Association between acetaminophen use and vitiligo in US women and men.

BACKGROUND/OBJECTIVES: Exposure to chemical phenols, which can act as tyrosine analogues and result in anti-melanocyte autoimmunity, has been associated with vitiligo. Acetaminophen (N-acetyl-p-aminophenol) is an over-the-counter analgesic of phenolic origin. The risk of vitiligo with systemic exposure to acetaminophen has not yet been evaluated. METHODS: We examined the risk of vitiligo with regular use acetaminophen in women, the Nurses' Health Study (NHS) and in men, the Health Professionals Follow-up Study (HPFS). Regular acetaminophen use was asked biennially from 1990 in NHS and from 1986 in HPFS, and the year of clinician-diagnosed vitiligo was asked retrospectively in 2012 in the cohorts. RESULTS: In NHS, a total of 161 vitiligo cases were identified during a follow-up of 571,724 person-years; in HPFS, a total of 183 vitiligo cases were identified during a follow-up of 680,313 person-years. Regular use of acetaminophen was associated with an increased vitiligo risk in NHS but not HPFS. The multivariable relative risk (RR) was 1.52 (95% confidence interval [CI] 1.03-2.25) in NHS and 1.09 (95% CI 0.76-1.55) in HPFS. The higher risk of vitiligo was similar by duration of acetaminophen use in women; the multivariable RRs were 1.47 (95% CI 0.98-2.21) for acetaminophen use under 5 years, and 1.78 (95% CI 1.11-2.84) for acetaminophen use over 5 years. CONCLUSIONS: Acetaminophen may be associated with a higher risk of vitiligo in women.

Association of blood mercury levels with nonmelanoma skin cancer in the U.S.A. using National Health and Nutrition Examination Survey data (2003-2016).

BACKGROUND: Some studies have reported increased incidence or mortality of lung and brain cancers associated with occupations involving potential mercury exposure. Epidemiological evidence related to skin cancer is also limited. OBJECTIVES: To investigate the association between blood mercury (Hg) levels and nonmelanoma skin cancer (NMSC). METHODS: We used National Health and Nutrition Examination Survey data from 2003 to 2016. The exposures were blood total (tHg), inorganic (iHg) and methylmercury (MeHg). The outcome was a self-reported diagnosis of NMSC. We included participants aged ≥ 20 years who had information on blood mercury and sociodemographic factors. We conducted a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of NMSC associated with quartiles of blood Hg, after adjusting for the sociodemographic factors and survey year. RESULTS: The number of participants was 29 413; mean age was 49 years and 52% were female. Compared with those with a tHg ≤ 0·47 µg L-1 (Q1), those with a tHg > 1·74 µg L-1 (Q4) had nearly double the odds of NMSC (OR 1·79, 95% CI 1·19-2·71; Ptrend = 0·004). Similarly, those in the highest quartile of MeHg (> 1·44 µg L-1 ) had 1·7 times greater odds of NMSC (OR 1·74, 95% CI 1·13-2·70; Ptrend = 0·01) than those in the lowest quartile (≤ 0·21 µg L-1 ). iHg levels were nonsignificantly positively associated with NMSC (Ptrend = 0·08). CONCLUSIONS: We found that higher blood tHg and MeHg levels were associated with a higher prevalence of NMSC. Linked Comment: Taylor. Br J Dermatol 2020; 183:413-414.

Diagnosis validation and clinical characterization of atopic dermatitis in Nurses' Health Study 2.

BACKGROUND: Epidemiologic studies of atopic dermatitis (AD) are often limited by case definitions that have not been validated. OBJECTIVE: In this study, we assessed the accuracy of self-report of AD in a large cohort of US female nurses, the Nurses' Health Study 2 (NHS2). We also provide clinical characteristics of AD in the cohort. METHODS: We sent an electronic questionnaire to NHS2 participants who previously reported ever having a diagnosis of AD. This questionnaire was designed to confirm cases of AD using previously validated algorithms with >85% specificity. We assessed the association of AD with asthma, comparing the results when different definitions of AD were applied. We also inquired about various aspects of participants' AD. RESULTS: Responses were received from 2509 of 5126 (49%) nurses who were sent the questionnaire, with an average age of 62. Most participants (1996/2509, 80%) reiterated their previously reported clinician diagnosis of AD. Application of the two diagnostic algorithms yielded confirmation of 1538 and 1293 prevalent cases, respectively. The association of AD with asthma was stronger when more stringent AD case definitions were applied. Participants generally reported mild disease (92% with ≤10% maximal body surface area involved) and a high proportion (57%) reported adult-onset disease. CONCLUSIONS: Self-report of AD diagnosis has good reliability, and future analyses will be strengthened by our ability to conduct sensitivity analyses with refined confirmed AD subgroups.

Incident alopecia areata and vitiligo in adult women with atopic dermatitis: Nurses' Health Study 2.

We aimed to determine the risk of alopecia areata (AA) and vitiligo associated with atopic dermatitis (AD) in a large cohort of US women, the Nurses' Health Study 2. We used logistic regression to calculate age- and multivariate-adjusted odds ratios to determine the risk of incident AA and vitiligo associated with AD diagnosed in or before 2009. A total of 87 406 and 87 447 participants were included in the AA and vitiligo analyses, respectively. A history of AD in 2009 was reported in 11% of participants. There were 147 incident cases of AA and 98 incident cases of vitiligo over 2 years of follow-up. AD was associated with increased risk of developing AA (OR 1.80, 95% CI 1.18-2.76) and vitiligo (OR 2.14, 95% CI 1.29-3.54) in multivariate models. In this study of US women, AD was associated with increased risk of incident vitiligo and AA in adulthood.

Atopic dermatitis and risk of hypertension, type 2 diabetes, myocardial infarction and stroke in a cross-sectional analysis from the Canadian Partnership for Tomorrow Project.

BACKGROUND: Atopic dermatitis (AD) has been associated with cardiovascular risk factors and diseases, but epidemiological studies to date have found conflicting results. OBJECTIVES: To determine the associations of AD with hypertension, type 2 diabetes (T2D), myocardial infarction (MI) and stroke. METHODS: We conducted a cross-sectional analysis of baseline data from the Canadian Partnership for Tomorrow Project, which includes Canadian residents aged 30-74 years living in British Columbia, Alberta, Ontario, Quebec and the Atlantic Provinces. We excluded participants with incomplete data on AD, hypertension, T2D, MI or stroke, who had type 1 or gestational diabetes or who developed any of the outcomes at an age prior to a diagnosis of AD. This left 259 119 participants in our analysis. We used logistic regression to calculate age- and sex-, and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between AD and subsequent hypertension, T2D, MI and stroke. RESULTS: AD was reported by 21 379 (8·4%) participants. In total, 52 787 cases of hypertension, 12 739 cases of T2D, 4390 cases of MI and 2235 cases of stroke were reported by participants at enrolment. In the multivariable-adjusted model, AD was associated with decreased odds of hypertension (OR 0·87, 95% CI 0·83-0·90), T2D (OR 0·78, 95% CI 0·71-0·84), MI (OR 0·87, 95% CI 0·75-1·00) and stroke (OR 0·79, 95% CI 0·66-0·95). CONCLUSIONS: We did not find evidence of a positive association between AD and subsequent hypertension, T2D, MI or stroke; AD was inversely associated with these outcomes in our study. Given our findings and the conflicting literature, AD is likely not a major risk factor for cardiovascular disease.

Atopic dermatitis is not independently associated with nonfatal myocardial infarction or stroke among US women.

We aimed to determine the association between atopic dermatitis (AD) and cardiovascular events in the Nurses' Health Study 2, a cohort of US women. We used logistic regression models to calculate age- and multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between history of AD and nonfatal MI and nonfatal stroke. Of the 78 702 participants in our analysis, 7916 (10%) had a history of AD. There were 392 and 391 cases of nonfatal MI and stroke, respectively. AD was not associated with MI in age- or multivariate-adjusted analyses. AD was significantly associated with stroke in the age-adjusted analysis (OR 1.38, 95% CI 1.03-1.85). This was no longer significant in multivariate models that adjusted for hypertension, hypercholesterolemia and diabetes (OR 1.31, 95% CI 0.98-1.76) and atopic comorbidities (OR 1.17, 95% CI 0.86-1.58). AD was not independently associated with nonfatal MI or stroke in this study.

Prevalence of psoriasis phenotypes among men and women in the USA.

BACKGROUND: We present the largest set of US prevalence data for psoriasis to date, obtained from three prospective cohort studies describing validated clinical phenotypes of psoriasis, including novel data about the prevalence of inverse (intertriginous) psoriasis in these groups. Nonplaque psoriasis phenotypes have been largely unmeasured in observational and interventional studies, and this has led to an under-recognition of this aspect of psoriatic disease. AIM: To describe the prevalence of nonplaque psoriasis phenotypes in a large prospective cohort. METHODS: We included 3179 women and 646 men in the analysis. Participants in the Nurses Health Study (NHS) and Health Professionals Follow-up Study (HPFS) with physician-diagnosed psoriasis completed a validated, self-administered questionnaire to assess plaque and nonplaque subsets of psoriasis. RESULTS: Psoriasis phenotypes were as follows: plaque 55%, scalp 52%, palmar-plantar 14%, nail 23% and inverse 21% in the NHS (n = 1604); plaque 60%, scalp 56%, palmar-plantar 16%, nail 27% and inverse 24% in the second NHS study (NHS II) (n = 1575); and plaque 55%, scalp 45%, palmar-plantar 12%, nail 27% and inverse 30% in the HPFS (n = 646). Scalp, nail, palmar-plantar and inverse disease represent highly prevalent phenotypes of psoriasis in the USA. CONCLUSION: Scalp, nail, palmar-plantar and inverse disease represent highly prevalent phenotypes of psoriasis.

Personal history of rosacea and risk of incident cancer among women in the US.

BACKGROUND: Rosacea is an inflammatory skin disease. We examined the association between personal history of rosacea and risk of incident cancers. METHODS: A total of 75 088 whites were included from the Nurses' Health Study II (1991-2011). Information on clinician-diagnosed rosacea and diagnosis year was collected in 2005. All cancers other than basal cell carcinoma (BCC) were confirmed. RESULTS: During 1 447 205 person-years, we identified 5194 cases with internal malignancies and 5788 with skin cancers. We did not observe significant associations between personal history of rosacea and internal malignancies, except for thyroid cancer (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.07-2.36). Among skin cancers, personal history of rosacea was associated with an elevated risk of BCC (HR=1.50, 95% CI=1.35-1.67). CONCLUSIONS: We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and BCC. Further studies are warranted to replicate our findings and to explore the underlying mechanisms.

Personal history of gallstones and risk of incident psoriasis and psoriatic arthritis in U.S. women.

BACKGROUND: Metabolic syndrome has been associated with both gallstones and psoriasis, suggesting a potential biological linkage between gallstones and psoriasis. However, the association between gallstones and psoriasis has not yet been studied. OBJECTIVES: To investigate the association between gallstones and psoriasis. METHODS: This was a prospective cohort study [Nurses' Health Study II (1991-2005)]. Women aged 25-42 years who were free from psoriasis at baseline and who responded to a 2005 follow-up questionnaire regarding their diagnosis of psoriasis were included (n = 89,230). The relative risk (RR) of developing psoriasis or psoriatic arthritis (PsA), which were self-reported and validated by supplemental questionnaires, was measured. RESULTS: In this population, 2206 participants had gallstones confirmed by a history of cholecystectomy at baseline. A total of 642 individuals had a diagnosis of incident psoriasis, of whom 157 had concomitant PsA. After adjusting for known risk factors of psoriasis besides body mass index (BMI), a baseline history of cholecystectomy-confirmed gallstones was associated with increased risk of psoriasis [multivariate-adjusted RR 2·20, 95% confidence interval (CI) 1·56-3·10] and concomitant PsA (multivariate-adjusted RR 4·41, 95% CI 2·70-7·18). After additionally adjusting for BMI, the fully adjusted RRs associated with a history of cholecystectomy-confirmed gallstones were 1·70 (95% CI 1·20-2·41) for psoriasis and 2·96 (95% CI 1·80-4·89) for PsA. CONCLUSIONS: Personal history of gallstones was associated with an increased risk of psoriasis and PsA, independent of obesity, in a cohort of U.S. women.

Risk of depression in women with psoriasis: a cohort study.

BACKGROUND: Psoriasis is a common, chronic and inflammatory disease of the skin, which has been associated with depression in cross-sectional studies with limited adjustment for confounders. OBJECTIVES: In this prospective cohort study, we investigated the risk of incident depression among individuals with psoriasis and psoriatic arthritis (PsA). METHODS: We included 50 750 US female nurses from the Nurses' Health Study who were free of depression at baseline in 2000. Those participants who had ever self-reported clinician-diagnosed depression or regular use of antidepressants, or had a Mental Health Inventory score of ≤ 52 were excluded. In 2008, we retrospectively asked participants if they had ever received a physician's diagnosis of psoriasis or PsA. We defined depression as self-report of clinician-diagnosed depression or regular use of antidepressant medication. Time-dependent Cox proportional hazard models were used to estimate age and multivariate-adjusted relative risks (RRs) of clinical depression. RESULTS: After adjusting for covariates including body mass index, physical activity, smoking and the presence of major chronic conditions, the multivariate-adjusted RRs of clinical depression were 1·29 [95% confidence interval (CI) 1·10-1·52] for women with psoriasis and 1·52 (95% CI 1·06-2·19) for women with psoriasis and concomitant PsA, compared with women without psoriasis. CONCLUSIONS: We found an increased risk of depression in US women with psoriasis compared with those without psoriasis. This risk was higher in those who reported concomitant PsA. Future studies are needed to confirm these findings in other populations and to identify pathophysiological mechanisms linking psoriasis to depression.

Cumulative ultraviolet radiation flux in adulthood and risk of incident skin cancers in women.

BACKGROUND: Solar ultraviolet (UV) exposure estimated based on residential history has been used as a sun exposure indicator in previous case-control and descriptive studies. However, the associations of cumulative UV exposure based on residential history with different skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), have not been evaluated simultaneously in prospective studies. METHODS: We conducted a cohort study among 108,578 women in the Nurses' Health Study (1976-2006) to evaluate the relative risks of skin cancers with cumulative UV flux based on residential history in adulthood. RESULTS: Risk of SCC and BCC was significantly lower for women in lower quintiles vs the highest quintile of cumulative UV flux (both P for trend <0.0001). The association between cumulative UV flux and risk of melanoma did not reach statistical significance. However, risk of melanoma appeared to be lower among women in lower quintiles vs the highest quintile of cumulative UV flux in lag analyses with 2-10 years between exposure and outcome. The multivariable-adjusted hazard ratios per 200 × 10(-4) Robertson-Berger units increase in cumulative UV flux were 0.979 (95% confidence interval (CI): 0.933, 1.028) for melanoma, 1.072 (95% CI: 1.041, 1.103) for SCC, and 1.043 (95% CI: 1.034, 1.052) for BCC. CONCLUSIONS: Associations with cumulative UV exposure in adulthood among women differed for melanoma, SCC, and BCC, suggesting a potential variable role of UV radiation in adulthood in the carcinogenesis of the three major skin cancers.

Interactions between adiposity and genetic polymorphisms on the risk of psoriasis.

BACKGROUND: Adiposity is a known risk factor for psoriasis. Genome-wide association studies (GWAS) have identified a number of genes associated with risk of psoriasis while the evidence on gene-environment interactions in psoriasis is very sparse. OBJECTIVES: To investigate the effect modification by adiposity measures on the association between single-nucleotide polymorphisms (SNPs) from published GWAS and risk of psoriasis. METHODS: Our psoriasis GWAS dataset comprised 9194 participants, including 337 individuals with psoriasis and 8857 controls from six GWAS, nested within the Nurses' Health Study (NHS), NHS II, and Health Professionals' Follow-up Study. Clinician-diagnosed psoriasis was ascertained with high validity. For stratified analyses, body mass index (BMI) was dichotomized at 25, and waist circumference was dichotomized at 30 (women) and 36 inches (men), while waist-hip ratio (WHR) was dichotomized at 0·8 (women) and 1·0 (men). RESULTS: Forty-one out of 44 previously reported psoriasis-related SNPs were included in our GWAS datasets. After excluding those with high linkage disequilibrium, 33 remained in the analysis. There were significant interactions between BMI and two SNPs in the IL12B (rs3212227) and IL23R (rs7530511) genes. Further analysis of these two SNPs indicated interactions between rs3212227 and waist circumference or WHR [P for interaction (P ) < 0·05], but not for rs7530511. These observations were confirmed among participants without type 2 diabetes or coronary heart disease. The interactions remained after simultaneously adjusting for BMI as a continuous variable. In addition, we did not observe a significant main effect for rs7530511. CONCLUSION: The association between a polymorphism in IL12B and psoriasis risk may be modified by measures of overall and central adiposity.

Obesity, waist circumference, weight change and the risk of psoriasis in US women.

OBJECTIVE: To evaluate the associations between body mass index (BMI), weight change, waist circumference, hip circumference and risk of incident psoriasis. METHODS: A prospective study of female nurses who were followed up over a 12-year period (1996-2008) in Nurses' Health Study, a cohort of 121,700 US women at the inception in 1976. The study included 67,300 women who responded to a question about a history of physician-diagnosed psoriasis in last 12 years in 2008 (mean age at 1996, 62 years). The primary outcome was self-reported, physician-diagnosed psoriasis. RESULTS: During the 12 years of follow-up, there were a total of 809 incident psoriasis cases. There was a graded positive association between BMI (both baseline and updated) and the risk of psoriasis (both P values for trend <0.0001). Compared to women with updated BMI of <25, the multivariate relative risks (RRs) of incident psoriasis were 1.21 (95% CI, 1.03-1.43) for a BMI of 25.0-29.9, 1.63 (95% CI, 1.33-2.00) for a BMI of 30.0-34.9 and 2.03 (95% CI, 1.58-2.61) for a BMI of 35.0 or greater. Higher waist circumference, hip circumference and waist-hip ratio were associated with a higher risk of incident psoriasis, but became non-significant after additionally adjusting for BMI. The BMI at age of 18 years was not associated with the risk of psoriasis. Weight gain since the age of 18 years was associated with an increased risk of psoriasis, and RR of 10 lb gain was 1.08 (95% CI, 1.06-1.11; P < 0.0001). CONCLUSION: This large prospective study indicates that higher BMI and weight gain are risk factors for incident psoriasis in older US women.

Host risk factors for the development of multiple non-melanoma skin cancers.

Non-melanoma skin cancer (NMSC) is the most common cancer in the US, and having multiple lesions conveys substantial cost and morbidity for the individual involved. Although there are data available on risk factors for NMSC, there are currently few studies that identify specific risk factors for development of multiple NMSCs. We evaluated host risk factors for multiple NMSCs among men (Health Professionals Follow-up Study) and women (Nurses' Health Study). Compared with individuals with a single NMSC, having greater number of sunburns was a risk factor for developing ≥ 2 NMSCs [≥ 10 sunburns, cumulative relative risk (RR) = 1.21, 95% confidence interval (CI): 1.07-1.36] and a higher risk of developing ≥ 11 NMSCs (≥10 sunburns, RR = 2.33, 95% CI: 1.57-3.46). Inability-to-tan was associated with risk of developing ≥ 2 NMSCs (cumulative RR = 1.29, 95% CI: 1.18-1.40) and a higher risk of developing ≥ 11 NMSCs (RR = 1.91, 95% CI: 1.50-2.43). Men had an increased risk of developing ≥ 2 NMSCs (cumulative RR = 1.53, 95% CI: 1.40-1.66). Risk of developing 2-4, 5-10 and ≥11 NMSCs increased with age. Other risk factors for developing ≥ 2 NMSCs included red natural hair colour (cumulative RR = 1.23, 95% CI: 1.07-1.42), family history of melanoma (cumulative RR = 1.15, 95% CI: 1.03-1.28), and having ≥ 6 nevi on the left arm (cumulative RR = 1.22, 95% CI: 1.07-1.40). In conclusion, physicians caring for individuals with incident NMSCs may consider paying special attention to those at highest risk for developing additional tumours, especially males and those with a history of ≥ 10 lifetime sunburns, by performing routine full skin examinations and counselling for aggressive photoprotection.

Depression and the risk of psoriasis in US women.

BACKGROUND: Depression is a common mental health condition that has been associated with psoriasis. In the absence of prospective data, it remains unclear whether depression precedes psoriasis as a risk factor. OBJECTIVES: To examine the association between depression and the risk of new-onset psoriasis. METHODS: A prospective cohort of 86 880 US female nurses, The Nurses' Health Study II, was followed up from 1993 to 2005. Participants reported anti-depressant use and completed the Mental Health Index (MHI), a subscale of the Short-Form 36 in 1993. The MHI assessed for depression and scores was categorized into four strata: 0-52, 53-75, 76-85 and 86-100, with lower scores associated with increasing depressive symptoms. We excluded participants with a history of psoriasis prior to 1993. A self-report of incident physician-diagnosed psoriasis constituted the main outcome measure. For a sensitivity analysis, we had a subset of confirmed psoriasis cases. RESULTS: Depression was associated with an increased risk of incident psoriasis. Compared to women in the non-depressed group (MHI 86-100), women who reported either having high depressive symptomatology (MHI scores < 52) or who were on anti-depressants had a multivariate relative risk (RR) of 1.59 for developing subsequent psoriasis (95% confidence interval [CI], 1.21-2.08). These associations became stronger among confirmed psoriasis cases. CONCLUSIONS: We found that depression was independently associated with an increased risk of psoriasis in this population of US women.

Non-steroidal anti-inflammatory drugs, acetaminophen, and risk of skin cancer in the Nurses' Health Study.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with lower risk of certain cancers, but data on the effect on skin cancer risk have been limited and contradictory. We prospectively examined whether use of NSAIDS or acetaminophen was associated with a lower risk of skin cancer in women. METHODS: The 92,125 Caucasian women in the Nurses' Health Study provided information on aspirin use in 1980. Other NSAIDs and acetaminophen were added in 1990. Medication use, frequency, and quantity were reassessed on biennial questionnaires. Through 2008, we confirmed 658 melanoma cases, 1,337 squamous cell carcinoma (SCC) cases, and had 15,079 self-reports of basal cell carcinoma (BCC). We used COX proportional hazards models to compute relative risks (RR) adjusted for known skin cancer risk factors. RESULTS: Neither aspirin nor non-aspirin NSAID use was associated with a lower risk of melanoma, SCC, or BCC, even for women with high quantity, frequency, or duration of use. Instead, we observed an increased risk of melanoma among current aspirin users (RR = 1.32, 95 % CI 1.03-1.70), though an increase of similar magnitude among past users and lack of a dose-response effect did not support a pharmacologic mechanism. We observed a mild reduction in SCC risk in current acetaminophen users (RR = 0.88, 95 % CI 0.75-1.02), with a linear decrease in risk with greater frequency of use (p = 0.04). CONCLUSIONS: Aspirin and other NSAIDs were not associated with a lower risk of melanoma, SCC, or BCC in women. Our large, prospective study does not support a chemoprotective effect of NSAIDs against skin cancers.