The Skin and Natural Cannabinoids-Topical and Transdermal Applications.

The chemical constituents of the Cannabis plant known as cannabinoids have been extensively researched for their potential therapeutic benefits. The use of cannabinoids applied to the skin as a potential method for both skin-related benefits and systemic administration has attracted increasing interest in recent years. This review aims to present an overview of the most recent scientific research on cannabinoids used topically, including their potential advantages for treating a number of skin conditions like psoriasis, atopic dermatitis, and acne. Additionally, with a focus on the pharmacokinetics and security of this route of administration, we investigate the potential of the transdermal delivery of cannabinoids as a method of systemic administration. The review also discusses the restrictions and difficulties related to the application of cannabinoids on the skin, emphasizing the potential of topical cannabinoids as a promising route for both localized and systemic administration. More studies are required to fully comprehend the efficacy and safety of cannabinoids in various settings.

Transforming Psoriasis Care: Probiotics and Prebiotics as Novel Therapeutic Approaches.

Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of probiotics (Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans (SC208), Bacillus licheniformis (SL307), and Bacillus clausii (SC109)) and precision prebiotics (fructooligosaccharides, xylooligosaccharides, and galactooligosaccharides) in patients with psoriasis receiving topical therapy, with an emphasis on potential metabolic, immunological, and gut microbiota changes. In total, 63 patients were evaluated, with the first 42 enrolled patients assigned to the intervention group and the next 21 assigned to the control group (2:1 ratio; non-randomized). There were between-group differences in several patient characteristics at baseline, including age, psoriasis severity (the incidence of severe psoriasis was greater in the intervention group than in the control group), the presence of nail psoriasis, and psoriatic arthritis, though it is not clear whether or how these differences may have affected the study findings. Patients with psoriasis receiving anti-psoriatic local therapy and probiotic and prebiotic supplementation performed better in measures of disease activity, including Psoriasis Area and Severity Index, Dermatology Life Quality Index, inflammatory markers, and skin thickness compared with those not receiving supplementation. Furthermore, in the 15/42 patients in the intervention group who received gut microbiota analysis, the gut microbiota changed favorably following 12 weeks of probiotic and prebiotic supplementation, with a shift towards an anti-inflammatory profile.

Correlation between quality of life and disease severity of pediatric patients with atopic dermatitis.

Atopic dermatitis (AD) is a complex, chronic skin disorder with a broad spectrum of clinical aspects, characterized by abnormal skin barrier function. This has a significant impact on patients' quality of life (QoL), which represents a crucial parameter for their wellbeing. This study assessed the QoL of patients with AD by following parameters such as itching, disturbance of sleep, disturbance of play activity, and community activities. The study included 64 patients clinically diagnosed with AD, aged 0 to 16 years. QoL of patients with AD was measured by evaluating the QoL indices for infants and young children (IDQoL-Infants' Dermatitis Quality of Life Index) and the QoL for children over 4 years (CDQoL-Children's Dermatology Life Quality Index). The severity of the disease was also monitored by evaluating the SCORAD index. The major symptom for atopic dermatitis, pruritus, was found most frequently in our study and influenced patients' QoL. The study showed that the above questionnaires are efficient tools for correlating AD severity with QoL even in younger patients and could be included in current guidelines. This is the first study that analyzed the QoL of pediatric patients with atopic dermatitis in Romania and can constitute the basis for elaborating a more comprehensive disease management guidelines.

High-frequency ultrasonography of psoriatic skin: A non-invasive technique in the evaluation of the entire skin of patients with psoriasis: A pilot study.

Psoriasis is a chronic, systemic, inflammatory disorder which accelerates the life process of skin cells, based on a genetically induced deviant immune response. High-frequency ultrasonography (HF-USG) is a painless, non-invasive imaging technique that can be performed and repeated whenever the need arises. We evaluated lesional and non-lesional skin of psoriatic patients with the use of HF-USG, focusing on the immune-induced inflammation and skin thickness. Previous studies suggested that HF-USG, being a non-invasive technique, is useful as an aid to clinical evaluation of the severity of psoriatic plaques. Our goal was to determine whether the skin of psoriatic patients is influenced by the background or habits of the patients. The study included a total of 27 patients affected by psoriasis vulgaris. The thickness of the epidermis and dermis and the skin echogenicity were documented for the active plaques, as well as for the non-affected skin of all the patients included in the study, using a high-frequency ultrasonographic system. The patient's local background, sex, family history of psoriasis, smoking habits and sun exposure were analyzed. HF-USG of the psoriatic plaques exposes a three-band structure that is easily distinguished from the surrounding unaffected skin, due to a hypoechoic band in the upper dermis. Although not specific for psoriasis, it is a strong marker of inflammation. The obtained results confirm that, indeed, skin thickness is greater in lesional skin compared to non-lesional skin, by a mean of 1,180 µm (±340 µm). We consider that skin HF-USG should be used as a quantitative method in the clinical evaluation of the patients with psoriasis and may help as an objective means of assessing inflammation in lesional skin.

The first nation-wide study revealing epidemiologic data and life quality aspects of psoriasis in Romania.

Psoriasis is a chronic, immune mediated, inflammatory condition, which primarily affects the patient's skin. It is known to associate a variable array of comorbidities such as cardiovascular, metabolic and psychiatric ones, with an important impact on the patients' quality of life. The purpose of this study is to provide a first image of the prevalence, comorbidities, as well as the social impact of psoriasis in Romania. We devised a questionnaire, and with the aid of general practitioners throughout the country, delivered it to patients seeking medical care in their office. The questionnaire assessed demographic criteria as well as patient-related issues. It was completed in the presence of the general practitioner, and clear written instructions for completion were included. After statistical analysis, the resulting data formed the basis of this study. The reported prevalence of psoriasis in Romania is 5.18%. Almost half of the subjects who completed the questionnaire stated they knew somebody affected by the disease, yet almost a third believed it is a contagious condition. Cardiovascular and psychiatric comorbidities, as well as negative impact on social interactions were reported by the subjects in the study. These findings indicate the clear need for better quality of life for patients in a social context and increased awareness of the disease. All these could, in turn, help decrease the rate of psoriasis complications in Romania.

Sea buckthorn extract in the treatment of psoriasis.

Psoriasis is one of the most common chronic dermatological conditions, with a strong impact on patients' quality of life. Currently, psoriasis benefits from conventional therapy with a high rate of adverse effects and an increase in non-compliance and self-medication of patients. As such, there is a need to pinpoint low-adverse effects and accessible remedies for this condition. Our single-blind, placebo-controlled study assessed the effect of sea buckthorn extract on psoriasis lesions in previously untreated patients. Our results showed an improvement in Psoriasis Area Severity Index (PASI) scores and in Dermatology Life Quality Index (DLQI) scores when compared to the baseline values, as well as at the 4- and 8-week time marks for the lesions treated with sea buckthorn extract. By contrast, the measurements for the placebo treated lesions showed no alteration at the 4-week mark, and significant worsening at the end of the trial. These findings provide a solid, optimistic base for the in-depth research of sea buckthorn as an adjuvant or a component in psoriasis care protocols.

Potential of high-frequency ultrasonography in the management of atopic dermatitis.

Atopic dermatitis (AD) is a chronic, highly pruritic skin disorder, with a broad spectrum of clinical manifestations, characterized by abnormal skin barrier function. High-frequency ultrasonography (HF-USG) is an instrument with potential use in a variety of skin conditions. Previous studies on HF-USG in AD reported that apparently non-lesional skin also presents barrier defects. We aimed to assess lesional and non-lesional skin of AD patients with the use of HF-USG, focusing on skin barrier function and inflammation. We included a group of AD patients and a control group. On both we performed analysis with the use of HF-USG. The thickness of the subepidermal low-echogenic band (SLEB) and the skin echogenity were recorded for active lesions, as well as non-lesional skin in all subjects included. For AD patients the clinical severity was measured using SCORing Atopic Dermatitis and correlated with Dermatology Life Quality Index (DLQI). The mean thickness of the hypoechoic band was wider in the lesional skin of AD. In the non-lesional skin of AD patients SLEB was identified to appear, but it was thinner. The skin echogenity of the control group was higher than that of AD patients. Our results indicate that skin ultrasonography is able to assess specific modifications of the AD skin. A hypoechoic band in the non-lesional skin of some AD patients may indicate subclinical eczematous lesions.

IL12B (p40) Gene Polymorphisms Contribute to Ustekinumab Response Prediction in Psoriasis.

BACKGROUND: Psoriasis is characterized by multiple genetic variations. Some of these variations, such as the presence of HLA-Cw6 or TNFAIP3 single-nucleotide polymorphisms (SNPs), have been correlated to the response to biologic treatments. OBJECTIVE: The aim of our study was to evaluate the effects of IL12B and IL6 SNPs on the response to ustekinumab. METHODS: We retrospectively analyzed the genotypes of 64 patients who had been treated with ustekinumab for up to 1 year. Efficacy data were evaluated using 'intention to treat-last observation carried forward' analysis. RESULTS: We confirmed the positive role of HLA-Cw6 as a predictor of the response to ustekinumab and discovered that presence of the GG genotype on the IL12B rs6887695 SNP and absence of the AA genotype on the IL12B rs3212227 SNP significantly increase the probability of therapeutic success in HLA-Cw6 positive patients. CONCLUSIONS: The availability of pharmacogenetic data will influence therapeutic decisions in the clinical management of psoriatic patients.

Nanotechnology approaches for pain therapy through transdermal drug delivery.

The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.

What happened after the clinical trials: long-term safety and efficacy of ustekinumab in daily clinical practice.

BACKGROUND: Ustekinumab has been investigated in patients with psoriasis by randomized clinical trials. There are few data on ustekinumab use under 'real life' conditions outside long-term registries. OBJECTIVE: The aim of our study was to evaluate the efficacy and safety of ustekinumab as a long-term therapy in real life. METHODS: We retrospectively analyzed the data of 71 patients who had been treated with ustekinumab up to 2 years. Efficacy data were analyzed both by 'as treated' and 'intention to treat-last observation carried forward'. RESULTS: A significant improvement in the Psoriasis Area and Severity Index score was observed at 4 weeks and further improvements were observed throughout the treatment. Adverse events were generally mild. CONCLUSIONS: In routine administration ustekinumab seems to be more efficient than reported by randomized clinical trials. Our results are encouraging and can answer the patients' biggest concern on whether ustekinumab is an effective and safe drug for long-term use.

Genetic variations in IL6 and IL12B decreasing the risk for psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory skin disorder. Recent studies associated a number of genetic variants to this immune-mediated pathology. OBJECTIVE: This study aims to assess whether the association between the non-susceptibility allelic variants of IL12B single-nucleotide polymorphism (SNPs) rs3212227 and rs6887695, IL23R SNPs rs11209026 and rs7530511, IL6 SNP rs1800795 and HLA-Cw6 could be correlated with decreased risk for psoriasis. MATERIAL AND METHODS: We genotyped 67 psoriasis patients and 69 healthy subjects for polymorphisms of IL12B rs3212227 and rs6887695, IL23R rs11209026 and rs7530511, IL6 rs1800795 and for the presence of HLA-Cw6. The patients and controls were recruited from Dermatology Department, part of "Tor Vergata" Clinic, Rome. Demographic data of the control group matched those of psoriasis patients, with a female:male ratio of 2.55 and mean age of 45.5±12.2 years for patients and 44.8±11.7 years for controls. RESULTS: The following genotypes were less frequent in patients: IL12B SNP rs6887695 CC (OR, 0.179; CI95% 0.046-0.699; p=0.01), IL6 SNP rs1800795 CG (OR, 0.367; CI95% 0.179-0.753; p=0.006) and IL6 SNP rs1800795 CC (OR, 0.069; CI95% 0.008-0.586; p=0.01). Also the HLA-Cw6 allele was rarely found in controls (OR, 0.459; CI95% 0.230-0.916; p=0.02). The multivariate analysis showed that the existence of at least one C allele in both IL12B SNP rs6887695 and IL6 SNP rs1800795 or the absence of HLA-Cw6 allele and at least one C allele in IL12B SNP rs6887695 or IL6 SNP rs1800795 is associated with a lower risk of psoriasis (OR, 0.185; CI95% 0.037-0.929; p=0.04). The presence of at least one C allele in both IL12B SNP rs6887695 and IL6 SNP rs1800795 and the absence of HLA-Cw6 allele decreased even further the risk of psoriasis (OR, 0.038; CI95% 0.006-0.244; p=0.001). CONCLUSION: We report carriers of variations in the IL6, IL12B and absence of HLA-Cw6 as having decreased risk for psoriasis.

Ultrasonographic assessment of skin structure according to age.

BACKGROUND: High-frequency ultrasound is a noninvasive tool that offers characteristic markers, quantifying the cutaneous changes of the physiological senescence process. AIMS: The aim was to assess the changes in skin thickness, dermal density and echogenicity, as part of the ageing process, with different age intervals. METHODS: The study was performed on 160 patients, aged 40.4 ± 21.2, divided into four age categories: <20, 21-40, 41-60, 61-80. Ultrasonographic images (Dermascan device) were taken from three sites: dorsal forearm (DF), medial arm (MA), zygomatic area (ZA). We assessed the thickness of epidermis and dermis (mm), number of low, medium, high echogenicity pixels, the ratio between the echogenicity of the upper and lower dermis (LEPs/LEPi), and SLEB (subepidermal low echogenicity band). The statistical analysis was performed using SPSS 15.00. A P value <0.05 was considered significant. RESULTS: On all examined sites, it was found that the dermal thickness increases in the 21 to 40 year interval (P<0.0001). After the 21 to 40 year interval, the number of low echogenic pixels increases significantly, especially on photoexposed sites. High-echogenic pixels follow the same pattern on all examined sites: they increase in the 21 to 40 year interval and decrease in the 3rd and 4th age category. The LEPs/LEPi ratio increases significantly with age, at all sites (P<0.05), due to an increase of hypoechogenic pixels in the upper dermis. CONCLUSIONS: High-frequency ultrasound is a noninvasive "histological" tool that can assess the cutaneous structure and age-related changes. It offers imagistic markers, comparable to the histological parameters and also characteristic ultrasonographic markers. Histology remains the gold standard for the investigation of the integumentary system.