Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the UK and Denmark
Authors: A.Y.S. Wong, A. Kjærsgaard, T. Frøslev, H.J. Forbes, K.E. Mansfield, R.J. Silverwood, H.T. Sørensen, L. Smeeth, S.A.J. Schmidt, S.M. Langan
Journal: British Journal of Dermatology (2020)

Partner bereavement and risk of chronic urticaria, alopecia areata and vitiligo: cohort studies in the United Kingdom and DenmarkDear Editor, The pathogeneses of skin diseases are not fully understood.Psychological stress has been proposed to be associated with skin diseases, but the epidemiological evidence is limited [1,2].We have recently reported the associations between partner bereavement (an extreme life stressor) and psoriasis, atopic eczema and melanoma [3,4].In this study, we further investigated whether partner bereavement was associated with urticaria, alopecia areata, or vitiligo.We conducted two cohort studies using data from the UK and Denmark (1997Denmark ( -2016)).In the UK, we used the Clinical Practice Research Datalink Gold to identify partners using a previously developed algorithm [3,4].In Denmark, we used the data from the Civil Registration System to identify partners with an algorithm developed by Statistics Denmark [3,4].Among eligible couples, we defined bereaved people (exposed) if their partner died and matched each with up to 10 non-bereaved partners on age, sex, and, county of residence within Denmark, or general practice in the UK on the bereavement date.We followed participants from bereavement until the first of: diagnosis of specific outcomes (urticaria, alopecia areata, or vitiligo), last data collection from primary care practice (UK), transfer out of the practice by either member of the couple (UK), emigration of either member of the couple (Denmark), death, or the study end.We used stratified Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome, adjusting for participants' Charlson Comorbidity Index (CCI) [5].In the fully-adjusted model, we additionally adjusted for education duration (Denmark), Index of Multiple Deprivation quintile (UK), body mass index (UK) and lifestyle variables (UK).As we hypothesized that the effect of bereavement would be most pronounced in the short-term, we further examined the associations by time since bereavement (0-30 days, 0-90 days, 0-365 days, and 0-1095 days for alopecia areata and vitiligo; 0-182 days, 0-365 days, and 0-1095 days for chronic urticaria, as its definition required two codes recorded six weeks apart).We stratified the main analysis by age, sex, and risk of partner death (deceased partner's age-adjusted CCI score and presence of terminal disease).We conducted analyses separately for the UK and Denmark, and combined the main results (from the adjusted models) in Stata using DerSimonian and Lairds' random-effects model.The overall median follow-up was 4 years in the UK and 6 years in Denmark.The overall pooled HRs (adjusted for participants' CCI scores) for associations between partner bereavement and chronic urticaria, alopecia areata, and vitiligo were 0.95 (95% CI, 0.85-1.07),0.90 (95% CI, 0.73-1.12)and 0.90 (95% CI, 0.74-1.10),respectively (Supporting information).We found similar results for chronic urticaria in analyses by time since bereavement (Table 1).Event rates for alopecia areata and vitiligo were low, specifically in early time periods.Similar results were seen in fully adjusted models (Table 1).For subgroup analyses, some evidence suggested that the HR for vitiligo differed by sex (lower HR among men) in the UK.No substantial differences were observed across other subgroups for other outcomes.This study investigated associations between partner bereavement and chronic urticaria, alopecia areata, and vitiligo in population-based cohorts in settings with universal healthcare (UK and Denmark), using harmonised methodology.Previous studies have been limited by small sample size, difficulty in measuring stress, and potential misclassification of adverse life events due to recall bias [6][7][8].We undertook our study in two similar cohorts enabling replication, and used partner bereavement as a proxy for acute severe stress with specific onset date.Limitations include a lack of information on the level and duration of stress arising from bereavement, individual responses to bereavement, social support, potential misclassification of partnership status, possible delay between disease onset and diagnosis, overrepresentation of severe cases in the Danish hospital setting, and absence (Denmark) and missingness (UK) of body mass index and lifestyle covariates.People with mild skin conditions may be less likely to seek medical advice immediately after bereavement, which may have led to underestimation during short-term follow-up and an overrepresentation of the most severe skin diseases.In conclusion, this large study showed no evidence of associations between partner bereavement and chronic urticaria, alopecia areata, or vitiligo.Despite a large study population, precision was limited by low event rates for alopecia areata and vitiligo, especially in early time periods.