Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Considerations for paediatric patients.

BACKGROUND: Treatment goals have been established in Australia to facilitate the management of adults with moderate to severe psoriasis. The Australasian College of Dermatologists sought to determine if and how these adult treatment goals could be modified to accommodate the needs of paediatric and adolescent patients. METHODS: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7-9 on a 9-point scale (1 strongly disagree; 9 strongly agree). RESULTS: Consensus was achieved on 23/29 statements in round 1 and 17/18 statements in round 2. There was a high level of concordance with treatment criteria in the adult setting. The limitations of applying assessment tools developed for use in adult patients to the paediatric setting were highlighted. Treatment targets in the paediatric setting should include objective metrics for disease severity and psychological impact on the patients and their family, and be based on validated, age-appropriate tools. CONCLUSION: While the assessment, classification and management of moderate to severe psoriasis in paediatric patients aligns with metrics established for adults, it is vital that nuances in the transition from childhood to adolescence be taken into account. Future research should focus on psoriasis severity assessment scales specific to the paediatric setting.

The Psychology of Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin condition characterised by pruritus and recurrent eczematous patches and plaques. It impacts sleep and its visibility can lead to stigmatisation, low self-esteem, social withdrawal, reduced quality of life (QOL), and psychological burden. This study explores the relationship between AD and mental health, including possible causation pathways. A literature review was conducted in PubMed without using limiters. AD carries higher odds of suicidality and an increased risk of depression, anxiety, alexithymia, and obsessive-compulsive disorder (OCD) across all severities. While some studies report an association of AD with attention deficit hyperactivity disorder (ADHD), and possibly autism spectrum disorder (ASD), others do not. There is increasing evidence that AD contributes to chronic low-grade inflammation and cognitive impairment (CI). Causative factors for mental health complications of AD likely include both psychosocial and biological variables. AD is associated with higher levels of cutaneous and circulating proinflammatory cytokines; these can breach the blood-brain barrier and trigger central nervous system events, including oxidative stress, neurotransmitter breakdown, altered serotonin metabolism, and reduced neurogenesis in several brain regions. Excessive inflammation in AD may thus contribute to CI, depression, and suicidality. AD providers should be vigilant about mental health.

Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2.

BACKGROUND: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. METHODS: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. RESULTS: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4-6, and 10 were associated with 0 days, 3-4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0-1, 4-5, and 10 were associated with 0-10%, 20-30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. CONCLUSION: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. CLINICAL TRIAL REGISTRATION: NCT03575871.

Atopic dermatitis (AD), also called atopic eczema, is a common skin disease that is associated with itch and reduced quality of life. Abrocitinib, a recently approved medicine for AD, was shown in clinical trials to improve itch, which is considered the most bothersome symptom to people with AD. Abrocitinib also improved sleep outcomes and work productivity in people with moderate or severe AD. It is unknown if improvement in itch can lead to improvement in sleep and work productivity. We analyzed data from the JADE MONO-2 study, which included 391 people who received treatment with abrocitinib or placebo for 12 weeks. We used mathematical modelling to study relationships between itch and sleep or work productivity. We also wanted to study if the improvements in itch and sleep with abrocitinib treatment had an impact on work productivity. We found that a relationship existed between itch, sleep disturbance, and work impairment; as itch improved, so too did sleep disturbance and work impairment. When people were treated with abrocitinib, they experienced relief from itch, which improved sleep, which in turn reduced work productivity loss. Larger and longer studies are needed to confirm these results. This analysis further informs the expectations of patients with moderate or severe AD as it relates to progression of symptom relief after treatment with abrocitinib.

Atopic dermatitis: A global health perspective.

The International Society of AD (ISAD) organized a roundtable on global aspects of AD at the WCD 2023 in Singapore. According to the Global Burden of Disease (GBD) consortium, at least 171 million individuals were affected with AD in 2019, corresponding to 2.23% of the world population, with age-standardized prevalence and incidence rates that were relatively stable from 1990 to 2019. Based on the panel experience, most AD cases are mild-to-moderate. Without parallel data on disease prevalence and severity, the GBD data are difficult to interpret in many regions. This gap is particularly important in countries with limited medical infrastructure, but indirect evidence suggests a significant burden of AD in low-and-medium resource settings, especially urban areas. The Singapore roundtable was an opportunity to compare experiences in World Bank category 1 (Madagascar and Mali), 3 (Brazil, China) and 4 (Australia, Germany, Qatar, USA, Singapore, Japan) countries. The panel concluded that current AD guidelines are not adapted for low resource settings and a more pragmatic approach, as developed by WHO for skin NTDs, would be advisable for minimal access to moisturizers and topical corticosteroids. The panel also recommended prioritizing prevention studies, regardless of the level of existing resources. For disease long-term control in World Bank category 3 and most category 4 countries, the main problem is not access to drugs for most mild-to-moderate cases, but rather poor compliance due to insufficient time at visits. Collaboration with WHO, patient advocacy groups and industry may promote global change, improve capacity training and fight current inequalities. Finally, optimizing management of AD and its comorbidities needs more action at the primary care level, because reaching specialist care is merely aspirational in most settings. Primary care empowerment with store and forward telemedicine and algorithms based on augmented intelligence is a future goal.

Exploration of associations between occupational exposures and current adult eczema.

OBJECTIVES: There is a scarcity of evidence on occupational exposures that may increase eczema in adults. We aimed to investigate potential associations between occupational exposures and eczema in middle-aged adults. METHODS: A lifetime work history calendar was collected from the Tasmanian Longitudinal Health Study participants when they were at age 53. Their work history was collated with the occupational asthma-specific job exposure matrix to define ever-exposure and cumulative exposure unit-years since no eczema job exposure matrix is available. Eczema was determined using the report of flexural rash that was coming and going for at least 6 months in the last 12 months. Skin prick tests were used to further subgroup eczema and atopic eczema (AE) or non-AE (NAE). Logistic and multinomial regression models were used to investigate the associations. RESULTS: Eczema prevalence was 9.1%. Current occupational exposure to animals (adjusted OR, aOR=3.06 (95% CI 1.43 to 6.58)), storage mites (aOR=2.96 (95% CI 1.38 to 6.34)) and endotoxin (aOR=1.95 (95% CI 1.04 to 3.64)) were associated with increased risk of current eczema. Furthermore, increased odds of NAE were associated with current exposure to animals (aOR=5.60 (95% CI 1.45 to 21.7)) and storage mites (aOR=5.63 (95% CI 1.45 to 21.9)). Current exposures to isocyanates (aOR=5.27 (95% CI 1.17 to 23.7)) and acrylates (aOR=8.41 (95% CI 1.60 to 44.3)) were associated with AE. There was no evidence of associations between cumulative exposures and eczema prevalence. Cumulative exposure to metalworking fluids (aOR=1.10 (95% CI 1.01 to 1.22)) was associated with NAE and acrylates (aOR=1.24 (95% CI 1.04 to 1.46)) with AE. CONCLUSIONS: In this exploratory assessment, multiple occupational exposures were associated with current eczema in middle-aged adults. Raising awareness and limiting these exposures during an individual's productive working life will likely have various health benefits, including reducing eczema prevalence.

Burden of Disease and Unmet Needs in the Diagnosis and Management of Atopic Dermatitis in Diverse Skin Types in Australia.

Atopic dermatitis (AD) is a common, chronic, inflammatory skin disease affecting Australians of all ages, races, ethnicities, and social classes. Significant physical, psychosocial, and financial burdens to both individuals and Australian communities have been demonstrated. This narrative review highlights knowledge gaps for AD in Australian skin of colour. We searched PubMed, Wiley Online Library, and Cochrane Library databases for review articles, systematic reviews, and cross-sectional and observational studies relating to AD in Australia for skin of colour and for different ethnicities. Statistical data from the Australian Institute of Health and Welfare and the Australian Bureau of Statistics was collected. In recent years, there has been substantially increased awareness of and research into skin infections, such as scabies and impetigo, among various Australian subpopulations. Many such infections disproportionately affect First Nations Peoples. However, data for AD itself in these groups are limited. There is also little written regarding AD in recent, racially diverse immigrants with skin of colour. Areas for future research include AD epidemiology and AD phenotypes for First Nations Peoples and AD trajectories for non-Caucasian immigrants. We also note the evident disparity in both the level of understanding and the management standards of AD between urban and remote communities in Australia. This discrepancy relates to a relative lack of healthcare resources in marginalised communities. First Nations Peoples in particular experience socioeconomic disadvantage, have worse health outcomes, and experience healthcare inequality in Australia. Barriers to effective AD management must be identified and responsibly addressed for socioeconomically disadvantaged and remote-living communities to achieve healthcare equity.

Once-Daily Crisaborole Ointment, 2%, as a Long-Term Maintenance Treatment in Patients Aged ≥ 3 Months with Mild-to-Moderate Atopic Dermatitis: A 52-Week Clinical Study.

BACKGROUND: Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy. OBJECTIVE: The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID). METHODS: CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥ 3 months with mild-to-moderate AD involving ≥ 5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥ 2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed. RESULTS: Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment. CONCLUSIONS: Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04040192, 31 July 2019.

Atopic dermatitis (AD) is an immuno-inflammatory skin disease that can last a long time. It causes skin lesions and intense itching. Topical AD treatments used reactively often fail to control the disease over a long period of time. Many are associated with safety concerns that limit long-term use. Crisaborole ointment is a nonsteroidal treatment for the skin and is used to treat mild-to-moderate AD. Previous studies showed that using crisaborole twice daily was effective and had few side effects in patients with mild-to-moderate AD. This study evaluated how effective and safe long-term treatment with once-daily crisaborole was compared with an ointment with no drug (vehicle). The study included patients aged ≥ 3 months with mild-to-moderate AD whose AD improved after previous treatment with twice-daily crisaborole. This study was designed to investigate how much crisaborole reduced the incidence of AD flares over 52 weeks in these patients.The study included 270 patients whose AD had improved after treatment with twice-daily crisaborole. Of these patients, 135 were randomly assigned to receive crisaborole once a day and 135 to receive vehicle once a day. Patients who received crisaborole had a significantly longer time before experiencing AD flares than those who received vehicle. Crisaborole was well tolerated, and no new or unexpected side effects were found when used as a once-daily maintenance treatment for 52 weeks. These results indicate that once-daily treatment with crisaborole could be a potential long-term maintenance treatment option in children and adults with mild-to-moderate AD.

Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis: Analysis of the Measure Up 1, Measure Up 2, and AD Up Randomized Clinical Trials.

Importance: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population. Objective: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents. Design, Setting, and Participants: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021. Interventions: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up). Main Outcomes and Measures: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points). Results: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate. Conclusions and Relevance: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile. Trial Registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).

Clinical overlap of PHACE and LUMBAR syndromes.

Segmental infantile hemangiomas affecting the upper body are associated with PHACE(S) (Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac anomalies, Eye anomalies, and Sternal defects) syndrome, whereas segmental infantile hemangiomas affecting the lower body are the cutaneous hallmark of LUMBAR (Lower body hemangioma and other skin defects, Urogenital anomalies and Ulceration, Myelopathy, Bony deformities, Anorectal malformations and Arterial anomalies, and Renal anomalies) syndrome. We present two individuals with concurrent features of both PHACE and LUMBAR syndromes demonstrating an overlap phenotype. The overlapping features seen in our patients suggest that these syndromes occur on the same phenotypic spectrum and derive from a common embryonic pathophysiology.

The association between domestic hard water and eczema in adults from the UK Biobank cohort study.

BACKGROUND: Eczema is a chronic inflammatory skin disease. Domestic water with high mineral content (hard water) is a risk factor for eczema in children, but this association has not been assessed in adults. OBJECTIVES: To examine the association between domestic hard water supply and eczema prevalence and incidence in adults aged 40-69 years and the contextual effect in eczema outcomes by postcode in adults in the UK. METHODS: We used data from the UK Biobank study collected in 2006-10 (baseline) and 2013-14 (follow-up). Eczema prevalence at baseline (2006-10) and at follow-up (2013-14) and incidence (new onset between baseline and follow-up) were determined from the touchscreen questionnaires and nurse-led interviews. Domestic hard water information was obtained in 2005 and 2013 from the local water supply companies in England, Wales and Scotland as CaCO3 concentrations. We fitted multilevel logistic regression models with random intercepts for postcode areas to examine the effect of domestic hard water on eczema outcomes, and we measured components of variance. RESULTS: In total, 306 531 participants with a mean age of 57 years nested across 7642 postcodes were included in the baseline analysis, and 31 036 participants nested across 3695 postcodes were included in the follow-up analysis. We observed an increase in the odds of eczema at baseline [odds ratio (OR) 1·02, 95% confidence interval (CI) 1·01-1·04] per 50 mg L-1 of CaCO3 increase. Furthermore, exposure to domestic hard water (> 200 mg L-1 of CaCO3 ) was associated with increased odds of prevalent eczema at baseline (OR 1·12, 95% CI 1·04-1·22). Moreover, there was a significant linear trend (P < 0·001) in which increasing levels of hard water increased eczema prevalence risk. No association was observed with incident eczema or eczema at follow-up. The intraclass correlation coefficient for postcode was 1·6% (95% CI 0·7-3·4), which remained unexplained by area-level socioeconomic measures. CONCLUSIONS: Increasing levels of domestic hard water, as measured by CaCO3 concentrations, were associated with an increased prevalence of eczema in adults but not increased incidence. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing the burden of eczema in adults. Further research is needed to explore area-level factors that may lead to eczema. What is already known about this topic? Hard water is formed when minerals are dissolved in water from filtration through sedimentary rocks. Several studies have reported a higher prevalence of eczema in areas with hard water. However, all studies on this topic have assessed this in infants and school-aged children, while this association has not been explored in adults. What does this study add? Our findings suggest that exposure to higher concentrations of domestic hard water is associated with an increase in eczema prevalence in adults aged 40-69 years. Ongoing efforts to reduce hard water exposure may have a beneficial effect in reducing eczema prevalence in adults.

Management of atopic dermatitis: a narrative review.

Atopic dermatitis (atopic eczema) is the most common inflammatory skin disease and has a significant burden on the quality of life of patients, families and caregivers. Its pathogenesis is a complex interplay between genetics and environment, involving impaired skin barrier function, immune dysregulation primarily involving the Th2 inflammatory pathway, itch, and skin microbiome. Restoration of skin barrier integrity with regular emollients and prompt topical anti-inflammatory therapies are mainstays of treatment. Systemic therapy is considered for moderate to severe disease. New understanding of inflammatory pathways and developments in targeted systemic immunotherapies have significantly advanced atopic dermatitis management. Dupilumab is a safe and effective treatment that is now available in Australia. Other promising agents for atopic dermatitis include Janus kinase, interleukin (IL)-13 and IL-31 inhibitors.

Establishing subclasses of childhood eczema, their risk factors and prognosis.

BACKGROUND: The heterogeneity of development and progression of eczema suggests multiple underlying subclasses for which aetiology and prognosis may vary. A better understanding may provide a comprehensive overview of eczema development and progression in childhood. Thus, we aimed to determine longitudinal eczema subclasses based on assessments and identify their associations with risk factors and allergic outcomes. METHODS: A total of 619 participants with a family history of allergic disease were assessed at 24 time-points from birth to 12 years. At each time, eczema was defined as the report of current rash treated with topical steroid-based preparations. Longitudinal latent class analysis was used to determine eczema subclasses. Subsequent analyses using regression models assessed the associations between eczema subclasses and potential risk factors and allergic outcomes at 18- and 25-year follow-ups (eczema, allergic rhinitis, asthma and allergic sensitization). RESULTS: We identified five eczema subclasses 'early-onset persistent', 'early-onset resolving', 'mid-onset persistent', 'mid-onset resolving' and 'minimal eczema'. Filaggrin null mutations were associated with the early-onset persistent (OR = 2.58 [1.09-6.08]) and mid-onset persistent class (OR = 2.58 [1.32-5.06]). Compared with 'minimal eczema', participants from early-onset persistent class had higher odds of eczema (OR = 11.8 [5.20-26.6]) and allergic rhinitis (OR = 3.13 [1.43-6.85]) at 18 and at 25 years eczema (OR = 9.37 [3.17-27.65]), allergic rhinitis (OR = 3.26 [1.07-9.93]) and asthma (OR = 2.91 [1.14-7.43]). Likewise, mid-onset persistent class had higher odds of eczema (OR = 2.59 [1.31-5.14]), allergic rhinitis (OR = 1.70 [1.00-2.89]) and asthma (OR = 2.00 [1.10-3.63]) at 18 and at 25 years eczema (OR = 6.75 [3.11-14-65]), allergic rhinitis (OR = 2.74 [1.28-5.88]) and asthma (OR = 2.50 [1.25-5.00]). Allergic and food sensitization in early life was more common in those in the persistent eczema subclasses. CONCLUSION: We identified five distinct eczema subclasses. These classes were differentially associated with risk factors, suggesting differences in aetiology, and also with the development of allergic outcomes, highlighting their potential to identify high-risk groups for close monitoring and intervention.

Drug induced vitiligo-like depigmentation from a CDK 4/6 inhibitor.

Ribociclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK 4/6) that is used in combination with an aromatase inhibitor in the first-line setting for advanced or metastatic hormone receptor positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We report two cases of drug-induced vitiligo-like depigmentation (DI-VLD) associated with ribociclib. The awareness of this side effect is important given the increasing use of this drug and others with a similar mechanism of action.

A comparison study of outcome measures for epidermolysis bullosa: Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and the Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB).

BACKGROUND: The success of clinical trials in Epidermolysis Bullosa (EB) is dependent upon the availability of a valid and reliable scoring tool that can accurately assess and monitor disease severity. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) were independently developed and validated against the Birmingham Epidermolysis Bullosa Severity Score but have never been directly compared. OBJECTIVE: To compare the reliability, convergent validity, and discriminant validity of the EBDASI and iscorEB scoring tools. METHODS: An observational cohort study was conducted in 15 patients with EB. Each patient was evaluated using the EBDASI and iscorEB-clinician scoring tools by 6 dermatologists with expertise in EB. Quality of life was assessed using the iscorEB-patient and Quality of Life in EB measures. RESULTS: The intraclass correlation coefficients for interrater reliability were 0.942 for the EBDASI and 0.852 for the iscorEB-clinician. The intraclass correlation coefficients for intrarater reliability was 0.99 for both scores. The two tools demonstrated strong convergent validity with each other. CONCLUSION: Both scoring tools demonstrate excellent reliability. The EBDASI appears to better discriminate between EB types and disease severities.

Association between ambient air pollution and development and persistence of atopic and non-atopic eczema in a cohort of adults.

BACKGROUND: There is limited information on risk factors for eczema in adults. Recent evidence suggests that air pollution may be associated with increased incidence of eczema in adults. We aimed to assess this possible association. METHODS: Ambient air pollution exposures (distance from a major road, nitrogen dioxide [NO2 ], fine particulate matter with an aerodynamic diameter ≤2.5 µm [PM2.5 ]) were assessed for the residential address of Tasmanian Longitudinal Health Study participants at ages 43 and 53 years. Eczema incidence (onset after age 43 years), prevalence (at 53 years), and persistence were assessed from surveys, while IgE sensitization was assessed using skin prick tests. The presence or absence of eczema and sensitization was classified into four groups: no atopy or eczema, atopy alone, non-atopic eczema, and atopic eczema. Adjusted logistic and multinomial regression models were fitted to estimate associations between ambient air pollution and eczema, and interaction by sex was assessed. RESULTS: Of 3153 participants in both follow-ups, 2369 had valid skin prick tests. For males, a 2.3 ppb increase in baselineNO2 was associated with increased odds of prevalent eczema (OR = 1.15 [95% CI 0.98-1.36]) and prevalent atopic eczema (OR = 1.26 [1.00-1.59]). These associations were not seen in females (p for interaction = 0.08, <0.01). For both sexes, a 1.6 µg/m3 increase in PM2.5 exposure at follow-up was associated with increased odds of aeroallergen sensitization (OR = 1.15 [1.03-1.30]). CONCLUSION: Increased exposure to residential ambient air pollutants was associated with an increased odds of eczema, only in males, and aeroallergen sensitization in both genders.

Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: A Phase IV Open-Label Study (CrisADe CARE 1).

BACKGROUND: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). OBJECTIVES: The aim of this study was to evaluate the safety, effectiveness, and pharmacokinetics (PK) of crisaborole in infants aged 3 to < 24 months with mild-to-moderate AD in an open-label study. METHODS: Infants (3 to < 24 months) with Investigator's Static Global Assessment (ISGA) of mild (2) or moderate (3) and percentage of treatable body surface area (%BSA) ≥ 5 received crisaborole twice daily for 28 days; a cohort with moderate AD per ISGA and %BSA ≥ 35 were included in a PK analysis. Endpoints included safety (primary), efficacy, and PK (exploratory). RESULTS: Included were 137 infants total (mean age [SD], 13.6 months [6.42]), with 21 in the PK cohort (12.7 months [6.58]). Treatment-emergent adverse events (TEAEs) were reported for 88 (64.2%) patients (98.9% rated as mild/moderate). TEAEs were considered treatment-related for 22 patients (16.1%); most frequently reported were application site pain (3.6%), application site discomfort (2.9%), and erythema (2.9%). ISGA clear/almost clear with ≥ 2-grade improvement at day 29 was achieved by 30.2% of patients. From baseline to day 29, mean percentage change in Eczema Area and Severity Index score was - 57.5%, and mean change in Patient-Oriented Eczema Measure total score was - 8.5. Crisaborole systemic exposures in infants were characterized and, based on nonlinear regression analysis, were comparable with that in patients aged ≥ 2 years. CONCLUSIONS: In this open-label study, crisaborole was well tolerated and effective in infants (3 to < 24 months) with mild-to-moderate AD with systemic exposures similar to patients aged ≥ 2 years. CLINICAL TRIAL REGISTRATION: NCT03356977.

Atopic dermatitis (AD) is a skin disease that causes inflamed and itchy skin. Crisaborole is an ointment that is approved to treat patients aged 2 years and older with mild-to-moderate AD. This clinical trial studied crisaborole in infants with mild-to-moderate AD who were 3 to under 24 months old. These infants were treated with crisaborole twice a day for 28 days. The trial studied crisaborole's safety, effectiveness, and absorption into the bloodstream. In total, 137 infants were treated. Although side effects of some sort occurred in about two-thirds of patients, only 1 in 6 patients experienced side effects that were attributed to crisaborole. When these side effects did occur, these were mainly pain, discomfort, or redness where crisaborole was applied. Fewer than 1 in 25 patients experienced each side effect where crisaborole was applied. The doctors saw improvement in the AD symptoms of some patients at day 29 of the study compared to the beginning of the study. Crisaborole blood-level measurements in this age group were consistent with those seen in patients aged 2 years and older. Overall, crisaborole was considered well tolerated and effective in infants (3 to under 24 months old) with mild-to-moderate AD. Safety, Effectiveness, and Pharmacokinetics of Crisaborole in Infants Aged 3 to < 24 Months with Mild-to-Moderate Atopic Dermatitis: An Open-Label, Phase 4 Study (MP4 40891 MB).

Artificial Intelligence in Dermatology-Where We Are and the Way to the Future: A Review.

Although artificial intelligence has been available for some time, it has garnered significant interest recently and has been popularized by major companies with its applications in image identification, speech recognition and problem solving. Artificial intelligence is now being increasingly studied for its potential uses in medicine. A sound understanding of the concepts of this emerging field is essential for the dermatologist as dermatology has abundant medical data and images that can be used to train artificial intelligence for patient care. There are already a number of artificial intelligence studies focusing on skin disorders such as skin cancer, psoriasis, atopic dermatitis and onychomycosis. This article aims to present a basic introduction to the concepts of artificial intelligence as well as present an overview of the current research into artificial intelligence in dermatology, examining both its current applications and its future potential.

Retrospective review of screening for Sturge-Weber syndrome with brain magnetic resonance imaging and electroencephalography in infants with high-risk port-wine stains.

BACKGROUND: There is a lack of consensus regarding how best to screen children with facial port-wine stains for Sturge-Weber syndrome. Many favor brain magnetic resonance imaging, and adjunctive electroencephalography is increasingly used. However, the sensitivity, specificity, and negative and positive predictive value of magnetic resonance imaging and electroencephalography and whether screening improves seizure recognition is unclear. METHODS: A retrospective review of children with high-risk port-wine stains presenting consecutively to the outpatient laser clinic of a tertiary pediatric hospital between December 2015 and November 2016 was undertaken. Primary outcome measures were yield, accuracy, age of and protocols for screening magnetic resonance imaging and electroencephalography, type of and age at presenting seizure, and percentage referred to neurology. RESULTS: Of 126 patients with facial port-wine stains, 25.4% (32/126) were at high risk of Sturge-Weber syndrome (hemifacial, median, and forehead PWS phenotypes); 43.7% of these (14/32) underwent screening magnetic resonance imaging. Sturge-Weber syndrome was detected in 7.1% (1/14). Magnetic resonance imaging had false-negative results in 23.1% (3/13) of those screened. Screening magnetic resonance imaging had sensitivity of 25%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9% for the detection of Sturge-Weber syndrome (hemifacial, median and forehead PWS phenotypes). Only one-third of those with false-negative magnetic resonance imaging were referred to neurology. Mean age of first seizure in those with false-negative screening magnetic resonance imaging was 28 months, vs 14 months in those not screened. Abnormal electroencephalographic signs were detected in the two infants who underwent presymptomatic electroencephalography. CONCLUSIONS: Findings from this small cohort of individuals with port-wine stains that put them at high risk of Sturge-Weber syndrome suggest that children with positive screening magnetic resonance imaging will almost certainly develop Sturge-Weber syndrome but that negative screening magnetic resonance imaging cannot exclude Sturge-Weber syndrome (in up to 23.1% of cases). False-negative magnetic resonance imaging may delay seizure recognition. Seizure education, monitoring, and consideration of adjunctive electroencephalography are important irrespective of magnetic resonance imaging findings.