Phosphodiesterase-4 inhibitors increase pigment cells proliferation and melanization in cultured melanocytes and within a 3D skin equivalent model.

Vitiligo is a common chronic autoimmune disease characterized by white macules and patches of the skin, having a negative impact on patients' life, and without any definitive cure at present. Identification of new compounds to reverse depigmentation is therefore a pressing need for this disease. The pharmacologic compounds phosphodiesterase-4 inhibitors (PDE4i) are small molecules with immunomodulatory properties, used for treatment of inflammatory dermatoses. PDE4i have shown repigmentation effects in vitiligo patients, in some case reports. We characterized the proliferative and melanogenic potential of two known PDE4i, crisaborole and roflumilast, and of a more recently designed compound, PF-07038124. We used two in vitro model systems, the primary human melanocyte culture and a 3D co-cultured skin model (MelanoDermTM), with an exploratory testing platform composed of complementary assays (spectrophotometry, melanin and proliferation assays, immunostaining, Fontana-Masson staining, qRT-PCR, western blot and whole transcriptome RNA-Sequencing). We identified that the treatment with PDE4i was associated with increased melanocyte proliferation and melanization in both in vitro models, and with increase in the melanogenic genes and proteins expression in cultured melanocytes. These effects were found to be enhanced by addition of α-MSH. Our findings support the further evaluation of PDE4i with or without α-MSH agonists in vitiligo trials.

The safety and efficacy of four different fixed combination regimens of adapalene 0.1%/benzoyl peroxide 2.5% gel for the treatment of acne vulgaris: results from a randomised controlled study.

BACKGROUND: Combined use of a retinoid and antimicrobial is recommended for acne, however, local tolerability issues may compromise patient adherence and treatment outcome. OBJECTIVES: This multicentre, single-blinded controlled study was designed to determine whether modified adapalene/benzoyl peroxide (A/BPO, Epiduo®, Galderma, France) regimens improve local tolerability during the first four weeks of treatment without impairing efficacy at Week 12. MATERIALS & METHODS: In total, 120 subjects with mild-to-moderate acne received, during the first four weeks, A/BPO daily overnight (A/BPO-EN), A/BPO daily for three hours (A/BPO-3h), A/BPO daily overnight and a provided moisturizer lotion (A/BPO-moisturizer), or A/BPO every other night (A/BPO-EoN). Local tolerance assessments included signs and symptoms, global worst score (GWS), and total sum score (TSS). Efficacy was assessed based on lesion counts, investigator global assessment (IGA), and total lesion count reduction. Adherence, subject satisfaction, and overall safety were also assessed. RESULTS: The mean TSS was significantly reduced at Week 1 with A/BPO-EoN vs. A/BPO-EN (p<0.05), and A/BPO-EoN led to the lowest GWS and a decrease in severity of stinging/burning and erythema (p<0.05). The A/BPO-moisturizer regimen prevented dryness and scaling compared with the A/BPO-EN regimen. The median decrease in lesions from baseline was similar in all groups: up to 67% for total, 72% for inflammatory, and 70% for non-inflammatory lesion counts. Adherence, IGA, patient satisfaction, and overall safety were excellent. CONCLUSIONS: Modulating treatment regimens during the first four weeks improved local tolerability without impacting overall efficacy outcome after 12 weeks and may improve treatment adherence during the first weeks of therapy.

Contribuição do mapeamento corporal total e dermatoscopia digital para o diagnóstico precoce do melanoma / The contribution of total body mapping and digital dermoscopy for the early diagnosis of melanoma

O prognóstico do melanoma cutâneo depende principalmente de sua espessura, sendo a detecção precoce do melanoma extremamente importante para a maior sobrevida dos pacientes. Com a utilização do exame dermatoscópico, pode-se alcançar acurácia de aproximadamente 90%. Melanomas iniciais podem não apresentar características dermatoscópicas específicas, sendo apenas diagnósticados pela mudança ao longo do tempo, observada pelo mapeamento corporal total e dermatoscopia digital seriados. Os grupos que apresentam maior sensibilidade para detecção do melanoma com esse exame são os de portadores de síndrome do nevo atípico e melanoma múltiplo familial.

The prognosis of cutaneous melanomas depends mainly on the lesions' thickness; early detection is of paramount importance for patient longer survival rates. An accuracy of approximately 90% can be achieved using dermoscopic assessment. Since early melanomas might not present specific dermoscopic features, they can only be diagnosed by observing alterations over time through total body mapping and serial digital dermoscopy. Patients with atypical nevus syndrome and multiple familial melanoma presented a higher sensitivity for the detection of melanoma using that technique.

Perspectivas no uso da microscopia confocal in vitro na prática do cirurgião dermatológico / In vivo confocal microscopy in the daily practice of the dermatologic surgeon

Novos métodos de imagem, como a tomografia óptica de coerência, a ressonância magnética e a ultrassonografia de alta frequência vem sendo desenvolvidos para uso na dermatologia. Entre estes novos métodos, destacamos a microscopia confocal de reflectância in vivo (MCR) como a que mais tem se difundido nos grandes centros de oncologia cutânea e que recentemente mais tem gerado publicações nos grandes periódicos, por permitir resolução semelhante à histológica. A microscopia confocal in vivo tem encontrado espaço nas muitas limitações que ainda se impõem ao diagnóstico dermatoscópico das neoplasias cutâneas, especialmente lesões acrômicas ou hipopigmentadas, lesões na face ou em mucosas. Ainda, alguns estudos tem sugerido grande utilidade na avaliação de margens cirúrgicas e na determinação do melhor local para a realização de biópsias excisionais. Este trabalho prtetende descrever brevemente o funcionamento do microscópio confocal de reflectância a laser e discutir algumas perspectivas que despontam para seu uso na prática cotidiana do cirurgião dermatológico.

New imaging methods, such as optical coherence tomography, magnetic resonance and high frequency ultrasonography, have been developed for use in dermatology. Among the new methods, in vivo reflectance confocal microscopy, has presented the fastest growth in large cutaneous oncology centers and has generated the greatest number of articles in the literature recently, due to its resolution ? similar to histological resolution. In vivo confocal microscopy has been particularly useful given the many limitations of the dermoscopic diagnosis of cutaneous neoplasias, especially of achromic or hypopigmented lesions, lesions in the face or in mucous membranes. Some studies have also suggested considerable utility in the assessment of surgical margins and in determining the best area of the body for carrying out excisional biopsies. This study briefly describes how the confocal laser reflectance microscope works and discusses some of the issues that arise in its use in the daily practice of dermatologic surgeons.

Dermatoscopia na gestação / Dermatoscopy in pregnancy

O prognóstico do melanoma cutâneo depende principalmente da sua espessura, sendo a detecção precoce de melanomas iniciais extremamente importante para a maior sobrevida dos pacientes. Com a utilização do exame dermatoscópico, pode-se alcançar acurácia de aproximadamente 90%. Alterações em lesões pigmentadas durante a gestação podem ocorrer, porém a dificuldade é saber se são benignas ou se correspondem a melanoma. O recurso diagnóstico da dermatoscopia permite aumentar a margem de acerto no diagnóstico e na detecção do melanoma nos estádios mais iniciais, melhorando o prognóstico e consequentemente a sobrevida do paciente.