Epidemiologic and genetic study of the skin phototype in patients with cutaneous basal cell carcinoma compared with controls

Introduction: Cutaneous basal cell carcinoma (BCC) is the most common form ofskin cancer in humans and its incidence is rising worldwide. There are only fewstudies of the epidemiologic and molecular (MC1R polymorphisms) risk factors forBCC development in the literature, and there is limited data concerning SouthernEuropean populations that are characterized by a darker skin and hair color, and adarker skin phototype.Aim: This is a study of epidemiologic and molecular risk factors associated with BCCdevelopment in a population from Greece.Methods: A standardized questionnaire was used to collect data from 199 patientswith histologically confirmed BCC and 200 healthy controls, about the type of sunexposure, the history of sunburning, sunprotection measures, skin phototype and thehistory of skin cancer. Patients and controls were examined for the presence ofmelanocytic nevi, actinic keratoses, and solar lentigines. The location and type ofBCC was recorded. The role of MC1R polymorphisms was studied with PCR andsequencing. A separate analysis of early onset BCC (diagnosed in patients youngerthan 50 years old) was made.Conclusions: Skin phototype was not found to be a valuable tool for estimating BCCrisk. On the other hand, fair skin color, the presence of objective markers of sunexposure (solar lentigines), the years of outdoor occupational sun exposure, and thesunburns after the age of 20, were associated with increased BCC risk.Subgroup analysis showed that different epidemiologic risk factors are associatedwith early onset BCC, including the presence of clinically dysplastic nevi, intermittentsun exposure during summer holidays and the history of sunburns during childhood.In the molecular study, MC1R polymorphisms (especially their number) were shownto be a predisposing risk factor for BCC development, independently of skin colorand phototype.Conclusions: Sunprotection and avoidance of sunburns should continue throughoutlifetime and not only during childhood, and this information should be included inskin cancer prevention campaigns in Greece. Also, it is suggested, that, like cutaneousmalignant melanoma, BCC is a heterogeneous tumor, with different subtypes (earlyonset versus late onset BCC) being associated with distinct risk factors.The study of epidemiologic and molecular risk factors of BCC development in theGreek population may provide new data for a better understanding of BCCpathogenesis, the design of better prevention policies, and the possibility ofindividualized diagnosis

Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne [version 1; referees: 2 approved]

The skin commensal Propionibacterium acnes, recently renamed Cutibacterium acnes, along with the other major pathophysiological factors of increased seborrhea, hyperkeratinization of the pilosebaceous unit, and inflammation, has long been implicated in the pathogenesis of acne. Recent advances have contributed to our understanding of the role of P. acnes in acne. Although there are no quantitative differences in P. acnes of the skin of patients with acne compared with controls, the P. acnes phylogenic groups display distinct genetic and phenotypic characteristics, P. acnes biofilms are more frequent in acne, and different phylotypes may induce distinct immune responses in acne. P. acnes plays a further important role in the homeostasis of the skin’s microbiome, interacting with other cutaneous commensal or pathogenic microorganisms such as Staphylococcus epidermidis, Streptococcus pyogenes, and Pseudomonas species. In the era of increasing antimicrobial resistance, the selection of acne treatment targeting P. acnes and the prevention of antibiotic resistance play a key role in improving outcomes in acne patients and public health

Immunotherapy and Its Timing in Advanced Basal Cell Carcinoma Treatment

For patients with advanced BCC, including locally advanced or metastatic BCC not amenable to curative surgery or radiotherapy, hedgehog pathway inhibitors (HHI) vismodegib and sonidegib are approved as first-line systemic treatment. Results from clinical trials highlight that the overall discontinuation rate of HHI treatment varies from 88% to 92% with vismodegib and is approximately 92% with sonidegib, and half of patients will discontinue HHI after approximately 8 to 12 months. The main factors weighing in on the decision to discontinue HHI, include efficacy (tumor response), adverse events and patient decision. In clinical practice, some of the patients that stop HHI may be re-evaluated if the tumor becomes amenable to surgery, or restart HHI at a later time, while others will need to switch to immunotherapy, depending on the reasons for HHI discontinuation. In this review, we revisit the therapeutic decisions considering a switch from HHI to immunotherapy with anti-PD-1 agent cemiplimab and we highlight the place of cemiplimab in the therapeutic ladder for patients with advanced BCC. We discuss the evidence on the efficacy and safety of anti-PD-1 agents as second-line systemic monotherapy, or in combination with other treatments, and the emergence of checkpoint immunotherapy as a neoadjuvant treatment

The Microbiome and Acne: Perspectives for Treatment

Abstract The skin microbiome consists of the microorganisms populating the human skin. Cutibacterium acnes (C. acnes, formerly named Propionibacterium acnes) is recognized as a key factor in acne development, regulating inflammatory and immune pathways. Dysbiosis has been described as the imbalance in skin microbiome homeostasis and may play a role in acne pathogenesis. Microbial interference has been shown to be a contributor to healthy skin homeostasis and staphylococcal strains may exclude acne-associated C. acnes phylotypes. In this review we present an update on the skin microbiome in acne and discuss how current acne treatments such as benzoyl peroxide, orally administered isotretinoin, and antibiotics may affect the skin microbiome homeostasis. We highlight the collateral damage of acne antibiotics on the skin microbiome, including the risk of antimicrobial resistance and the dysregulation of the microbiome equilibrium that may occur even with short-term antibiotic courses. Consequently, the interest is shifting towards new non-antibiotic pharmacological acne treatments. Orally administered spironolactone is an emerging off-label treatment for adult female patients and topical peroxisome proliferator-activated receptor gamma (PPARγ) modulation is being studied for patients with acne. The potential application of topical or oral probiotics, bacteriotherapy, and phage therapy for acne are further promising areas of future research

An Epidemiological Update on Indoor Tanning and the Risk of Skin Cancers

Indoor tanning (sunbeds, solarium) uses artificial ultraviolet radiation (UVR) to stimulate cosmetic tanning of the skin. Indoor tanning has been officially classified as a human carcinogen in 2009 by the International Agency for Research on Cancer of the World Health Organization (WHO). The differences in the prevalence of sunbed use across countries and over the years highlight underlying legislative, climatic, and cultural differences. Indoor tanning-seeking behaviors may be driven by motivations for an appealing appearance, largely influenced by gender and age, and several misconceptions that a prevacation tan safeguards the skin, that sunbeds can be used to treat acne or to increase vitamin D, or that tanning is a healthy habit. This review provides an epidemiological update on the prevalence of sunbed use, who tends to use sunbeds and why, and details the current evidence on the association of sunbeds with skin cancers, including cutaneous melanoma, basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (cSCC). A statistically significant higher risk of cutaneous melanoma, BCC and cSCC with the use of sunbeds has been consistently demonstrated. This risk of skin cancer is even higher with the more frequent use of sunbeds, underscoring a dose–response relationship, and in those first exposed to sunbeds at a younger age. Preventive measures against sunbed use include legislation restricting sunbed use, educational campaigns to inform and discourage from indoor tanning, as well as using the internet, online advertising messages and the social media to reach larger audiences and to promote an untanned appearance

The Association of Nevus-Associated Melanoma with Common or Dysplastic Melanocytic Nevus: A Systematic Review and Meta-Analysis

Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. Objectives: To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. Methods: A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I2 statistic. Results: A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39–63%) with high heterogeneity at I2: 95.8% (p in situ NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63–78%). Conclusions: The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype

Isotretinoin‐associated acne fulminans: A multicenter, retrospective study of the European Academy of Dermatology and Venereology Task Force on Acne, Rosacea and Hidradenitis Suppurativa

International audienceAbstract Background Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. Objectives To investigate the occurrence of isotretinoin‐associated AF, clinical characteristics and prognosis at follow‐up. Methods An international, multicenter, retrospective study was performed in 8 hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin‐associated acne fulminans, IAF) were compared with non‐IAF (NAF). Results Forty‐nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD: 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs 61.9%, respectively, p=0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre‐existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%) (p=0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%) (p<0.001). At a median follow‐up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. Conclusions No specific clinical or demographic characteristics of IAF when compared with NAF could be detected, a fact that does not support IAF as a district clinical entity