Fair-skinned Individuals Research Articles

Visible light and human skin pigmentation: The importance of skin phototype.

Melanin is synthesised within melanocytes and transferred to keratinocytes in human skin, thereby regulating skin colour and protecting skin cells against UVR-induced damage. We commonly divide human skin into six phototypes (SPT)-I to -VI (Fitzpatrick scale) according to the skin's tanning response to UVR. In this pilot study, we investigated the impact of UVR (maximum 311nm), blue (peak 450nm) and green visible light (peak 530nm) on melanin production and type in healthy human skin histocultures (SPT-I, -II and -III). UVR, blue and green light stimulated a surface tanning response in SPT-II and -III, but not SPT-I. Using the Warthin-Starry stain for sensitive melanin detection, all three light treatments induced melanogenesis in SPT-II and -III skin. Surprisingly, blue and green light (but not UVR) stimulated melanin synthesis in SPT-I skin. Moreover, melanin synthesis induced by blue and green visible light in SPT-I, SPT-II, and SPT-III skin was not associated with a detectable increase in DNA damage or cell apoptosis. By contrast, both responses were detected after UVR. These data suggest that blue and green visible light can stimulate melanin production in fair-skinned individuals without, at least some of, the harmful consequences of UVR-induced pigmentation. We are currently examining the molecular basis of UVR-independent melanogenesis in fair skin.

Skin cancer in women of color: Epidemiology, pathogenesis and clinical manifestations.

Malignant melanoma and nonmelanoma skin cancers (NMSC), which include basal cell carcinoma and squamous cell carcinoma, account for 40% of all neoplasms in white patients, making these cancers the most common malignancy in the United States. Given the large number of NMSC cases in white patients, there is a correspondingly large body of literature addressing various aspects of epidemiology, pathogenesis, and treatment. The incidence of both malignant melanoma and NMSC is well established and remains significantly lower in patients with skin of color (SoC) when compared with white patients. Although there is a lower incidence of skin cancer in SoC, there is often a poorer prognosis among this group. There is even more limited data focusing on women of color, making an accurate determination of incidence and mortality difficult. This gender disparity causes decreased skin cancer awareness and index of suspicion among patients and providers, hindering appropriate evaluation and care. Therefore, there is a need for an increased understanding of skin cancer in women of color. In the traditional sense, SoC refers to people of African, Asian, Native American, Middle Eastern, and Hispanic backgrounds. Patients in these ethnic groups have richly pigmented skin that is usually categorized as Fitzpatrick types III through VI and thus have notable differences in skin disease and presentation compared with fair-skinned individuals. We present this review of skin cancer in women of color to give a reasonably comprehensive representation of the literature to advance our understanding and knowledge in this unique population.

Pulsed dye laser followed by intradermal botulinum toxin type-A in the treatment of rosacea-associated erythema and flushing.

Rosacea is a common inflammatory skin disease characterized by erythema, episodes of flushing, and inflammatory lesions. It typically affects the face and is more prevalent among fair skin individuals affecting women more than men. Various treatments are available for rosacea with light-based therapies commonly used in the management of erythema. The use of intradermal botulinum toxin type-A has been reported to be beneficial in the treatment of rosacea-associated erythema and flushing with good results and a low side-effect profile. In this article, we present our experience on the successful combination of both pulsed dye laser and intradermal botulinum toxin type-A in erythema and flushing in 20 rosacea patients. In addition to subjective improvement, we measured the degree of erythema using a 3D Antera camera in order to quantify our results. We demonstrated high efficacy and satisfaction rate with this combined approach and a low side-effect profile. To our knowledge, the combination of laser and intradermal botulinum toxin in the management of rosacea has not been previously reported.

Actinic keratosis

Actinic keratoses (AK) are common precancerous cutaneous lesions in fair-skinned individuals as aresult of cumulative exposure to ultraviolet radiation. Due to their high prevalence, AK account for alarge disease burden, in particular in older persons. As AK may potentially progress into invasive cutaneous squamous cell carcinoma, guidelines recommend early and consequent treatment. Numerous lesion- and field-directed interventions with different efficacy and safety profiles are currently licensed in Germany. The appropriate intervention should be chosen together with the patient based on his or her motivation and expectations towards the treatment.

Assessment of Parameters Influencing Physiologic Gingival Pigmentation Using a Novel Classification System

Background: Depigmentation has become an important treatment modality among the general population due to the growing esthetic concern about the pigmentation. Previous studies have not considered parameters such as anatomical distribution of gingiva, intensity of pigmentation, and skin color in their classification systems. The purpose of this study was to assess physiologic gingival pigmentation in individuals based on certain gingival parameters and their correlation with skin color for better treatment strategies using a new classification system. Methods: The study was carried out in Ragas Dental College using a cross-sectional design. A total of 112 female dental students were examined for skin color and gingival parameters. The facial gingiva of upper anterior teeth was assessed for gingival phenotype, intensity and distribution of pigmentation. Descriptive statistics were used to describe the data and the associations between variables were done using chi-square test (P < 0.05). Results: It was found that skin color has a significant association with the intensity of pigmentation (P = 0.0001). In both dark and fair skinned individuals, Class II pigmentation (47%, 23.2%) with thick phenotype (62.5%, 35%) was most prevalent. Dark-skinned individuals were also found to have a generalized distribution of melanin pigmentation (19%) with high intensity of pigmentation (28.5%) predominantly. Fair-skinned individuals had a patchy distribution of melanin pigmentation with low intensity of pigmentation (37%). Conclusions: The association of skin color with various parameters affecting gingival pigmentation can help in determining the depigmentation treatment strategies.

Review of Clinical Evidence over 10Years on Prevention and Treatment of a Film-Forming Medical Device Containing Photolyase in the Management of Field Cancerization in Actinic Keratosis.

Actinic keratosis (AK) is a common pathology that afflicts sun-exposed areas of the skin. It predominantly affects older and fair-skinned individuals suggesting an accumulative damage attributable to chronic sun exposure. The prevalence of AK has risen in the past decades and is expected to continue to rise. Apart from visible hyperkeratotic, hyperplastic lesions, AK is also associated with the presence of subclinical lesions adjacent to tumor tissue, which has led to the use of the concept “cancerization field”. Although lesion- and field-targeting treatments are currently available, many are associated with local side effects and recurrence of new lesions. This review provides information on AK pathophysiology and treatment options and summarizes the available clinical evidence supporting the use of Eryfotona AK-NMSC, a film-forming medical device with SPF 100+ containing the DNA repair enzyme photolyase, for managing AK, based on the analysis of the results of 228 patients treated with the product.FundingISDIN funded the Article Processing Charges.Electronic supplementary materialThe online version of this article (10.1007/s13555-019-0294-1) contains supplementary material, which is available to authorized users.

Who, why, where: an overview of determinants of sunbed use in Europe

Although exposure to indoor tanning has been established as a clear risk factor for skin cancer, sunbeds are still commonly used in Europe. Understanding the determinants of sunbed use in Europe is key to plan educational interventions, behavioural strategies and legislative measures, which should be tailored to subgroups with different risk profiles. Evidences show that the typical sunbed users in Europe are young-adult women, with intermediate skin type, a current employment and a medium/high socio-economic status. Typical users display sun-seeking behaviours and other risky behaviours such as smoking. Indoor tanning seems more common in northern than southern Europe. However, sunbed use remains common in fair-skinned individuals and among adolescents/pre-adolescents. Commonly reported reasons for sunbed use in Europe include aesthetic motives (i.e. looking attractive), the pursue of a prevacation tan, the influence of peers/parents engaging in the same habit, and the treatment of health conditions. The most commonly reported places to get an artificial tan in Europe are tanning studios and beauty salons. However, sunbeds are also available in sport venues, such as swimming pools and gyms, hotels and private houses. All these factors should be taken into account when planning educational, behavioural and legislative interventions to reduce the popularity of artificial tanning in Europe.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 2: Treatment, Prevention and Follow-up.

Basal cell carcinoma (BCC) is the most common malignant tumor among fair-skinned individuals, and its incidence had been steadily rising in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 2 addresses issues such as proper risk stratification, the various therapeutic approaches, and prevention as well as follow-up of patients with basal cell carcinoma.

S2k Guidelines for Cutaneous Basal Cell Carcinoma - Part 1: Epidemiology, Genetics and Diagnosis.

Basal cell carcinoma is the most common malignant tumor among fair-skinned individuals, and its incidence has been rising steadily in the past decades. In order to maintain the highest quality of patient care possible, the German S2k guidelines were updated following a systematic literature search and with the participation of all professional societies and associations involved in the management of the disease. Part 1 highlights new developments in genetics in particular as well as aspects regarding epidemiology, diagnosis, and histology.

CAMP-mediated regulation of melanocyte genomic instability: A melanoma-preventive strategy.

Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage. There is now ample evidence that suggests that the melanocortin 1 receptor (MC1R) is a major melanoma risk factor. Inherited loss-of-function mutations in MC1R are common in melanoma-prone persons, correlating with a less melanized skin complexion and poorer recovery from mutagenic photodamage. We and others are interested in the MC1R signaling pathway in melanocytes, its mechanisms of enhancing genomic stability and pharmacologic opportunities to reduce melanoma risk based on those insights. In this chapter, we review melanoma risk factors, the MC1R signaling pathway, and the relationship between MC1R signaling and DNA repair.

A basic way to tan

Skin Biology Darker-skinned individuals have more melanin in their skin and a lower risk for skin cancers. The production of melanin in organelles called melanosomes is pH sensitive. Zhou et al. found that the enzymatic activity of soluble adenylyl cyclase (sAC) resulted in decreases in both melanosome pH and melanin synthesis. sAC deficiency or inhibitors increased melanosome pH and pigmentation in mice. This mechanism for rapidly regulating melanin synthesis could potentially be exploited to reduce skin cancer risk for fair-skinned individuals. Sci. Signal. 11 , eaau7987 (2018).

Cytological, histopathological and immunohistochemical features of merkel cell carcinoma- A case report

Merkel cell carcinoma (MCC) is a rare, potentially aggressive primary cutaneous neuroendocrine carcinoma. MCC commonly occurs on sun-exposed skin in fair-skinned elderly individuals. It usually presents as a banal-appearing lesion, and the diagnosis is rarely suspected at the time of biopsy. We describe the cytomorphologic, histopathological, and immunohistochemical characteristics of MCC in a 76-year-old male patient presenting with rapidly evolving large red raised lesion over cheek for 1 month. Cytohistopathological evaluation suggested MCC. Immunohistochemistry revealed that the tumor cells were negative for leukocyte common antigen, S-100 protein, HMB45, and cytokeratin 20 and positive for neuron specific enolase. Because of the documented aggressiveness and rising incidence, early diagnosis of this rare tumor is necessary for the management of MCC.

Nickel, chromium and cobalt: the relevant allergens in allergic contact dermatitis. Comparative study between two periods: 1995-2002 and 2003-2015

BackgroundMetals are common agents of allergic contact dermatitis, occupational or not, with decreasing incidence over the last years in some countries that have regulated the amount of nickel in objects.ObjectivesTo analyze and compare with previous studies the profile of metal sensitization between 2003-2015.MethodsPatients who underwent patch testing between 2003-2015 were evaluated retrospectively regarding the sensitization rates to metals, the associations between them, the relationship with profession and epidemiology.ResultsOf the 1,386 patients tested, 438 (32%) had positive test to some metal, similar results to the 404/1,208 (33%) of the previous study (1995-2002) performed at the same service (p=0.32). The frequency of nickel (77%), cobalt (32%) and chromium (29%) changed slightly (p=0.20). Most cases of sensitization to chromium were related to the occupation (64%), in contrast to nickel and cobalt (p<0.0001). There was a predominance of females among those sensitized to metal in both studies (p=0.63) and the age group of 20-49 years old (p=0.11); the number of fair-skinned individuals increased (p<0.001), as well as the lesions in the cephalic segment (50.5%; p<0.0001) and hands (45%; p<0.0001), which are not the most frequent location anymore. The number of cleaners decreased (39% vs. 59%; p<0.0001), which still lead in front of bricklayers/painters, which increased (14% vs. 9%; p=0.013). The frequency of wet work reduced (65% vs. 81%; p<0.0001).Study limitationsThe study included a single population group; only patients with positive tests to metals were considered - the others were not evaluated for the possibility of false negatives.ConclusionThe sensitization to metals, occupational or not, has been significant over the last 21 years, with few epidemiological changes.

Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum

Basal cell carcinoma is the most common form of cancer in humans and comprises the vast majority of skin cancers. It predominantly affects fair-skinned individuals, and its incidence is rapidly increasing. The objective of the study is to identify the epidemiology, its topography and different histological subtypes of basal cell carcinoma in patients with or without Xeroderma Pigmentosum. A cross-sectional descriptive study was conducted at Manipal Teaching Hospital, Pokhara from Jan 2009 to Dec 2016. Ethical approval was taken from MEMG/IRC/GA. The study included patients with a confirmed diagnosis of basal cell carcinoma irrespective of their age and sex. This study showed 77 individuals with 91 biopsies of BCC including 5 cases of Xeroderma Pigmentosum. The predominant histological subtype was nodular with 41 (53.94%) cases, followed by the 14 (18.42%) cases of pigmented and 10 (13.15%) cases baso-squamous subtype. The most frequent sites of involvement were the head and neck, with predominance in the nasal and orbital region. The mean age was 57.68 years but the basal cell carcinoma in cases of Xeroderma Pigmentosum was seen more in younger age groups. There were 43 (55.84 %) male patients and 34 (44.16 %) female patients with a male to female ratio of 1.26:1. Nodular and pigmented varieties were the most frequent subtypes with nose being the commonest site of involvement. Basal cell carcinomas in cases of Xeroderma Pigmentosum were noted in younger age group with multiple lesions.

Decreased expression of the mitochondrial solute carrier SLC25A43 in basal cell carcinoma compared with healthy skin.

Basal cell carcinoma is the most common type of cancer in fair-skinned individuals, and its incidence is rapidly increasing. The aim of the present study was to investigate the gene and protein expression of the mitochondrial solute carrier family 25 member 43 (SLC25A43) in basal cell carcinoma. SLC25A43 has previously been identified to be genetically altered and associated with cell proliferation in human epidermal growth factor receptor 2-positive breast cancer. However, the knowledge about SLC25A43 is limited, and its role in other cancers is unknown. The SLC25A43 gene and protein expression was analysed in 14 basal cell carcinomas and healthy skin samples from the same individuals by quantitative polymerase chain reaction and immunohistochemistry, respectively. The results demonstrated a significantly lower (≥50%) SLC25A43 gene expression in all carcinomas compared with that in healthy skin. In addition, SLC25A43 protein expression was absent in >90% of all visual fields in the basal cell carcinomas, and the H-score was significantly lower in tumours compared with the adjacent epidermis. These results demonstrate that SLC25A43 expression is altered at the gene and protein levels in basal cell carcinoma. The underlying mechanisms and the clinical relevance of these data must be elucidated in additional experimental and clinical studies.

Divergence of cAMP signalling pathways mediating augmented nucleotide excision repair and pigment induction in melanocytes.

Loss-of-function melanocortin 1 receptor (MC1R) polymorphisms are common in UV-sensitive fair-skinned individuals and are associated with blunted cAMP second messenger signalling and higher lifetime risk of melanoma because of diminished ability of melanocytes to cope with UV damage. cAMP signalling positions melanocytes to resist UV injury by upregulating synthesis of UV-blocking eumelanin pigment and by enhancing the repair of UV-induced DNA damage. cAMP enhances melanocyte nucleotide excision repair (NER), the genome maintenance pathway responsible for the removal of mutagenic UV photolesions, through cAMP-activated protein kinase (protein kinase A)-mediated phosphorylation of the ataxia telangiectasia-mutated and Rad3-related (ATR) protein on the S435 residue. We investigated the interdependence of cAMP-mediated melanin upregulation and cAMP-enhanced DNA repair in primary human melanocytes and a melanoma cell line. We observed that the ATR-dependent molecular pathway linking cAMP signalling to the NER pathway is independent of MITF activation. Similarly, cAMP-mediated upregulation of pigment synthesis is independent of ATR, suggesting that the key molecular events driving MC1R-mediated enhancement of genome maintenance (eg PKA-mediated phosphorylation of ATR) and MC1R-induced pigment induction (eg MITF activation) are distinct.

What is new in basal cell carcinoma?

Basal cell carcinoma (BCC) is the most common skin cancer in fair-skinned individuals. Although lymph node or visceral metastases are observed in less than 0.5 % of all cases, BCC can have afatal course due to its highly invasive growth pattern. To provide acomprehensive update on diagnosis, treatment, and prevention of BCC. We review the current literature and recommendations of the German guidelines on treatment and prevention of skin cancer. The most pertinent developments are summarized in this review article. The use of optical coherence tomography and reflectance confocal microscopy can significantly improve the diagnosis of BCC compared with clinical assessment and dermoscopy alone. Mohs micrographic surgery remains the therapeutic gold standard for tumors in the head and facial area and tumors with high-risk features. The application of imiquimod, 5‑fluorouracil, or photodynamic therapy should be restricted to low-risk superficial tumors. Topical inhibitors of the sonic hedgehog (SHH) pathway are currently being evaluated in early clinical trials. In contrast, vismodegib and sonidegib have been approved for the systemic treatment of locally advanced and metastatic BCC with good response rates. The most common adverse events of both agents are muscle cramps, dysgeusia, diffuse alopecia, weight loss, and fatigue. In an Australian phaseIII trial, oral nicotinamide (vitamin B3) reduced the occurrence of new BCC by 20 % in skin cancer patients. Targeted therapy with SHH inhibitors has improved the prognosis of locally advanced and metastatic BCC, albeit at the cost of asignificant number of adverse events.

Diagnosis and Management of Hereditary Basal Cell Skin Cancer.

Basal cell carcinoma (BCC) is the most common cancer in Caucasians worldwide and its incidence is rising. It is generally considered a sporadic tumour, most likely to affect fair-skinned individuals exposed to ultraviolet (UV) radiation. This chapter focusses on the approach to recognising the relatively few individuals in whom a high-risk hereditary susceptibility may be present. Gorlin syndrome is the main consideration and the gene most commonly mutated is PTCH1, a key regulator of the Hedgehog developmental pathway. Recently, loss of function of another gene in the same pathway, SUFU, has been found to explain a subset of families. Understanding the pathogenesis of familial BCCs has advanced the understanding of the biology of sporadic tumours and led to targeted therapy trials. The management of familial BCCs remains a challenge due to significant unmet needs for non-surgical treatments and a high burden of disease for the individual. Together with the prospect of advances in gene discovery and translation, these challenges highlight the need for ongoing review of at-risk and affected individuals by a multidisciplinary team.

Current diagnosis and treatment of basal cell carcinoma.

Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor.

Variants of the melanocortin-1 receptor: do they matter clinically?

The melanocortin 1 receptor (MC1R) gene encodes for a seven-pass transmembrane receptor primarily expressed on melanocytes and melanoma cells. Single nucleotide polymorphisms (SNPs, also termed variants) in MC1R frequently cause red hair, fair skin and are associated with melanoma and keratinocyte-derived skin cancer development. Activation of wild-type (WT) MC1R in skin assists cutaneous photoprotection whereas reduced MC1R signalling, seen with MC1R variants, impairs ultraviolet radiation (UVR)-protective responses. As ancestral humans migrated out of Africa, the evolutionary advantage of MC1R variants may have related to improved cutaneous vitamin D synthesis and higher birthweight reported with certain MC1R variants. Reduced photoprotection secondary to MC1R dysfunction involves pigmentary and non-pigmentary mechanisms (reduced DNA repair, effects on cell proliferation and possibly immunological parameters), leading to clonal expansion of mutated cells within skin and subsequent carcinogenesis. Recent investigations suggest an association between MC1R genotype and vitiligo, with preliminary evidence that a MC1R agonist, [Nle4-D-Phe7]-alpha-MSH, in combination with UVB, assists repigmentation. Future development of compounds to correct defective MC1R responses secondary to MC1R variants could result in photoprotective benefits for fair-skinned individuals and reduce their skin cancer risk.