Incidence of cancer in the general population and in patients with or without atopic dermatitis in the U.K.

Background Atopic dermatitis (AD) affects approximately 20% of children and 1–3% of adults in developed countries. Objective To study the incidence of cancer in patients with AD in the U.K. general population. Methods We conducted a follow‐up study in the U.K. using The Health Improvement Network (THIN) database. We calculated the incidence rate (IR) of the first occurrence of overall cancer, lymphoma, melanoma and nonmelanoma skin cancer (NMSC) in the general population, in patients with AD and in individuals without AD. In addition we calculated the IR ratio (IRR) of overall cancer and subtypes of cancer in patients with AD vs. those without. Results The study population included 4 518 131 patients [2 336 230 (51·7%) female]. There were 129 972 subjects [68 688 (52·8%) female] with a diagnosis of cancer (excluding NMSC). The IR (per 10 000 person‐years) of cancer (excluding NMSC) was 42·41 [95% confidence interval (CI) 42·18–42·64]; of lymphoma 1·70 (95% CI 1·65–1·74); of skin melanoma 1·71 (95% CI 1·67–1·76) and of NMSC 11·76 (95% CI 11·64–11·88). The age‐ and sex‐adjusted IRR for cancer (excluding NMSC) was 1·49 (95% CI 1·39–1·61); for lymphoma 2·21 (95% CI 1·65–2·98); for melanoma 1·74 (95% CI 1·25–2·41); and for NMSC 1·46 (95% CI 1·27–1·69). Conclusions Our results indicate an increased incidence of cancer overall as well as of specific cancer subtypes, including lymphoma, in patients with AD. Further studies are needed to disentangle the effects of treatment for AD from AD itself.     

Histological regression in primary melanoma: not a predictor of sentinel lymph node metastasis in a cohort of 397 patients

Background Regression has been proposed as a potential marker of dissemination in thin melanomas. Previous studies have shown conflicting results. Objective To determine if regression in melanoma is associated with an increased risk of sentinel lymph node (SLN) metastasis. Methods A cohort analysis was conducted. Data on all patients were collected on a standardized case report form during 10 years. A total of 397 consecutive patients with melanoma who underwent a SLN biopsy were analysed. All cases of melanoma and SLN biopsies were examined by the same two pathologists. Differences between melanomas with and without SLN metastasis were compared using Fisher’s exact test or the two‐sample t‐test and the χ² test. Multivariable logistic regression was used to adjust for possible confounding factors. Results We analysed 397 patients (411 melanomas) who underwent a SLN biopsy. The median Breslow index was 1·8 mm (interquartile range 1·1–3). Regression was observed in 23% (n = 94). SLN metastases were observed in 26% (n = 106). The frequency of SLN metastasis was 16% in melanomas with regression and 29% without regression (P = 0·012). The adjusted odds ratio (OR) for regressive melanoma was 0·9 [95% confidence interval (CI) 0·4–1·9; P = 0·777]. The risk of SLN metastasis was increased in melanoma cases with a Breslow index from 1·5 to < 2·0 mm (adjusted OR 3·1; 95% CI 1·4–7·1; P = 0·006) and ≥ 2·0 mm (adjusted OR 3·5; 95% CI 1·7–7·4; P = 0·001) and ulceration of the melanoma (adjusted OR 1·8; 95% CI 1·1–3·2; P = 0·03). Conclusion Regression is not an independent predictor of the risk of SLN metastasis in melanoma.     

Recent skin self‐examination and doctor visits in relation to melanoma risk and tumour depth

Background Little is known about the potential benefit of skin self‐examination for melanoma prevention and early detection. Objectives To determine whether skin self‐examination is associated with reduced melanoma risk, self‐detection of tumours, and reduced risk of deeper melanomas. Methods We used data from a population‐based case–control study (423 cases, 678 controls) to assess recent skin self‐examination in relation to self‐detection, melanoma risk and tumour depth ( ≤1 mm; > 1 mm). Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for associations of interest. Results Skin self‐examination conducted 1–11 times during a recent year was associated with a possible decrease in melanoma risk (OR 0·74; 95% CI 0·54–1·02). Melanoma risk was decreased for those who conducted skin self‐examination and saw a doctor (OR 0·52; 95% CI 0·30–0·90). Among cases, those who examined their skin were twice as likely to self‐detect the melanoma (OR 2·23; 95% CI 1·47–3·38), but self‐detection was not associated with shallower tumours. Tumour depth was reduced for those who conducted skin self‐examination 1–11 times during a recent year (OR 0·39; 95% CI 0·18–0·81), but was not influenced by seeing a doctor, or by conducting skin self‐examination and seeing a doctor. Conclusions Risk of a deeper tumour and possibly risk of melanoma were reduced by skin self‐examination 1–11 times annually. Melanoma risk was markedly reduced by skin self‐examination coupled with a doctor visit. We cannot, however, exclude the possibility that our findings reflect bias or confounding. Additional studies are needed to elucidate the potential benefits of skin self‐examination for melanoma prevention and early detection.     

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.     

The angiotensin‐converting enzyme gene insertion/deletion polymorphism in Indian patients with vitiligo: a case–control study and meta‐analysis

Background  Vitiligo is a common, acquired, idiopathic depigmenting skin disorder. Although the exact pathogenesis remains unknown, genetic susceptibility and autoimmune responses play a role in vitiligo development. Previous studies have suggested that the D allele of the insertion/deletion (I/D) polymorphism of the angiotensin‐converting enzyme (ACE) gene is associated with vitiligo in Indians and Koreans. Furthermore, significantly higher serum ACE levels have been demonstrated in patients with some autoimmune and autoinflammatory disorders. Objectives  The objectives were to investigate any association between the ACE I/D polymorphism and vitiligo susceptibility in an Indian population, and to compare serum ACE levels in patients with vitiligo and healthy subjects. Methods  The ACE I/D genotypes of 79 patients with vitiligo and 100 normal individuals were determined by polymerase chain reaction amplification. A meta‐analysis was done to compare the distribution of the ACE I/D alleles and genotypes in the current and three previous studies. Serum ACE levels were evaluated by enzyme‐linked immunosorbent assay. Results  A significant increase in the frequency of the ACE I/D D allele was evident in patients with vitiligo in both the case–control study [P = 0·005; odds ratio (OR) 1·87; 95% confidence intervals (CI) 1·22–2·85] and the meta‐analysis (P = 0·044; OR 1·44; 95% CI 1·01–2·06). Serum ACE levels were significantly increased in patients with vitiligo compared with healthy subjects (P < 0·0001). Conclusions  In agreement with earlier reports, the ACE I/D D allele is associated with vitiligo susceptibility in the Indian population. The significantly elevated serum ACE levels in our cohort of patients with vitiligo concur with those previously found in patients with some other autoimmune diseases.     

Metabolic risk factors and skin cancer in the Metabolic Syndrome and Cancer Project (Me-Can)

Background Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). Objectives To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me‐Can). Methods During a mean follow‐up of 12 years of the Me‐Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z‐scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. Results Blood pressure per unit increase of z‐score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04–1·31 and HR 1·18, 95% CI 1·03–1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58–3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P‐trend 0·02) and there was a trend with triglyceride concentration (P‐trend 0·09). Conclusion These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.     

Quality of life issues in nonmetastatic skin cancer

Background Current knowledge of quality of life (QOL) issues affecting patients with nonmetastatic skin cancer is unsatisfactory, being based either on the use of QOL questionnaires derived from dermatology patients with predominantly benign lesions or inflammatory skin rashes, or on the use of general health QOL questionnaires. Objectives We sought to determine the impact of nonmetastatic skin cancer on patients’ lives by asking such patients for their written opinions. Methods An open‐ended ‘Skin Cancer Quality of Life Question Sheet’ was given to 100 consenting patients with nonmetastatic skin cancer [50 with malignant melanoma (MM) and 50 with nonmelanoma skin cancer (NMSC)]. Results In total, 82 ‘Skin Cancer Quality of Life Question Sheets’ were returned complete (40 MM and 42 NMSC). There were 44 different patient concerns voiced overall in the responses. The concerns were grouped into 10 main themes. Patients with MM were significantly more likely than those with NMSC to mention ‘a sense of relief/gratitude following treatment and/or a commitment to enjoy life here on’ (P = 0·001), ‘feelings of anxiety/depression/guilt/stress towards oneself or family/friends’ (P < 0·001) and ‘strengthening of emotional relationships with family and/or friends’ (P = 0·02). Patients with NMSC were significantly more likely than those with MM to mention ‘concern about the public’s lack of understanding and recognition of skin cancer’ (P = 0·02). The theme ‘realization of one’s mortality’ was commoner among patients with MM than with NMSC, while the theme ‘concern regarding possible scarring/disfigurement or the reaction of others’ was commoner among patients with NMSC than with MM, although neither of these two differences was statistically significant (P = 0·07 and P = 0·11, respectively). Conclusions QOL issues expressed by patients with nonmetastatic skin cancer highlight concerns we must address during their care. A disease‐specific QOL measure suitable for both nonmetastatic MM and nonmetastatic NMSC is needed. The psychosocial impact on patients with nonmetastatic MM must not be underestimated.     

A functional single-nucleotide polymorphism in the catechol-<Emphasis Type="Italic">O</Emphasis>-methyltransferase gene alter vitiligo risk in a Chinese population

Vitiligo is an acquired hypomelanotic skin disorder resulting from the loss of functional melanocytes. The COMT-158 polymorphism can reduce COMT enzyme activity and may thus lead to the overproduction of toxic radicals in the melanocyte microenvironment. To determine whether this polymorphism in the COMT gene is associated with an increased risk of vitiligo in Chinese populations, we used a polymerase chain reaction sequence-specific primer (PCR-SSP) technique to determine the frequency of the polymorphism COMT-158 G > A in 749 vitiligo patients and 763 healthy controls. We found that compared to the COMT-158 GG genotype, the COMT-158 GA genotype (adjusted odds ratio [OR], 1.39; 95% confidence interval [CI], 1.13–1.72) and the combined GA + AA genotype (adjusted OR, 1.41; 95% CI, 1.15–1.74) were associated with an increased risk of generalized vitiligo. The association was more pronounced in patients with early-onset vitiligo (adjusted OR, 1.95; 95% CI, 1.45–2.60), those with a family history of vitiligo (adjusted OR, 3.84; 95% CI, 2.47–5.96), and female patients (adjusted OR, 1.74; 95% CI, 1.29–2.36). When we further clinically stratified the vitiligo patients according to their disease types, we found that the combined GA + AA genotype was associated with vitiligo vulgaris (adjusted OR, 1.31; 95% CI, 1.02–1.68), focal vitiligo (adjusted OR, 1.62; 95% CI, 1.17–2.25), and universal vitiligo (adjusted OR, 1.50; 95% CI, 0.98–2.30), but not with acrofacial vitiligo (adjusted OR, 1.53; 95% CI, 0.86–2.73) or segmental vitiligo (adjusted OR, 1.35; 95% CI, 0.72–2.51). In conclusion, this COMT gene polymorphism may have contributed to the etiology of vitiligo in our Chinese population. Larger population-based studies are required to verify our findings.     

Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study

Background Bullous pemphigoid (BP) has been associated with neurological and psychiatric diseases; however, large‐scale population‐based study of different comorbid diseases in patients with BP is quite limited. Objectives We sought to analyse the prevalence of neurological, psychiatric, autoimmune and inflammatory skin diseases prior to the diagnosis of BP and their associations with BP among patients with BP from a nationwide database in Taiwan. Methods A total of 3485 patients with BP and 17 425 matching controls were identified from the National Health Insurance Database in Taiwan from 1997 to 2008. Conditional logistic regression analyses for a nested case–control study were performed to examine the prevalence of comorbidities prior to the diagnosis of BP between these two groups. Results Overall, our results showed that stroke [odds ratio (OR) 3·30; 95% confidence interval (95% CI) 3·03–3·60], dementia (OR 4·81; 95% CI 4·26–5·42), Parkinson disease (OR 3·49; 95% CI 3·05–3·98), epilepsy (OR 3·97; 95% CI 3·28–4·81), schizophrenia (OR 2·56; 95% CI 1·52–4·30) and psoriasis (OR 2·02; 95% CI 1·54–2·66) were significantly associated with BP. Among them, the association with schizophrenia and psoriasis was predominant in female and male patients, respectively, with BP. It remains for all these comorbid diseases to be independently associated with BP by multivariate analysis. Conclusions Patients with BP are more likely to have various neurological diseases, schizophrenia and psoriasis prior to the diagnosis of BP, supporting associations found in other studies. Further research is required to elucidate the tentative causal association with BP.     

The prevalence of thyroid disease in patients with vitiligo: a systematic review

Background Thyroid disease has been suggested to be associated with vitiligo. However, the outcomes of prevalence studies on thyroid disease in vitiligo vary widely. Objectives To summarize and critically appraise current evidence of the prevalence of thyroid diseases in vitiligo. Methods A systematic review was performed searching the electronic databases OVID MEDLINE, OVID EMBASE and PubMed. Guidelines for the critical appraisal of studies on prevalence of a health problem were adapted to evaluate the methodological quality of the included studies. Results were analysed in a meta‐analysis with a risk ratio (RR). Results Forty‐eight studies published between 1968 and 2012 met the inclusion criteria. Most of the studies (50%) were of fair methodological quality, whereas 18 studies (38%) were of poor quality and six studies (12%) were of good quality. Thyroid disease, autoimmune thyroid disease and presence of thyroid‐specific autoantibodies showed a mean prevalence of, respectively, 15·1%, 14·3% and 20·8% in patients with vitiligo and an RR of, respectively, 1·9, 2·5 and 5·2 (all statistically significant). This review shows an increased prevalence and an increased risk of (autoimmune) thyroid disease in patients with vitiligo compared with nonvitiligo. This risk seems to increase with age. Conclusions Clinicians should be aware of this increased risk in patients with vitiligo and should be attentive for symptoms of thyroid disease. To make recommendations on screening for thyroid disease in patients with vitiligo future research of good methodological quality, including differentiation of vitiligo types and the use of standardized outcome measures, is needed.     

Trends in incidence of nonmelanoma skin cancers in Alberta,Canada, 1988–2007

Background Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting caucasian populations and has been seeing global increases in incidence for decades. Objectives The objective of this study was to determine trends in incidence of NMSC in Alberta, Canada from 1988 to 2007. Methods A retrospective analysis of patients from Alberta diagnosed with NMSC from 1988 to 2007 inclusive was conducted with data retrieved from the Alberta Cancer Registry (ACR). Sex‐, age‐ and anatomical location‐specific incidence rates and trends were examined. Results From 1988 to 2007, there were 66 192 basal cell carcinomas, 19 959 invasive squamous cell carcinomas (SCC) and 12 494 in situ SCC. ACR coding for the 2007 data was not completed at the time of this study; hence, data from this year were not included in the trend analyses. Incidence of NMSC in women has been stable since 2000 [annual percentage change (APC) 0·08, P = 0·88] and has declined in men since 2001 (APC −1·28, P = 0·026). BCC incidence has been stable since 2000 (APC −0·80, P = 0·09). In situ and invasive SCC also showed a trend towards stabilization in 2000 (APC 0·36, P = 0·77) and 1995 (APC 0·01, P = 0·98), respectively. NMSC primarily affects the elderly and is rarely seen in individuals before the age of 40 years. Although the head and neck region was the location most often involved with NMSC (71·1%), it revealed a stabilizing trend, whereas most other anatomical regions demonstrated an increasing NMSC incidence rate. Conclusions NMSC incidence in Alberta has stabilized in women and declined in men. As 95–99% of NMSC occurs in patients aged 40 years or older, and with its increased frequency in traditionally clothed areas, the authors recommend regular complete skin examinations starting at 40 years of age.     

Frequencies of BRAF and NRAS mutations are different in histological types and sites of origin of cutaneous melanoma: a meta-analysis

Background There have been conflicting data regarding the prevalence and clinicopathological characteristics of BRAF and NRAS mutations in primary cutaneous melanoma. Objectives To solve this controversy, this study used a meta‐analysis to evaluate the frequencies of BRAF and NRAS mutations, and the relationship between these mutations and clinicopathological parameters of cutaneous melanoma. Methods Data from studies published between 1989 and 2010 were combined. The BRAF and NRAS mutations were reported in 36 and 31 studies involving 2521 and 1972 patients, respectively. The effect sizes of outcome parameters were calculated by odds ratios (OR). Results BRAF and NRAS mutations were reported in 41% and 18% of cutaneous melanomas, respectively. The mutations were associated with histological subtype and tumour site, but not with age and sex. The BRAF mutation was frequently detected in patients with superficial spreading melanoma (OR = 2·021; P < 0·001) and in melanomas arising in nonchronic sun‐damaged skin (OR = 2·043; P = 0·001). In contrast, the NRAS mutation was frequently evident in patients with nodular melanoma (OR = 1·894; P < 0·001) and in melanomas arising in chronic sun‐damaged skin (OR = 1·887; P = 0·018). Conclusions This pooled analysis shows that the incidences of BRAF and NRAS mutations in cutaneous melanomas differ according to histological type and tumour location based on the degree of sun exposure.     

Risks for Staphylococcus aureus colonization in patients with psoriasis: a systematic review and meta‐analysis

Evidence on whether patients with psoriasis have a higher risk for staphylococcal colonization than healthy controls remains controversial. To synthesize the current literature, we performed a systematic review on the prevalence and relative risk (RR) of Staphylococcus aureus colonization in patients with psoriasis. We modified the QUADAS‐2 instrument to assess the reporting quality of individual studies and applied random‐effects models in meta‐analysis. Overall we identified 21 eligible studies, of which 15 enrolled one or more comparison groups. The pooled prevalence of staphylococcal colonization in patients with psoriasis was 35·3% [95% confidence interval (CI) 25·0–45·6] on lesional skin and 39·2% (95% CI 33·7–44·8) in the nares. Patients with psoriasis were 4·5 times more likely to be colonized by S. aureus than healthy controls were on the skin (RR 5·54, 95% CI 3·21–9·57) and 60% more in the nares (RR 1·60, 95% CI 1·11–2·32). Cutaneous and nasal colonization by meticillin‐resistant S. aureus also appeared higher in patients with psoriasis (pooled prevalence 8·6%) than in healthy controls (2·6%), yet the difference was not statistically significant (P = 0·74). In contrast, despite of a similar risk for nasal staphylococcal colonization (RR 0·67, 95% CI 0·38–1·18), patients with psoriasis were less likely to carry S. aureus on lesional skin than atopic patients (RR 0·64, 95% CI 0·40–1·02). In summarizing the current literature, we found that patients with psoriasis were at an increased risk for staphylococcal colonization compared with healthy individuals. Prospective studies on how bacterial loads correlate with disease activity can guide the clinical management of bacterial colonization while preventing the emergence of drug‐resistant strains.     

Lack of evidence for a protective effect of prolonged breastfeeding on childhood eczema: lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

Summary Background Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease. Objectives To investigate whether exclusive breastfeeding protects against childhood eczema. Methods Study subjects comprised 51 119 randomly selected 8‐ to 12‐year‐old schoolchildren in 21 countries. Information on eczema and breastfeeding was gathered by parental questionnaire. Children were also examined for flexural eczema and underwent skin prick testing. Odds ratios (ORs) were calculated for each study centre and then pooled across populations. Results There was a small increase in the risk of reported ‘eczema ever’ in association with ‘breastfeeding ever’ and breastfeeding < 6 months [pooled adjusted OR 1·11, 95% confidence interval (CI) 1·00–1·22 and OR 1·10, 95% CI 1·02–1·20, respectively]. There was no significant association between reported ‘eczema ever’ and breastfeeding > 6 months (pooled adjusted OR 1·09, 95% CI 0·94–1·26). Risk estimates were very similar for exclusive breastfeeding < 2 months, 2–4 months and > 4 months and for eczema symptoms in the past 12 months and eczema on skin examination. As for more severe eczema, breastfeeding per se conveyed a risk reduction on sleep disturbed eczema (pooled adjusted OR 0·71, 95% CI 0·53–0·96), but this effect was lost where children had been exclusively breastfed for > 4 months (pooled adjusted OR 1·02, 95% CI 0·67–1·54). Allergic sensitization and a history of maternal allergic disease did not modify any of these findings. Conclusions Although there was a protective effect of ever having been breastfed on more severe disease, we found no evidence that exclusive breastfeeding for 4 months or longer protects against eczema. Our results are consistent with findings from a recent systematic review of prospective studies. The U.K. breastfeeding guidelines with regard to eczema should be reviewed. Intervention studies are now required to explore how and when solids should be introduced alongside breastfeeding to aid protection against eczema and other allergic diseases.     

Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta‐analysis of observational studies

Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of the study was to systematically review the literature and critically answer the question: In patients with HS, do cardiovascular risk factors appear at a significantly higher rate compared with controls? The main search was conducted in Medline, Embase and the Cochrane Central Register. Studies eligible for inclusion were of case–control, cross‐sectional and cohort design, and included comparison of any cardiovascular risk factor(s) in patients with HS with those of control groups. An I² value > 50% was considered to show substantial heterogeneity. In this case, DerSimonian and Laird random‐effect models were considered to compute pooled odds ratios (OR). Otherwise, a fixed‐effects model was suitable. Nine studies, with 6174 patients with HS and 24 993 controls, were included. Significant association of HS with obesity [OR 3·45, 95% confidence interval (CI) 2·20–5·38, P < 0·001], central obesity (OR 2·97, 95% CI 1·41–6·25, P = 0·004), active smoking (OR 4·34, 95% CI 2·48–7·60, P < 0·001), history of smoking (OR 6·34, 95% CI 2·41–16·68, P < 0·001), hypertriglyceridemia (OR 1·67, 95% CI 1·14–2·47, P = 0·009), low high‐density lipoprotein (HDL) (OR 2·48, 95% CI 1·49–4·16, P < 0·001), diabetes (OR 2·85, 95% CI 1·34–6·08, P = 0·007) and metabolic syndrome (OR 2·22, 95% CI 1·62–3·06, P < 0·001) was detected. Associations were significant both in population and hospital patients with HS, with hospital HS groups having uniformly higher ORs than the population HS groups. Causality could not be assessed. Heterogeneity was substantial in all analyses. This systematic review indicated that cardiovascular risk factors appear at a significantly higher rate in patients with HS compared with controls. The need for screening of patients with HS for modifiable cardiovascular risks is emphasized.     

Multivariate analysis of factors associated with early-onset segmental and nonsegmental vitiligo: a prospective observational study of 213 patients

Background Although mixed forms have been described recently, segmental (SV) and nonsegmental vitiligo (NSV) are considered as clinically distinct. However, limited epidemiological data are available to help distinguish associated factors, and recent genome‐wide association studies have been restricted to NSV. The higher prevalence of SV in children is helpful when comparing the two major presentations of the disease. Objective To compare factors associated with SV and NSV, especially for markers of autoimmunity or autoinflammation. Methods We conducted a single‐centre prospective observational study in patients aged 17 years or under with a confirmed diagnosis of SV or NSV at the vitiligo clinic between 1 January 2006 and 1 July 2010. The Vitiligo European Task Force questionnaire was completed for each patient, and thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Other forms of vitiligo (focal, mucosal, not classifiable) were excluded. Results A total of 213 children were included, 142 with NSV, 59 with SV and 12 with mixed vitiligo. There was no significant statistical difference for sex or age at onset between patients with SV and NSV. Halo naevi were significantly more frequent in NSV than in SV [odds ratio (OR) 7·58, P < 0·01). Patients with NSV more frequently had a positive family history of vitiligo (OR 2·25, P = 0·02) and a marked familial autoimmunity background (OR 2·22, P = 0·01). Conclusions Our study clearly shows that features of inflammation (pruritus)/autoimmunity (halo naevi, thyroid antibodies) are strongly linked to NSV, together with a familial background of vitiligo and autoimmunity.     

Risk factors for genital lichen sclerosus in men

Background Lichen sclerosus (LS) is an inflammatory disease of the skin and mucous membranes. Its aetiology is still unknown. Objectives To determine risk factors for genital LS in men. Methods In a case–control study, 73 patients with LS, consecutively diagnosed at the City Dispensary for Skin and Venereal Diseases in Belgrade, were compared with 219 male patients visiting the same institution because of tinea cruris. Univariate and multivariate logistic regression analyses were used for analysis of data collected. Results According to multivariate logistic regression analysis, risk factors for male LS were as follows: a personal history of genital injury [odds ratio (OR) 28·1, 95% confidence interval (CI) 5·2–150·8], vitiligo (OR 23·1, 95% CI 2·2–240·2), alopecia areata (OR 8·8, 95% CI 1·1–68·5) and hypercholesterolaemia (OR 3·1, 95% CI 1·1–8·2), and a family history of alopecia areata (OR 24·3, 95% CI 2·1–280·7), diseases of the thyroid gland (OR 9·1, 95% CI 2·3–36·2) and other autoimmune diseases (OR 8·6, 95% CI 1·3–58·6). Conclusions The results of the present study are in line with the hypothesis that trauma of the penis is a possible trigger of symptoms in genetically predisposed individuals and that personal and family histories of autoimmune disorders are risk factors for male LS.     

Seropositivity for human papillomavirus and incidence of subsequent squamous cell and basal cell carcinomas of the skin in patients with a previous nonmelanoma skin cancer

Background Infection with human papillomaviruses (HPVs) is a risk factor for several epithelial cancers, but its relationship with keratinocyte tumours has not yet been established. Objective In this prospective study we investigated the possible role of different HPVs in the incidence of a subsequent nonmelanoma skin cancer (NMSC). Methods One hundred and fifty‐three patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) enrolled in a previous case–control study were re‐contacted, and a follow‐up visit was offered. Demographic and clinical data, date of first NMSC presentation, Fitzpatrick skin type and history of NMSC during the follow‐up period were ascertained. Recurrences and new second cancers were considered together as ‘outcomes’ in time‐to‐event analyses and in Cox proportional hazard models. Results Clinical data were obtained in 107 patients. HPV seropositivity at baseline was strongly associated with the risk of developing a second SCC after 5 years for a number of beta and gamma HPV types. For example, HPV‐24‐seropositive patients with an SCC at baseline had a 4‐fold increased risk of developing a subsequent SCC (hazard ratio 4·35, 95% confidence interval 1·2–15·6, P = 0·024). No association between serological status for any HPV type tested and an increased risk of BCC was found. Conclusions We observed a consistent pattern of a positive association between seropositivity for beta and gamma HPV types and the risk of a subsequent SCC in patients with a previous SCC. Our data corroborate the results of previous case–control studies and may spur further prospective studies on the causal role of HPVs in NMSC.     

Willingness-to-pay and quality of life in patients with vitiligo

Background Vitiligo is a chronic pigmentary disorder of the skin, affecting 1–2% of the general population. Although not life threatening, vitiligo may considerably influence patients’ health‐related quality of life (QoL) and psychological well‐being. Willingness‐to‐pay (WTP) is a construct reflecting disease burden and QoL reduction which has not yet been used in vitiligo. Objectives To assess the WTP and the QoL of patients with vitiligo. Methods Patients with vitiligo were included in a nationwide German postal survey. WTP was assessed by two standardized items, and QoL was evaluated using the Dermatology Life Quality Index (DLQI) and the EuroQol (EQ‐5D) questionnaire. QoL data were compared with n = 1511 patients from a national survey on psoriasis. Results The questionnaire was completed by 1023 patients (71·5% women, mean age 44·4 years, mean disease duration 20·3 years) with vitiligo. The mean DLQI was 7·0 (7·5 in women, 5·5 in men) compared with 8·6 in psoriasis. Of the patients with vitiligo, 24·6% had a DLQI > 10 which indicates severe QoL reductions, compared with 34·1% in patients with psoriasis. The highest mean DLQI value was observed in the patient group aged 20–29 years. EQ‐5D mean score was 83·6 compared with 75·3 in psoriasis. Of the patients with vitiligo, 32·9% would pay more than 5000 Euro in order to achieve complete disease remission. WTP was highest among middle‐aged patients (30–60 years). There was a significant correlation between DLQI scores and WTP (χ² = 65·43, P < 0·001). Moreover, WTP significantly correlated with duration of disease, and with body surface area affected (P < 0·001). Conclusions Vitiligo causes substantial disease burden as reflected by QoL impairment and high WTP, especially in women. These results should draw the attention of physicians to this disease, as appropriate education and treatment are likely to improve the QoL of patients with vitiligo and may support patients’ compliance and empowerment.