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

Clinical onset of atopic eczema: results from two nationally representative British birth cohorts followed through mid-life

BackgroundAtopic eczema onset is described primarily in early childhood; the frequency and characteristics of adult-onset disease remain controversial.ObjectiveTo determine the proportion of individuals who report atopic eczema symptoms between birth and mid adulthood, and to examine demographic, immunologic, and genetic factors associated with period of symptom onset.MethodsWe conducted a longitudinal study using data from two nationally representative community-based birth cohorts from the United Kingdom: the British Cohort Studies 1958 and 1970. Individuals were followed from birth through age 42-50. The primary outcome was the age period of self-reported atopic eczema symptom onset based on repeated measures of self-reported atopic eczema at each survey wave.ResultsThe annual period prevalence of atopic eczema ranged from 5-15% in two cohorts of over 17,000 participants each followed from birth through mid-age. There was no clear trend in prevalence by age, and among adults reporting active atopic eczema during a given year, only 38% had symptom onset reported in childhood. When compared with individuals whose eczema started in childhood, those with adult-onset disease were more likely to be women, from Scotland or Northern England, of lower childhood socio-economic group, smokers in adulthood, and less likely to have a history of asthma. In a sub-analysis using data from the 1958 cohort only, genetic mutations previously associated with atopic eczema, including filaggrin null mutations, and allergen-specific IgE were more common among those with childhood-onset disease.ConclusionRates of self-reported atopic eczema remain high after childhood, and adult-onset atopic eczema has different risk factor associations than childhood-onset eczema

Relationship of atopic dermatitis with obesity and its related inflammatory metabolic disturbances in an adult general population cohort

Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant patient and population burden. It has been observed that obesity is associated with a higher risk of AD. However, the underlying mechanisms are not clear. The purpose of this thesis is to assess the relationship of AD and obesity in a general adult population cohort and explore possible underlying mechanistic links. Specifically, there are five different aims to determine epidemiological associations, skin physiology differences, skin microbiome diversity, serum inflammatory biomarkers profile and genomic associations between AD and obesity. These are specifically to address the various hypotheses based on our current understanding of AD’s pathophysiological mechanisms. Participants of the Health for Life in Singapore (HELIOS) study cohort, aged 30 to 85 years old from the general population, were included in the analysis. Participants were screened for AD using the modified UK Working Party criteria and obesity classified according to anthropometric, bio-impedance and dual x-ray absorptiometry measures. Skin physiology parameters such as trans epidermal water loss (TEWL), skin surface moisture and pH were also measured for all participants. In addition, skin microbiome profiling and serum inflammatory biomarkers proteomics analysis were performed in 300 selected Chinese participants (150 AD participants age and gender matched in a 1:1 ratio with healthy controls). Genetic associations and the concept of Mendelian randomisation (MR) were also used to explore causal relationship between obesity, and AD using genetic data published in public domain. Finally, analysis was performed to integrate results from the skin microbiome and serum proteomic studies to evaluate interactions between the various omics platforms. A total of 5560 participants were recruited from initiation till January 2020. About 8.8% of participants had AD while 40.2% were overweight or obese. Participants with higher visceral fat mass were more likely to have AD after adjusting for age, gender and ethnicity (Odds Ratio (OR): 1.52; p=0.028). Skin physiology, skin microbiome and serum proteomic profile related to AD were found to be significant with increasing body mass index (BMI). Obese participants (BMI ≥ 30 kgm-2 had a significantly higher trans-epidermal water loss (TEWL) values (Beta=0.059 p < 0.001) while having a lower skin surface hydration (Beta= - 0.047 p = 0.003). Serum proteomic analysis revealed that levels of 98 specific serum biomarkers were significantly different with increasing BMI. Known biomarkers of obesity such as serum leptin and IL6 and several AD related chemokines such as CCL17, CCL20, CCL3 and CCL4 were among these significantly different serum biomarkers. The IL18 family of cytokines, previously hypothesized to play a role in initiating AD like dermatitis, were also found to be significantly elevated with increasing BMI. While the diversity of the skin microbiome was similar between the obese and the lean, there were increased proportions of Corynebacterium species, Staphylococcus hominis and Malassezia globosa and reduced proportions of Propionibacterium (Cutibacterium) acnes in participants with increasing BMI. Finally, with MR analysis, it has been observed that genetically determined increase in obesity is associated with increased risk of AD (OR of AD 1.08; p = 0.015). This study provided new evidence to improve our understanding of how obesity is associated with the risk of AD. Obesity, particularly abdominal/visceral obesity was associated with an increased risk of AD. It was established by the MR analyses that the direction of this relationship likely reflects an effect of obesity on the risk of developing AD. This was further reinforced by the observations that obese participants exhibited features of skin barrier dysfunction. Serum proteomic and skin microbiome analyses also revealed unique profile among obese participants. These findings provided basis for future studies to evaluate possible underlying mechanistic pathways of this relationship.Doctor of Philosoph

Dupilumab‐associated head and neck dermatitis: Rapid response with abrocitinib treatment

Abstract Development or exacerbation of head and neck dermatitis (HN‐D) in association with dupilumab has been reported. Severity of HN‐D varies, and may persist even with discontinuation of dupilumab. Development or exacerbation of HN‐D is not yet completely understood, and various hypotheses have been made about the possible underlying pathophysiology. To date, there is no established treatment for HN‐D in association with dupilumab. We report 2 cases of HN‐D occurring following dupilumab treatment, with significant improvement of HN‐D following treatment with abrocitinib

Tofu, urinary phytoestrogens, and melanoma: An analysis of a national database in the United States

Background/Objectives: Phytoestrogens are naturally occurring estrogen-like compounds commonly found in foods, especially soybeans and soy products. There have been recent interests as well as evidence in animal studies suggesting that phytoestrogens may protect against cancers, including skin cancers such as melanoma. To date, no human or epidemiological studies have been performed to evaluate this association with melanoma. The objective of this study was to investigate the relationship between tofu consumption, urinary phytoestrogen, and diagnosis of melanoma in a national epidemiologic database. Methods: Data on the history of melanoma and measured urinary phytoestrogen levels (daidzein, O-desmethylangolensin, equol, enterodiol, genistein, and enterolactone) from the United States National Health and Nutrition Examination Survey database from 1999 to 2010 were obtained and analyzed with univariate and multivariate tests. Using information about tofu consumption and sun-protective behaviors, we analyzed the data for the period 2003–2006. Results: Patients who were older or with higher body mass index (BMI) were significantly more likely to be diagnosed with melanoma in the past [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.05–1.07; p < 0.001; and OR 1.04; 95% CI 1.02–1.06; p < 0.001, respectively]. Those with a history of melanoma had lower levels in five of the six measured creatinine-adjusted urinary phytoestrogens. However, this relationship was not statistically significant after adjusting for confounding factors such as age, sex, ethnic groups, and BMI. A diet with tofu had a significant positive correlation with the levels of measured urinary phytoestrogens. By contrast, the association between a history of melanoma and such diet did not achieve statistical significance. Conclusion: In our study, patients with a history of melanoma tend not to consume tofu in their diet and have lower urinary phytoestrogens levels. The relationship was not statistically significant and more studies need to be carried out

Risk of herpes zoster and family history: A Meta-analysis of case–control studies

Background: Herpes zoster (HZ) results from the reactivation of latent varicella zoster virus (VZV) residing in dorsal root and cranial nerve ganglia. Advanced age and dysfunctional cell-mediated immune responses are well-established risk factors for VZV reactivation. There have been recent interests in whether there is an increased risk of the disease associated with a positive family history. Aims and Objectives: We aimed to conduct a meta-analysis to evaluate the association between HZ infection and family history. In addition, we investigated the dose-response relationship between HZ infection and the number of relatives with a history of HZ. Materials and Methods: Observational studies were searched from MEDLINE, EMBASE, and Cochrane Central Register from inception to April 15, 2015. The Meta-analysis of Observational Studies in Epidemiology guidelines were followed in conducting this study. To estimate the pooled odds ratio, random-effects model of DerSimonian and Laird was used. Heterogeneity between studies was assessed using the I2 statistic. A dose-response meta-analysis with studies that reported appropriate data were done using the generalized least squares for trend method. Results: Five studies, yielding a total of 4169 subjects, were identified for meta-analysis. Cases with HZ were 3.03 (95% confidence interval [CI]: 1.86–4.94, P < 0.001) and 3.27 (95% CI: 1.75–6.10, P < 0.001) times more likely to report the first-degree relatives and total relatives with a history of HZ, respectively. A significant positive dose-response relationship between the risk of HZ infection and the number of relatives with a history of HZ was also demonstrated (P < 0.001). Conclusions: This meta-analysis demonstrated that family history is a significant risk factor for HZ infection. This risk has a dose-response relationship with the number of relatives with a history of HZ

Smoking and Hand Dermatitis in the United States Adult Population

Background: Hand dermatitis is a common chronic relapsing skin disease resulting from a variety of causes, including endogenous predisposition and environmental exposures to irritants and allergens. Lifestyle factors such as smoking have been implicated in hand dermatitis. Objective: To evaluate the association between tobacco exposure and hand dermatitis using the 2003~2004 National Health and Nutrition Examination Survey (NHANES) database. Methods: Data were retrieved and analyzed from 1,301 participants, aged 20~59 years, from the 2003~2004 NHANES questionnaire study who completed health examination and blood tests. Diagnosis of hand dermatitis was based on standardized photographs of the dorsal and palmar views of the hands read by two dermatologists. Results: There were 38 diagnosed cases of active hand dermatitis out of the 1,301 study participants (2.9%). Heavy smokers (>15 g tobacco daily) were 5.11 times more likely to have active hand dermatitis (odds ratio [OR], 5.11; 95% confidence interval [CI], 1.39~18.88; p=0.014). Those with serum cotinine >3 ng/ml were also more likely to have active hand dermatitis, compared with those with serum cotinine ≤3 ng/ml (OR, 2.50; 95% CI, 1.26~4.95; p=0.007). After adjusting for confounding factors such as age, atopic diathesis, occupational groups, and physical activity, the association between tobacco exposure and active hand dermatitis remained significant. Conclusion: Smoking has a significant association with the presence of active hand dermatitis. It is important to consider smoking cessation as part of management of hand dermatitis

Hand hygiene and hand eczema: a systematic review and meta-analysis

Hand eczema is a common inflammatory condition of the skin that has been linked to hand hygiene. This systematic review and meta-analysis aims to determine the risks of hand eczema associated with hand hygiene, including frequency of hand washing, wet work and use of alcohol hand rub. A comprehensive search of MEDLINE, EMBASE and Cochrane Library was performed for cohort, case-control or cross-sectional studies that analysed the association between hand hygiene and risk of hand eczema. Results of individual studies were presented in respective forest plots and pooled summary relative risks were estimated using a random-effects model. Forty-five studies were included in the analysis. Hand washing at least 8-10 times daily significantly increased risk of hand eczema (relative risk [RR] 1.51; 95% confidence interval [CI]: 1.35-1.68; p < 0.001). The risk was related to hand washing frequency, with higher pooled RR of 1.66 (95% CI: 1.51-1.83; p < 0.001) with increased hand washing at least 15-20 times daily. However, use of alcohol-based hand sanitizer was not significantly associated with risk of hand eczema. Given the widespread implementation of hand hygiene practices during the COVID-19 pandemic, there is a pertinent need to understand skin care habits specific to the hands to avoid a greater incidence of hand eczema

Investigating causal relationships between genetically determined increased risk of attention-deficit/hyperactivity disorder (ADHD) and atopic dermatitis (AD): A Mendelian randomization analysis

Atopic dermatitis (AD) is a chronic, inflammatory skin condition with a huge disease burden. Attention-deficit/hyperactivity disorder (ADHD) is often diagnosed in children, and is associated with symptoms of inattention, hyperactivity and impulsive behaviour. Observational studies have demonstrated associations between AD and ADHD. However, to date, there has been no formal assessment of causal relationship between the two. We aim to evaluate causal relationships between genetically increased risk of AD and ADHD using Mendelian randomization (MR) approach. Two-sample bi-directional MR was conducted to elucidate potential causal relationships between genetically increased risk of AD and ADHD, using the largest and most recent genome-wide association study datasets for AD and ADHD-EArly Genetics & Lifecourse Epidemiology AD consortium (21 399 cases and 95 464 controls) and Psychiatric Genomics Consortium (20 183 cases and 35 191 controls). Genetically determined increased risk of AD is not associated with ADHD based on genetic information: odds ratio (OR) of 1.02 (95% CI -0.93 to 1.11; p = 0.705). Similarly, genetic determined increased risk of ADHD is not associated with an increased risk of AD: OR of 0.90 (95% CI -0.76 to 1.07; p = 0.236). Horizontal pleiotropy was not observed from the MR-Egger intercept test (p = 0.328) Current MR analysis showed no causal relationship between genetically increased risk of AD and ADHD in either direction in individuals of European descent. Any observed associations between AD and ADHD in previous population studies could possibly be due to confounding lifestyle factors such as psychosocial stress and sleeping habits.Published versio