Classifying atopic dermatitis: a systematic review of phenotypes and associated characteristics.

Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies.

Inflammatory skin diseases and the risk of chronic kidney disease: population-based case-control and cohort analyses.

BACKGROUND: Emerging evidence suggests an association between common inflammatory skin diseases and chronic kidney disease (CKD). OBJECTIVES: To explore the association between CKD stages 3-5 (CKD3-5) and atopic eczema, psoriasis, rosacea and hidradenitis suppurativa. METHODS: We undertook two complementary analyses; a prevalent case-control study and a cohort study using routinely collected primary care data [UK Clinical Practice Research Datalink (CPRD)]. We matched individuals with CKD3-5 in CPRD in March 2018 with up to five individuals without CKD for general practitioner practice, age and sex. We compared the prevalence of CKD3-5 among individuals with and without each inflammatory skin disease. We included individuals in CPRD with diabetes mellitus (2004-2018) in a cohort analysis to compare the incidence of CKD3-5 among people with and without atopic eczema and psoriasis. RESULTS: Our study included 56 602 cases with CKD3-5 and 268 305 controls. Cases were more likely than controls to have a history of atopic eczema [odds ratio (OR) 1·14, 99% confidence interval (CI) 1·11-1·17], psoriasis (OR 1·13, 99% CI 1·08-1·19) or hidradenitis suppurativa (OR 1·49, 99% CI 1·19-1·85), but were slightly less likely to have been diagnosed with rosacea (OR 0·92, 99% CI 0·87-0·97), after adjusting for age, sex, practice (matching factors), index of multiple deprivation, diabetes, smoking, harmful alcohol use and obesity. Results remained similar after adjusting for hypertension and cardiovascular disease. In the cohort with diabetes (N = 335 827), there was no evidence that CKD3-5 incidence was associated with atopic eczema or psoriasis. CONCLUSIONS: Atopic eczema, psoriasis and hidradenitis suppurativa are weakly associated with CKD3-5. Future research is needed to elucidate potential mechanisms and the clinical significance of our findings.

Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.

BACKGROUND: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity. OBJECTIVES: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. METHODS: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results. RESULTS: There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other. CONCLUSIONS: Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.

Using electronic health records to inform trial feasibility in a rare autoimmune blistering skin disease in England.

BACKGROUND: Trials of novel agents are required to improve the care of patients with rare diseases, but trial feasibility may be uncertain due to concerns over insufficient patient numbers. We aimed to determine the size of the pool of potential participants in England 2015-2017 for trials in the autoimmune blistering skin disease bullous pemphigoid. METHODS: The size of the pool of potential participants was estimated using routinely collected healthcare data from linked primary care (Clinical Practice Research Datalink; CPRD) and secondary care (Hospital Episode Statistics; HES) databases. Thirteen consultant dermatologists were surveyed to determine the likelihood that a patient would be eligible for a trial based on the presence of cautions or contra-indications to prednisolone use. These criteria were applied to determine how they influenced the potential pool of participants. RESULTS: Extrapolated to the population of England, we would expect approximately 10,800 (point estimate 10,747; 95% CI 7191 to 17,239) new cases of bullous pemphigoid to be identified in a three-year period. For a future trial involving oral prednisolone (standard care), the application of cautions to its use as exclusion criteria would result in approximately 365 potential participants unlikely to be recruited, a further 5332 could be recruited with caution, and 5104 in whom recruitment is still possible. 11-17% of potential participants may have pre-existing dementia and require an alternative consent process. CONCLUSIONS: Routinely collected electronic health records can be used to inform the feasibility of clinical trials in rare diseases, such as whether recruitment is feasible nationally and how long recruitment might take to meet recruitment targets. Future trials of bullous pemphigoid in England may use the data presented to inform trial design, including eligibility criteria and consent processes for enrolling people with dementia.

Perceived psychological stress and risk of herpes zoster: a nationwide population-based cohort study.

BACKGROUND: Psychological stress may reduce cellular immunity, but its role in triggering latent infections, including herpes zoster (HZ), is controversial. OBJECTIVES: To examine the association between perceived psychological stress and risk of HZ. METHODS: In a linked registry-based cohort study, we followed 77 310 persons aged 40 years or older who participated in the 2010 Danish National Health Survey from 1 May 2010 until HZ diagnosis, death, emigration or 1 July 2014, whichever occurred first. We computed hazard ratios (HRs) of HZ associated with Cohen's Perceived Stress Scale (PSS) score (range 0-40) using Cox regression with age as the timescale, adjusted for sex, immunosuppressive and selected chronic conditions, immunosuppressive drugs, and sociodemographic, lifestyle and anthropometric factors. The PSS measures chronic stress perceived by an individual in response to various demands of daily life. We modelled the PSS score using quintiles and a restricted cubic spline function. RESULTS: The unadjusted rate of HZ varied from 5·53 to 7·20 per 1000 person-years from the lowest to the highest PSS score quintile. Compared with the lowest PSS score quintile, the adjusted HR for HZ was 1·00 [95% confidence interval (CI) 0·86-1·16], 1·08 (95% CI 0·92-1·26), 1·05 (95% CI 0·90-1·23) and 1·14 (95% CI 0·97-1·34) for the second to the fifth quintile, respectively. In cubic spline analyses, PSS scores < 20 were not associated with increased HR of HZ, but thereafter the HR increased linearly from 1·10 (95% CI 0·85-1·41) to 2·22 (95% CI 1·32-3·75). CONCLUSIONS: Our study indicated that high levels of psychological stress are associated with increased risk of HZ.

An updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013-2018.

Introduction: The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods: We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population-based cancer registry and pathology report data, 2013-18. Results: Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013-18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013-18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013-18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non-melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions: We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

The global burden of atopic dermatitis: lessons from the Global Burden of Disease Study 1990-2017.

BACKGROUND: The Global Burden of Disease (GBD) Study provides an annually updated resource to study disease-related morbidity and mortality worldwide. OBJECTIVES: Here we present the burden estimates for atopic dermatitis (AD), including data from inception of the GBD project in 1990 until 2017. METHODS: Data on the burden of AD were obtained from the GBD Study. RESULTS: Atopic dermatitis (AD) ranks 15th among all nonfatal diseases and has the highest disease burden among skin diseases as measured by disability-adjusted life-years (DALYs). Overall, the global DALY rate for AD in 1990 was 121 [95% uncertainty interval (UI) 65·4-201] and remained similar in 2017 at 123 (95% UI 66·8-205). The three countries with the highest DALY rates of AD were Sweden (327, 95% UI 178-547), the UK (284, 95% UI 155-478) and Iceland (277, 95% UI 149-465), whereas Uzbekistan (85·1, 95% UI 45·2-144), Armenia (85·1, 95% UI 45·8-143) and Tajikistan (85·1, 95% UI 46·1-143) ranked lowest. CONCLUSIONS: The global prevalence rate of AD has remained stable from 1990 to 2017. However, the distribution of AD by age groups shows a bimodal curve with the highest peak in early childhood, decreasing in prevalence among young adults, and a second peak in middle-aged and older populations. We also found a moderate positive correlation between a country's gross domestic product and disease burden. GBD data confirm the substantial worldwide burden of AD, which has remained stable since 1990 but shows significant geographical variation. Lifestyle factors, partially linked to affluence, are likely important disease drivers. However, the GBD methodology needs to be developed further to incorporate environmental risk factors, such as ultraviolet exposure, to understand better the geographical and age-related variations in disease burden.

Risk of hospitalization and death due to infection in people with psoriasis: a population-based cohort study using the Clinical Practice Research Datalink.

BACKGROUND: Psoriasis is associated with risk factors for serious infections, but the independent relationship between psoriasis and serious infection is as yet unclear. OBJECTIVES: To determine whether people with psoriasis have a higher risk of hospitalization due to any infection, respiratory infections, soft-tissue and skin infections, or a higher risk of death due to infection. METHODS: We conducted a cohort study of people (≥ 18 years) with psoriasis using the UK Clinical Practice Research Datalink (CPRD GOLD) linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records between 1 April 2003 and 31 December 2016, and matched with up to six comparators on age, sex and general practice. Hospitalization was ascertained from HES records; death was ascertained from ONS mortality records. Stratified Cox proportional hazard models were estimated, with stepwise adjustment in different models for potential confounders or mediators between psoriasis and serious infection. RESULTS: There were 69 315 people with psoriasis and 338 620 comparators who were followed up for a median (interquartile range) of 4·9 (5·9) and 5·1 (6·3) years, respectively. People with psoriasis had a higher incidence rate of serious infection [20·5 per 1000 person-years, 95% confidence interval (CI) 20·0-21·0, n = 7631] compared with those without psoriasis (16·1 per 1000 person-years, 95% CI 15·9-16·3, n = 30 761). The fully adjusted hazard ratio for the association between psoriasis and serious infection was 1·36 (95% CI 1·31-1·40), with similar results across the other outcomes. CONCLUSIONS: Psoriasis is associated with a small increase in the risk of serious infection. Further research is needed to understand how psoriasis predisposes to a higher risk of infection.

Incidence, prevalence and mortality of bullous pemphigoid in England 1998-2017: a population-based cohort study.

BACKGROUND: A rising incidence and high mortality were found for bullous pemphigoid (BP) over a decade ago in the UK. Updated estimates of its epidemiology are required to understand the healthcare needs of an ageing population. OBJECTIVES: To determine the incidence, prevalence and mortality rates of BP in England from 1998 to 2017. METHODS: We conducted a cohort study of longitudinal electronic health records using the Clinical Practice Research Datalink and linked Hospital Episode Statistics. Incidence was calculated per 100 000 person-years and annual point prevalence per 100 000 people. Multivariate analysis was used to determine incidence rate ratios by sociodemographic factors. Mortality was examined in an age-, sex- and practice-matched cohort, using linked Office of National Statistics death records. Hazard ratios (HRs) were stratified by matched set. RESULTS: The incidence was 7·63 [95% confidence interval (CI) 7·35-7·93] per 100 000 person-years and rose with increasing age, particularly for elderly men. The annual increase in incidence was 0·9% (95% CI 0·2-1·7). The prevalence almost doubled over the observation period, reaching 47·99 (95% CI 43·09-53·46) per 100 000 people and 141·24 (95% CI 125·55-158·87) per 100 000 people over the age of 60 years. The risk of all-cause mortality was highest in the 2 years after diagnosis (HR 2·96; 95% CI 2·68-3·26) and remained raised thereafter (HR 1·54; 95% CI 1·36-1·74). CONCLUSIONS: We report a modest increase in the incidence rate of BP, but show that the burden of disease in the elderly population is considerable. Mortality is high, particularly in the first 2 years after diagnosis.

Atopic eczema and obesity: a population-based study.

BACKGROUND: Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations. OBJECTIVES: To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index. METHODS: We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without. RESULTS: We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07-1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06-1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema. CONCLUSIONS: We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.

Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data.

BACKGROUND: Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. OBJECTIVES: To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. METHODS: We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. RESULTS: In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). CONCLUSIONS: Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN.

The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.

BACKGROUND: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. OBJECTIVES: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. METHODS: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. RESULTS: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60). CONCLUSIONS: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.

The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

Partner bereavement and risk of psoriasis and atopic eczema: cohort studies in the U.K. and Denmark.

BACKGROUND: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. OBJECTIVES: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. METHODS: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta-analysis. RESULTS: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98-1·04) across the entire follow-up. Similar results were found in other shorter follow-up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84-1·12) across the entire follow-up, 1·09 (95% CI 0·86-1·38) within 0-30 days, 1·18 (95% CI 1·04-1·35) within 0-90 days, 1·14 (95% CI 1·06-1·22) within 0-365 days and 1·07 (95% CI 1·02-1·12) within 0-1095 days. CONCLUSIONS: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long-term risk of psoriasis and atopic eczema following bereavement.