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Background: A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. Here, health‐related quality of life (QoL) for this patient population is reported. Methods: Adult patients with mBCC were treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks/cycle then 4 treatment cycles of 12 weeks/cycle. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life‐Core 30 (QLQ‐C30) and Skindex‐16 questionnaires at baseline and Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales. Results: Patients reported low symptom burden and moderate‐to‐high functioning at baseline. Maintenance for QLQ‐C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline. Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue. On the Skindex‐16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%–88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales. Conclusions: The majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Greece on familial melanoma, a type of skin cancer that runs in families. The researchers aimed to identify genetic variations associated with familial melanoma in a Greek cohort and to understand how these variations relate to family and patient characteristics. The study found that the CDKN2A gene was the most common gene implicated in familial melanoma in Greece, with a higher frequency of pathogenic variations compared to other Mediterranean populations. Carriers of these variations were more likely to develop multiple primary melanomas at a younger age and had an increased number of nevi and atypical nevi. The study highlights the importance of genetic counseling and testing for families with a history of melanoma. [Extracted from the article]

Establishing and expanding protected areas (PAs) has become a key conservation tool in efforts to halt global declines in biodiversity. Given the ubiquity of past and present human influence, PAs inevitably include landscapes and seascapes with varying levels of human modification.We briefly review the geographical biases in England's terrestrial PA network, noting that landscape‐scale PAs (National Parks and Areas of Outstanding Natural Beauty) across England disproportionately occupy rugged upland terrain of low agricultural value as a result of the specific history of PA creation, but that this also biases which historic landscapes compose PAs.We explore these biases using Historic Landscape Characterisation (HLC). Analysis of HLC revealed that PAs in our focal region in northern England are defined by land‐use changes and landscape reorganisation processes of the 18th and 19th centuries, primarily that of enclosure. The impact this landscape transformation had on biodiversity should now form a priority for further research.This historic landscape influence on PA designation has resulted in PAs being typically owned by large estates with consequences for their biodiversity, management and wider social impact (e.g. greater wealth inequalities).The results highlight that historic landscape perspectives are useful to address conservation priorities and practices related to the protection of biodiversity and could be especially helpful in understanding the interaction between biodiversity protection and historic land‐uses, ownership, management, access and other social impacts. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Cutaneous melanoma may have an adjacent nevus remnant on histological examination in 30% of cases (nevus‐associated melanoma, NAM), while it may appear de novo, without a precursor lesion, in the remaining 70% of cases. Nevus‐associated melanoma and the concept of acquired melanocytic nevi serving as precursors of melanoma has long been considered as a controversial topic. This controversy is, in part, due to their overall low rate of transformation to melanoma and scarce data on the natural history of progression. Another matter of debate regarded the possibility that the reported differences in NAM vs. de novo melanoma were due to an underestimation of NAM in thicker lesions due to obliteration of the nevus component by the tumour. During the last few years, several evidence has accumulated in order to address these controversies. In this review, we present a comprehensive synthesis of the epidemiological, clinical, dermoscopic and genetic findings in NAM, including thin NAM, compared to de novo melanoma. Answering the questions on nevus‐associated melanoma may provide further insight into the classification of these tumours and disentangle their biology and route of development from that of de novo melanoma. [ABSTRACT FROM AUTHOR]

This article discusses the challenges of securing funding for research in dermatovenereology and highlights various funding opportunities in the EU framework program for skin disease. The authors emphasize the importance of advocating for better care for skin cancer patients in Europe and present examples of funded projects in the field. They also mention funding opportunities in the Innovative Health Initiative and Horizon Europe, specifically in the areas of personalized prevention in non-communicable diseases and cancer research. The article concludes by emphasizing the significance of EU funding opportunities in fostering innovation, research, and collaboration in dermatovenereology. [Extracted from the article]

Background: Several studies have started investigating the safety of temporal rejuvenation using soft tissue fillers. However, as the temporal region is highly vascularized, adverse events due to intravascular injection are of primary concern. The scarcity of treatment guidelines to date have focused primarily on avoiding the superficial and middle temporal arteries. The aim of the present anatomical study was to describe the topography of the deep temporal arteries (DTAs) with reference to superficial landmarks, to aid clinicians who perform temporal injections. Methods: The tissue layers of eight fresh‐frozen cephalic cadavers were dissected and assessed, bilaterally in the temporal region (N = 16). Distance (D) of the anterior (D1 and D3) and posterior (D2 and D4) arteries was measured from (i) the zygomaticofrontal suture line at the lateral orbital rim (D1 and D2) and (ii) the junction of the superior border of the zygomatic arch and lateral orbital rim (D3 and D4). The distance between the anterior and posterior DTAs was also recorded, at the two regions (D5). Results: Bifurcations of the DTAs were observed in 18.75% (3/16) and 12.5% (2/16) of cases, for the anterior and posterior branches, respectively. On average [mean (standard deviation)], D1 (anterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 1.56 cm (0.59); D2 (posterior DTA to the zygomaticofrontal suture line at the lateral orbital rim) = 2.98 cm (0.70); D3 (anterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 1.14 cm (0.63); D4 (posterior DTA to the junction of the superior border of the zygomatic arch and lateral orbital rim) = 2.37 cm (0.62); and D5 (distance between the anterior and posterior DTAs) = 1.54 cm (0.68). Conclusion: To help avoid vascular adverse events while performing temporal injections, aesthetic clinicians should be conscientious of safety implications related to the anatomical location of the DTAs and their ramifications. [ABSTRACT FROM AUTHOR]

Cutaneous invasive squamous cell carcinoma (cSCC) most commonly presents as a typically indolent tumour with five‐year cure rates of >90%. Advanced cSCC has been defined as locally advanced or metastatic (locoregional or distant) cSCC. The epidemiological data on advanced cSCC are rare due to underreporting or exclusion of cSCC from national cancer registries. Although the frequency of local recurrence has been reported, there is no clear evidence on the incidence or mortality of locally advanced cSCCs, e.g. locally infiltrating or locally recurrent cSCCs that are not further amenable to curative surgery or radiotherapy. This gap of knowledge on the epidemiology of locally advanced cSCC, highlights the need for standardisation in defining and reporting both locally advanced and metastatic cSCC. Even though metastatic cSCCs are a small part of cSCCs (3%–5%), their aggressive characteristics contribute to significant morbidity, higher mortality and are those likely to require systemic treatments. Locally recurrent and metastatic cSCC may occur more frequently in high‐risk cSCCs (up to 35%). The site of metastasis involves in the vast majority the regional lymph nodes, with the head and neck lymph nodes or parotid most commonly affected. Metastasis occurs mostly within 2–3 years of the primary cSCC diagnosis. The knowledge of the incidence and prognosis of advanced cSCC and the risk stratification of patients, who may progress to advanced cSCC, emerge as pressing research areas with important implications for cost‐efficiency planning and optimisation of patient care. [ABSTRACT FROM AUTHOR]

Summary: Re‐evaluation of recorded sites and new field survey have identified 30 island dwellings in Shetland which are argued to be part of the wider Scottish Iron Age crannog building tradition. Four were subject to field survey above and below water and found to be at least partly artificial. The morphology, distribution and chronology of Shetland's artificial islands are discussed and compared to the rest of Scotland emphasizing their parallels. The results support the recent move towards considering islet duns and brochs as crannogs. These newly identified sites in Shetland underline the ubiquity of the crannog building tradition in Scotland. Through discussion of the morphology, distribution and chronology of crannogs in Shetland and the rest of Scotland, it is argued that artificial island dwelling is a widely shared cultural practice and an underlying principle of Scottish Iron Age settlement. [ABSTRACT FROM AUTHOR]

Melanoma is the 5th most common cancer in both males and females in Europe and the United States and remains the most serious form of skin cancer. In a retrospective multicentre DeCOG study,[10] Kahler et al showed that early macular rash within 6 weeks after therapy start was correlated to therapy outcome in patients treated with vemurafenib plus cobimetinib. [Extracted from the article]

Background: Imiquimod 3.75% is a field‐directed treatment for actinic keratosis that can detect and treat clinical and subclinical lesions across an entire sun‐exposed field. The detection of subclinical lesions is evidenced by an increase in lesions to the maximum lesion count during treatment (Lmax). We report clinical outcomes for the first 15 patients treated with imiquimod 3.75% in daily clinical practice in Greece. Methods: Fifteen patients with actinic keratosis lesions were treated with imiquimod 3.75% in an outpatient setting in two 2‐week treatment cycles separated by a 2‐week treatment‐free interval. Actinic keratosis lesions were counted before treatment, at the end of the first treatment cycle (Week 2; Lmax), and 2 weeks after the second treatment cycle (Week 8). Local skin reactions (LSR) were also evaluated at Weeks 2 and 8. Results: The median baseline actinic keratosis lesion count was 25, which increased to a median Lmax of 29 at Week 2 and decreased to a median of 5 at Week 8. The median percentage and absolute reduction in actinic keratosis lesions from Lmax to Week 8 were 87% and 23%, respectively. Most of the LSR were mild‐to‐moderate in intensity at Week 2 and had resolved by Week 8. Conclusion: Imiquimod 3.75% effectively detected and cleared both the clinical and subclinical actinic keratosis lesions across the entire sun‐exposed field in this cohort of Greek patients. Treatment was well tolerated. [ABSTRACT FROM AUTHOR]

Insulin‐like growth factor‐I (IGF‐I) regulates cell proliferation and apoptosis, and is thought to play a role in tumour development. Previous prospective studies have shown that higher circulating concentrations of IGF‐I are associated with a higher risk of cancers at specific sites, including breast and prostate. No prospective study has examined the association between circulating IGF‐I concentrations and melanoma risk. A nested case–control study of 1,221 melanoma cases and 1,221 controls was performed in the European Prospective Investigation into Cancer and Nutrition cohort, a prospective cohort of 520,000 participants recruited from 10 European countries. Conditional logistic regression was used to estimate odds ratios (ORs) for incident melanoma in relation to circulating IGF‐I concentrations, measured by immunoassay. Analyses were conditioned on the matching factors and further adjusted for age at blood collection, education, height, BMI, smoking status, alcohol intake, marital status, physical activity and in women only, use of menopausal hormone therapy. There was no significant association between circulating IGF‐I concentration and melanoma risk (OR for highest vs lowest fifth = 0.93 [95% confidence interval [CI]: 0.71 to 1.22]). There was no significant heterogeneity in the association between IGF‐I concentrations and melanoma risk when subdivided by gender, age at blood collection, BMI, height, age at diagnosis, time between blood collection and diagnosis, or by anatomical site or histological subtype of the tumour (Pheterogeneity≥0.078). We found no evidence for an association between circulating concentrations of IGF‐I measured in adulthood and the risk of melanoma. What's new? A possible association between the insulin‐like growth factor (IGF‐I) and the risk of melanoma has been proposed, but with inconclusive results so far. In this prospective study, the authors found no evidence for an association between circulating IGF‐I concentrations and melanoma risk. Although details on major risk factors like sun exposure were missing, the large sample size with more than 1000 incident melanoma cases underscores the relevance of the finding. [ABSTRACT FROM AUTHOR]

The role of tumor infiltrating immune cells in cancer development and progression is a new, promising field in oncological research. An increasing number of novel anti‐cancer agents are focussing on the tumor microenvironment. Various studies have reported on B‐cell infiltrates in mycosis fungoides (MF), but despite the substantial volume of interesting findings, solid evidence regarding their specific role in cancer is still vague. We present a case of tumor stage MF responding to rituximab. We support the hypothesis that lymphoma‐infltrating B‐cells have a significant impact on cutaneous lymphoma course and seem to be both an important and effective therapeutic target. The reduction of B‐cell population led to disease's overall remission, probably by restoring patient's immunologic tumor control. [ABSTRACT FROM AUTHOR]

Background: Many melanoma observational studies have been carried out across different countries and geographic areas using heterogeneous assessments of epidemiologic risk factors and clinical variables. Aim: To develop a consensus questionnaire to standardize epidemiologic and clinical data collection for melanoma risk assessment. Methods: We used a stepwise strategy that included: compilation of variables from case–control datasets collected at various centres of the MelaNostrum Consortium; integration of variables from published case–control studies; consensus discussion of the collected items by MelaNostrum members; revision by independent experts; addition of online tools and image‐based charts; questionnaire testing across centres and generation of a final draft. Results: We developed a core consensus questionnaire (MelanoQ) that includes four separate sections: A. general and demographic data; B. phenotypic and ultraviolet radiation exposure risk factors and lifestyle habits; C. clinical examination, medical and family history; and D. diagnostic data on melanoma (cases only). Accompanying online tools, informative tables, and image‐based charts aid standardization. Different subsections of the questionnaire are designed for self‐administration, patient interviews performed by a physician or study nurse, and data collection from medical records. Conclusions: The MelanoQ questionnaire is a useful tool for the collection and standardization of epidemiologic and clinical data across different studies, centres, cultures and languages. This will expedite ongoing efforts to compile high‐quality data for pooled analyses or meta‐analyses and offer a solid base for the design of clinical, epidemiologic and translational studies on melanoma. [ABSTRACT FROM AUTHOR]

For anthropophilic tinea capitis ( TC), household spread and asymptomatic scalp carriage ( ASC) is considered an important route of transmission and incomplete clearance. To investigate ASC in household contacts of patients diagnosed with TC in a tertiary hospital in Athens, Greece, we retrospectively reviewed the medical files of household contacts that were screened for ASC from 1997 to 2011. Only 34 household contacts of 15 index cases agreed to come for screening. Thirty-three (97%) household contacts were asymptomatic scalp carriers. The most commonly isolated species was Trichophyton violaceum (59%). There was a statistically significant association of ASC with the isolated dermatophyte species ( T. violaceum, P-value: 0.029), and with the age of younger than 16 years old ( P-value: 0.005), while there was no association with gender ( P-value: 0.672). A small number of household contacts accepted to proceed for screening. ASC was found in nearly all screened household contacts and was associated with T. violaceum and younger age. The low number of household contacts that accepted screening may reflect the ignorance of the general population about the possibility of ASC among household contacts in case of a patient with TC. [ABSTRACT FROM AUTHOR]

Epigenetic mechanisms participate in melanoma development and progression. The effect of histone modifications and their catalysing enzymes over euchromatic promoter DNA methylation in melanoma remains unclear. This study investigated the potential association of p16 INK 4A promoter methylation with histone methyltransferase SETDB1 expression in Greek patients with sporadic melanoma and their correlation with clinicopathological characteristics. Promoter methylation was detected by methylation-specific PCR in 100 peripheral blood samples and 58 melanoma tissues from the same patients. Cell proliferation (Ki-67 index), p16 INK4A and SETDB1 expression were evaluated by immunohistochemistry. High-frequency promoter methylation (25.86%) was observed in tissue samples and correlated with increased cell proliferation ( P = 0.0514). p16 INK 4A promoter methylation was higher in vertical growth-phase (60%) melanomas than in radial (40%, P = 0.063) and those displaying epidermal involvement ( P = 0.046). Importantly, p16 INK 4A methylation correlated with increased melanoma thickness according to Breslow index ( P = 0.0495) and marginally with increased Clark level (I/ II vs III/ IV/V, P = 0.070). Low (1-30%) p16 INK4A expression was detected at the majority (19 of 54) of melanoma cases (35.19%), being marginally correlated with tumor lymphocytic infiltration ( P = 0.078). SETDB1 nuclear immunoreactivity was observed in 47 of 57 (82.46%) cases, whereas 27 of 57 (47.37%) showed cytoplasmic immunoexpression. Cytoplasmic SETDB1 expression correlated with higher frequency of p16 INK 4A methylation and p16 INK4A expression ( P = 0.033, P = 0.011, respectively). Increased nuclear SETDB1 levels were associated with higher mitotic count (0-5/mm2 vs >5/mm2, P = 0.0869), advanced Clark level ( III-V, P = 0.0380), epidermal involvement ( P = 0.0331) and the non-chronic sun exposure-associated melanoma type ( P = 0.0664). Our data demonstrate for the first time the association of histone methyltransferase SETDB1 with frequent methylation of the euchromatic p16 INK 4A promoter and several prognostic parameters in melanomas. [ABSTRACT FROM AUTHOR]

TNF is critically involved in the pathogenesis of psoriasis. TL1A is a TNF-like cytokine, which, after binding to death domain receptor DR3, provides costimulatory signals to lymphocytes, amplifies Th1- and Th17-mediated immune responses and induces apoptotic cell death. These functions are inhibited when TL1A associates to decoy receptor DcR3. In the present study, we investigated the expression profiles for TL1A, DR3 and DcR3 in the normal skin and in psoriatic skin lesions. By use of immunohistochemistry, we were able to demonstrate constitutive cutaneous expression of DR3 and DcR3 but not of TL1A in healthy skin. On the other hand, in patients with active psoriasis, we observed abundant immunostaining for TL1A and significant upregulation of its receptors ( P < 0.05 in comparison to healthy skin). TL1A, DR3 and DcR3 proteins, as well as mRNA transcripts reflecting in situ production of TL1A and DcR3, were also specifically increased in lesional as compared to non-lesional skin from patients with psoriasis ( P < 0.05). These proteins were upregulated in cell populations that are critically involved in the pathogenesis of chronic skin inflammation, such as keratinocytes, macrophages in deep dermis and cells at the perivascular/endothelial area. Finally, we provide evidence for the existence of nuclear localization of TL1A in inflammatory cells from psoriatic lesions. This was also observed in inflamed synovia from patients with rheumatoid arthritis, but not in neoplastic TL1A-expressing cell lines. We conclude that interactions between TL1A and its two receptors may be involved in the pathogenesis of chronic skin inflammation that takes place in psoriasis. [ABSTRACT FROM AUTHOR]

The significance of human cutaneous pigmentation lies in its protective role against sun-induced DNA damage and photocarcinogenesis. Fair skin and red hair are characterized by a low eumelanin to pheomelanin ratio, and have been associated with increased risk of skin cancer. Cutaneous pigmentation is a complex genetic trait, with more than 120 genes involved in its regulation, among which the melanocortin 1 receptor gene ( MC1R) plays a key role. Although a large number of single nucleotide polymorphisms (SNPs) have been identified in pigmentation genes, very few SNPs have been examined in relation to human pigmentary phenotypes and skin cancer risk. Recent GWAS have identified new candidate determinants of pigmentation traits, but MC1R remains the best characterized genetic determinant of human skin and hair pigmentation as well as the more firmly validated low-penetrance skin cancer susceptibility gene. In this review, we will address how the melanocortin system regulates pigmentation, the effect of MC1R variants on the physiologic function of the MC1 receptor, and how specific MC1R variants are associated with distinct human pigmentation phenotypes. [ABSTRACT FROM AUTHOR]

Background: Basal cell carcinoma (BCC) is the most common form of skin cancer with increasing incidence rates worldwide. Methods: To assess the association of BCC with epidemiologic risk factors in a Southern European population from Greece, we conducted a hospital-based case-control study of 199 patients with BCC and 200 controls. Results: In the multivariate analysis, fair skin colour was associated with increased risk of BCC (OR: 4.9, 95% CI: 2.4- 10.0). However, darker skin phototypes III/IV (patient's reported sun sensitivity/tanning ability) showed a higher BCC risk (OR: 3.9, 95% CI: 1.8-8.5). Persons with occupational UV exposure of 5 years or more had a 2.7-fold increased risk (95% CI:1.4-5.3). There was an increased risk of BCC related to the number of sunburns after the age of 20 years (OR: 3.2, 95% CI: 1.4-7.3) and solar lentigines (OR: 6.8, 95% CI: 3.6-12.8). Subgroup analysis showed that different risk factors are associated with early onset BCC including the presence of dysplastic nevi (OR: 6.4, 95% CI: 1.5-27.2), the number of weeks per year spent at the beach during childhood (OR: 8.9, 95% CI: 3.3-24.1) and the history of sunburns during childhood (OR:5.0, 95% CI: 1.3-19.1). Conclusions: Fair skin colour was significantly associated with BCC risk. The relation of sunburns during adulthood with BCC underlies the importance of sunburn prevention throughout life time. Early onset BCCs seem to have a different pathogenetic background and were associated with dysplastic nevi as well as intermittent sun exposure and sunburns during the early years of life. [ABSTRACT FROM AUTHOR]

Use of biological agents has been shown to be an efficacious approach in psoriasis, when traditional treatments fail. However, there are limited data on the effectiveness and safety of switching from one biological agent to another. We aimed to evaluate the effectiveness and safety of etanercept as a sequential treatment in patients previously treated with efalizumab, and to evaluate different transition strategies from efalizumab to etanercept. We present a retrospective study in patients with high-need plaque psoriasis who were unable to continue efalizumab and were immediately switched to etanercept. We included 35 patients during a 4.5-year period. At 24 weeks of etanercept therapy, 57% of patients had a PASI reduction of 75%, suggesting that alternating between biological agents is feasible. We used three different switching approaches: (i) etanercept in combination with cyclosporine as bridge therapy, (ii) etanercept in combination with methotrexate as bridge therapy, (iii) etanercept monotherapy. Combination therapy was efficacious in all patients, including eight patients with rebound phenomenon with efalizumab. Etanercept was discontinued in two patients as a result of serious adverse events that consisted of an oral squamous cell carcinoma and a diffuse B-cell-non-Hodgkin lymphoma. In our experience, it seems that etanercept alone may not be sufficient when transitioning from efalizumab in high-need patients with severe worsening or rebound of psoriasis. In such patients, combination of etanercept with cyclosporine or methotrexate is a more effective approach. Non-response to efalizumab did not preclude clinical response after switching to etanercept. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common skin cancer in white populations with an increasing incidence worldwide, thereby imposing an important public health problem. Its etiology is still unclear, but existing data indicate that the risk for BCC development is of multifactorial origin and results from the interplay of both constitutional and environmental factors. Yet, UV radiation (UVR) is believed to be the predominant causative risk factor in the pathogenesis of BCC. For years, BCC and squamous cell carcinoma (SCC) have been grouped together as “nonmelanoma skin cancer.” However, it seems that there are considerable biologic differences between BCC and SCC, and thus each type of epithelial cancer should be addressed separately. The present review provides an overview of the intriguing etiologic link of BCC with UVR and attempts a comprehensive review of recent epidemiologic and molecular evidence that supports this association. [ABSTRACT FROM AUTHOR]

Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. The discovery of genes that regulate melanocytic development and function and the identification of disease-causative mutations have greatly improved our understanding of the molecular basis of pigmentary genodermatoses and their underlying pathogenetic mechanisms. Pigmentation mutants can account for hypo-/amelanosis, with or without altered melanocyte number, resulting in different phenotypes, such as Waardenburg syndrome, piebaldism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, oculocutaneous albinism and Griscelli syndrome. In this review, we summarize the basic concepts of melanocyte biology and discuss how molecular defects in melanocyte development and function can result in the development of hypopigmentary hereditary skin diseases. [ABSTRACT FROM AUTHOR]

There is a limited literature reporting on acne in childhood. Childhood acne can be classified in neonatal, infantile, mid-childhood, and prepubertal acne, depending on the age of onset. In this review we will present an update on the clinical approach and therapeutic options when facing prepubertal acne in a child. The use of tetracyclines is contraindicated in children younger than 8 years, and oral isotretinoin is not recommended in children younger than 12 years of age according to the FDA and the European Commission. Nevertheless, there are case reports of 10 patients successfully treated with oral isotretinoin for recalcitrant infantile acne with scarring. Further studies are needed to investigate whether isotretinoin may improve the long-term prognosis of infantile acne, which may be associated with more severe acne in adolescence. [ABSTRACT FROM AUTHOR]

Objective: Skin cancer campaigns have only recently been implemented in a wide scale in Greece. In order to better target those individuals at risk, we aimed to explore sun exposure behaviors in a sample of the Greek population. Methods: A total of 802 subjects, randomly selected among the residents of the two largest Greek cities, underwent a questionnaire-based telephone interview, assessing the degree of sun exposure patterns and knowledge of skin cancer risk factors. Results: Females more commonly (90%) used sunscreens compared with males (67.5%), and among sunscreen users, only 8% used products with SPF <10. Almost half of the participants (48%) preferred going to the beach during the midday hours. Over exposure to the sun was mostly reported by individuals with phototypes III/IV and of younger age (18–35 years). Most participants were aware of sun exposure as a cause of skin cancer, but among those who did not, 41% were younger than 34 years of age. Conclusions: In our survey, significant differences in age, sex and phototypes were observed with regard to sun exposure patterns and sunscreen use. Educational campaigns should focus more on younger age groups, encouraging a more complete set of photoprotective measures. However, potential trial limitations inherent in self-reported measures should be taken into account. [ABSTRACT FROM AUTHOR]

The popularity of sunscreens dramatically increased since ultraviolet irradiation was implicated in the pathogenesis of skin cancer and skin ageing. The absorption properties, safety, photostability of different organic and inorganic filters are reviewed: para-aminobenzoic acid, salicylates, cinnamates, benzophenones, butylmethoxydibenzoylmethane (Parsol 1789), drometrizole trisulphonic (Mexoryl XL), terephthalydene dicamphor sulphonic acid (Mexoryl SX), methylene bisbenzotriazol tetramethylbutylphenol (Tinasorb M), anisotriazine (Tinasorb S), titanium dioxide and zinc oxide. Furthermore, this review discusses the optimal methods for measuring the protection that a sunscreen offers, the role of sunscreen use in melanoma prevention and future trends in sunscreen filters development. [ABSTRACT FROM AUTHOR]

Background Several investigators have described a seasonal variation in the diagnosis of cutaneous melanoma. Limited data exist on the seasonality of melanoma diagnosis in Southern European countries. Patients and methods The seasonal pattern of diagnosis was analyzed in 404 Greek patients diagnosed with cutaneous melanoma (CM) between 1996 and 2004. A summer-to-winter ratio was determined overall and in relation to gender, age, anatomic site, histopathologic type, and tumor thickness. Results The summer-to-winter ratio was 1.53 for all patients (95% CI [confidence interval]: 1.15–2.02) with a ratio of 1.83 for women (95% CI: 1.20–2.78) and 1.28 for men (95% CI: 0.87–1.88). A seasonal pattern of melanoma diagnosis was observed for patients younger than 50 years of age (1.70, 95% CI: 1.05–2.74) and between 50 and 69 years (1.64, 95% CI: 1.05–2.56), for melanoma located on the upper or lower extremities (2.50, 95% CI: 1.12–5.56 and 2.23, 95% CI: 1.19–4.18, respectively), for superficial spreading and nodular melanomas (1.73, 95% CI: 1.12–2.69 and 1.52 95% CI: 0.96–2.41) and for melanomas with a tumor thickness of 1–2 mm (1.69, 95% CI: 0.91–3.12) and > 4 mm (2.13, 95% CI: 1.04–4.35). Conclusions No major differences were seen in the seasonal distribution of CM diagnosis in a Mediterranean population compared to previously reported results. A better ascertainment of the skin during the summer and an increased awareness due to the melanoma screening campaigns are the more likely reasons for the seasonality of melanoma diagnosis in Greece. [ABSTRACT FROM AUTHOR]

Cutaneous hypermelanoses are frequently encountered conditions that can have severe adverse psychosocial and emotional effects on affected patients. Melasma, postinflammatory hyperpigmentation, drug-induced pigmentation, and erythema dischromicum perstans are among the most common cutaneous disorders leading to acquired skin hyperpigmentation. The treatment of these disorders is often challenging and requires a great deal of patience from the patient and a wealth of experience and knowledge from the dermatologist. Current treatments include depigmenting agents, chemical peels, and lasers. The ideal bleaching agent has to fulfill certain pharmacologic criteria. It should have a potent bleaching effect with a rapid time of onset, carry no side effects, and lead to a permanent removal of undesired pigment. We review the established treatment approaches of cutaneous hyperpigmentation based on literature review and our personal experience. [ABSTRACT FROM AUTHOR]

Laser resurfacing of photodamaged or scarred skin has traditionally involved the use of ablative lasers with their associated limitations and side effects. Nonablative skin rejuvenation is a relatively new concept in facial rejuvenation, which aims to induce dermal remodeling without visible epidermal disruption. A number of laser devices and light sources, emitting at various wavelengths, have been shown to effectively enhance the appearance of facial skin through nonablative mechanisms. Among the conditions that can be treated with this novel modality are erythema, telangiectasia, pigmentation, lentigines, and textural imperfections ranging from fine and moderate rhytides to other surface irregularities such as acne scarring. A major attraction of nonablative laser therapy is the very limited downtime after each treatment, making it an ideal method for patients seeking a minimally invasive procedure with an excellent safety profile. [ABSTRACT FROM AUTHOR]

Sunlight precipitates a series of genetic events that lead to the development of skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The p53 tumour suppressor gene, which plays a pivotal role in cell division and apoptosis, is frequently found mutated in sunlight-induced skin tumours.To investigate the immunoreactivity of the p53 gene in non-melanoma skin cancers and to correlate its expression with apoptotic and cell proliferation markers.We analysed 35 non-melanoma tumours including 19 BCCs and 16 SCCs from sun-exposed skin areas. p53 protein expression was studied immunohistochemically using the DO7 monoclonal antibody against wild-type and mutant p53 forms. The percentage of p53-immunopositive nuclei was measured by image analysis. Cell proliferation and apoptosis were also assessed by image analysis following Ki-67 immunostaining and application of the TUNEL method on paraffin sections, respectively.The percentage of p53-expressing cells varied from 3.5 to 90 in BCCs (median value 54.4%) and from 3.7 to 94 in SCCs (median value 40.3%). The mean value of Ki-67-positive cells was comparable in both groups of tumours with a mean value of 40.6% in BCCs and 34.6% in SCCs. Conversely, the TUNEL assay showed sporadic staining of apoptotic cells within the tumours with a mean value of 1.12% in BCCs and 1.8% in SCCs. p53 protein expression was correlated positively with cell proliferation (r = 0.75,P = 0.000001) and negatively with apoptosis (r = −0.23,P = 0.05).p53 immunoreactivity was high in the majority of the skin carcinomas examined and correlated positively with cell proliferation and negatively with apoptosis. The p53 protein overexpression appears to be related to an inactivated protein resulting from mutations of the p53 gene or other unclear molecular mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Background Idiopathic photodermatoses are considered to be common disorders in the population of northern latitude countries, presumably because of the dominance of more “sun-sensitive” individuals with a light-skinned complexion. The incidence of these disorders in the Mediterranean or tropical countries is often under-appreciated because of the higher degree of perennial presence of sunlight and the prevalence of darker skin-type individuals who are seemingly more resistant to the development of sun sensitivity. Methods We performed a retrospective, chart-based review of all patients who were diagnosed with idiopathic photodermatoses at a photodermatology referral center in Athens, Greece, during a period of 10 years. Our aim was to assess the pattern of idiopathic photosensitivity disorders in a Mediterranean country and to determine their epidemiological, clinical, and photobiological profile. Results A total of 310 patients were referred to our center with symptoms of photosensitivity. One hundred and forty-six patients (47.0%) were diagnosed with an idiopathic photosensitivity disorder by means of history, clinical examination, biochemical screening, histology, and phototesting. The most prevalent disorder was polymorphous light eruption, which was diagnosed in 95 patients (65.0%) of our cohort. Chronic actinic dermatitis occurred in 15 patients (10.2%), solar urticaria in 26 patients (17.8%), actinic prurigo in three patients (2.0%), hydroa vacciniforme in one patient (0.6%) and juvenile spring eruption in six patients (4.1%). Conclusions Compared with the results of other studies, the prevalence of idiopathic photodermatoses appears to have a similar trend to that of higher latitude countries. Distinct features in our series include the higher incidence of idiopathic photosensitivity in patients with a fair-skinned complexion (skin types II–III) and the frequent appearance of photo-induced eruptions during sunny weather... [ABSTRACT FROM AUTHOR]

Melanocortin 1 receptor ( MC1R) gene variants are a major contributor to pigmentation characteristics and the modulation of sporadic basal cell carcinoma ( BCC) risk. This is a hospital-based, case-control study to investigate the association of MC1R variants and pigmentary characteristics with the risk of BCC development in a Southern European population in Greece. In total, 141 patients with BCC and 166 controls were studied. Increased BCC risk was found for the presence of 2 or more MC1R variants ( OR:3.07, 95% CI:1.13-8.34), or 2 or more variants of which at least 1 was major function ( OR:7.15, 95% CI:1.37-5.52), after adjustment for the 'red hair colour' ( RHC) phenotype. Increased BCC risk persisted in the presence of 2 or more MC1R variants ( OR:4.15, 95% CI:1.35-12.72), after adjustment for potential confounding factors including skin color ( P:0.237) and atypical nevi ( OR:9.57, 95% CI:2.19-41.81, P:0.003). MC1R genotype is a risk factor for the development of BCC in Greek patients independently of pigmentary characteristics, and the combination of MC1R variants may modulate this risk. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the use of infliximab in treating a patient with central retinal vein occlusion (CRVO).

The SLC24A5 gene, the human orthologue of the zebrafish golden gene, has been shown to play a key role in human pigmentation. In this study, we investigate the prevalence of the variant allele rs1426654 in a selected sample of Greek subjects. Allele-specific polymerase chain reaction was performed in peripheral blood samples from 158 attendants of a dermatology outpatient service. The results were correlated with pigmentary traits and MC1R genotype. The vast majority of subjects (99%) were homozygous for the Thr 111 allele. Only two subjects from the control group (1.26%) were heterozygous for the alanine and threonine allele. Both of these Thr 111 /Ala 111 heterozygotes carried a single polymorphism of MC1R (one with the V92M variant and another with the V60L variant). Following reports of the rs1426654 polymorphism reaching fixation in the European population, our study of Greek subjects showed a prevalence of the Thr 111 allele, even among subjects with darker skin pigmentation or phototype. [ABSTRACT FROM AUTHOR]

Linear scleroderma is an unusual form of localised scleroderma, mainly affecting the legs and occurring primarily in children. Sometimes the linear lesions may extend to involve the underlying muscles and bones, with severe disturbances in growth and possibly flexion deformities of the legs.1,2,3,4. In this study, two cases suffering from linear scleroderma of the legs are presented. [ABSTRACT FROM AUTHOR]

The article presents a study of a 34-year-old woman who became pregnant during adalimumab therapy. The woman received adalimumab for psoriasis with excellent response for 3 months prior to conception and during 5 weeks of gestation. It notes that the number of reported pregnancies exposed to anti-tumor necrosis factor (TNF) therapies is small and no conclusion can be drawn on its safety during pregnancy. TNF is also important for the development of immune system.

A letter to the editor is presented in response to the article "Arthralgia as an adverse event to infliximab: a reactive arthritis or triggering of psoriatic arthritis? Successful management by switching to etanercept".

Background: Most of large epidemiological studies on melanoma susceptibility have been conducted on fair skinned individuals (US, Australia and Northern Europe), while Southern European populations, characterized by high UV exposure and dark-skinned individuals, are underrepresented., Objectives: We report a comprehensive pooled analysis of established high- and intermediate-penetrance genetic variants and clinical characteristics of Mediterranean melanoma families from the MelaNostrum Consortium., Methods: Pooled epidemiological, clinical and genetic (CDKN2A, CDK4, ACD, BAP1, POT1, TERT, and TERF2IP and MC1R genes) retrospective data of melanoma families, collected within the MelaNostrum Consortium in Greece, Italy and Spain, were analysed. Univariate methods and multivariate logistic regression models were used to evaluate the association of variants with characteristics of families and of affected and unaffected family members. Subgroup analysis was performed for each country., Results: We included 839 families (1365 affected members and 2123 unaffected individuals). Pathogenic/likely pathogenic CDKN2A variants were identified in 13.8% of families. The strongest predictors of melanoma were ≥2 multiple primary melanoma cases (OR 8.1; 95% CI 3.3-19.7), >3 affected members (OR 2.6; 95% CI 1.3-5.2) and occurrence of pancreatic cancer (OR 4.8; 95% CI 2.4-9.4) in the family (AUC 0.76, 95% CI 0.71-0.82). We observed low frequency variants in POT1 (3.8%), TERF2IP (2.5%), ACD (0.8%) and BAP1 (0.3%). MC1R common variants (≥2 variants and ≥2 RHC variants) were associated with melanoma risk (OR 1.4; 95% CI 1.0-2.0 and OR 4.3; 95% CI 1.2-14.6, respectively)., Conclusions: Variants in known high-penetrance genes explain nearly 20% of melanoma familial aggregation in Mediterranean areas. CDKN2A melanoma predictors were identified with potential clinical relevance for cancer risk assessment., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. National and international associations have issued evidence- and consensus-based guidelines to offer clinicians a framework to optimally manage patients with invasive cSCC. Current updated guidelines regarding the recommendations on the management of patients with high-risk and advanced cSCC include EDF/EADO (European) Guidelines 2020, US National Comprehensive Cancer Network guidelines 2021, American Academy of Dermatology guidelines 2018, British Association of Dermatology guidelines 2020 and German guidelines 2020. This review presents the guideline recommendations on the definition of high-risk and advanced cSCC, surgical treatment and safety margins, definitive and adjuvant radiotherapy and systemic treatments. The recommendations across guidelines may converge, diverge or in some cases not be able to provide a recommendation, highlighting open questions to be answered by future studies., (© 2021 European Academy of Dermatology and Venereology.)

Background: Retinoids have long been used in the treatment of cutaneous T-cell lymphomas. However, data on acitretin use for mycosis fungoides (MF) are very limited., Objectives: To evaluate treatment outcomes of acitretin in patients with MF attending three academic referral centres in different regions of Greece., Methods: Data on effectiveness, safety and drug survival of acitretin as monotherapy or as adjuvant regimen were collected in a multicentre, register-based, retrospective study., Results: Overall, 128 patients (64.8% male; mean age at MF diagnosis 59.7 years) were included. Folliculotropic MF was present in 24 (18.8%) cases. Most patients (n = 118; 92.2%) had early-stage disease (≤IIA) at acitretin initiation. In all, 28 (21.9%) patients received acitretin monotherapy, while 100 (78.1%) subjects on acitretin concomitantly received phototherapy (n = 65; 50.8%) or topical steroids (n = 27; 21.1%). Acitretin was given as a first-line agent in 73 (57%) cases. A 77.3% overall response rate was noted: 44.5% and 32.8% for complete and partial responses, respectively. Acitretin was more effective as first-line than as a subsequent agent (P = 0.008). A trend towards better response was observed in the combination arm compared to patients receiving acitretin alone (P = 0.056). Median time to best response was 6.9 months (IQR 4.4-9.4); median duration of response was 23.7 months (IQR 11.9-35.4). Overall, the mean length of all treatment patterns was 569 days (SD 718.8). Therapy was discontinued in 5 (3.9%) cases due to drug intolerance. Adverse effects were recorded in 62 (48.4%) cases with dyslipidaemia (n = 31; 24.2%), xerosis (n = 24; 18.6%) and hair loss (n = 10; 7.8%) being the most commonly recorded., Conclusions: Acitretin, either alone or as adjuvant, showed a stable long-term effectiveness in this cohort, especially when used in the first-line setting. This RAR-selective agonist may serve as an attractive option for treatment of MF and should be further evaluated., (© 2020 European Academy of Dermatology and Venereology.)

Background: The incidence of skin cancers has been increasing steadily over the last decades. Although there have been significant breakthroughs in the management of skin cancers with the introduction of novel diagnostic tools and innovative therapies, skin cancer mortality, morbidity and costs heavily burden the society., Objective: Members of the European Association of Dermato-Oncology, European Academy of Dermatology and Venereology, International Dermoscopy Society, European Dermatology Forum, European Board of Dermatovenereology of the European Union of Medical Specialists and EORTC Cutaneous Lymphoma Task Force have joined this effort to emphasize the fundamental role that the specialist in Dermatology-Venereology has in the diagnosis and management of different types of skin cancer. We review the role of dermatologists in the prevention, diagnosis, treatment and follow-up of patients with melanoma, non-melanoma skin cancers and cutaneous lymphomas, and discuss approaches to optimize their involvement in effectively addressing the current needs and priorities of dermato-oncology., Discussion: Dermatologists play a crucial role in virtually all aspects of skin cancer management including the implementation of primary and secondary prevention, the formation of standardized pathways of care for patients, the establishment of specialized skin cancer treatment centres, the coordination of an efficient multidisciplinary team and the setting up of specific follow-up plans for patients., Conclusion: Skin cancers represent an important health issue for modern societies. The role of dermatologists is central to improving patient care and outcomes. In view of the emerging diagnostic methods and treatments for early and advanced skin cancer, and considering the increasingly diverse skills, knowledge and expertise needed for managing this heterogeneous group of diseases, dermato-oncology should be considered as a specific subspecialty of Dermatology-Venereology., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Although considered as a first-group carcinogen, indoor tanning is a common practice in Europe. Euromelanoma is a pan-European skin cancer prevention campaign., Objectives: To compare several European countries in terms of the prevalence and determinants of sunbed use., Methods: Participants in the Euromelanoma campaigns filled in questionnaires containing demographics and risk factors, including type/duration of sunbed use. Multivariate analyses adjusted for age, gender, education, skin type and year of survey were employed to assess factors independently associated with sunbed use in each country., Results: In total, 227 888 individuals (67.4% females, median age 44, 63.4% highly educated, 71.9% skin types III-VI) from 30 countries participated. Overall, the prevalence of sunbed ever use was 10.6% (≤19-year-olds: 5.9%; 20 to 35-year-olds: 17.0%; >35-year-olds: 8.3%). Females displayed a higher prevalence than males in all countries. Balkan countries displayed the highest female/male ratios (≥4). Sunbed use was significantly more prevalent among skin type III-VI (14/30 countries) and highly educated participants (11/30 countries). Significant correlations were found between sunbed use prevalence and countries' latitude (P < 0.001) and sunshine (P = 0.002); Italy and Spain represented exceptions towards excessive exposure. Very different prevalence rates were found for Spain (19.3%) and Portugal (2.0%). Scandinavian countries ranked highest in sunbed use among ≤19-year-olds, Baltic countries among 20 to 35-year-olds., Conclusions: Sunbed use prevalence was higher in northern, sun-deprived countries, with the exception of Italy and Spain. The main determinants of sunbed use were age (young adults) and gender (females), whereas education and skin type had a less relevant effect. Geographic particularities were found in four regions: Iberian (prevalence ten times higher in Spain than Portugal), Balkan (prevalence disproportionately higher among women), Baltic (highest prevalence among young adults) and Scandinavian (highest prevalence among adolescents). These data have public health relevance for future interventions aimed at reducing sunbed use in Europe., (© 2019 European Academy of Dermatology and Venereology.)