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.

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.

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.

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.

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.

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.

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.

The skin as a target for prevention of the atopic march.

OBJECTIVE: Allergic diseases have increased dramatically in the developed world during the past few decades, yet the understanding of risk factors and effective prevention approaches remain limited. In this review, we summarize the evidence supporting the hypothesis that skin-barrier impairment and early-life atopic dermatitis (AD) could play a causal role in the development of sensitization and subsequent food allergies and allergic airways disease (allergic asthma and rhinitis). We further discuss the potential to target the skin barrier as a means to lower the incidence of allergic disease. DATA SOURCES: Review of published literature. STUDY SELECTIONS: Narrative. RESULTS: There is a strong link between AD and sensitization, food allergy, asthma, and allergic rhinitis, particularly AD that is severe and commences in the first 6 months of life. There also is emerging evidence that regular use of prophylactic emollients can significantly decrease the expression of AD, at least while treatment continues. Studies are exploring whether decreased AD expression might modulate the allergic response at a more fundamental level and potentially alter the association between early-life AD and subsequent development of food allergy and allergic airways disease. CONCLUSION: Although at this point there is only indirect evidence that early-life emollient use might prevent AD and food allergy, early studies are encouraging. The results of high-quality prevention trials that are in progress are eagerly anticipated. If found to be effective, then neonatal emollient use could be a simple public health measure to lower the incidence of AD, food allergies, and allergic airways disease in future generations.

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.

Screening for Sturge-Weber syndrome: A state-of-the-art review.

Infants with a high-risk distribution of port-wine stains are commonly screened for Sturge-Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port-wine stain phenotypes to screen, optimal timing, screening sensitivity, or whether presymptomatic diagnosis improves neurodevelopmental outcomes. This state-of-the-art review examines the evidence in favor of screening for Sturge-Weber syndrome, based on its effect on neurodevelopmental outcomes, against the risks and limitations of screening magnetic resonance imaging and electroencephalography. A literature search of PubMed/MEDLINE was conducted between January 2005 and May 2017 using key search terms. Relevant articles published in English were reviewed; 34 articles meeting the search criteria were analyzed according to the following outcome measures: neurodevelopmental outcome benefit of screening, diagnostic yield, financial costs, procedural risks, and limitations of screening magnetic resonance imaging and electroencephalography. There is no evidence that a presymptomatic Sturge-Weber syndrome diagnosis with magnetic resonance imaging results in better neurodevelopmental outcomes. The utility of electroencephalographic screening is also unestablished. In Sturge-Weber syndrome, neurodevelopmental outcomes depend on prompt recognition of neurologic red flags and early seizure control. Small numbers and a lack of prospective randomized controlled trials limit these findings. For infants with port-wine stain involving skin derived from the frontonasal placode (forehead and hemifacial phenotypes), we recommend early referral to a pediatric neurologist for parental education, counselling, and monitoring for neurologic red flags and seizures and consideration of electroencephalography regardless of whether magnetic resonance imaging is performed or its findings.

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council.

BACKGROUND: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. OBJECTIVE: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. METHODS: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. RESULTS: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. LIMITATIONS: Our work is a consensus statement, not a systematic review. CONCLUSION: The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies.

A Review of 52 Pedigrees with Epidermolysis Bullosa Simplex Identifying Ten Novel Mutations in KRT5 and KRT14 in Australia.

Epidermolysis bullosa simplex (EBS) is a rare heritable skin fragility disorder, most commonly caused by dominant mutations in KRT5 and KRT14. EBS shows clinical heterogeneity with localised, intermediate and generalised severe forms, which tend to correlate with the location and nature of the disease causing mutations. We therefore aimed to identify the KRT5 and KRT14 mutations in patients diagnosed with EBS in Australia, and explore in depth the genotype to the phenotype correlations in patients with novel variants. Australian patients who were diagnosed with EBS after referral to the Australian National Diagnostic Laboratory for EB were offered mutation screening in the KRT5 and KRT14 genes. From this, 32 different mutations in KRT5 and KRT14 were identified within 39 of 52 pedigrees. Ten of these mutations from 9 different pedigrees were novel, a further fatal case caused by KRT5 E477K is reported and in addition the third reported case of digenic inheritance in EBS was also observed.

Debunking the Myth of Wool Allergy: Reviewing the Evidence for Immune and Non-immune Cutaneous Reactions.

Although wool is commonly believed to cause irritant (non-immune) and hypersensitivity (immune) cutaneous reactions, the evidence basis for this belief and its validity for modern garments have not been critically examined. Publications from the last 100 years, using MEDLINE and Google Scholar, were analysed for evidence that wool causes cutaneous reactions, both immune-mediated (atopic dermatitis exacerbation, contact urticaria, allergic contact dermatitis) and non-immune-mediated (irritant contact dermatitis, itch). Secondary aims of this paper were to examine evidence that lanolin and textile-processing additives (formaldehyde, chromium) cause cutaneous reactions in the context of modern wool-processing techniques. Current evidence does not suggest that wool-fibre is a cutaneous allergen. Furthermore, contact allergy from lanolin, chromium and formaldehyde is highly unlikely with modern wool garments. Cutaneous irritation from wool relates to high fibre diameters (≥ 30-32 µm). Superfine and ultrafine Merino wool do not activate sufficient c-fibres to cause itch, are well tolerated and may benefit eczema management.

Association Between Discoid Lupus Erythematosus and Chronic Granulomatous Disease--Report of Two Cases and Review of the Literature.

Discoid lupus erythematosus (DLE) is known to be associated with chronic granulomatous disease (CGD), but most DLE occurs in female carriers of X-linked CGD, with few reports of these lesions in CGD-affected individuals--this observation is unexplained. We describe two cases of DLE-like lesions in boys with CGD: one boy with partial neutrophil function and another whose lesions were related to voriconazole use. Reviewing other previously reported cases, we conclude that the risk of developing DLE-like lesions appears to be greater primarily in two subsets of the population with CGD: those with partial neutrophil function and those with near-absent neutrophil function in whom there is a second trigger. In light of recent literature on the role of neutrophils in lupus pathogenesis, we propose that pathogenesis of DLE in CGD may be related to NETosis, neutrophil dysfunction and a deficiency of reactive oxygen species, which medications such as voriconazole also influence.

Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI).

BACKGROUND: There is a lack of validated standardized outcome measures for epidermolysis bullosa (EB) that can separate activity from damage. OBJECTIVE: We sought to develop and validate an instrument for inherited EB of all ages and subtypes, the EB Disease Activity and Scarring Index (EBDASI), which scores activity responsive to therapy separately from scarring. METHODS: The EBDASI was validated by comparing its reliability and validity against the Birmingham EB Severity (BEBS) score (partially validated with activity mixed with scarring), using the Physician Global Assessment (PGA) scale as a reference measurement. Sixteen patients with EB (7 EB simplex, 5 dominant dystrophic EB [DDEB], 2 junctional EB, and 2 recessive dystrophic EB) were assessed by 5 EB experts using the EBDASI, BEBS, and PGA, and data from 9 additional patients assessed on an ad hoc basis during routine patient clinic were also included. RESULTS: For interrater reliability, the overall total score intraclass correlation coefficients (95% confidence intervals) were: EBDASI 0.964 (0.929-0.986), BEBS 0.852 (0.730-0.937), and PGA 0.873 (0.765-0.946). For intrarater reliability, the intraclass correlation coefficients were: EBDASI 0.994 (0.976-0.998), BEBS 0.926 (0.748-0.981), and PGA 0.932 (0.764-0.982). The EBDASI had a higher correlation with PGA (ρ = 0.871) than BEBS with PGA (ρ = 0.852). Intraclass correlation coefficients scatterplots showed the EBDASI was better at distinguishing milder forms of EB, with better correlations at higher severity scores than the BEBS. LIMITATIONS: A limited number of patients were recruited for this study. An independent study will be required to demonstrate the responsiveness of the EBDASI. CONCLUSION: The EBDASI demonstrated excellent reliability and validity, as compared with 2 other outcome measures.

Unsuspected allergic contact dermatitis to alcohol swabs following neurosurgery.

We report a case of a 12-year-old girl with severe allergic contact dermatitis following neurosurgery secondary to topical use of isopropyl alcohol swabs. Alcohol swabs should not be overlooked as potential allergens. In our case, it was initially assumed that the cause of her reaction was either tapes or topical local anaesthetic.

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.

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.