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.

Prevalence and burden of skin diseases among the elderly in Singapore: a 15-year clinical cohort study.

BACKGROUND: Populations around the world are rapidly ageing. The profile of skin diseases in the elderly is likely to present unique demands on the healthcare system. OBJECTIVES: To provide current data on the burden of skin diseases in Singaporean patients and identify differences in the pattern of skin diseases between elderly patients and the rest of the population. METHODS: This was a retrospective cohort study of 858 117 patients who attended the National Skin Centre between 2004 and 2018. Prevalence was calculated by grouping International Classification of Diseases codes into different categories of skin conditions based on Global Burden of Disease and American Academy of Dermatology classifications. Years lost to disability (YLDs) and disability-adjusted life years (DALYs) were calculated to report the morbidity and mortality of skin diseases. Differences of each skin condition between age groups were compared. RESULTS: The three most prevalent dermatoses across all age groups were dermatitis (33.3%), acne vulgaris (8.3%) and viral skin diseases (7.5%). The top three most common skin conditions among the elderly were dermatitis (37.7%), viral skin diseases (6.2%) and fungal skin diseases (4.3%). Decubitus ulcers, keratinocyte carcinomas and scabies represented a significant proportion of YLD per 100 000 in the elderly (P < 0.001). Malignant melanomas, keratinocyte carcinomas, cellulitis, pyoderma and decubitus ulcers contributed to high DALYs in patients aged 70-80 years. CONCLUSION: Aligning health systems with specific healthcare needs will reduce the disproportionately high burden of skin disease observed in the elderly.

Lifetime prevalence and determinants of hand eczema in an adolescent population in Germany: 15-year follow-up of the LISA cohort study.

BACKGROUND: Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. OBJECTIVES: We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. METHODS: This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1468/1736) had clearly reported whether they have ever had hand eczema. All the data were based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. RESULTS: One thousand four hundred and sixty-eight adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR = 1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. CONCLUSION: Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in paediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation.

The cost of childhood atopic dermatitis in a multi-ethnic Asian population: a cost-of-illness study.

BACKGROUND: Childhood atopic dermatitis can often have a negative impact on quality of life for affected children and their caregivers. The condition contributes to increased healthcare costs and can pose heavy economic burdens on healthcare systems and societies. OBJECTIVES: The objective of this study is to provide a comprehensive estimate of the economic burden of childhood atopic dermatitis in a Singaporean sample and to investigate associated factors. METHODS: This cross-sectional cost-of-illness study applied a societal perspective. Data was collected between December 2016 and December 2017 in Singapore. Caregivers to children below 16 years of age with a physician-confirmed diagnosis of atopic dermatitis were recruited and sociodemographics, clinical characteristics, health service utilization data and time spent on caregiving were collected from all eligible participants. RESULTS: The average annual cost per child with atopic dermatitis was estimated at U.S. dollars (USD) 7943 (mild USD 6651, moderate USD 7935 and severe USD 14 335) in 2017 prices. The major cost was for informal caregiving (46% of the total cost) followed by out-of-pocket expenses (37%). Healthcare utilization contributed to 17% of the total cost of which 43% was for medications. CONCLUSIONS: Childhood atopic dermatitis imposes substantial costs with a large proportion arising from informal caregiving and out-of-pocket expenses. The costs related to atopic dermatitis are also strongly related to disease severity. This information is important for policy makers and other health planners when considering how to better support affected families. What's already known about the topic? Childhood atopic dermatitis is a costly disease for society. However, comprehensive cost estimations are lacking. Previous cost studies are old, based on small sample sizes or are healthcare-setting specific. What does this study add? This study comprises a health economic evaluation assessing different levels of care and includes various categories of costs. The result showed that informal caregiving was the most prominent cost for children with atopic dermatitis.

The Patient-Oriented Eczema Measure: estimating the minimal important change in an outpatient clinic cohort.

BACKGROUND: Patient-Oriented Eczema Measure (POEM) measures patient-reported symptoms in atopic dermatitis (AD). It is the recommended core outcome instrument to capture the symptoms domain in AD clinical trials. Understanding the minimal important change (MIC) in the POEM score is therefore important in both trial and clinical care settings. Previous studies have mainly evaluated MIC estimates among children in trial settings. The MIC estimate for POEM in a clinical setting is often lacking. OBJECTIVES: We aim to estimate the MIC of the POEM using both distribution-based and anchor-based methods in a clinical cohort of adult eczema patients. METHODS: Both distribution-based and anchor-based methods were used to calculate the MIC of the POEM in a clinical cohort of Asian adult patients attending the eczema clinic at a tertiary dermatology centre in Singapore. Scoring AD (SCORAD) was used as the disease severity anchor for the anchor-based methods. The smallest detectable change (SDC) for POEM was also calculated as the threshold for any measurement error. RESULTS: There were a total of 85 adult AD patients in the cohort that contributed a total of 114 paired measurements of both POEM and SCORAD. The SDC in our study was 1.68. The MIC estimates were 3.64 and 1.46 based on 0.5 standard deviation (SD) and 0.2 SD distribution-based methods. Anchor-based methods such as the receiver operating curve and predictive modelling methods yielded MIC values of 0.50 and 1.05, respectively. CONCLUSIONS: Minimal important change for POEM varied according to the methods and approaches used. Only a change of two points or more in POEM could be considered beyond any measurement errors and clinically important. This finding is consistent even in a clinical setting of Asian adults with eczema.

Vitiligo and depression: a systematic review and meta-analysis of observational studies.

Vitiligo is a common depigmenting disorder with profound psychosocial impacts. Previous observational studies have suggested a link between vitiligo and psychiatric morbidity, such as depression. However, variability in study design makes it difficult to quantify accurately the relationship between vitiligo and depression. We aimed to investigate the underlying prevalence and risk of depression among patients with vitiligo. A comprehensive search of MEDLINE, Embase and the Cochrane Library was conducted. Cross-sectional, case-control or cohort studies that assessed the prevalence of depression among patients with vitiligo or the relationship between vitiligo and depression were included. DerSimonian and Laird random-effects models were utilized to calculate the pooled prevalence and relative risks. Publication bias was evaluated by funnel plots and Egger's tests. Twenty-five studies with 2708 cases of vitiligo were included. Based on diagnostic codes, the pooled prevalence of depression among patients with vitiligo was 0·253 [95% confidence interval (CI) 0·16-0·34; P < 0·001)]. Using self-reported questionnaires, the pooled prevalence of depressive symptoms was 0·336 (95% CI 0·25-0·42; P < 0·001). The pooled odds ratio of depression among patients with vitiligo was 5·05 vs. controls (95% CI 2·21-11·51; P < 0·001). Moderate-to-high heterogeneity was observed between the studies. Patients with vitiligo were significantly more likely to suffer from depression. Clinical depression or depressive symptoms can be prevalent, with the actual prevalence differing depending on screening instruments or, possibly, geographical regions. Clinicians should actively evaluate patients with vitiligo for signs/symptoms of depression and provide appropriate referrals to manage their psychiatric symptoms accordingly.

Bullous pemphigoid and its association with neurological diseases: a systematic review and meta-analysis.

Bullous pemphigoid (BP) is a chronic, autoimmune vesiculobullous disease that frequently occurs in the elderly population. Previous epidemiological studies have suggested an association between BP and neurological diseases; some studies, however, showed conflicting results. This study aimed to investigate if patients with BP have significantly higher risks for neurological disorders, compared to controls. A comprehensive search was performed using MEDLINE, EMBASE and Cochrane library databases. Case-control and cohort studies that assessed the relationship between BP and neurological diseases were included. DerSimonian and Laird random-effects models were utilized to calculate the pooled relative risks (RRs). Publication bias was evaluated qualitatively by constructing a funnel plot and quantitatively by conducting Egger's test. Fourteen studies, with 23 369 BP cases and 128 697 controls were included in this meta-analysis. Patients with BP were significantly more likely to have stroke (RR 2.68, 95% CI: 2.07-3.46), Parkinson's disease (PD; RR 3.42, 95% CI: 3.01-3.87), dementia (RR 4.46, 95% CI: 3.23-6.16), epilepsy (RR 2.98, 95% CI: 1.42-6.28), multiple sclerosis (RR 12.40, 95% CI: 6.64-23.17) and any aforementioned neurological disease (RR 4.93, 95% CI: 3.62-6.70), compared to controls. Moderate to high heterogeneity were observed for analyses of most neurological diseases, except for PD and multiple sclerosis. This study provided support for a significant association between BP and neurological diseases. Clinicians should be aware of this association and manage modifiable risk factors for neurological diseases accordingly.

Psoriasis and uric acid: a population-based cross-sectional study.

BACKGROUND: Psoriasis has been reported to be associated with raised serum uric acid levels and gout, and uric acid has been demonstrated to mediate inflammatory pathways via secretion of pro-inflammatory chemokines. AIM: To evaluate the association between psoriasis, serum uric acid levels and gout in a cross-sectional study using the US National Health and Nutrition Examination Survey (NHANES) database. METHODS: Data on clinical history of psoriasis, gout and other relevant medical conditions from the questionnaire as well as laboratory parameters for serum uric acid and lipid levels in the periods 2003-2006 and 2011-2012 were analysed. Multivariate analysis with logistic regression modelling was performed, with hyperuricaemia as the dependent variable, and age, sex, ethnicity, body mass index, metabolic syndrome, current smoking status, alcohol consumption and history of psoriasis as the independent variables. RESULTS: Of the 11 282 study participants, 297 (2.6%) reported a history of psoriasis and 1493 (13.2%) were found to have hyperuricaemia. Patients with psoriasis were at increased risk of having hyperuricaemia, compared with those without psoriasis (OR = 1.37; P = 0.04). They were also more likely to report a history of gout (OR = 1.83; P < 0.05). However, neither association was significant after adjusting for potential confounders with multivariate logistic regression. CONCLUSION: In conclusion, there was insufficient evidence to show that psoriasis is an independent risk factor of hyperuricaemia or gout. A raised serum uric acid level may be a consequence of metabolic syndrome, which in turn is associated with psoriasis.

An update of fixed drug eruptions in Singapore.

BACKGROUND: Fixed drug eruptions (FDE) are most commonly caused by antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs). The list of causative drugs changes with time and prescribing patterns but there has been no recent data on FDE seen in an outpatient setting in Singapore. OBJECTIVE: We aimed to evaluate the epidemiology, clinical features and causative drugs in patients with FDE in Singapore. METHODS: We performed a retrospective chart review of all patients seen with suspected FDE in the National Skin Centre, Singapore between 2008 and 2012. Using criteria adapted from the WHO-UMC causality assessment criteria, patients were classified into categories of definite (confirmed with patch test or drug provocation test), probable (causative drug identified based on patient's history), possible (clinically consistent but unable to identify causative drug) or unlikely FDE. RESULTS: We reviewed the charts of 126 patients who were seen for suspected FDE. Ten patients (7.0%) were classified as having definite FDE, 52 patients (41.3%) probable FDE, 61 patients (48.4%) possible FDE and three patients (2.4%) unlikely FDE. Clinical features were similar to those described in previous studies. Among the 62 patients with definite or probable FDE, etoricoxib was the most common cause (24 patients, 38.7%). Other common causes included paracetamol, other NSAIDs and doxycycline. Antihistamines caused FDE in three patients. CONCLUSION: Etoricoxib was the most frequent cause of FDE in our study. Other NSAIDs, paracetamol and doxycycline remain common causes of FDE but we caution that antihistamines, such as cetirizine, should also be considered.

Knowledge and beliefs on corneal donation in Singapore adults.

AIM: To assess the knowledge and willingness of Singapore adults towards corneal donation. METHODS: The study population consists of a cluster random sample of the population living in Bedok North (an area in the eastern part of Singapore). The study population comprised residents aged 21-65 years living in 675 randomly sampled housing units. The participation rate was 65.9% (544/825). All participants were interviewed face to face with a questionnaire formulated according to the modified Horton and Horton model. Knowledge, values, attitudes, and spiritual beliefs of participants were assessed to evaluate their willingness to donate their corneas. RESULTS: 67.0% of participants were willing to donate their corneas. Ethnicity (Chinese) and religion (Christians, Hindus, or those with no religion) were associated with increased willingness to donate corneas. Greater knowledge and increased altruistic values were also associated with increased willingness to donate corneas. CONCLUSION: A proportion of participants were willing to donate their corneas. Awareness of corneal donation is high but specific knowledge should be further increased among adults.