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.

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.

Skin barrier and microbiome in acne.

Acne is an immune-mediated chronic inflammatory disease. Although several factors are involved in its pathophysiology, this process is not completely understood. Androgen hormone activity increases sebum production inside the pilosebaceous follicle, adjusting the environment for the development of Propionibacterium acnes which triggers inflammation. Knowing how others factors such as the skin barrier and microbiome are involved in acne, can help in understanding more about the disease and may help to conduct a better treatment.

Allergic sensitization to laboratory animals is more associated with asthma, rhinitis, and skin symptoms than sensitization to common allergens.

BACKGROUND: Workers exposed to laboratory animals have a high risk of developing laboratory animal allergy (LAA). Atopy seems to be the main risk factor for LAA. We hypothesized that occupational sensitization is a better predictor for the development of asthma, rhinitis, and bronchial hyperresponsiveness (BHR) than common sensitization. OBJECTIVE: To investigate the association between occupational sensitization to laboratory animals and clinical outcomes. METHODS: This was a cross-sectional study performed at two universities on students and employees dealing with small rodents. The subjects were allocated in groups: non-sensitized, common sensitization, or occupational sensitization, according to the results of the skin prick test (SPT). All subjects answered a questionnaire about animal exposures, symptoms, allergic diseases, and underwent spirometry and bronchial challenge test with mannitol. Multivariate analysis was performed using Poisson regression to estimate the prevalence ratio (PR). RESULTS: Data from 453 volunteers were analysed. Non-sensitized group comprised 237 subjects; common sensitization group, 142 subjects; and occupational sensitization group, 74 subjects. Occupational sensitization was associated with greater risk for all outcomes studied. When the common sensitization group was reference, skin symptoms had PR of 1.36, 95% confidence interval (CI): 1.01-1.85; wheezing had PR of 1.75, CI 95%: 1.21-2.53; rhinitis had PR of 1.25, 95%: 1.11-1.40; nocturnal dyspnoea had PR of 2.40, 95% CI: 1.31-4.40; bronchial hyperresponsiveness (BHR) had PR of 2.47, 95% CI: 1.50-4.09; and confirmed asthma had PR of 2.65, 95% CI: 1.45-4.85. In addition, the overlap of asthma, rhinitis, and skin symptoms in a same subject was significantly more prevalent in the occupational sensitization group, 16.2% versus 4.9% in the common sensitization group. CONCLUSION AND CLINICAL RELEVANCE: Occupational sensitization is associated with allergic symptoms and respiratory diseases. SPT with occupational allergens along with other parameters may contribute to detection of risk for allergic and respiratory diseases associated with exposure to laboratory animals.

Forearm skin aging: characterization by instrumental measurements.

BACKGROUND: The intrinsic ageing and photoaged skin present biomechanical and morphological differences, which are reflected in the appearance of roughness, superficial and deep wrinkles, atrophy, reduced elasticity, hypo- and hyperpigmentation and actinic keratosis. OBJECTIVE: To evaluate and compare the characteristics of the flexor (with a predominance of intrinsic ageing) and extensor (chronically exposed to sunlight and other environmental factors, with a predominance of photoageing) skin surfaces of the forearms. METHODS: Interventional, prospective, diagnostic study, including 23 females, aged over 60 years. The extensor and flexor faces of forearms were compared in relation to clinical parameters and non-invasive instrumental measurements, such as skin surface, elasticity, hydration as well as dermal thickness and echogenicity. RESULTS: Regarding the water content of the stratum corneum, the flexor face presented an average value higher than the extensor face. The average of measures obtained through images of high-frequency ultrasound demonstrated greater echogenicity of flexor face compared to the extensor face. The measurements of the skin surface showed significant differences between the faces. The roughness and scaliness were lower in the flexor face. Regarding the depth of wrinkles, there was no significant difference between the faces. The average of the measurements was slightly higher in the flexor face, which demonstrated that wrinkles are present in the intrinsic ageing and photoageing. The presence of elastosis and the reduction in elasticity in the clinical aspect of the photoaged face of forearms were according to the results of the non-invasive measurements. CONCLUSION: Meaningful differences in the biophysical characteristics of the extensor and flexor faces of the forearms were detected. Because the non-invasive instrumental measurements correlated with clinical findings, they may represent useful tools to assess efficacy and safety of skin ageing treatments in clinical research.

Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial.

Malassezia spp in skin microbiome scalp has been implicated in seborrheic dermatitis pathogenesis. Thus, treatment based in antifungal combined to topical keratolitic agents have been indicated as well as oral isotretinoin as it reduces the sebum production, glandular's size and possesses anti-inflammatory properties. This randomized, comparative and therapeutic trial aimed toper form the genotypic identification of Malassezia species before and after low-dose oral isotretinoin or topical antifungal treatments for moderate to severe seborrhea and/or seborrheic dermatitis on scalp. Scales and sebum of the scalp were seeded in the middle of modified Dixon and incubated at 32°C. For genotypic identification polymerase chain reaction primers for the ITS and D1/D2 ribossomal DNA were used and followed by samples sequencing. The procedure was conducted before and after therapeutic and randomized intervention for moderate to severe seborrhea/seborrheic dermatitis on the scalp, including oral isotretinoin, 10 mg, every other day and anti-seborrheic shampoo (piroctone olamine), over six months. The M. globosa and M. restricta were the most frequent species isolated on the scalp before and after both treatments. Other non-Malassezia species were also identified. The Malassezia spp. were maintained in the scalp after both treatments that were equally effective for the control of seborrhea/seborrheic dermatitis clinical signs.

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.

Mutational status of naevus-associated melanomas.

BACKGROUND: The origin of melanoma has always been a debated subject, as well as the role of adjacent melanocytic naevi. Epidemiological and histopathological studies point to melanomas arising either de novo or from a naevus. OBJECTIVES: To evaluate the presence of mutations in genes from well-known melanomagenesis pathways in a large series of naevus-associated melanomas. MATERIALS AND METHODS: Sixty-one melanomas found in association with a pre-existing naevus were microdissected, after careful selection of cell subpopulations, and submitted to Sanger sequencing of the BRAF, NRAS, c-KIT, PPP6C, STK19 and RAC1 genes. Each gene was evaluated twice in all samples by sequencing or by sequencing and another confirmation method, allele-specific fluorescent polymerase chain reaction (PCR) and capillary electrophoresis detection or by SNaPshot analysis. Only mutations confirmed via two different molecular methods or twice by sequencing were considered positive. RESULTS: The majority of cases presented concordance of mutational status between melanoma and the associated naevus for all six genes (40 of 60; 66.7%). Nine cases presented concomitant BRAF and NRAS mutations, including one case in which both the melanoma and the adjacent naevus harboured V600E and Q61K double mutations. In two cases, both melanoma and associated naevus located on acral sites were BRAF mutated, including an acral lentiginous melanoma. CONCLUSIONS: To our knowledge this is the largest naevus-associated melanoma series evaluated molecularly. The majority of melanomas and adjacent naevi in our sample share the same mutational profile, corroborating the theory that the adjacent naevus and melanoma are clonally related and that the melanoma originated within a naevus.

Development and Validation of a Clinical Scale for the Evaluation of Forearm Skin Photoaging.

BACKGROUND: Despite the focus on facial photoaging ratings, there are few classifications developed for forearm skin aging assessment. OBJECTIVE: To develop and validate a clinical scale for the evaluation of forearm skin aging. METHODS: Three clinical dermatology faculty members selected, discussed, and appraised the main signs of forearm photoaging. The validation of the resulting scale was performed by 5 assessors who were previously trained to classify 102 photographs of forearms with different degrees of aging. Retests were performed in 15 days. RESULTS: There was significant correlation between the selected variables and the subjective global aging scale. The developed scale showed high internal consistency (Cronbach's α=0.87) and high correlation with the global photoaging scale (rho=0.92). Inter- and intraobserver final scores showed high agreement. CONCLUSION: A validated clinical photoaging scale for forearms with internal consistency, reliability, and validity was developed.

Cellulite: poor correlation between instrumental methods and photograph evaluation for severity classification.

BACKGROUND: Cellulite refers to skin relief alterations in women's thighs and buttocks, causing dissatisfaction and search for treatment. Its physiopathology is complex and not completely understood. Many therapeutic options have been reported with no scientific evidence about benefits. The majority of the studies are not controlled nor randomized; most efficacy endpoints are subjective, like not well-standardized photographs and investigator opinion. Objective measures could improve severity assessment. Our purpose was to correlate non-invasive instrumental measures and standardized clinical evaluation. METHODS: Twenty six women presenting cellulite on buttocks, aged from 25 to 41, were evaluated by: body mass index; standardized photography analysis (10-point severity and 5-point photonumeric scales) by five dermatologists; cutometry and high-frequency ultrasonography (dermal density and dermis/hypodermis interface length). Quality of life impact was assessed. Correlations between clinical and instrumental parameters were performed. RESULTS: Good agreement among dermatologists and main investigator perceptions was detected. Positive correlations: body mass index and clinical scores; ultrasonographic measures. Negative correlation: cutometry and clinical scores. Quality of life score was correlated to dermal collagen density. CONCLUSION: Cellulite caused impact in quality of life. Poor correlation between objective measures and clinical evaluation was detected. Cellulite severity assessment is a challenge, and objective parameters should be optimized for clinical trials.

Could adult female acne be associated with modern life?

In recent years, the prevalence of adult female acne has increased, but the reason for this increase remains unclear. Acne is one of the most common skin disorders. It can be triggered or worsened by endogenous and exogenous factors, including genetic predisposition, hormone concentrations, diet, smoke and stress; although the interaction with this last factor is not well understood. Modern life presents many stresses including urban noises, socioeconomic pressures and light stimuli. Women are especially affected by stress during daily routine. The recent insertion in the labor market is added to the duties of the mother and wife. Women also have a higher risk of developing psychiatric disorders such as depression and anxiety. Sleep restriction is added to these factors, with several negative consequences on health, including on hormonal secretion and the immune system. This is further complicated by the natural variation in sleep architecture across the menstrual cycle. Recent studies have brought new data about the mechanisms and possible factors involved. This review aims to establish a connection between stress, sleep deprivation and adult female acne.

The reliability of counting actinic keratosis.

Many epidemiological studies and clinical trials have been performed concerning actinic keratoses. The most eligible endpoint in the majority of articles is counting of actinic keratoses before and after treatments, nevertheless some authors support that this is not a reliable form of evaluation. The aim of this study was to evaluate the actinic keratoses counting by various raters and suggest approaches to increase the reliability. Cross-sectional study: forty-three patients were evaluated by four raters (inter- and intra-rater assessment) on the face and forearms. The mean actinic keratoses counts on the face and forearms were 7.7 and 9.1. The overall agreement among the raters for the facial and forearm actinic keratoses was 0.74 and 0.77. The intra-rater assessment showed high rates of agreement for the face (ICC=0.93) and forearms (ICC=0.83). Higher agreement occurred when counting up to five lesions. Four raters led to increased measurement variability and loss of reliability. Higher rates of agreement may be achieved with small number of lesions, limitation and/or segmentation of body areas to reduce their number, in AK prevention designs, are strategies that may lead to a greater reliability of these measurements.

Long-wave infrared radiation reflected by compression stockings in the treatment of cellulite: a clinical double-blind, randomized and controlled study.

BACKGROUND: Cellulite refers to changes in skin relief on the thighs and buttocks of women, with a prevalence of 80-90%, causing dissatisfaction and search for treatment. Etiopathogenesis is multifactorial, as follows: herniation of the hypodermis towards the dermis, facilitated by perpendicular fibrous septa, changes in the dermal extracellular matrix, decreased adiponectin, genetic polymorphism, microcirculation alterations and inflammatory process. There are numerous therapeutic approaches, with little evidence of effectiveness. The long-wave infrared (LWIR) radiation interacts with water, improves microcirculation and stimulates metabolic processes. To date, the use of tissues with potential reflection of LWIR radiation has not been systematically investigated as adjuvant treatment for cellulite. OBJECTIVE: To investigate the efficacy and safety of the treatment of cellulite through the use of compression stockings made with thread reflecting LWIR radiation. PATIENTS AND METHODS: Clinical study of therapeutic intervention, controlled and double-blind, including 30 women, aging from 25 to 40 years, with cellulite of grades II and III on the thighs and buttocks who used compression stockings, "pantyhose" model, made with reflector thread of LWIR radiation, on only one randomized side. Women under other treatments for cellulite and with venous and/or blood insufficiencies were excluded. Evaluation of efficacy by clinical parameters, photographs, Dermatology Life Quality Index (DLQI), cutometry and high frequency ultrasonography and security by observation of adverse events and venous EcoDoppler recordings. RESULTS: DLQI scores showed significant reduction; the two-dimensional high-frequency ultrasonography showed an insignificant increase in dermal echogenicity as well as other efficacy parameters demonstrated no or slight improvement, with no differences between the sides exposed or not to LWIR; and there were no severe adverse events. CONCLUSION: Compression stockings, with or without thread reflector of LWIR, showed slight effects in the appearance of cellulite, but the treatment determined a positive impact on women quality of life.

Adult female acne: a new paradigm.

In the adult female, acne is a chronic condition with a substantial negative psychological, social and emotional impact. Based on time of onset, two subtypes of adult female acne are recognized: 'persistent acne' is a continuation of the disease from adolescence, while 'late-onset acne' first presents in adulthood. The morphological characteristics of adult female acne are often distinct from adolescent acne. In adults, inflammatory lesions (particularly papules, pustules and nodules) are generally more prominent on the lower chin, jawline and neck, and comedones are more often closed comedones (micro cysts). Adult acne is mainly mild-to-moderate in severity and may be refractory to treatment. A holistic approach to acne therapy should be taken in adult females, which combines standard treatments with adjunctive therapy and cosmetic use. A number of factors specific to the adult female influence choice of treatment, including the predisposition of older skin to irritation, a possible slow response to treatment, a high likelihood of good adherence, whether of child-bearing age, and the psychosocial impact of the disease. Adherence to therapy should be encouraged through further patient education and a simplified regimen that is tailored to suit the individual patient's needs and lifestyle. This article reviews the specific characteristics of adult female acne, and provides recommendations for acne therapy in this patient group.

Radiolabelled somatostatin analogs for diagnosis and radio-guided surgery of neuroendocrine breast cancer undetectable with conventional imaging procedures.

Some neoplasms are classified as primary neuroendocrine tumours (NETs) because of their positivity for neuroendocrine markers [chromogranins A and B (CgA, CgB) and neuron-specific enolase (NSE)]. Neuroendocrine differentiation has been reported, for example, in both "in situ" and infiltrating breast cancer. Diagnosis of NET is bio-humoral (CgA, NSE, synaptophysin) and instrumental. Even if the final diagnosis is made by open biopsy, radionuclide imaging using radiolabelled somatostatin analogs, such as In-111 pentetreotide, may detect neuroendocrine primary tumours and metastases before they become detectable using traditional and advanced imaging modalities [mammography (MX), ultrasound (US) and magnetic resonance imaging (MRI)]. When neuroendocrine breast lesions are not detectable, radio-guided surgery (RGS) is able to localise cancer. We report a case of a woman with a palpable lymph node in the left axilla. She underwent a US-guided lymph node biopsy, which was positive for massive metastases, probably of neuroendocrine breast origin. Mammary plus axillary US showed only lymphadenopathy in the left axilla. MX and breast MRI were negative. Neoplastic markers (CEA, CA 15.3, CA 125 and CA 19.9) were negative too. On the other hand, neuroendocrine markers (NSE and CgA) were positive. A whole body scintigraphic scan plus thorax and abdomen single photon emission computed tomography (SPECT) with In-111 pentetreotide (222 MBq; 6 mCi) showed an uptake in the left mammary gland. No other pathological localisations were observed. The day after the intravenous injection of In-111 pentetreotide, the patient underwent RGS breast tumour resection and left axillary lymphadenectomy. In conclusion, we would like to emphasise: (1) the role of radionuclide imaging for the detection of breast NETs in relation to conventional diagnostic procedures; (2) the role of RGS in localising and removing a non-palpable breast NET that was undetectable with the use of conventional imaging techniques.

Asbestos-related diseases of the lungs and pleura: uses, trends and management over the last century.

Asbestos is a descriptive term for a group of naturally occurring minerals known to mankind since ancient times. The main types of asbestos (chrysotile, and the amphiboles crocidolite and amosite) differ in chemical structure, biopersistence in human tissue and toxicity. Commercial exploitation, with little thought for environmental controls, increased over the twentieth century, particularly after World War II, to accommodate globalisation and the demands of the world's burgeoning cities. As its ill-health effects, both non-malignant (fibrosis of the lungs or asbestosis; pleural effusion, plaques and thickening) and malignant (mesothelioma, lung and other cancers), became evident, public pressure rose to control its use. The last decades of the last century saw decreases in exposure and rates of asbestosis in industrialised and in some less-industrialised countries, where pleural plaques and malignant mesothelioma are currently the most frequent manifestations of asbestos exposure. Longer follow-up of asbestos-exposed cohorts in mining and manufacturing has also strengthened the evidence of a fibre gradient in toxicity, with chrysotile exhibiting lower toxicity than the amphiboles, and amosite lower toxicity than crocidolite. The last decades of the twentieth century saw stabilisation and/or declines in mesothelioma rates in several industrialised countries. In less-industrialised countries, data on disease are sparse, exposure generally high and rates may peak in the future. Management of asbestos-related disease in the workplace requires collaboration between workers and unions (responsible for monitoring workplace dust levels, to which they must have access) and companies (responsible for engineering controls), reinforced by appropriate government regulations and by community support.