgM+IgG, P

Background A recent systematic evaluation of vitiligo and psoriasis comorbidity has not yet been reported in a large series of patients with vitiligo. Objective To investigate the practical/clinical implications in subjects with both vitiligo and psoriasis compared to those with vitiligo alone. Methods This was a case-control study on 463 vitiligo patients in our clinic from March 2008 to April 2011. Medical assessment was performed by dermatologists using the modified Vitiligo European Task Force form. Results In an univariate analysis, inflammation/pruritus [odds ratio (OR) 2.42, P = 0.03], use of drugs that can induce psoriasis (OR 2.74, P = 0.01), a family history (FH) of psoriasis (OR 2.87, P = 0.02), cardiovascular disease (OR 5.70, P = 0.001), hypertension (OR 4.7, P = 0.006) and type 2 diabetes mellitus (OR 3.87, P = 0.004), were significantly correlated with patients exhibiting vitiligo and psoriasis comorbidity. A trend was found in personal history of cardiovascular disease in patients with both diseases (OR 2.99, P = 0.07). FH of vitiligo was significantly associated with patients having only vitiligo (OR 0.35, P = 0.05). Multivariate analysis demonstrated that inflammation/pruritus in vitiligo macules (OR 2.56, P = 0.047) and a FH of cardiovascular disease (OR 4.07, P = 0.02) were the most significant predictors of patients having both psoriasis and vitiligo, while the presence of organ-specific autoantibodies (OR 0.24, P = 0.007) was significantly associated with patients having only vitiligo. Conclusion The presence of vitiligo and even mild psoriasis is significantly correlated with a family history of cardiovascular disease, a factor that requires greater attention and follow-up with respect to that necessary for vitiligo patients.

Objectives: The aim of this study was to evaluate the clinical and epidemiological profile of hair and scalp disorders in children referred to the Pediatric Dermatology Outpatient Clinic. Materials and Methods: We performed a retrospective study of children with hair loss problems or scalp diseases who turned to the Pediatric Dermatology Service, Anna Meyer Pediatric Hospital, Florence, Italy, from January 1, 2009, to December 31, 2009. Demographics, personal and familial medical history, laboratory tests, clinical examination, final diagnosis and therapeutic interventions were obtained from the manual chart review. Results: Of the 2,640 children who had access to the Pediatric Dermatology Service, 190 (7.19%) had a hair or scalp disorder. Among the 190 children, 60 (31.57%) presented with nonscarring alopecia, 56 (29.47%) had benign neoplasias, hamartomas or vascular malformations of the scalp, 51 (26.84%) had scalp inflammatory diseases, 14 (7.36%) had scarring alopecia, 5 (2.63%) had infections and 2 (1.05%) had infestation of the scalp. A case of constitutional hypertrichosis (0.52%) and also a case (0.52%) of lamellar ichthyosis were diagnosed. Conclusions: Our results underline that hair and scalp diseases represent an important percentage of admittances to a dermatological pediatric outpatient clinic. The variety and complexity of the diseases observed in this study included diseases commonly found also in adulthood.

Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo.Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo.Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption.Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P=0.04; OR 0.4), stress at onset (P=0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P=0.003; OR = 0.23), and thyroid nodules (P=0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P=0.003; OR = 2.87) and Koebner phenomenon (P<0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P=0.014).Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients.

Introduction Vitiligo is a common pigmentary skin disorder, characterized by the appearance of white macules on the skin, mucosal or hair. Treatment is often a tough challenge and involves a wide range of therapies. Areas covered This review focuses on available first- and second-line pharmacological treatments for vitiligo. In particular, the mechanisms of action, the main indications, the efficacy and the most important side effects are reviewed. Moreover, a brief discussion is provided, regarding other nonpharmacological treatments, such as phototherapy and surgical options, due to their importance and successful outcomes in vitiligo treatment. Finally, a concise overview regarding the future directions in vitiligo therapy is presented. Expert opinion The promising outcomes reported here demonstrate that it is possible to achieve a satisfactory and often stable repigmentation of vitiligo lesions. Topical corticosteroids, calcineurin inhibitors, phototherapy and photochemotherapy represent the first-line therapeutic options, due to their safety and efficacy, whereas vitamin D analogues, targeted phototherapy, oral corticosteroids and surgery should be used as second-line therapies. Other therapies, such as antioxidants, can be used in association with other therapeutic options, whereas depigmenting agents should be used only in cases of extensive vitiligo, recalcitrant to other treatments.

Background Although non-segmental vitiligo is commonly considered an autoimmune disease, the possible differences between non-segmental vitiligo patients with and without autoimmune signals have not been clearly established. Objective To perform a comparison of non-segmental vitiligo patients with autoimmune signals (AIS) vs. those without autoimmune signals (NAIS) in regards to clinical characteristics and toxic/drug exposure. Methods 112 vitiligo patients were selected for a sex and age matched (1 : 1) case control study at an university based dermatology outpatient hospital specialized in pigmentary disorders. Medical assessment was performed by dermatologists using the modified Vitiligo European Task Force form and serological and clinical signs of autoimmunity were evaluated. Results Disease duration, age of onset, patient history of cardiovascular disease, past smoking history, use of drugs, and consummation of goitrogenic foods were all significantly increased in the AIS group using McNemar’s test for matched pairs. In our conditional regression model, the simultaneous presence of disease duration, use of prescription drugs, and consummation of goitrogenic foods were the best predictors of AIS vitiligo patients. Conclusion The evaluation of non-segmental vitiligo patients according to the presence vs. the absence of autoimmune signals allows us to correlate patients exhibiting autoimmune phenomenon with certain clinical characteristics, namely long disease duration, use of prescription drugs, and consumption of goitrogenic substances. In the presence of the aforementioned clinical profile, we suggest an evaluation of autoimmune signals.

Background Current studies have treated a limited portion of the subjective aspects of vitiligo patients and have yet to elucidate possible psychological differences between those with autoimmune markers (AIM) with respect to those without autoimmune markers (NAIM). Objective To perform an age and gender-matched 1 : 1 case–control study through a comparison of non-segmental vitiligo patients with autoimmune features vs. those without autoimmune features in regards to psychiatric features, psychosomatic aspects and social parameters. Methods A total of 112 non-segmental vitiligo patients have been examined at the Florence University dermatology outpatient service (2nd dermatology unit). Vitiligo with an autoimmune background was defined by the presence of autoimmune antibodies and/or autoimmune diseases. Psychiatric screening was performed by dermatologists using the modified Middlesex Healthcare Questionnaire (MHQ); psychosomatic aspects and social impact were analysed with a standardized, Florentine questionnaire. Results Upon performing a conditional regression model, age, phobia and obsession were significantly predictive of the presence of AIM and a low total MHQ score was significantly predictive of NAIM in vitiligo patients. With univariate analysis, we found significant differences in: identifiable stress related to the onset of vitiligo, vitiligo triggered by stress, and modified interpersonal relationships related to vitiligo, which were associated with the subgroup containing autoimmunity markers. Conclusions We found a higher prevalence of age, obsession and phobia among vitiligo patients AIM as compared to vitiligo patients NAIM. Thus, in the presence of demonstrated autoimmunity, screening for particular psychiatric aspects may be useful in the clinical practice of vitiligo.

Vitiligo is a cosmetically disfiguring condition, and, although there is no therapeutic full solution yet, some treatment may induce good results in most patients. The disease can be successfully treated with various medical options. Both nonfocused or focused narrowband ultraviolet B phototherapy represents the current treatment of choice, to minimize side effects and reach optimal clinical results. Topical novel approaches are also considered. Surgical methods, consisting of autologous transplantation methods, is generally recommended for focal/stable vitiligo, after medical therapy has failed. Finally, for patients with extensive vitiligo, depigmentation of the residual melanin should be taken into account.

Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo.

A 63-year-old woman living in the countryside referred to our department with a 2-month history of a red nodule localized on the right breast. Histological examination, immunohistochemical analyses and serologic evaluation conducted with ELISA and Western blot were performed. Clinical diagnosis of borrelial lymphocytoma was not possible solely on the clinical presentation of a classical nodular form without lymphoadenopathy. An absence of a referred prior tick bite and a previous or concomitant erythema migrans at clinical presentation rendered a more challenging diagnosis. The fact that the patient lived in the countryside, the appearance of the breast nodule in September, and serologic, histologic, and immunohistochemical analysis facilitated the diagnosis of borrelial lymphocytoma. We report this case to highlight the importance of an investigation of Lyme borreliosis when a patient living in the countryside presents with a red nodule of the nipple and areola.

Phyllanthus emblica, vitamin E, and caroteinods are compounds showing antioxidative, anti-inflammatory, and repigmenting effects, whose role in vitiligo treatment has not been evaluated so far. Sixty-five subjects (group A) were treated with one tablet of an oral supplement containing P. emblica (100 mg), vitamin E (10 mg), and carotenoids (4.7 mg) three times/day for 6 months and compared with a control group (group B, 65 patients), which instead was not treated with antioxidants. Both groups were simultaneously treated with a comparable topical therapy and/or phototherapy. After a 6 months follow-up, a significantly higher number of patients in group A had a mild repigmentation on the head/neck regions (p = 0.019) and on the trunk (trend, p = 0.051). The number of patients who presented no repigmentation in head/neck, trunk, upper, and lower limbs was significantly higher in group B (respectively, p = 0.009, p = 0.001, p = 0.001, p = 0.025). Moreover, group B patients showed higher signs of inflammation (p = 0.002), a more rapid growth of the lesions (p = 0.039), a higher percentage of worsening disease (p = 0.003), and more erythema (p = 0.059), whereas group A patients showed a higher percentage of steady disease (p = 0.065). Our results suggest that the supplement with antioxidants in patients with vitiligo might represent a valuable instrument to increase the effectiveness of other vitiligo treatments. [Correction added after online publication 06-Oct-2014: the dosages of vitamin E and carotenoids have been updated.].

Behçet's disease is a multisystem inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. The cause of Behçet's disease remains unknown, but epidemiologic findings suggest that an autoimmune process is triggered by an environmental agent in a genetically predisposed individual. An infectious agent could operate through molecular mimicry, and subsequently the disease could be perpetuated by an abnormal immune response to an autoantigen in the absence of ongoing infection. Potentia bacterial are Saccharomyces cerevisiae, mycobacteria, Borrelia burgdorferi, Helicobacter pylori, Escherichia coli, Staphylococcus aureus, and Mycoplasma fermentans, but the most commonly investigated microorganism is Streptococcus sanguinis. The relationship between streptococcal infections and Behçet's disease is suggested by clinical observations that an unhygienic oral condition is frequently noted in the oral cavity of Behçet's disease patients. Several viral agents, including herpes simplex virus-1, hepatitis C virus, parvovirus B19, cytomegalovirus, Epstein-Barr virus and varicella zoster virus, may also have some role.

ejd.2011.1459 Auteur(s) : Samantha Berti1 s.berti@meyer.it, Laura Amato1, Meena Arunachalam1, Adelina Spallanzani1, Francesca Prignano1, Romina Nassini2, Daniela Massi3, Roberta Colucci1, Silvia Moretti1 1 Departments of Dermatological Sciences 2 Preclinical and Clinical Pharmacology 3 Pathological Anatomy, University of Florence, Piazza Indipendenza 11, 50129 Florence, Italy Stem cell factor (SCF), produced by keratinocytes and endotheliocytes, acts as a ligand for the c-KIT receptor which is expressed [...]

There are very few studies in the current literature that have analyzed vitiligo and autoimmune thyroid disease (AIT) using both univariate and multivariate analyses. Thus, we sought to investigate the practical/clinical implications in subjects with both vitiligo and AIT compared to those with vitiligo alone. Verification of data was done by using medical records from the patient's family physician.We performed a prospective, case control study concerning 194 vitiligo patients, older than 18, seen [...]

Three cases of adult, non-segmental vitiligo patients in which primary, common variable immunodeficiency (CVID) was present are described. In two of the three cases, psoriasis was also present. Onset of CVID was diagnosed before vitiligo in two patients, and subsequent to the onset of vitiligo in the remaining patient. A family history of CVID was negative in all three cases. In contrast, a family history of vitiligo was present in two cases and a family history of psoriasis was present in one case. In regards to vitiligo, disease onset was gradual, with active disease in two cases, while the third case had an abrupt disease onset with borderline activity during clinical presentation. Cutaneous disease extension ranged from 2% to 12.3% in the three cases. Upon physical exam, Koebner phenomenon and signs of inflammation, such as pruritus were present in two patients; one of whom had scalp leukotrikia as well. Stress was a triggering factor in the development of vitiligo in two cases. The presence of CVID due to drugs or diseases known to cause secondary antibody deficiency were excluded in all three patients. Lastly, all patients were under treatment with immunoglobulin replacement therapy, which did not change the outcourse of vitiligo.

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.

The incidence of melanoma, the most aggressive type of cutaneous malignant tumor, is currently on the rise. Treatment in advanced stages is still unsuccessful compared with other malignant tumors, thus it is important to indentify the key mechanisms responsible for melanoma progression and metastasis. Genetic and molecular components, in particular, that are up- or downregulated in melanoma cells, affect the invasive potential of melanoma. Another possible important cofactor highlighted by recent studies is chronic stress, involving environmental and psychological factors, which can be an important cofactor in not only cancer progression in general but also in melanoma spreading. The negative effects of chronic stress have been evaluated epidemiologically in patients with breast and prostate cancer. In particular, the effects of stress mediators, namely, catecholamines have been studied on various human malignancies, including melanoma and have highlighted a significant increase of progression-related molecules. As such, this could be the starting point for a new approach in the treatment of advanced melanoma, in which the negative effects of stress are reduced or blocked.

Vitiligo pathogenesis is very puzzling, and novel mechanisms possibly involved in the development of this disorder are frequently explored. Recently, some authors proposed an interplay between oxidative stress and immune system at the basis of melanocyte loss. According to the experimental evidence, they suggest that exposition to environmental agents might lead to an association between vitiligo and other autoimmune diseases. Accordingly, it is proposed that increased reactive oxygen species due to environmental agents could induce a modification of both melanocytic structures and other tissue proteins, or might disregulate the immune system, influencing the appearance of vitiligo and autoimmune comorbidities.

ejd.2012.1708 Auteur(s) : Roberta Colucci1, Meena Arunachalam1 marunac@yahoo.com, Federica Dragoni1, Massimiliano Galeone1, Samantha Berti2, Siliva Moretti1 1 Critical Care Medicine and Surgery, Section of Clinical, Preventive and Oncologic Dermatology, Villa S. Chiara, Piazza dell’Indipendenza, 11, 50129 Florence, Italy 2 Unit of Dermatology, “A.Meyer” Children's Hospital, Florence, Italy We report the case of a 44 year old man who presented to our outpatient clinic with large, well defined, [...]