BACKGROUND:Head and neck melanoma is a clinical challenge. Indeed, cutaneous head and neck melanoma shows a worse prognosis in comparison to melanomas of other body sites. Although the emphasis on facial cosmetic preservation plays a pivotal role in comparison to other body areas, specific Facial Aesthetic Units (FAU) could also play a key role in the prognostic evaluation of the malignancy.METHODS:The aim of the current study was to evaluate the general outcome and clinicopathological features of head and neck melanoma and to detect prognostic differences according to each FAU. The Kaplan-Meier product was used to calculate survival curves, while Cox proportional-hazard regression was performed to evaluate the predictive value of each FAU.RESULTS:A total of 221 head and neck melanoma patients was included in our analysis. In the nasal FAU, we found a high rate of local recurrence, which affected significantly disease-free survival. The worse prognosis was observed in melanoma of the scalp, which showed a greater tendency to skip metastases in internal organs. Moreover, we found that scalp showed a low incidence of non-melanoma skin cancers, if compared to other FAU, highlighting that the scalp local milieu might play a more prominent role in melanoma biology than chronic UV exposition.CONCLUSIONS:Although FAUs have an aesthetic function, they could also play a role in the evaluation and follow-up of melanoma.

Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun-exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

Dermatologic TherapyVolume 32, Issue 2 e12788 Letter to the Editor Sequential treatment of daylight photodynamic therapy and imiquimod 5% cream for the treatment of superficial basal cell carcinoma on sun exposed areas Giovanni Paolino, Giovanni Paolino orcid.org/0000-0002-3032-2217 Dermatology Clinic, La Sapienza-Università di Roma, Rome, Italy Dermatology and Cosmetology Unit, San Raffaele Hospital, Milan, ItalySearch for more papers by this authorDario Didona, Corresponding Author Dario Didona dariodidona85@gmail.com orcid.org/0000-0002-6119-1870 Klinik für Dermatologie und Allergologie, Universitätsklinikum Marburg, Marburg, Germany Correspondence Dario Didona, Klinik für Dermatologie und Allergologie, Universitätsklinikum Marburg, Baldingerstraße, Marburg 35043, Germany. Email: dariodidona85@gmail.comSearch for more papers by this authorMarco Scarnò, Marco Scarnò Super Computing Applications and Innovation (SCAI), CINECA, Rome, ItalySearch for more papers by this authorMariagrazia Tallarico, Mariagrazia Tallarico Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorFranca Cantoresi, Franca Cantoresi Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorStefano Calvieri, Stefano Calvieri Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorSanto Raffaele Mercuri, Santo Raffaele Mercuri Dermatology and Cosmetology Unit, San Raffaele Hospital, Milan, ItalySearch for more papers by this authorDomenico Piccolo, Domenico Piccolo Italian Association Outpatient Dermatologists, Pescara, ItalySearch for more papers by this authorUgo Bottoni, Ugo Bottoni Dermatology Clinic, University Magna Grecia, Catanzaro, ItalySearch for more papers by this authorAikaterini Kyriakou, Aikaterini Kyriakou Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorCarmen Cantisani, Carmen Cantisani orcid.org/0000-0003-2181-951X Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this author Giovanni Paolino, Giovanni Paolino orcid.org/0000-0002-3032-2217 Dermatology Clinic, La Sapienza-Università di Roma, Rome, Italy Dermatology and Cosmetology Unit, San Raffaele Hospital, Milan, ItalySearch for more papers by this authorDario Didona, Corresponding Author Dario Didona dariodidona85@gmail.com orcid.org/0000-0002-6119-1870 Klinik für Dermatologie und Allergologie, Universitätsklinikum Marburg, Marburg, Germany Correspondence Dario Didona, Klinik für Dermatologie und Allergologie, Universitätsklinikum Marburg, Baldingerstraße, Marburg 35043, Germany. Email: dariodidona85@gmail.comSearch for more papers by this authorMarco Scarnò, Marco Scarnò Super Computing Applications and Innovation (SCAI), CINECA, Rome, ItalySearch for more papers by this authorMariagrazia Tallarico, Mariagrazia Tallarico Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorFranca Cantoresi, Franca Cantoresi Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorStefano Calvieri, Stefano Calvieri Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorSanto Raffaele Mercuri, Santo Raffaele Mercuri Dermatology and Cosmetology Unit, San Raffaele Hospital, Milan, ItalySearch for more papers by this authorDomenico Piccolo, Domenico Piccolo Italian Association Outpatient Dermatologists, Pescara, ItalySearch for more papers by this authorUgo Bottoni, Ugo Bottoni Dermatology Clinic, University Magna Grecia, Catanzaro, ItalySearch for more papers by this authorAikaterini Kyriakou, Aikaterini Kyriakou Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this authorCarmen Cantisani, Carmen Cantisani orcid.org/0000-0003-2181-951X Dermatology Clinic, La Sapienza-Università di Roma, Rome, ItalySearch for more papers by this author First published: 30 November 2018 https://doi.org/10.1111/dth.12788Citations: 6Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume32, Issue2March/April 2019e12788 RelatedInformation

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual's diagnosis and/or help clarify risk in healthy populations.

Scleroderma is divided into a systemic form called systemic sclerosis and a localized form also called morphea. According to 2013 ACR/EULAR Classification Criteria for Systemic Sclerosis, developed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for a patient to be classified as having scleroderma. Histological examination is not included in the diagnostic criteria and is not routinely performed. Skin biopsy is recommended only in the case of diagnostic doubt with other scleroderma like disorders (scleromyxedema, scleredema, nephrogenic systemic fibrosis). Alternatively, skin biopsy is also often performed for research purposes. Indeed, the first step analysis of new cytokines or pathways that may contribute to the pathogenesis of the disease requires the evaluation of their expression or activation in the skin of scleroderma patients compared to healthy controls. The histological picture of the skin in bot localized and systemic scleroder shows initially microvascular alterations and chronic inflammation while in the more advanced stages skin fibrosis prevails. Localized scleroderma (LS) or morphea includes a number of subtypes which are classified more according to their clinical presentation rather than histopathological pictures. However, some histopathologic changes may be useful in differentiating each entity from the others and from other sclerodermoid disorders.

Melanoma is a severe form of cancer, resistant to conventional therapies. According to in vitro studies, sulforaphane, a dietary component, has been considered a promising antineoplastic candidate. The present study analyzes the in vitro biological effects of sulforaphane in A375 melanoma cell line with or without the addition of Nerve Growth Factor. For the first time, our results show that a supplementation of Nerve Growth Factor partially reverses the sulforaphane-induced: i) inhibition of cell migration, ii) pro apoptotic changes in cell cycle and iii) modulation of active caspase-3. Furthermore, we report the sulforaphane-induced modulation in the expression of Nerve Growth Factor receptors TrKA and p75NTR, shifting their ratio from pro survival to pro apoptotic. In conclusion, the present study evidences that in vivo the antineoplastic effects of sulforaphane may be reduced by the contemporaneous presence of other biological elements such as Nerve Growth Factor and it contributes to a better definition of the real in vivo potentiality of sulforaphane as antineoplastic candidate.

Actinic keratosis (AK) is a clinical condition characterized by keratinocytic dysplastic lesions of the epidermis, affecting individuals chronically exposed to sunlight. Topical therapies allow the treatment of a whole area of affected skin and currently include diclofenac sodium gel, 5-fluorouracil cream, 5-fluorouracil and acetylsalicylic acid solution, imiquimod cream, and ingenol mebutate gel. Due to the comparable efficacy of 3% diclofenac, ingenol mebutate, and 3.75% imiquimod in treating AK multiple lesions, a pharmacoeconomic evaluation of cost-effectiveness of the three treatments was needed. A cost-efficacy analysis comparing 3% diclofenac sodium with ingenol mebutate and 3.75% imiquimod was performed. In this analysis, efficacy data were combined with quality-of-life measurement derived from previous studies as well as the costs associated with the management of these lesions in Italy. Patients’ demographics and clinical characteristics were assumed to reflect those from the clinical studies considered.

PURPOSE:Human melanoma is a highly aggressive incurable cancer due to intrinsic cellular resistance to apoptosis, reprogramming, proliferation and survival during tumour progression. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, plays a role in carcinogenesis in many cancer types. However, the cytotoxic molecular mechanisms and gene expression profiles promoted by SFN in human melanoma remain unknown.METHODS:Three different cell lines were used: two human melanoma A375 and 501MEL and human epidermal melanocytes (HEMa). Cell viability and proliferation, cell cycle analysis, cell migration and invasion and protein expression and phosphorylation status of Akt and p53 upon SFN treatment were determined. RNA-seq of A375 was performed at different time points after SFN treatment.RESULTS:We demonstrated that SFN strongly decreased cell viability and proliferation, induced G2/M cell cycle arrest, promoted apoptosis through the activation of caspases 3, 8, 9 and hampered migration and invasion abilities in the melanoma cell lines. Remarkably, HEMa cells were not affected by SFN treatment. Transcriptomic analysis revealed regulation of genes involved in response to stress, apoptosis/cell death and metabolic processes. SFN upregulated the expression of pro-apoptotic genes, such as p53, BAX, PUMA, FAS and MDM2; promoted cell cycle inhibition and growth arrest by upregulating EGR1, GADD45B, ATF3 and CDKN1A; and simultaneously acted as a potent inhibitor of genotoxicity by launching the stress-inducible protein network (HMOX1, HSPA1A, HSPA6, SOD1).CONCLUSION:Overall, the data show that SFN cytotoxicity in melanoma derives from complex and concurrent mechanisms during carcinogenesis, which makes it a promising cancer prevention agent.

Background The anti-BAFF monoclonal antibody, belimumab, was approved about five years ago by the US Food and Drug Administration for the treatment of adult SLE patients. The utility of belimumab for management of resistant systemic lupus erythematosus (SLE) has been demostrated but concerning skin manifestations only scarce evidences have been reported. We describe our experience of using this new drug for the successful management of recalcitrant cutaneous lupus. Case report A 38-year-old man with a five year history of SLE presented, in May 2017, at our outpatient clinic for a disease flare with severe cutaneous involvement. On examination the patient presented malar rash and erythematous-infiltrated discoid lesions in the region of head and neck and erythematosus papules also on the extensor surface of the hands. Additional tests showed also systemic involvement by detecting low levels of C3 and C4, leukopenia (WBC 3000/µL) and positivity of ANA (1:1280 by IFI) and anti-dsDNA (42.8 UI/ml by ELISA, nv <30 UI/ml). SLE Disease Activity Index (SLEDAI) was 9, Cutaneous Lupus Disease Area and Severity index- activity and damage scores (CLASI) was 22 for activity and 1 for damage and Physician Global Assessment (PGA) was 8 cm. The patient failed previous treatment with HCQ, MTX, AZA, MMF and at time of our observation was taking, since December 2016, prednisone (12,5 mg daily) without improvement. Belimumab was added to concomitant steroid therapy at recommended dose (10 mg/kg). Early as 3 months after its initiation Belimumab therapy led to impressive clinical improvement in the lesions upper the hands and slighter in that in the region of head. Belimumab use also provided a significant steroid-sparing effect as well as facilitating the rapid improvement in skin symptoms and in systemic involvement. Conclusion In this case report, the addition of belimumab to steroid monotherapy, in patient who failed previous immunosuppressive treatment improved the signs and symptoms of refractory cutaneous lupus. This report highlights the utility of belimumab for the treatment of severe skin involvement in SLE refractory to conventional therapies. Additional studies should be performed to assess the use of belimumab in the treatment of cutaneous lupus.

(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

Background The initial treatment of Psoriatic Arthritis (PsA) is largely based on the extent of muscoloskeletal involvement and disease severity according to the stepwise approach of EULAR and GRAPPA recommendations for PsA management, but without reagard to the age of onset. Objectives This prospective observational study aimed1 to describe treatment prescribing patterns in PsA over the first 2 years of follow-up and2 to determine if the treatment patterns are contidioned by the age of onset. Methods Patients with at least 2 years of follow-up within the PsArT (Psoriatic arthritis Age-related Treatment patterns) study were included. Patients with a diagnosis of early (symptom duration <52 weeks) PsA, made by rheumatologists with long-standing expertise in PsA, were consecutively recruited and divided into Adult-Onset (AOPsA) (age <60 years) and Late-Onset (LOPsA) (onset age ≥60 years) PsA according to the age at the onset of musculoskeletal manifestations. For the aim of this study, patient’s data were collected at the enrollemet (baseline) (T0), at 12 months (T12) and at 24 months (T24). Clinical, laboratory features and treatment patterns, over 2 years were described according to the age stratification. Results 46 PsA patients (22 M, 24 F; age 49±16, range 16–90 years) with a disease duration of 20±15 weeks (range 1–52) were enrolled. Compared to the 31 patients with AOPsA, the 15 patients with LOPsA had a signifcant shorter disease duration (17±15 vs. 21±15 weeks, p<0.05) and showed more frequently increased levels of ESR (75% vs. 43%, p<0.05) and CRP (87% vs. 52%, p<0.01). In addition, patients with LOPsA developed more frequently infammatory extremity swelling with pitting oedema (IESPE) over the dorsum of hands and/or of the feet (56% vs. 13%, p<0.01). There were no other significant differences between the 2 groups even though more males were observed in the LOPsA group (56% vs. 42%, p>0.05). The sensitivity of the CASPAR criteria was similar in AOPsA (78%) and LOPsA (75%). Of 46 patients during the first year 80.4% received non steroidal anti-inflammatory drugs, 32.6% received oral corticosteroids, 13.0% received local corticosteroids, 19.5% received synthetic disease-modifying anti-rheumatic drugs (sDMARDs) and 6.5% received biologics (bDMARDs: IFX, ADA, GOL, ETN). During the second year of follow up 73.9% received non steroidal anti-inflammatory drugs, 30.4% received oral corticosteroids, 50% received synthetic disease-modifying anti-rheumatic drugs (sDMARD), 15.2% received biologics (IFX, ADA, GOL, ETN) and received 30.4% local corticosteroids. (see figure) About the drug intake the only statistical significant difference betwen the two groups was the rate of patients using NSAIDs in LoPsA group during the first year (100% vs. 70.9%, p value 0.02). There were no other significant differences in drug intake, therapy changes, discontinuation, add-on therapy according to the age of PsA onset. Conclusions During the two years of follow up period a high proportion of patient received NSAIDs in LoPsA group during the first year. The main limit of our study is the low number of patients, therefore a greater number could help to understand whether the age of onset may affect the use of specific type of drugs. Acknowledgements The authors would like to express their special appreciation and thanks to Prof. Ignazio Olivieri Disclosure of Interest None declared

The sun plays a major role in prematurely aging our skin. Our skin is at the mercy of many forces as we age: sun, harsh weather, and bad habits. But we can take steps to help our skin stay supple and fresh-looking. Sunlight is a major cause of skin aging. The increasing knowledge of the genetic bases of several common multifactorial diseases paves the way to personalized medicine that means preventive and therapeutic interventions that are tailored to individuals on the basis of their genetic profiles. The aging process, as well as multi factorial diseases, depends on a complex crosstalk between intrinsic (genetic and hormonal) andextrinsic (nutrition, lifestyle etc.) factors. Skin changes are the most visible signs of senescence process, and a field of increasing interest ina society that places more and more interest in appearance and beauty. skin disease characterized by increased trans-epidermal water loss and skin barrier abnormalities and disruption. On this subject, numerous environmental events such as: chemical injuries, traumatic wounds, UV exposure and genomic characteristics can compromise the barrier activity. To date, the mutational spectrum of FLG gene comprises different variations that show an ethno-specific distribution profile, especially among north European and Mediterranean populations. The study was conducted in 100 Italian volunteers, with an age between 21 and 66 years old (23 males and 77 females). All selected patients were Caucasian (people with European origin), belonging to Fitzpatrick skin type 2 and 3. Subjects underwent medical history and clinical examination; exclusion criteria included systemic diseases or presence of genetic diseases which were clinically evident. All patients signed written informed consent. The examination of each subject was conducted using a lifestyle questionnaire and, to evaluate the impact of lifetime sun exposure (LSE), using the Sun Exposure and Behavior Inventory (SEBI). For the aging process, like to multi-factorial and polygenic diseases, is known that single genetic polymorphism has only a modest effect since the interaction of each gene and its polymorphism with other ones (gene-gene interaction) and with environmental factors (gene-environment interaction) has a crucial role in the development of the pathology. Moreover, the diversity of ethnic background may be a possible bias in such research. In the light of these considerations we selected Caucasian, Italian subjects only, and we constructed a literature based genetic risk score for skin aging with the aim to evaluate the contribution of individual genetic variability to skin aging. Prior skin aging studies have analyzed intrinsic and extrinsic skin aging parameters, believed to reflect genetic and environmental factors contributing to skin aging feature. Heritability analyses in twins have shown that genetic component of skin deterioration process accounts for about 60% [3]. In recent years, research on genetic polymorphisms indicate that Genetic Risk Scores (GRSs) allow the composite assessment of genetic risk in complex traits. Although some authors have expressed doubts as to whether a candidate gene approach can ever add significantly to risk prediction, because of the modest impact on risk, and the apparent inconsistency of effect, other authors demonstrate that, depending on the prevalence and heritability of the disease, few genetic variants may have a strong predictive power. Our results indicate that the use of the genetic risk score including 8single nucleotide polymorphisms This work is partly presented at International Conference on Aesthetic Medicine and Cosmetology, May 21-22 2018A¢Â”‚Singapore Vol.4 No.2 Extended Abstract Skin Diseases & Skin Care 2019 involved in aging process aspreviously described in literature, could be promising to predict skinproperties evolution and address antiA¢Â€Âaging and skin treatment againstspecific metabolic target. Keywords:

BACKGROUND: Dermatofibrosarcoma protuberans is a malignant tumor that affects exclusively the skin. It is a low-grade malignant tumor of subcutaneous tissues, characterized by a local recurrence but it seldom metastasizes. This study aimed to evaluate the impact of different clinical parameters on disease free survival and overall survival of dermatofibrosarcoma protuberans patients. METHODS: A retrospective study of data including seventeen cases of dermatofibrosarcoma protuberans (eleven male, six female) retrieved from the files of the Dermatology Clinics of La Sapienza University, Rome. We evaluated three clinical parameters (age, sex and anatomic site of the primary tumor) using the Kaplan-Meier product and the Log-Rank Test. RESULTS: The results highlighted that patients with an age <= 49 years showed a median disease free survival of 36 months, while patients with an age >= 50 years of 4 months (P<0.0003). In addition, performing Rank-correlation, only the variable age (P<0.0001) reached the statistical significance. Regarding overall survival, performing Rank-correlation only the variable age reached the statistical significance (P=0.02). CONCLUSIONS: Our data suggests that age has a statistically significant role on disease free survival and overall survival of dermatofibrosarcoma protuberans patients.

Background Patients with multiple actinic keratoses (AKs) should be treated with field-directed therapy. Such treatments challenge patients' adherence due to out-of-pocket costs, length of treatment and severity of local skin reactions (LSRs). Effective physician-patient communication (PPC) may buffer therapy-related distress, thus improving quality of life, treatment satisfaction and adherence. Objectives We evaluated the interplay between PPC, LSR intensity (safety) and lesion clearance rates (effectiveness) on treatment satisfaction, quality of life and treatment adherence among patients with multiple AKs receiving topical field-directed therapies. Methods In this observational, multicentre, longitudinal, cohort study, we included 1136 adult patients with discrete, clinically detectable, visible, multiple (three or more lesions in a 25 cm(2) area), Grade I/II AKs, for whom the attending dermatologist has prescribed treatment with a topical field-directed therapy. We matched self-reported data and medical information recorded by dermatologists in standard clinical forms. Patients were followed up at two time points (T1: 8 days; T2: 25-30 days) Results Most patients were elderly, married, men with poor socio-economic status and multiple lesions of the scalp or face. The majority (n = 961) had a prescription of ingenol mebutate (IMB) and 175 received either diclofenac 3% in hyaluronic acid (DHA) or imiquimod 5% (IMQ). Clearance rate at 1 month was 84%. Most patients felt very supported (n = 819, 73%) and rated dermatologist's explanations very clear (n = 608, 54%). Treatment satisfaction (effectiveness and convenience scales) increased along the follow-up, especially for those on IMB (Delta(pre-post) = -4.00; other: Delta(pre-post) = -0.25; interaction P < 0.001). Communication clarity was associated with higher treatment satisfaction scores (beta = 0.4-0.6, P < 0.01) and lower risk of non-adherence among IMB patients (risk difference: 16%, P < 0.01). Conclusion Communication clarity was associated with patient-reported outcomes and adherence beyond AK-related clinical parameters. Our study questions the current episodic approach to AK management and provides the rationale to develop chronic care models fostering patients' engagement and treatment alliance.