Melasma and reflectance confocal microscopy: from baseline to treatment monitoring.

Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non-invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring.

Laser Treatment Monitoring with Reflectance Confocal Microscopy.

Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment.

Nd:YAG laser in association with pulsed dye laser for the treatment of PHACES syndrome.

The acronym PHACES stands for posterior fossa malformations, hemangiomas, arterial anomalies (cardiovascular or cerebrovascular), coarctation of the aorta/cardiac defects, eye abnormalities, and sternal defects. The characteristic dermatological clinical manifestation of PHACES syndrome is a segmental and extensive hemangioma, usually on the face. A combined therapy with 1,064 nm Nd-YAG/595-nm pulsed dye laser was performed in a young 15-year-old patient with PHACES syndrome, who presented a hemangioma on the left side of the face, located in the periorbital region. A first session with Nd-YAG laser (2,5 mm spot size, fluence 100 J/cm2, pulse duration 7 ms) for the treatment of teleangectasias and subsequently, three treatment sessions with pulsed dye laser (12 mm spot size, fluence 7 J/cm2, pulse duration 0,5 ms, repetition rate 0,6 Hz), once every 2 months, were performed. No postoperative complications were recorded, except for transient purpura after the pulsed dye laser sessions. The vascular lesion had a decrease in size bigger than 75%, and these results was maintained 6 months after the last treatment. Combined therapy Nd- YAG/pulsed dye laser is an effective and noninvasive procedure for hemangiomas in patients with PHACES syndrome.

Proteomic analysis from skin swabs reveals a new set of proteins identifying skin impairment in atopic dermatitis.

Atopic Dermatitis (AD) is a common inflammatory skin disease characterized by skin and systemic inflammation, and barrier dysfunction. Herein, we investigate the proteomic profile of AD skin barrier to identify a unique signature with an easy-performed sampling approach. We enrolled 8 moderate-to-severe AD patients and 8 age- and gender-matched healthy controls. Swabs were obtained from non-lesional skin of retroauricular area and antecubital fold. Peptide mixtures obtained through protein precipitation and in-solution digestion were analysed using NanoLC-MS/MS. Label-free quantification and statistical analysis were conducted in MaxQuant and Perseus. Bioinformatics analysis was performed using Gene Ontology and STRING. We identified 908 proteins and 35 differentially expressed proteins were selected (fold change 2, FDR < 0.05). Particularly, AD skin showed downregulation of skin hydration factors, structural and epidermal proteins, abnormalities in protease-proteasome complex and lipid metabolism profile. Imbalance of antioxidant and inflammatory processes, along with TDRD15 upregulation was also observed. Our result showed partial overlap with skin biopsy/tape-strips studies, showing the reliability of our sampling approach which could be an easier method of detection of hallmark barrier proteins in AD. Furthermore, we displayed a new differentially expressed set of proteins, not yet explored in AD which can have a potential role in AD pathomechanisms.

Daylight photodynamic therapy with 5-aminolevulinic acid 5% gel for the treatment of mild-to-moderate inflammatory acne.

BACKGROUND: Acne vulgaris is a chronic inflammatory disease that frequently occurs in adolescence. This common condition is often treated with topical or systemic therapies according to severity. Photodynamic therapy (PDT) with topical delta-aminolaevulinic acid is a novel drug-sparing, but time-consuming approach. Recently, sunlight exposure has been considered a quicker, safer, cheaper and more agreeable alternative light source for PDT, but efficacy has only been proven in the oncological field. This study aimed to evaluate the efficacy and tolerability of daylight PDT (DL-PDT) for the treatment of inflammatory acne vulgaris of face, chest and trunk lesions. METHODS: Twenty patients with mild-to-moderate acne vulgaris were enrolled and treated with a topical gel based on 5% delta-aminolaevulinic acid, administered 4 times at 14-day intervals. Efficacy was assessed with mean lesion count, Physician Global Assessment (PGA), Investigator's Global Assessment (IGA) and patients' self-assessment (10-point scale). RESULTS: Compared to T0, mean inflammatory lesions count decreased in all patients at FU1, from 16.7±4.4 to 5.2±3.3 (P). No adverse events were reported, and no patients were lost to follow-up. PGA results of "excellent" or "good" improvement were reported in 95% at T3 and 90% at FU1. Patients' self-assessments was 7.6±1.0 (T3). Discomfort was 0.5±0.2 (T3 and FU1). CONCLUSIONS: DL-PDT seems to be an effective and tolerable therapy for the treatment of mild-to-severe inflammatory acne. This novel regimen seems to be a viable option in the panorama of acne therapies.

Arsenic and chromium levels in hair correlate with actinic keratosis/non-melanoma skin cancer: results of an observational controlled study.

BACKGROUND: The role of heavy metals in carcinogenetic process has been widely established; however, information on the most common environmental metals that serve as major risk factors for actinic keratosis (AK)/non-melanoma skin cancer (NMSC) are still lacking. The aim of this study was to evaluate levels of the most common environmental heavy metals in hair of patients with AK/NMSC as compared to healthy controls. METHODS: Thirty-one patients diagnosed with AK/NMSC and 34 healthy controls were enrolled. Patients were interviewed for heavy metals exposure and underwent hair analysis for detection of arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni) and lead (Pb). Continuous variables were analyzed using Wilcoxon Non-Parametric Rank Test and proportions were compared by Fisher's Exact Test. Statistical significance was determined by P<0.05. RESULTS: In our cohort we observed 48.4% patients had AKs, 16.1% basal cell carcinoma (BCC), 9.7% squamous cell carcinoma (SCC) and 25.9% of patients presented with a combination of these lesions. There were significantly elevated levels of As and Cr in AK-NMSC group as compared to controls. CONCLUSIONS: We identified a strong positive correlation between As and Cr concentration and AK/NMSC adding new clues to the scenery of NMSC risk factors that should be taken under consideration in exposed populations.

Sulforaphane-Loaded Ultradeformable Vesicles as A Potential Natural Nanomedicine for the Treatment of Skin Cancer Diseases.

Sulforaphane is a multi-action drug and its anticancer activity is the reason for the continuous growth of attention being paid to this drug. Sulforaphane shows an in vitro antiproliferative activity against melanoma and other skin cancer diseases. Unfortunately, this natural compound cannot be applied in free form on the skin due to its poor percutaneous permeation determined by its physico-chemical characteristics. The aim of this investigation was to evaluate ethosomes® and transfersomes® as ultradeformable vesicular carriers for the percutaneous delivery of sulforaphane to be used for the treatment of skin cancer diseases. The physico-chemical features of the ultradeformable vesicles were evaluated. Namely, ethosomes® and transfersomes® had mean sizes <400 nm and a polydispersity index close to 0. The stability studies demonstrated that the most suitable ultradeformable vesicles to be used as topical carriers of sulforaphane were ethosomes® made up of ethanol 40% (w/v) and phospholipon 90G 2% (w/v). In particular, in vitro studies of percutaneous permeation through human stratum corneum and epidermis membranes showed an increase of the percutaneous permeation of sulforaphane. The antiproliferative activity of sulforaphane-loaded ethosomes® was tested on SK-MEL 28 and improved anticancer activity was observed in comparison with the free drug.

New trends in botulinum toxin use in dermatology.

BACKGROUND: Recent studies have highlighted new botulinum neurotoxin (BoNT) applications in the field of dermatology. OBJECTIVE: To review current knowledge of BoNT use in dermatology. METHODS: The literature of the last 5 five years has been reviewed. RESULTS: We describe interesting protocols of BoNT treatment for hyperhidrosis (HH), hypertrophic scars and keloids, Raynaud phenomenon, facial flushing, oily skin, psoriasis, Hailey-Hailey disease, and cutaneous lesions like painful lesions and periorbital syringomas. CONCLUSIONS: Several skin conditions eligible for BoNT treatment have been described. After the wide application for HH treatment, scars as well as vascular and inflammatory skin disorders, oily skin and cutaneous lesions represent fields of application of BoNT.

Hypodermal Adipose Tissue Sonoelastography for Monitoring Treatment Response in Patients with Plaque Psoriasis.

BACKGROUND: Psoriasis (PsO) is a multifactorial chronic and relapsing skin disease that affects about 125 million people in the world. Several studies have demonstrated the link between adipose tissue, inflammation, and PsO. The purpose of our study is to evaluate hypodermal adipose tissue inflammation underneath PsO plaques quantifying tissue elasticity with sonoelastography before and after treatment. The study was conducted at the Department of Dermatology of the University of "Rome Tor Vergata" and Department of Radiology of the University of "Rome Tor Vergata." METHODS: We enrolled 60 patients with plaque PsO and a PASI score of ≥5 divided in three groups of treatment: biologic drugs therapy (Group A), systemic therapy with DMARDS (Group B), and topic therapy (Group C). Each Patient underwent sonoelastography examination (TE: transient elastography) at baseline (T0) and after 1 month (T1) of treatment. The region of interest (ROI) 5 × 5 mm area and the strain ratio was obtained dividing muscular elasticity (referral tissue) by hypodermal elasticity. RESULTS: The difference between T0 and T1 was referred as Δ strain. Sonoelastography is able to identify hypodermal adipose tissue involvement in plaque PsO and on the basis of our experience it could represent a valid method to assess early therapy response in patient with plaque PsO. CONCLUSIONS: This is the first report regarding the use of sonoelastography in psoriatic patients. Sonoelastography is easy to use, rapid, and is a portable technique that does not use ionizing radiation. The result showed the mean lesional strain ratio significantly higher than the nonlesional one at baseline examination. In the future, the role of ultrasound sonoelastography is likely to be complementary to conventional imaging techniques in providing an additional tool.

Monochromatic excimer light 308 nm in monotherapy and combined with topical khellin 4% in the treatment of vitiligo: a controlled study.

Vitiligo is an acquired depigmentation disorder affecting 1-4% of the world's population. Conventional therapies include steroids, photosensitive topical agents, surgical treatments, and phototherapy. The aim of the study was to evaluate the efficacy of monochromatic excimer light 308 nm (MEL), both as a monotherapy and in combination with khellin 4% ointment in vitiligo. Forty-height patients (36 male and 12 female) affected with vitiligo were enrolled in this open prospective study. Patients were selected and divided into three groups: group I included 16 patients treated with MEL 308 nm once-weekly and oral vitamin E; group II included 16 patients treated with MEL 308 nm once-weekly combined with khellin 4% ointment (MEL-K) and oral vitamin E; group III (control group) included 16 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation. Group I (MEL-group) showed a moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 10/16 (62.5%), and excellent repigmentation in 4/16 (25%) patients. Group II (MEL-K group) presented moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 5/16 (31.25%), and excellent repigmentation in 9/16 (56.25%). Group III (control group) showed a moderate repigmentation in 3/16 patients (18.75%), a good repigmentation in 1/16 (6.25%) patient, while 10/16 (62.5%) patients did not show signs of repigmentation. The clinical response achieved in group I and II was higher compared with group III (control group) without showing significant differences. MEL 308 nm, alone and/or combined with khellin 4% offered encouraging results and it may be considered a valid therapeutic option worthy of consideration in the treatment of vitiligo.

Treatment of folliculitis with monochromatic excimer light (308 nm).

BACKGROUND/AIMS: 308-nm excimer light has been reported to be safe and effective in the treatment of chronic skin diseases. The aim of the study was to prove the efficacy of 308-nm monochromatic excimer light in the treatment of recalcitrant and antibiotic-resistant folliculitis. METHODS: Eight patients affected with folliculitis were enrolled and treated twice weekly with the 308-nm excimer light. The follow-up was 12 weeks from the end of the treatment. RESULTS: A mean number of 13 sessions (range 10-20) was performed with increasing dosage according to the patient's photo-type and response. Remission, in terms of number and infiltration of papulopustular elements, was achieved in all patients after 4-16 therapeutic sessions. At the end of the follow-up period, recurrence of folliculitis was observed in 2 patients. CONCLUSIONS: These results suggest that the 308-nm excimer light is a valid therapeutic option for the treatment of resistant forms of folliculitis especially in difficult-to-treat areas.

Monochromatic excimer light (308 nm) in the treatment of prurigo nodularis.

Three hundred and eight nanometre excimer light has been reported to be safe and effective in the treatment of chronic skin diseases, but the range of potential applications has not been fully explored. Our objective was to assess the efficacy of monochromatic excimer light (MEL) in the treatment of prurigo nodularis (PN). Eleven patients were enrolled in this pilot study. Patients were treated weekly and an average of eight sessions of MEL was given. Follow-up was 4 months. Partial or complete clinical and histological remission was observed in all patients who completed the study (81%).