A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis.

BACKGROUND: Ectoine is a widespread osmolyte enabling halophilic bacteria to withstand high osmotic stress that has many potential applications ranging from cosmetics to its use as a therapeutic agent. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of ectoine 1% and hyaluronic acid 0.1% containing (EHA) cream with a vehicle cream in children with mild-to-moderate atopic dermatitis (AD). METHODS: A randomized, controlled, observer-blind, multicenter clinical trial was conducted in children aged 2-18 years, diagnosed with mild-to-moderate AD (SCORAD ≤20). Patients were randomized to either receiving EHA cream or vehicle cream twice daily for 4 weeks. The primary outcome measure was the mean change in objective SCORAD from baseline to the final visit. The secondary outcome measures included the mean change in Investigator's Global Assessment score, patient's judgment of efficacy and patient's assessment of pruritus. Safety of EHA cream was also assessed. RESULTS: A total of 70 patients (35 in each group) were randomized and 57 were included in the final analysis set. Based on SCORAD measurements, patients using EHA cream achieved superior clinical improvement compared to the control group at 28 days (p < .001). EHA cream was also superior to the vehicle cream regarding all secondary outcome measures. Eight (23.5%) patients receiving EHA cream and two (5.7%) patients receiving vehicle cream experienced mild cutaneous adverse events (AEs). CONCLUSIONS: In children 2-18 years old with mild-to-moderate AD, EHA cream was superior to vehicle cream, with minor AEs.

A Comparison of Psoriasis Severity in Pediatric Patients Treated With Methotrexate vs Biologic Agents.

Importance: Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children. Objective: To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children. Design, Setting, and Participants: A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016. Main Outcomes and Measures: PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe). Results: Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18). Conclusions and Relevance: Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.

Safety of Systemic Agents for the Treatment of Pediatric Psoriasis.

Importance: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. Objective: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. Design, Setting, and Participants: A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used systemic medications or phototherapy for at least 3 months from December 1, 1990, to September 16, 2014. Main Outcomes and Measures: The minimal core data set included age, sex, severity of psoriasis, systemic interventions, monitoring, adverse events (AEs), and reason for discontinuation. Results: For 390 children (203 girls and 187 boys; mean [SD] age at diagnosis, 8.4 [3.7] years) with psoriasis who used 1 or more systemic medications, the mean interval between diagnosis and starting systemic therapy was 3.0 years. Methotrexate was used by 270 patients (69.2%), biologic agents (primarily etanercept) by 106 (27.2%), acitretin by 57 (14.6%), cyclosporine by 30 (7.7%), fumaric acid esters by 19 (4.9%), and more than 1 medication was used by 73 (18.7%). Of 270 children taking methotrexate, 130 (48.1%) reported 1 or more AEs associated with methotrexate, primarily gastrointestinal (67 [24.8%]). Folic acid 6 days per week (odds ratio, 0.16; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 0.08-0.58; P = .003) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Methotrexate-associated hepatic transaminase elevations were associated with obesity (35 of 270 patients [13.0%]), but a folic acid regimen was not. Injection site reactions occurred in 20 of 106 patients (18.9%) treated with tumor necrosis factor inhibitors, but did not lead to discontinuation of treatment. Having 1 or more AEs related to medication, gastrointestinal AE, laboratory abnormality, or AE leading to discontinuation of the drug was more likely with methotrexate than tumor necrosis factor inhibitors, but having 1 or more infections related to medication (predominantly upper airway) was less likely. Six patients developed a serious treatment-related AE (methotrexate, 3; fumaric acid esters, 2; and adalimumab, 1), but methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. No patient developed tuberculosis or a malignant neoplasm. Conclusions and Relevance: Medication-related AEs occur less often with tumor necrosis factor inhibitors than with methotrexate. Folic acid administration 6 or 7 times per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis.

Stress-related skin disorders.

Emerging research has suggested that the skin is not only a target of organismal distress but also an active participant of the stress response through production of local "HPA axis" components, peripheral nerve endings, and resident skin cells, including keratinocytes, mast cells, and immune/immune accessory cells. There are also bidirectional communication pathways between the brain and the skin, which play significant roles in integrating these interactions. In this review, we summarize the intricate relations between stress and several skin conditions. We have tried to identify the underlying mechanisms that link stress to the common dermatoses according to the latest scientific findings.

Retrospective analysis of the relationship between infantile seborrheic dermatitis and atopic dermatitis.

A growing number of dermatologists dispute the existence of infantile seborrheic dermatitis (ISD) as an independent clinical entity. Therefore the aim of the present study was to estimate the epidemiologic features of ISD in a defined population of Greek children, assess its course, and identify associations, if any, with other common dermatoses of childhood. Children from the region of Athens who were examined and diagnosed with typical clinical features of ISD between 1997 and 2011 were included in the study. The relevant data were collected retrospectively from their medical records using a standardized form. Eighty-seven children were enrolled (50 boys, 37 girls; mean age 3.1 mos at the time of ISD diagnosis). The main body areas affected were the scalp and face for the majority of the children (78/87), whereas the trunk and limbs were less frequently involved (9/87). In all cases, erythema and scaling of affected patients were mild to moderate. Forty-nine of the 87 children were followed up over a period of 5 years. Thirty children in this group developed features of atopic dermatitis (AD) at a later stage, according to the UK diagnostic criteria of AD, and 23 of these children were diagnosed with AD, at an average time interval of 6.4 months from ISD onset, and seven presented with clinical features of AD at the time of ISD diagnosis. The remaining 19 children in the follow-up group progressed without developing any other chronic skin disease, and all recovered within 6 months of its onset. Thirty-eight had no further follow-up after their initial ISD diagnosis. In spite of the lack of information on the disease course for the last group, assuming they all recovered, the prevalence of AD (34.4%) in our ISD sample was significantly higher than the prevalence of AD (10.7%) in the general population for the same age group, as shown in a previous study performed in the municipality of Athens (p < 0.001). A significant number of children were found to develop AD shortly after their ISD diagnosis. This finding demonstrates a strong association in the clinical course between the two diseases or indicates that the two diseases may be in the same clinical spectrum. Further epidemiologic studies must be conducted to assess the significance of this finding.