DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo.

BACKGROUND: Malar melasma has a chronic and recurrent character that may be related to epigenetic changes. OBJECTIVE: To recognize the expression and DNA methylation of DNA methyltransferases (DNMTs) in malar melasma and perilesional skin, as well as the changes in DNMTs after their treatment with sunscreen in combination with 4% niacinamide, 0.05% retinoic acid, or placebo. METHODS: Thirty female patients were clinically evaluated for the expression of DNMT1 and DNMT3b using real-time PCR and immunofluorescence. These initial results were compared to results after eight weeks of treatment with sunscreen in combination with niacinamide, retinoic acid, or placebo. RESULTS: The relative expression of DNMT1 was significantly elevated in melasma compared with unaffected skin in all subjects, indicating DNA hypermethylation. After treatment, it was decreased in all groups: niacinamide (7 versus 1; p<0.01), retinoic acid (7 versus 2; p<0.05), and placebo (7 versus 3; p<0.05), which correlates with clinical improvement. DNMT3b was not overexpressed in lesional skin but reduced in all groups. CONCLUSIONS: We found DNA hypermethylation in melasma lesions. Environmental factors such as solar radiation may induce cellular changes that trigger hyperpigmentation through the activation of pathways regulated by epigenetic modifications. However, limiting or decreasing DNA methylation through sunscreen, niacinamide, and retinoic acid treatments that provide photoprotection and genetic transcription can counteract this.

Repigmentation patterns induced by NB-UVB and their relationship with melanocytic migration and proliferation in vitiligo.

BACKGROUND/PURPOSE: Vitiligo is the most commonly acquired depigmentation disorder of the skin and is characterized by the destruction of melanocytes. Ultraviolet phototherapy with narrow band (UVB-NB) induces proliferation, differentiation, maturation, and migration of melanocytes. The clinical repigmentation is featured by follicular, marginal, and diffuse patterns. The aim of this study was to observe the process involved in the melanocyte migration and proliferation among these patterns and the unresponsive lesions following UVB-NB phototherapy. The focal adhesion kinase (FAK) and c-KIT were used as markers of melanocyte migration and differentiation, respectively. METHODS: A total of 17 vitiligo patients under UVB-NB therapy were selected. The patients expressed the three repigmentation patterns as well as unresponsive lesions at the conclusion of a 30-session cycle. Skin biopsies were evaluated by immunohistochemistry and qRT-PCR. RESULTS: We found an increased expression of c-KIT in the follicular pattern compared to the diffuse pattern that was expressed predominantly of FAK. Marginal pattern expressed both proteins. The unresponsive achromic lesions showed poor expressions of both markers. CONCLUSION: Proliferation was prominent in the follicular pattern, but migration was prominent in the diffuse pattern. For the marginal pattern, both dynamics were present. The absence of these markers in vitiligo lesions suggests a lack of response to UVB-NB.

Relationship between transient receptor potential vanilloid-1 expression and the intensity of sensitive skin symptoms.

BACKGROUND: Sensitive skin (SS) is a hyper-reactive condition of the skin secondary to external factors, without objective signs of lesion. Its pathogenesis is still under investigation. Transient receptor potential vanilloid-1 (TRPV1) is a cation channel that responds to low pH and is related to nociception, neurogenic inflammation, and pruritus. AIMS: To determine the expression of TRPV1 in subjects with SS and correlate it with the degree of symptoms and skin pigmentation. PATIENTS/METHODS: We included 31 subjects self-diagnosed as having SS. Colorimetric values were obtained for assessment of skin phototype, and the lactic acid stinging test (LAST) was performed. Two skin biopsies from the nasolabial fold of each volunteer were obtained. Qualitative analysis of TRPV1 was carried out with immunohistochemistry. Quantitative analysis of TRPV1 was carried out with qRT-PCR. RESULTS: LAST was positive in 74% of the subjects, 56% of those having tan and brown skin. Immunohistochemistry staining for TRPV1 was greater in positive subjects (P = 0.03), but showed no correlation with the intensity of symptoms. Positive subjects also had higher TRPV1 mRNA expression compared to negative subjects (P < 0.001). This expression showed a positive correlation with the intensity of referred symptoms (R = 0.75, P < 0.001) and skin pigmentation (R = 0.63, P < 0.001). CONCLUSIONS: TRPV1 expression is upregulated in subjects with sensitive skin, and it correlates with the intensity of the symptoms. Our findings suggest a role for this receptor in the pathogenesis of sensitive skin syndrome.

CD4, IL-17, and COX-2 Are Associated With Subclinical Inflammation in Malar Melasma.

The pathogenesis of melasma, a common, photo-induced hyperpigmentary disorder, is not clearly understood. Significant factors linked to melasma are ultraviolet radiation exposure and genetic predisposition. Histological analysis has demonstrated that melasma is caused by a network of cellular interactions among melanocytes, keratinocytes, mast cells, fibroblasts, and dermal vasculature exhibits, features similar to chronic sun damage. Dermal inflammation caused by ultraviolet radiation might play an important role in the hyperpigmentation and reactivation of melasma lesions through the production of melanogenic cytokines and growth factors. Because the role of inflammation in this disorder is unknown, we used histochemistry, immunohistochemistry, and quantitative real-time polymerase chain reaction to evaluate melasma lesions from healthy female patients (n = 20) with malar melasma. Lesional skin without specific solar exposure or photoprotection measures within the previous 4 weeks was compared with nonlesional skin. The increased lymphocytic infiltrate in lesional skin was mainly composed of CD4 T cells, mast cells, and macrophages. Levels of the cytokine interleukin (IL)-17 and the proinflammatory mediator cyclooxygenase (COX)-2 were significantly elevated in affected skin compared with healthy skin. In addition, the Melasma Activity and Severity Index score, fraction of solar elastosis, and epidermal melanin were positively associated with COX-2 expression. There was no statistically significant difference in IL-1α, IL-1ß, R-IL1, IL-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor alpha expression levels. Together, these data indicated that melasma under unchallenged conditions is characterized by chronic inflammatory cells and mediators, which may explain its recurrent nature.

α-Synuclein inclusions in the skin of Parkinson's disease and parkinsonism.

OBJECTIVE: The presence in the brain of α-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD). The discovery of α-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease. Our goals were, first, to demonstrate the presence of α-synuclein inclusions in the skin and, second, to detect quantitative differences between patients with PD and atypical parkinsonism (AP). METHODS: Skin biopsies were taken from 67 patients and 20 controls. The biopsies underwent immunohistochemistry (IHC) and immunofluorescence (IF) testing for α-synuclein, whereupon its presence was quantified as the percentage of positive cells. Patients were divided into those with PD and those with AP. AP patients included AP with neurodegenerative disease (proteinopathies) and secondary AP. RESULTS: Sixty-seven patients (34 with PD) and 20 controls were recruited. In the PD group, α-synuclein was detected in 58% of the cells in the spinous cell layer (SCL), 62% in the pilosebaceous unit (PSU), and 58% in the eccrine glands (EG). The AP-proteinopathies group showed 7%, 7%, and 0% expression of α-synuclein, respectively. No expression was found in the skin of the control group. CONCLUSIONS: The expression of α-synuclein in the skin was relatively high in the PD group, scarce in AP, and null for the individuals in the control group. While these findings require further confirmation, this minimally invasive technique may aid in the improvement of the accuracy of PD diagnoses.

Near-visible light and UV photoprotection in the treatment of melasma: a double-blind randomized trial.

BACKGROUND: Melasma is an acquired hyperpigmentation on sun-exposed areas. Multiple approaches are used to treat it, but all include broad ultraviolet (UV)-spectrum sunscreens. Visible light (VL) can induce pigmentary changes similar to those caused by UV radiation on darker-skinned patients. OBJECTIVE: To assess the efficacy of sunscreen with broad-spectrum UV protection that contains iron oxide as a VL-absorbing pigment (UV-VL) compared with a regular UV-only broad-spectrum sunscreen for melasma patients exposed to intense solar conditions. METHODS: Sixty-eight patients with melasma were randomized in two groups to receive either UV-VL sunscreen or UV-only sunscreen, both with sun protection factor ≥ 50, over 8 weeks. All patients received 4% hydroquinone as a depigmenting treatment. At onset and at conclusion of the study, they were assessed by the Melasma Activity and Severity Index (MASI; a subjective scale), colorimetry (L*) and histological analysis of melanin. RESULTS: Sixty-one patients concluded the study. At 8 weeks, the UV-VL group showed 15%, 28% and 4% greater improvements than the UV-only group in MASI scores, colorimetric values and melanin assessments, respectively. CONCLUSIONS: UV-VL sunscreen enhances the depigmenting efficacy of hydroquinone compared with UV-only sunscreen in treatment of melasma. These findings suggest a role for VL in melasma pathogenesis.

Topical niacinamide 4% and desonide 0.05% for treatment of axillary hyperpigmentation: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Axillary hyperpigmentation is a frequent cause of cosmetic consultations in dark-skinned women from tropical areas, including Latin America. Currently, there is no widely accepted treatment for the disorder, but it is usually treated with bleaching agents because it is considered a variant of inflammatory hyperpigmentation. The purpose of this study was to assess the efficacy of niacinamide 4% and desonide 0.05% emulsions compared with placebo in the treatment of axillary hyperpigmentation. METHODS: Twenty-four women aged 19-27 years with hyperpigmented axillae (phototype III-V) were randomly assigned to receive the study treatments in the axillary region. Improvement was assessed at baseline, then clinically and by colorimetry 9 weeks later. Quantitative evaluation including melanin, inflammatory infiltrates, NKI/Beteb, CD1a, CD68, and collagen type IV content was performed by histochemistry and immunohistochemistry, assisted by computerized morphometric analysis. RESULTS: Both niacinamide and desonide induced significant colorimetric improvement compared with placebo; however, desonide showed a better depigmenting effect than niacinamide. A good to excellent response was achieved in 24% of cases for niacinamide, 30% for desonide, and 6% for placebo. We observed a marked disruption of the basal membrane in axillary hyperpigmentation and an inflammatory infiltrate that improved after treatment. Decreased pigmentation in the desonide-treated axillae was associated with recovery of disruption at the basal membrane. CONCLUSION: Niacinamide and desonide showed depigmenting properties in women with axillary hyperpigmentation. These findings may be explained by their antimelanogenic and anti-inflammatory properties, respectively.

A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma.

Background. Multiple modalities have been used in the treatment of melasma with variable success. Niacinamide has anti-inflammatory properties and is able to decrease the transfer of melanosomes. Objective. To evaluate the therapeutic effect of topical niacinamide versus hydroquinone (HQ) in melasma patients. Patients and Methods. Twenty-seven melasma patients were randomized to receive for eight weeks 4% niacinamide cream on one side of the face, and 4% HQ cream on the other. Sunscreen was applied along the observation period. They were assessed by noninvasive techniques for the evaluation of skin color, as well as subjective scales and histological sections initially and after the treatment with niacinamide. Results. All patients showed pigment improvement with both treatments. Colorimetric measures did not show statistical differences between both sides. However, good to excellent improvement was observed with niacinamide in 44% of patients, compared to 55% with HQ. Niacinamide reduced importantly the mast cell infiltrate and showed improvement of solar elastosis in melasma skin. Side effects were present in 18% with niacinamide versus 29% with HQ. Conclusion. Niacinamide induces a decrease in pigmentation, inflammatory infiltrate, and solar elastosis. Niacinamide is a safe and effective therapeutic agent for this condition.

[Assessment of moisturizing creams available in México]. / Evaluación de cremas humectantes disponibles en México.

UNLABELLED: There is a broad diversity of moisturizers for the treatment of dry skin; however, we do not know their real effectiveness. The objective here was to evaluate different products through their capacity to increase the epidermal hydration level (EHL) and to reduce the transepidermal water loss (TEWL). MATERIALS AND METHODS: We evaluated twenty moisturizers in sixteen individuals. The analysis was made on volar forearm and basal measurements were made for EHL and TWEL with the later application of 8 gm of each moisturizer on a 2 cm2 area. RESULTS: For the EHL we found significant differences among the products (p < 0.0001), but only 35% (n = 7) of the moisturizers registered ascending levels of hydration in the course of measurements. The variance analysis for TEWL also was significant (p < 0.0001). CONCLUSIONS: In the short term only a few products induced a significant change in EHL. This study demonstrates the necessity to obtain objective information in order to avoid false publicity claims that may erroneously influence our prescription habits.

Histochemical and immunohistochemical study in melasma: evidence of damage in the basal membrane.

The pathogenesis of melasma has not been clearly elucidated. Using Fontana Masson; diastase-resistant periodic acid-Schiff stains; and immunohistochemistry to stem cell factor (SCF), its receptor c-kit, anti-mast cell tryptase, and anti-collagen type IV antibody, we evaluated melasma lesions and compared them with perilesional skin and photoprotected skin. Samples were taken from lesional and photoprotected nonlesional skin in 24 patients. In other 24 patients, we took biopsies of lesional and perilesional skin. With Fontana Masson, we observed many pigmented basal cells protruding into the dermis of the melasma skin. Periodic acid-Schiff stain and anti-collagen type IV showed damage on the basal membrane in 95.5% and 83%, respectively, in melasma lesion. The immunoreactivity of SCF and the prevalence of mast cells were increased in the dermis of melasma compared with perilesional dermis. The expression of c-kit was significantly increased at lesional epidermis; a frequent protrusion of c-kit-positive basal cells into the dermis was evident in 70% versus that in 29% of perilesional skin. The expression of c-kit was increased at lesional dermis of melasma compared with perilesional skin. We found a low correlation between c-kit expression and prevalence of mast cells; these were increased in melasma skin. The results may suggest a role of SCF, c-kit, and mast cells in the pathogenesis of melasma. We were surprised by the unexpected evidence of damage to basal membrane (BM), which could facilitate the fall or the migration of active melanocytes and melanin into the dermis allowing the constant hyperpigmentation in melasma.

Acrocordones: ¿marcadores cutáneos de obesidad y/o diabetes mellitus? / Skin tags: cutaneous marker for obesity and/or diabetes mellitus?

Los acrocordones son proliferaciones epiteliales y de tejido conectivo benignas localizadas en axila, cuello, ingles y párpados. Se les ha asociado a la presencia de obesidad y también de diabetes mellitus en el adulto. Se realizó un estudio con 213 individuos para establecer si la presencia de más de 5 acrocordones se asociaba a diabetes mellitus, obesidad o hiperinsulinemia. Se encontro asociación positiva para obesidad e hiperinsulinemia, así como también se descubrió aumento del receptor del factor de crecimiento de fibroblastos básicos en algunas lesiones. Los acrocordones parecen constituir un marcador cutáneo de enfermedad interna