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.

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.

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.

Report from the first European Dermato-Epidemiology Network forum.

The first European Dermato-Epidemiology Network (EDEN) forum was held on 30-31 March 2017 in Madrid, Spain. Dermatoepidemiology describes the study of causes, prevention, health services research and evaluation of interventions of skin diseases. EDEN aims to promote high-quality research, share expertise and facilitate collaboration. These aims were achieved during the EDEN forum by including a preconference course on skin cancer epidemiology; having excellent world-leading guest speakers on causality, quality of care, pharmacoepidemiology and missing data analysis; and including delegates who presented and discussed innovative research findings. The meeting brought together delegates from 11 different countries. We welcome everyone with an interest in clinical research and epidemiology related to skin disease to attend next year's meeting in March 2018 in Berlin.

Herpes zoster as a marker of occult cancer: A systematic review and meta-analysis.

OBJECTIVES: Researchers have advocated for an increased awareness of occult cancer among herpes zoster patients, but there are no systematic reviews to support these claims. We therefore conducted a systematic review and meta-analysis of evidence on zoster and risk of occult cancer. METHODS: Through February 18, 2016, we searched PubMed, EMBASE and references of relevant papers for studies on zoster and risk of any cancer. One author screened retrieved papers by title and abstract; included papers were reviewed by two authors for eligibility, data extraction, and potential biases. Despite statistical heterogeneity, associations were consistently in the same direction and we therefore computed pooled relative risks using random-effects models. RESULTS: We identified 46 eligible studies, 10 of which considered all cancer types combined. The pooled relative risk for any cancer was 1.42 (95% confidence interval: 1.18, 1.71) overall and 1.83 (95% confidence interval: 1.17, 2.87) at one year after zoster. Considering cancer subtypes, the highest estimates were generally reported for occult hematological cancer. The absolute risk of any cancer at one year after presentation with zoster was 0.7-1.8%. CONCLUSION: This study supports an association between zoster and occult cancer, but the low absolute risk of cancer limits the clinical implications.

Mortality in cancer patients previously diagnosed with herpes zoster in the hospital setting: a nationwide cohort study.

BACKGROUND: Herpes zoster (HZ) is associated with underlying immunodeficiency and may thereby predict mortality of subsequent cancer. METHODS: By using Danish nationwide medical databases, we identified all cancer patients with a prior hospital-based HZ diagnosis during 1982-2011 (n=2754) and a matched cancer cohort without prior HZ (n=26 243). We computed adjusted mortality rate ratios (aMRRs) associating prior HZ with mortality following cancer. RESULTS: Prior HZ was associated with decreased mortality within the year after cancer diagnosis (aMRR 0.87; 95% confidence interval (CI): 0.81-0.93), but not thereafter (aMRR 1.07; 95% CI: 0.99-1.15). However, prior HZ predicted increased mortality throughout the entire follow-up among patients aged <60 years (aMRR 1.39; 95% CI: 1.15-1.68) and those with disseminated HZ (aMRR 1.18; 95% CI: 1.01-1.37). The increased mortality rates were observed primarily for haematological and immune-related cancers. CONCLUSIONS: Overall, HZ was not a predictor of increased mortality following subsequent cancer.

Use of antihypertensive drugs and risk of skin cancer.

BACKGROUND: Several antihypertensive drugs are photosensitizing and may therefore act as cocarcinogens with ultraviolet radiation. OBJECTIVE: To examine whether antihypertensive drug use is associated with squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma (MM). METHODS: We used population-based databases to conduct a case-control study including all first-time cases of SCC (n = 2282), BCC (n = 17,242), and MM (n = 3660) in northern Denmark, 1991-2010. We matched approximately 10 controls (n = 231,743) to each case by age, sex and county using risk-set sampling. We used conditional logistic regression to compute odds ratios (ORs) for skin cancer with 95% confidence intervals comparing ever users of antihypertensives (>2 previous prescriptions) with non-users (≤2 previous prescriptions). We adjusted for comorbidity and comedications. We further analysed use by duration (short term: <5 years; long term: ≥5 years) and intensity (low intensity or high intensity: <50% or ≥50% prescription coverage during total duration of use, respectively). RESULTS: Ever users of diuretics were at increased risk of SCC (OR 1.19; 1.06-1.33), driven by potassium-sparing agents alone (OR 1.40; 1.09-1.80) or with low-ceiling diuretics (OR 2.68; 2.24-3.21) and by long-term use (OR 1.41; 1.16-1.72 at low intensity; OR 1.44; 0.98-2.14 at high intensity). Ever users of sulphonamides (OR 1.49; 1.04-2.12) and non-aldosterone antagonist potassium-sparing agents (OR 2.26; 0.85-6.01) were at increased MM risk. The latter was also associated with BCC (OR 1.47; 1.00-2.17), as was low-ceiling diuretics combined with potassium-sparing agents (OR 1.23; 1.12-1.35). Long-term, low-intensity (OR 1.53; 1.05-2.23) and high-intensity (OR 1.44; 0.56-3.69) angiotensin receptor blocker use was associated with MM. Estimates for angiotensin-converting enzyme inhibitors, ß-blockers, and calcium channel blockers were inconsistent or weak (<20% increased). CONCLUSION: Long-term angiotensin receptor blocker use was associated with risk of MM. Moreover, long-term diuretic use was associated with SCC risk, driven by potassium-sparing agents alone or in combination with low-ceiling diuretics.