A Retrospective Study of Diameter and Breslow Thickness in Invasive Melanomas.

INTRODUCTION: A diameter larger than 6 mm is included in the criteria used in public health messages to detect a cutaneous melanoma. We aimed to investigate the independent association of Breslow thickness with the melanoma diameter. METHODS: A retrospective study was performed in patients with invasive melanomas of the nodular melanoma (NM) or superficial spreading melanoma (SSM) subtype. The quartiles of the diameter (lower, median, upper) were studied in non-parametric quantile regression model. RESULTS: In total, 537 cases of invasive melanomas were included and 60% had Breslow thickness ≤1.0 mm. There were 429 SSM (79.9%) and 108 NM (20.1%). Although NMs were significantly thicker (median Breslow thickness: 2.7 mm vs. 0.7 mm, respectively, p < 0.0001), they were not associated with larger diameter compared to SSMs (p = 0.71). After adjustment for age and sex, melanoma location and subtype, having Breslow thickness ≤1.0 mm was not significantly associated with the lower quartile, median and upper quartile of the diameter (p values: 0.063, 0.083, and 0.791, respectively). CONCLUSION: In our study including melanomas of the NM or SSM subtype, Breslow thickness was not associated with the diameter, adding evidence to support the limitations of using diameter larger than 6 mm for the detection of invasive melanomas and indicating the potential of smaller melanomas to be thicker tumors.

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

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, multicentre, retrospective study was performed in eight 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 compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.

A Sensitivity Meta-Analysis of Disease-Specific Death in Localized Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Patients with localized cutaneous squamous cell carcinoma (cSCC) have different risk for disease-specific death (DSD) from patients with metastatic cSCC. PATIENTS AND METHODS: We conducted a sensitivity meta-analysis to identify the risk factors associated with DSD, in patients with localized cSCC at initial diagnosis (without locoregional or distant metastasis). RESULTS: Nine studies, with 5,205 patients, were included. Median follow-up ranged from 18 to 81 months. The number of deaths due to cSCC ranged from 3 to 40. Patients with immunosuppression were almost 2 times more likely to die from cSCC compared to immunocompetent patients (risk ratio: 1.85, 95% CI: 1.32-2.61). There was a positive but nonsignificant overall association with DSD for depth beyond fat, tumor diameter, presence of perineural invasion, location, and thickness. These results should be interpreted with caution, as there was limited evidence-based data on DSD in localized cSCC, due to the small number of studies reporting DSD, the absence of reporting the margin status, the variability of selected risk factors across studies, and the variability of definition of risk factors. CONCLUSIONS: In our meta-analysis, in localized cSCC at initial diagnosis, patients with immunosuppression were at significantly higher risk to die from cSCC. Our findings further highlight the need for a standardized set of risk factors to be included in studies on prognosis of cSCC and for including margin status and DSD among the studied outcomes.

Antibiotics and Antimicrobial Resistance in Acne: Epidemiological Trends and Clinical Practice Considerations.

Antimicrobial resistance is an increasing public health problem worldwide. The interest of a focus on antimicrobial resistance in acne lies on the facts that acne vulgaris (acne) is the most common skin disease worldwide, that the bacterium Cutibacterium acnes (C. acnes, formerly Propionibacterium acnes) plays a key role in the pathogenesis of acne, while at the same time being part of the skin flora, and that antibiotics are commonly recommended for acne treatment. The overuse of topical and/or systemic antibiotics, the long treatment courses used for acne, and the availability of over-the-counter antibiotic preparations, have led to the worldwide emergence of resistant strains in acne patients. In this review, we discuss the epidemiological trends of antimicrobial resistance in acne, the need to avoid the perturbation of the skin microbiome caused by anti-acne antibiotics, and the clinical practice considerations related to the emergence of resistant strains in acne patients. In light of the increasing risk of antimicrobial resistance, raising concerns over the misuse of antibiotics, prescribing patterns can be a critical target for antibiotic stewardship efforts. Also, the selection of non-antibiotic therapies for acne, whenever possible, may offer significant advantages.

Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition.

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

A Practical Guide for the Follow-Up of Patients with Advanced Basal Cell Carcinoma During Treatment with Hedgehog Pathway Inhibitors.

The Hedgehog pathway inhibitors (HPIs), vismodegib and sonidegib, are increasingly employed in the treatment of patients with advanced basal cell carcinoma (BCC). The aim of this review is to create a synthesis of available information in the literature regarding the follow-up of patients with advanced BCC treated with HPIs and to provide the treating physician with a structured practical guide to standardize clinical practice. Several challenges during treatment are addressed: to optimally evaluate tumor responses, to differentiate between resistance (HPI rechallenge not possible) and recurrence (HPI rechallenge may be possible) in case of BCC regrowth, to readily assess for toxicity and tolerability issues, to provide patients with practical ways and behaviors to effectively cope with adverse events, and to improve patient adherence and quality of life. IMPLICATIONS FOR PRACTICE: This is a practical guide for clinical practice regarding the monitoring and follow-up of patients with advanced basal cell carcinoma (BCC) during treatment with the Hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib. This review aims to bridge the gap in knowledge of assessing tumor response for BCC with both an externally visible component and an infiltrating component measurable with imaging. Furthermore, it addresses the follow-up for adverse events as a challenging multistep process involving practices aiming to readily assess new-onset symptoms of HPI toxicity, perform total-body skin examination, and improve patient adherence and quality of life.

Use of vismodegib for the treatment of multiple basal cell carcinomas in a patient with xeroderma pigmentosum.

A female patient with xeroderma pigmentosum and multiple basal cell carcinomas was treated with a hedgehog pathway inhibitor (vismodegib), which successfully treated the majority of her basal cell carcinomas while preventing the appearance of new lesions. The sum diameter of lesions showed a 61% decrease after 16.5 months of treatment, although after 18.5 months of treatment, a persistent lesion showed progression and metatypical characteristics; adverse events included persistent alopecia muscle cramps, dysgeusia, and amenorrhea. Despite these limitations, vismodegib may have a role in the treatment of some patients with xeroderma pigmentosum.

Quality of Life and Psychosocial Implications in Patients with Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a long-term skin disorder associated with high levels of psychological distress and significant life impact. OBJECTIVE: To evaluate the quality of life, depression, anxiety, loneliness, and self-esteem in patients with HS. METHODS: Ninety-four patients with HS were enrolled in the study. The quality of life, depression, anxiety, loneliness, and self-esteem of the patients were assessed using the Dermatology Life Quality Index (DLQI), the Hospital Anxiety and Depression Scale (HADS), the UCLA Loneliness Scale (UCLA-Version 3), and the Rosenberg Self-Esteem Scale (RSES), respectively. RESULTS: The DLQI mean score was 11.43 ± 6.61 in patients with HS. The patients with HS presented statistically significantly higher anxiety (6.41 ± 3.31 vs. 5.00 ± 1.59, p < 0.001), depression (5.45 ± 2.79 vs. 4.16 ± 1.54, p < 0.001), and loneliness and social isolation scores (42.86 ± 8.63 vs. 35.57 ± 6.17, p < 0.001) and lower self-esteem scores (18.91 ± 1.79 vs. 19.77 ± 2.53, p = 0.008) than the healthy controls. CONCLUSIONS: HS is a distressing, recurrent disease that impairs quality of life. We can suggest services that allow an integrated approach, which includes psychosocial support, offering the patients relief from isolation and an opportunity to share common experiences.

Erythema Ab Igne in Three Girls with Anorexia Nervosa.

We present three girls with the eating disorder anorexia nervosa (AN) presenting with erythema ab igne (EAI), a benign, reticular, erythematous dermatosis caused by repeated prolonged skin exposure to mild heat. AN has been associated with abnormal peripheral vascular response to cold, vasoconstriction of the limbs, low hand blood flow, exaggerated response to cold stimuli, subnormal core temperature, and a general feeling of cold that may encourage prolonged heat exposure and induce EAI.

A case-control study of MC1R variants in Greek patients with basal cell carcinoma: increased risk independently of pigmentary characteristics.

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.

Vismodegib for the treatment of basal cell carcinoma: results and implications of the ERIVANCE BCC trial.

The need for effective treatment of patients with locally advanced or metastatic basal cell carcinoma (BCC), in conjunction with major advances in the elucidation of the molecular basis of this tumor has led to the advent of new targeted therapies - namely, hedgehog inhibitors. The rationale for their use in patients with advanced BCC is based on their inhibitory effect on the hedgehog pathway, which is aberrantly activated in BCCs due to mutations of its primary components, PTCH1 and SMO genes. Vismodegib (GDC-0449) is an orally bioavailable hedgehog pathway inhibitor that selectively inhibits SMO. The ERIVANCE BCC study is a Phase II, international, multicenter clinical trial evaluating the efficacy and safety of vismodegib 150 mg once daily in patients with locally advanced or metastatic BCC. Vismodegib has been approved for the treatment of adult patients with metastatic BCC, or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy. This article will outline the rationale, design and available results from the ERIVANCE BCC study and discuss the clinical implications of vismodegib in the management of patients with BCC. Challenges regarding vismodegib use include the recurrence of BCC after drug discontinuation, the development of acquired resistance, the dramatic efficacy in patients with Gorlin syndrome, and class-related drug toxicity. Ongoing clinical trials aim to explore the role of vismodegib in the neoadjuvant setting prior to surgery, the potential use of alternate dosing regimens in order to limit chronic adverse events, as well as the identification of patients with BCC that are more likely to respond to this targeted therapy based on genotypic and/or phenotypic characteristics.

Screening for asymptomatic scalp carriage in household contacts of patients with tinea capitis during 1997-2011: a retrospective hospital-based study.

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.

The Microbiome and Acne: Perspectives for Treatment.

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.

Diagnosis of invasive cutaneous squamous cell carcinoma, imaging and staging.

The assessment of patients with a lesion raising the suspicion of an invasive cutaneous squamous cell carcinoma (cSCC) is a frequent clinical scenario. The management of patients with cSCC is a multistep approach, starting with the correct diagnosis. The two main diagnostic goals are to differentiate from other possible diagnoses and correctly recognize the lesion as cSCC, and then to determine the tumor spread (perform staging), that is if the patient has a common primary cSCC or a locally advanced cSCC, or a metastatic cSCC (with in-transit, regional lymph nodal, or rarely distant metastasis). The multistep diagnostic approach begins with the clinical characteristics of the primary cSCC, it is complemented with features with dermoscopy and, if available, reflectance confocal microscopy and is confirmed with histopathology. The tumor spread is assessed by physical examination and, in some cases, ultrasound and/or computed tomography or magnetic resonance imaging, mainly to investigate for regional lymph node metastasis or for local infiltration into deeper structures. In the last step, the clinical, histologic and radiologic findings are incorporated into staging systems.

Simultaneous melanomas in the setting of multiple primary melanomas.

It is estimated that about 1-13% of melanoma patients will develop multiple primary melanomas. Although the occurrence of subsequent tumors has been described during the last few years, the development of simultaneous melanomas has not yet been extensively studied. We reviewed our registries to identify patients with multiple primary melanomas. We studied epidemiological, clinical, and histological characteristics of patients who were diagnosed with simultaneous melanomas and compared them with those of patients who developed non-synchronous multiple primary melanomas. As simultaneous were defined subsequent melanomas that were diagnosed either at the same visit or within a time-period of maximum of 1 month. Between 2000 and 2020, 2500 patients were diagnosed with melanoma at Andreas Syggros Hospital. 86 (3.4%) patients presented multiple primary melanomas and among them, 35 (40.7%) developed simultaneous melanomas. Patients with simultaneous melanomas developed more frequently more than 2 tumors. First tumors of patients with non-synchronous melanomas were significantly thicker than second tumors while those of patients with simultaneous melanomas did not differ significantly. Slight differences in the tumor localization, staging and histologic type were observed between the two groups. However significant differences were ascertained between first and second tumors in both groups. Simultaneous melanomas occupy an important proportion of multiple primary melanomas, affecting a non-negligible number of patients. Slight differences between simultaneous and non-synchronous multiple primary melanomas seem to define a distinct subcategory of multiple primary melanomas.

Immunotherapy and Its Timing in Advanced Basal Cell Carcinoma Treatment.

For patients with advanced basal cell carcinoma (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.