Recurrence rate of basal cell carcinoma among different micrographic surgery techniques: systematic review with meta-analysis.

In high-risk basal cell carcinomas (BCCs), micrographic surgery (MS) has high tissue preservation and low recurrence rates. The Mohs technique is the most commonly used technique, with limited use of other MS techniques. No studies have been designed to compare the MS methods. This review aimed to assess BCC recurrence rates of different MS techniques. A systematic review and meta-analysis were conducted to search for related studies in PubMed, LILACS, EMBASE, SCOPUS, WEB OF SCIENCE, CINHAL and COCHRANE until March 2021. Randomized clinical trials (RCTs) and observational studies involving patients with BCC and indications for different MS techniques were included. Study selection and data extraction were performed independently by three peer reviewers, as was the risk of bias assessment using the Joanna Briggs Institute tool. Pooled estimates were assessed using the random-effects model (Logit), and heterogeneity was assessed by the chi-squared test (χ2 ). Stata Software version 17.0 was used for analysis. Eighteen studies were included, two RCTs and sixteen observational studies. The overall recurrence rate was 2% (95% CI, 1.0-3.0%; χ2 = 46.2; P = 0.00; 18 studies, 10 424 BCCs). In studies using the Mohs technique, the recurrence rate was 3.0% (95% CI, 1.0-5.0%; χ2 = 11.0; P = 0.00; 6 studies; 1,582 BCCs), with the Munich technique 3.0% (95% CI, 2.0-5.0%; χ2 = 0.0; no heterogeneity; 3 studies; 404 BCCs), with Tubingen technique 1% (95% CI, 1.0-2.0%; χ2 = 12.1; P = 0.00; 8 studies; 8374 BCCs) and with the Muffin technique 0.0% (95% CI, 0.0-6.0%; 1 study; 64 BCCs). Relapse rates between MS techniques were low and appeared to be similar. However, the design of this review and the absence of primary studies that directly compare the techniques do not allow us to assert the superiority between them.

French maritime pine bark extract (pycnogenol) in association with triple combination cream for the treatment of facial melasma in women: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Melasma can be recalcitrant to treatment, and relapses are common. Pycnogenol has been reported to be effective in treating melasma. OBJECTIVE: To compare the efficacy, safety and tolerability of 75 mg pycnogenol taken orally twice a day vs. a placebo, in association with the triple combination and broad-spectrum sunscreen for the treatment of facial melasma. METHODS: A randomized, double-blind, parallel, placebo-controlled study was conducted on 44 women with facial melasma in a single centre from May 2019 through November 2019. Patients with melasma were randomly assigned to orally take 75 mg pycnogenol (PYC) or a placebo (PLAC) twice a day for 60 days. Both groups also received tinted sunscreen [Sun Protection Factor (SPF) 50; Persistent Pigment Darkening (PPD) 17] for daytime use and a topical triple combination at bedtime. The primary outcome was a change from the baseline Modified Melasma Area Severity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life (MELASQoL), colorimetric indices and Global Aesthetic Improvement Scale (GAIS). RESULTS: All participants completed the trial. The mean (SD) age of the participants was 39 (7) years, and 91% were phototypes III-IV. Both groups exhibited a reduction in mMASI scores, MELASQoL scores and colour contrast (P < 0.01). The mean (CI 95%) reductions of the mMASI scores were 49% (36-61%) for PYC and 34% (16-47%) for PLAC. The reductions in mMASI scores and colorimetric contrast were superior for the PYC group (P < 0.05). The analysis of GAIS resulted in an improvement of 86% (CI 95%: 68-96%) for the participants in the PYC group and 55% (CI 95%: 32-73%) for those in the PLAC group. There were no adverse effects related to oral treatment. CONCLUSION: Pycnogenol is well-tolerated and increases the effectiveness of broad-spectrum sunscreen and the triple combination in the treatment of facial melasma in women.

Efficacy and safety of topical isobutylamido thiazolyl resorcinol (Thiamidol) vs. 4% hydroquinone cream for facial melasma: an evaluator-blinded, randomized controlled trial.

BACKGROUND: Melasma can be refractory to treatment, and relapses are frequent. Thiamidol is a new potent tyrosinase inhibitor that has been found effective as a cosmeceutical for the depigmenting of melasma. OBJECTIVE: This study compared the efficacy and tolerability of topical 0.2% Thiamidol vs. 4% hydroquinone for facial melasma. METHODS: Fifty women with facial melasma participated in a randomized, evaluator-blinded, controlled study from September through November 2020. Patients were randomly assigned to apply a double layer of 0.2% Thiamidol twice a day or 4% hydroquinone cream at bedtime, for 90 days. Both groups received tinted sunscreen (sun protection factor 60, PPD 20). The primary outcome was the change from the baseline Modified Melasma Area Seve:rity Index (mMASI) score. Secondary outcomes were improvements in the patients' quality of life [Melasma Quality of Life Index (MELASQoL)], colourimetry, and Global Aesthetic Improvement Scale (GAIS) evaluation. RESULTS: One participant, from the hydroquinone group, did not complete the study (unrelated to adverse effects). The mean (SD) age of the participants was 43 (6) years, and 86% were phototypes III-IV. Both groups exhibited a reduction in mMASI, MELASQoL, and colour contrast scores (P < 0.01). The mean [95% confidence interval (CI 95%)] reductions of the mMASI scores were 43% (35-50%) for Thiamidol and 33% (23-42%) for hydroquinone. There was no difference between the groups in the reductions in mMASI, MELASQoL, colourimetric contrast and GAIS scores (P ≥ 0.09). The GAIS analysis resulted in an improvement of 84% (CI: 95% 67-97%) for participants in the Thiamidol group and 74% (CI: 95% 61-93%) for those in the hydroquinone group. There were only mild adverse effects in the Thiamidol group, but allergic contact dermatitis was evidenced in two (8%) participants. CONCLUSION: The melasma improvement achieved using 0.2% Thiamidol did not differ from that of 4% hydroquinone cream. Thiamidol can be considered a suitable option for melasma patients with poor tolerability or treatment failure with hydroquinone.

A large familial cluster and sporadic cases of frontal fibrosing alopecia in Brazil reinforce known human leucocyte antigen (HLA) associations and indicate new HLA susceptibility haplotypes.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a lymphocytic scarring alopecia whose worldwide incidence is rising. Environmental triggers combined with genetic predisposition represent one of the current hypotheses in FFA aetiology. Familial clusters are opportunities to investigate the genetic basis of diseases. OBJECTIVES: Assess human leucocyte antigen (HLA) genetic variability in a Brazilian sample of a large familial cluster (six sisters and one daughter) with FFA, unnafected familiar members and sporadic cases of FFA. METHODS: We addressed the HLA-A, HLA-B, HLA-C, HLA-G and HLA-E genetic variability in this family and in seven sporadic FFA cases, comparing allele frequencies with those reported for the São Paulo State from Brazil. RESULTS: Two susceptibility haplotypes, C*17:01:01:02/B*42:01:01:01 and C*07:02:01:03/B*07:02:01:01, were identified among familial cases and also in sporadic cases. The first haplotype is rare among Brazilians, and it was not previously reported as being associated with FFA. Both alleles were found in some different unaffected familiars, what emphasizes the role of environmental triggers in disease development. HLA-A, HLA-G and HLA-E genes were not associated to familiar nor FFA sporadic cases. CONCLUSION: The identification of susceptibility haplotypes in FFA reinforces the genetic predisposition to the disease.

Effectiveness and safety of 0·5% colchicine cream vs. photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratosis and skin field cancerization of the forearms: a randomized controlled trial.

BACKGROUND: Skin field cancerization (SFC) is a process that occurs in areas of the skin that have undergone genomic alterations induced by ultraviolet radiation. Actinic keratosis (AK) is a sign of its activity. OBJECTIVES: To evaluate the effectiveness and safety of 0·5% colchicine (COL) cream vs. methyl aminolaevulinate photodynamic therapy (MAL-PDT) in the treatment of AK and SFC. METHODS: We conducted a randomized, open, intrasubject controlled trial. A total of 36 participants with 3-10 AKs on each forearm were treated with either COL cream (twice daily for 10 days) or a single session of MAL-PDT and were reassessed after 60 days. The clinical evaluation was performed using AK count, forearm photoageing scale (PAS) and AK degree (AKD). Patients underwent central forearm biopsies and histopathological evaluation by keratinocyte intraepithelial neoplasia (KIN) assessment, epithelial atrophy and immunohistochemistry (p53/Ki67). RESULTS: Overall, 50% of patients were male. The mean age was 70·9 years (SD 8·6) and phototypes I and II were predominant (89%). Total clearance was observed in six (17%) forearms treated with COL and seven (19%) forearms treated with MAL-PDT (P = 0·76); partial clearance was observed in 44% of forearms in the COL group and 67% of forearms in the MAL-PDT group (P = 0·07). In both COL and MAL-PDT groups, reductions in PAS (-6% vs. -6%) and AKD (-45% vs. -40%) were observed. KIN normalized in 28% of patients treated with MAL-PDT and 20% of those treated with COL. Epithelial atrophy reduced after treatment (P < 0·01). Expression levels of Ki67 and p53 were also assessed. Mild or moderate adverse effects were similar for both groups. CONCLUSIONS: COL 0·5% cream and MAL-PDT are safe and effective for treating SFC.

Tretinoin (0.05% cream vs. 5% peel) for photoaging and field cancerization of the forearms: randomized, evaluator-blinded, clinical trial.

BACKGROUND: Topical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness. OBJECTIVE: To compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms. METHODS: Clinical trial with therapeutic intervention, prospective, randomized (computer-generated randomization list), parallel, comparative (intrasubject) and evaluator-blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high-frequency ultrasound, histology (haematoxylin-eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl-2, Ki67 and collagen I) were assessed. RESULTS: One participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens. CONCLUSION: Tretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.

Factors associated with quality of life in facial melasma: a cross-sectional study.

BACKGROUND: Melasma is a common chronic focal hypermelanosis that affects photexposed areas as face, mainly in women at fertile age. It inflicts a significant impact in quality of life; nevertheless, quality of life scores (e.g. MELASQoL) are not strongly correlated with clinical severity (e.g. MASI) in facial melasma, suggesting that different factors can influence the perception of disease beyond the clinical extension or the intensity of pigmentation. OBJECTIVES: To explore clinical and socio-demographic aspects that influences MELASQoL scores. METHODS: Cross-sectional study enrolling 155 adults (>18 y.o.) with facial melasma. MELASQoL, MASI, clinical and demographic information were assessed. The associations among factors were explored by multivariable methods. RESULTS: The mean (SD) age of the participants was 39 (8) years, and 134 (86%) were females. The correlation (Spearman's rho) between MELASQoL and MASI was 0.35 (P < 0.05). In a multivariate regression, MELASQoL score was associated (P ≤ 0.05) to MASI score (ß = 0.6), lower income (ß = 6.8), be single (ß = 4.2) and low education level (ß = 5.0). At multiple correspondence analysis, MASI, sex, marriage, education and income were associated with MELASQoL, as well as MASI was associated to skin phototypes, income and education level. CONCLUSION: The perception of life quality impairment in melasma is influenced by low scholarly, low family income, single marital status and greater clinical severity.

Exploring pathways for sustained melanogenesis in facial melasma: an immunofluorescence study.

BACKGROUND: The physiopathology of epidermal hypermelanization in melasma is not completely understood. Several cytokines and growth factors are increased in skin with melasma, nevertheless, nor the pathways involved in the increased αMSH expression have been adequately evaluated, nor a model for sustained focal melanogenesis is available. OBJECTIVE: To explore stimulatory pathways for epidermal pigmentation in facial melasma related to αMSH: those linked to ultraviolet radiation, oxidative stress, inflammation, neural crest pigmentation cell differentiation and antagonism of αMSH. METHODS: Paired skin biopsies (3 mm) from 26 women with facial melasma and from normal adjacent skin (<2 cm far) were processed for immunofluorescence with markers for p53, p38, αMSH, MC1R, Melan-A, IL-1α, COX2, Wnt1, WIF-1 and ASIP. RESULTS: The fluorescence intensity in the skin from melasma was higher for MC1R, αMSH at epidermis as at melanocytes (P < 0.05). There were no differences between the sites in epidermal protein expression of COX2, IL-1α, p53, WIF-1 and ASIP (P > 0.1). P53 was expressed only in epidermis, without difference between sites (P = 0.92). WNT1 was remarkable in the epidermis of melasma (P < 0.01), but not in dermis. Positive p38 cells were prominent in the upper dermis of melasma (P < 0.01), despite no marking in epidermis. CONCLUSION: Melanogenesis in melasma involves epithelial secretion of αMSH and activation of the Wnt pathway; nevertheless, it seems to be independent of the stimulation by ultraviolet radiation/p53, IL-1α, COX2/PgE2 , WIF-1 and ASIP. Damaged cells at upper dermis suggest the role of senescence/autophagy in sustained pigmentation in melasma.

Reliable assessment of forearm photoageing by high-frequency ultrasound: a cross-sectional study.

OBJECTIVE: High-frequency ultrasound is a non-invasive tool used in skin ageing research to assess dermis thickness and echogenicity. This study evaluated the reliability of a range of high-frequency ultrasound parameters and tested their correlation with age and a validated clinical scale for the assessment of forearm skin photoageing; the difference between two body sites according to environmental exposition patterns was also investigated. METHODS: Twenty-three volunteers aged 28-82 years were divided into three groups according to forearm photoageing degree. A 20 MHz ultrasound unit was used to obtain cross-sectional images of the skin by two trained investigators on two different sites: the dorsal forearm (chronically photoexposed skin) and the proximal medial arm (non-photoexposed skin). Several echogenicity parameters were studied for each skin compartment: total dermis, upper dermis and lower dermis, and the ratio between upper and lower dermis. RESULTS: The intraclass correlation coefficient (for complete agreement) between investigators was higher for upper and total dermis echogenicity measures compared with the lower dermis. At the non-photoexposed site, the upper and lower dermis parameter ratio was better correlated with age. At the photoexposed area, total dermis parameters demonstrated higher correlations with clinical score. CONCLUSION: The authors discuss the choice of parameters for forearm photoageing assessment using high-frequency ultrasound.

Apoptosis in follicles of individuals with female pattern hair loss is associated with perifollicular microinflammation.

OBJECTIVE: The objective of this study is to evaluate apoptosis in hair follicles of patients with female pattern hair loss (FPHL) and its association with follicular microinflammation. METHOD: Cross-sectional study involving 17 women with FPHL and five controls. Scalp skin samples were processed for HE and TUNEL assays. The variables were compared according to the categories of follicles (terminal versus miniaturized) and groups of patients (FPHL vs. controls). RESULTS: There was a higher apoptosis index among miniaturized follicles and among the test cases (P < 0.01). Microinflammation was prominent among miniaturized follicles, especially from FPHL (P = 0.02). In addition, a positive correlation between inflammatory infiltrate and apoptosis in miniaturized follicles (rS = 0.68; P < 0.01) was found. CONCLUSIONS: Apoptosis was prominent in hair follicles from the FPHL group, as well as in miniaturized ones. Moreover, it was also correlated with the inflammatory infiltrate, which suggests that inflammation can lead to apoptosis and play a role in the pathogenesis of follicle miniaturization.

Changes in nuclear morphology and chromatin texture of basal keratinocytes in melasma.

BACKGROUND: The pathogenesis of melasma and the role of keratinocytes in disease development and maintenance are not completely understood. Dermal abnormalities, the expression of inflammatory mediators, growth factors, epithelial expression of melanocortin and sexual hormones receptors suggest that not only melanocytes, but entire epidermal melanin unit is involved in melasma physiopathology. OBJECTIVES: To compare nuclear morphological features and chromatin texture between basal keratinocytes in facial melasma and adjacent normal skin. METHODS: We took facial skin biopsies (2 mm melasma and adjacent normal skin) from women processed for haematoxylin and eosin. Thirty non-overlapping basal keratinocyte nuclei were segmented and descriptors of area, highest diameter, perimeter, circularity, pixel intensity, profilometric index (Ra) and fractal dimension were extracted using ImageJ software. RESULTS: Basal keratinocyte nuclei from facial melasma epidermis displayed larger size, irregular shape, hyperpigmentation and chromatin heterogeneity by fractal dimension than perilesional skin. CONCLUSION: Basal keratinocytes from facial melasma display changes in nuclear form and chromatin texture, suggesting that the phenotype differences between melasma and adjacent facial skin can result from complete epidermal melanin unit alterations, not just hypertrophic melanocytes.