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.     

Contralateral distribution of nonmelanoma skin cancer between older Hispanic/Latino and non‐Hispanic/non‐Latino individuals

Background A recent review of the SEER database revealed that melanoma and Merkel cell carcinoma occur more commonly on the left side of the body. Similarly, a trend was reported in which nonmelanoma skin cancers (NMSCs) were found to be distributed more frequently on the left side of the body. Objectives To compare the sidedness of NMSC in a large patient population. There were five primary objectives of the present study: (i) to confirm or refute the left‐sided trend of NMSC in the largest patient population studied for asymmetry to date; (ii) to determine whether the left‐sided trend existed in Hispanic/Latino individuals; (iii) to examine skin cancer in older individuals across ethnicities; (iv) to compare distribution across anatomical location and ethnicity; and (v) to measure gender differences in the distribution of NMSC. Methods The last 3026 cases referred to the Mohs surgical unit at the University of Miami Miller School of Medicine during 2008–2011 were reviewed. The patient’s age, gender, tumour side, tumour type, anatomical location and ethnicity were recorded. Results There were 1505 (50·2%) right‐sided tumours and 1495 (49·8%) left‐sided tumours (P = 0·52). The Hispanic/Latino group had a nonsignificant right‐sided trend with 607 (52·7%) right‐sided cases and 545 (47·3%) left‐sided cases (P = 0·06). The non‐Hispanic/non‐Latino group between the ages of 60 and 85 years had 605 (46·9%) right‐sided tumours and 686 (53·1%) left‐sided tumours (P = 0·024). The Hispanic/Latino group between the ages of 60 and 85 years demonstrated 404 (54·0%) right‐sided tumours and 344 (46·0%) left‐sided tumours (P = 0·028). One hundred and fifty‐four skin cancers were located on the upper extremities of non‐Hispanic/non‐Latino individuals with 64 (41·6%) being right sided and 90 (58·4%) left sided (P = 0·036). Seventy‐eight skin cancers were located on the upper extremities of Hispanic/Latino individuals with 49 (62·8%) being right sided and 29 (37·2%) left sided (P = 0·024). Males had most of the skin cancers at 2125 (70·8%) cases and females had 875 (29·2%) cases (P < 0·001). Conclusions NMSC appears to be more common on the left side of older non‐Hispanic/non‐Latino individuals, while it is more common on the right side of older Hispanic/Latino individuals. This is likely to be secondary to an environmental factor, such as ultraviolet radiation. NMSC is significantly more common in males relative to females, which may be attributed to differences in gender roles or referral practices.     

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.     

The Skin Cancer Quality of Life Impact Tool (SCQOLIT): a validated health‐related quality of life questionnaire for non‐metastatic skin cancers

Background Quality of life (QOL) issues in patients with non‐metastatic skin cancer are not satisfactorily demonstrated when using existing QOL questionnaires. Objective To construct and validate a 10 item disease‐specific QOL questionnaire, the Skin Cancer Quality of Life Impact Tool (SCQOLIT), for use in patients following treatment of non‐metastatic skin cancer. Methods The SCQOLIT was constructed and administered initially to 120 patients with non‐metastatic skin cancer, 60 with malignant melanoma (MM) and 60 with non‐melanoma skin cancer (NMSC) following treatment, then repeated in half this cohort at seven days, and the other half at three months. Data was collected on age, gender, skin cancer type and Breslow thickness. Statistical validation was undertaken. Results There were 113 valid SCQOLIT responses at initial completion (54 in the MM group, and 59 in the NMSC group). Initial SCQOLIT median scores (interquartile range [IQR], range) for the two groups were 10 (12, 0–28) MM, and 4 (5, 0–19) NMSC. Amongst the cohort readministered the SCQOLIT at three months (23 in the MM group, 25 in the NMSC group) median scores (IQR, range) were 6 (6, 0–26) MM and 3 (4, 0–20) NMSC. Conclusions The SCQOLIT is a validated disease‐specific QOL questionnaire for use in patients following treatment of non‐metastatic skin cancer. Higher SCQOLIT scores are observed in MM patients than NMSC patients, but diminish with time in the MM group. Patients with persistently elevated SCQOLIT scores merit additional attention.     

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.     

Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3 months of age

Background Filaggrin loss‐of‐function (FLG) mutations are associated with eczema and skin barrier impairment, but it is unclear whether skin barrier impairment precedes phenotypic eczema in FLG mutation carriers. Objectives To study the association between FLG mutations, skin barrier impairment and clinical eczema at 3 months of age. Methods A total of 88 infants were examined for eczema. Disease severity was determined by the SCORAD eczema severity score. Transepidermal water loss (TEWL) was measured on unaffected forearm skin. Venous blood samples were screened for the four most common FLG mutations found in the U.K. white population (R501X, 2282del4, R2447X and S3247X). Median SCORAD and TEWL measurements in children with and without eczema and FLG mutations were compared. Results Thirty‐three per cent (29/88) of children had clinical eczema. Median SCORAD was 10·6 (range 3·5–31·0). TEWL (g m^?2 h^?1) was higher in children with eczema compared with unaffected infants (median TEWL 14·24 vs. 11·24, P < 0·001). Higher TEWL was associated with more severe disease (r = 0·59, P < 0·001, median TEWL, SCORAD < 15, 13·1 vs. 29·6, SCORAD ≥ 15, P = 0·029). Clinically dry skin was associated with higher TEWL, even in the absence of eczema (median TEWL 17·55 vs. 11·08, P = 0·008). Seventeen per cent (15/88) of children carried at least one FLG mutation. FLG mutation carriers were significantly more likely to have clinically dry skin, even in the absence of eczema [odds ratio (OR) 8·50, 95% confidence interval (CI) 1·09–66·58, P = 0·042]. FLG mutation carriers were also more likely to have eczema by 3 months of age (OR 4·26, 95% CI 1·34–13·57, P = 0·014). FLG mutations were significantly associated with higher median TEWL (all children, FLG‘yes’ 21·59 vs. FLG‘no’ 11·24, P < 0·001), even without clinical eczema (FLG‘yes’ 15·99 vs. FLG‘no’ 10·82, P = 0·01). Conclusions By the age of 3 months, FLG mutations are associated with an eczema phenotype, dry skin and TEWL. The observation that TEWL is elevated in unaffected FLG mutation carriers suggests that skin barrier impairment precedes clinical eczema.     

The determinants of periorbital skin ageing in participants of a melanoma case-control study in the U.K

Background Skin ageing is said to be caused by multiple factors. The relationship with sun exposure is of particular interest because the detrimental cutaneous effects of the sun may be a strong motivator to sun protection. We report a study of skin ageing in participants of an epidemiological study of melanoma. Objectives To determine the predictors of periorbital cutaneous ageing and whether it could be used as an objective marker of sun exposure. Methods Photographs of the periorbital skin in 1341 participants were graded for wrinkles, degree of vascularity and blotchy pigmentation and the resultant data assessed in relation to reported sun exposure, sunscreen use, body mass index (BMI), smoking and the melanocortin 1 receptor (MC1R) gene status. Data were analysed using proportional odds regression. Results Wrinkling was associated with age and heavy smoking. Use of higher sun‐protection factor sunscreen was protective (P = 0·01). Age, male sex, MC1R variants (‘r’, P = 0·01; ‘R’, P = 0·02), higher reported daily sun exposure (P = 0·02), increased BMI (P = 0·01) and smoking (P = 0·02) were risk factors for hypervascularity. Blotchy pigmentation was associated with age, male sex, higher education and higher weekday sun exposure (P = 0·03). More frequent sunscreen use (P = 0·02) and MC1R variants (‘r’, P = 0·03; ‘R’, P = 0·001) were protective. Conclusions Periorbital wrinkling is a poor biomarker of reported sun exposure. Vascularity is a better biomarker as is blotchy pigmentation, the latter in darker‐skinned individuals. In summary, male sex, sun exposure, smoking, obesity and MC1R variants were associated with measures of cutaneous ageing. Sunscreen use showed some evidence of being protective.     

Stratum corneum integrity as a predictor for peristomal skin problems in ostomates

Background Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Methods Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0·25%]. Results Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0·0001 for both groups). The skin barrier of normal‐looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0·002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0·02). Conclusion Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.     

Shrinkage of skin excision specimens: formalin fixation is not the culprit

Background Discrepancies between cutaneous specimen sizes reported by the dermatosurgeon and the pathologist are important to evaluate because of their legal implications for malignant tumours and the downcoding of surgical acts. Objectives The objective of this study was to determine the magnitude of changes in size and the factors influencing the retraction of routine skin excision specimens. Methods Three measurements of 82 skin excision specimens—consisting of length and width of the planned surgical excision (in vivo), length, width and depth of the specimens following excision (ex vivo) and of the specimens after formalin fixation (in vitro)—were performed and compared using a nonparametric paired test. Factors (age, sex, type and location of the lesions and initial measures) that could influence the amount of shrinkage were analysed using multiple linear regression models. Results The mean in vivo to in vitro shrinkage was 16% for length and 18% for width (P < 0·001). The shrinkage was significant between in vivo and ex vivo measures (P < 0·001), while no difference was observed between ex vivo to in vitro measures. In multivariate analysis, length shrinkage increased significantly with initial length (regression coefficient of 0·24, P = 0·001) and limb location (1·25, P = 0·048), and decreased significantly with initial width (?0·19, P = 0·016). After adjusting for initial width, width shrinkage was neither significantly associated with type of lesion (malignant or not, P = 0·20), nor with location (P = 0·35). Conclusions Shrinkage of skin excision specimens occurred immediately after surgical excision and prior to formalin fixation. Patients’ age, sex and type of skin lesion did not influence the amount of shrinkage. Length shrinkage was more important for specimens excised from the extremities and increased with initial length and smaller width.     

A new scalp formulation of calcipotriol plus betamethasone dipropionate compared with each of its active ingredients in the same vehicle for the treatment of scalp psoriasis: a randomized, double-blind, controlled trial

Background There is a need for new treatments for scalp psoriasis, as many topical treatments are cosmetically unacceptable and difficult to apply, resulting in poor compliance. Objectives To compare the efficacy and safety of a new, once‐daily, two‐compound scalp formulation (Xamiol^®; LEO Pharma A/S, Ballerup, Denmark) containing calcipotriol 50 μg g^?1 plus betamethasone 0·5 mg g^?1 (as dipropionate), with the active ingredients as single compounds in the same vehicle. Methods This 8‐week, multicentre, double‐blind, parallel‐group study, randomized adult patients with scalp psoriasis involving > 10% of the scalp to the two‐compound scalp formulation (n = 568), betamethasone dipropionate 0·5 mg g^?1 (n = 563), or calcipotriol 50 μg g^?1 (n = 286). The primary efficacy measure was the proportion of patients with ‘absence of disease’ or ‘very mild disease’ according to investigators’ assessments at week 8. Results The proportion of patients with ‘absence of disease’ or ‘very mild disease’ at week 8 was significantly higher in the two‐compound group (68·4%) than the betamethasone dipropionate (61·0%, P = 0·0079) or calcipotriol (43·4%, P < 0·0001) groups. The proportion of patients rating their scalp psoriasis as ‘clear’ or ‘almost clear’ was significantly higher for the two‐compound scalp formulation (69·6%) than for betamethasone dipropionate (59·9%, P = 0·0006) or calcipotriol (44·7%, P < 0·0001). The incidence of lesional/perilesional adverse events was lower in the two‐compound and betamethasone dipropionate groups than the calcipotriol group. Conclusions The two‐compound scalp formulation was well tolerated and more effective in the treatment of scalp psoriasis than either of its individual components in the same vehicle.     

A cosmetic 'anti-ageing' product improves photoaged skin: a double-blind, randomized controlled trial

Summary Background  Very few over‐the‐counter cosmetic ‘anti‐ageing’ products have been subjected to a rigorous double‐blind, vehicle‐controlled trial of efficacy. Previously we have shown that application of a cosmetic ‘anti‐ageing’ product to photoaged skin under occlusion for 12 days can stimulate the deposition of fibrillin‐1. This observation infers potential to repair and perhaps clinically improve photoaged skin. Objective  We examined another similar over‐the‐counter cosmetic ‘anti‐ageing’ product using both the patch test assay and a 6‐month double‐blind, randomized controlled trial (RCT), with a further 6‐month open phase to assess clinical efficacy in photoaged skin. Methods  For the patch test, a commercially available test product and its vehicle were applied occluded for 12 days to photoaged forearm skin (n = 10) prior to biopsy and immunohistochemical assessment of fibrillin‐1; all‐trans retinoic acid (RA) was used as a positive control. Sixty photoaged subjects were recruited to the RCT (test product, n = 30 vs. vehicle, n = 30; once daily for 6 months, face and hands) with clinical assessments performed at recruitment and following 1, 3 and 6 months of use. Twenty‐eight volunteers had skin biopsies (dorsal wrist) at baseline and at 6 months treatment for immunohistochemical assessment of fibrillin‐1 (test product, n = 15; vehicle, n = 13). All volunteers received the test product for a further 6 months. Final clinical assessments were performed at the end of this open period. Results  In the 12‐day patch test assay, we observed significant immunohistological deposition of fibrillin‐1 in skin treated with the test product and RA compared with the untreated baseline (P = 0·005 and 0·015, respectively). In the clinical RCT, at 6 months, the test product produced statistically significant improvement in facial wrinkles as compared to baseline assessment (P = 0·013), whereas vehicle‐treated skin was not significantly improved (P = 0·11). After 12 months, there was a significant benefit of the test product over that projected for the vehicle (70% vs. 33% of subjects improving; combined Wilcoxon rank tests, P = 0·026). There was significant deposition of fibrillin‐1 in skin treated for 6 months with the test product [(mean ± SE) vehicle 1·84 ± 0·23; test product 2·57 ± 0·19; ancova P = 0·019). Conclusions  In a double‐blind RCT, an over‐the‐counter cosmetic ‘anti‐ageing’ product resulted in significant clinical improvement in facial wrinkles, which was associated with fibrillin‐1 deposition in treated skin. This study demonstrates that a cosmetic product can produce significant improvement in the appearance of wrinkles and further supports the use of fibrillin‐1 as a robust biomarker for the repair of photoaged dermis.     

Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study

Background Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first‐line option in the treatment of moderate to severe acne vulgaris. Objectives To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%–BPO 2·5% (A/BPO) fixed‐dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. Methods A total of 378 subjects were randomized in a double‐blind, controlled trial to receive once‐daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects ‘clear’ or ‘almost clear’), skin tolerability, adverse events and patients’ satisfaction. Results The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (?74·1%) than in the lymecycline with vehicle group (?56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were ‘very satisfied’ was significantly greater (P = 0·031). Conclusion These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.     

Population‐based incidence of basal cell carcinoma in a Spanish Mediterranean area

Background Considering the latitude of Spain, the reported age‐adjusted incidence rates of basal cell carcinoma (BCC) in this country, similar to those of Northern Europe, are lower than expected. Objectives To estimate the actual incidence of BCC in a Mediterranean population from the eastern coast of Spain. Methods A registry of BCC cases newly diagnosed between 16 January 2006 and 16 January 2007 was established for the population of residents in the Barcelonès Nord county (369 622 inhabitants). All dermatologists of this area agreed to register their patients. All tumours were registered as ‘definite’ or ‘probable’ BCC cases according the existence or not of a proven microscopic diagnosis. If a patient had more than one tumour at different sites, each was counted and registered separately. Sex‐specific, age‐specific and age‐standardized incidence rates were calculated by direct standardization to the World and European Standard Population. Results Among the 936 cases registered, 81·2% were classified as ‘definite’ BCC and 18·8% as ‘probable’ BCC. The overall crude incidence rate was 253·2 per 100 000 person‐years, and was 128 per 100 000 person‐years and 195·5 per 100 000 person‐years after standardizing for the World and European population, respectively. After the age of 65 years, the BCC age‐adjusted incidence rates showed a significantly higher increase in men than in women (P = 0·01). Conclusions The incidence rates found in our study are higher than those previously reported in Spain. Age‐adjusted incidence rates revealed that BCC increases with age in both sexes, this increase being particularly evident in men older than 65 years.     

In vivo study for the discrimination of cancerous and normal skin using fibre probe‐based Raman spectroscopy

Raman spectroscopy has proved its capability as an objective, non‐invasive tool for the detection of various melanoma and non‐melanoma skin cancers (NMSC) in a number of studies. Most publications are based on a Raman microspectroscopic ex vivo approach. In this in vivo clinical evaluation, we apply Raman spectroscopy using a fibre‐coupled probe that allows access to a multitude of affected body sites. The probe design is optimized for epithelial sensitivity, whereby a large part of the detected signal originates from within the epidermal layer's depth down to the basal membrane where early stages of skin cancer develop. Data analysis was performed on measurements of 104 subjects scheduled for excision of lesions suspected of being malignant melanoma (MM) (n = 36), basal cell carcinoma (BCC) (n = 39) and squamous cell carcinoma (SCC) (n = 29). NMSC were discriminated from normal skin with a balanced accuracy of 73% (BCC) and 85% (SCC) using partial least squares discriminant analysis (PLS‐DA). Discriminating MM and pigmented nevi (PN) resulted in a balanced accuracy of 91%. These results lie within the range of comparable in vivo studies and the accuracies achieved by trained dermatologists using dermoscopy. Discrimination proved to be unsuccessful between cancerous lesions and suspicious lesions that had been histopathologically verified as benign by dermoscopy.     

A clinical trial and molecular study of photoadaptation in vitiligo

Background Photoadaptation to ultraviolet (UV) B phototherapy is due to both pigmentary and nonpigmentary influences. Objectives To measure photoadaptation in vitiliginous skin and to compare it with normal pigmented skin. Methods Seventeen patients with Fitzpatrick skin phototypes III–VI with vitiligo received six to nine UVB treatments, two to three times weekly. Minimal erythema dose (MED) testing was done at baseline and after all treatments; the percentage change in MED was analysed as a measure of photoadaptation. The percentage decrease in cyclobutane pyrimidine dimers (CPDs) over 24 h after a single exposure of 1 MED was analysed on vitiliginous and normal skin. Results The mean ± SD percentage change in MED from before to after treatments was: treated vitiliginous skin 28·5 ± 39·9% (P = 0·015), treated normal skin 35·9 ± 49·9% (P = 0·015), untreated vitiliginous skin 11·9 ± 22·6% (P =0·070), untreated normal skin 25·1 ± 41·3% (P = 0·041). Of these patients, two‐thirds had a positive percentage change in MED (photoadaptation). The mean amount of CPDs induced per megabase of DNA immediately after exposure was significantly higher in vitiliginous skin. The mean ± SD percentage decrease in CPDs (rate of repair) in 24 h was 35·7 ± 26·8% in vitiliginous skin (P = 0·027) and 46·2 ± 19·5% in normally pigmented skin (P = 0·001); no difference was noted in the repair in vitiliginous skin compared with normal skin (P = 0·4). Conclusions Photoadaptation in vitiliginous and normal skin was observed in two‐thirds of patients. Vitiliginous skin had significantly more CPDs following UVB exposure; the rate of repair of UVB‐induced DNA damage was equivalent to that in normal skin.     

Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: a survey among 1307 patients and their partners

Background Vitiligo is a common skin disease characterized by autoimmune melanocyte destruction. Recent genetic studies suggest a lower susceptibility to melanoma in patients with vitiligo; however, lifetime melanoma prevalence in patients with vitiligo has not previously been studied. Nonmelanoma skin cancer (NMSC) prevalence has been studied, but only in small studies and with contradictory results. Objectives This retrospective, comparative cohort survey was designed to assess lifetime prevalences of melanoma and NMSC in patients with vitiligo compared with nonvitiligo controls. Methods Patients with nonsegmental vitiligo, who visited our clinic between January 1995 and September 2010, and were aged 50 years or older at the time of the study, were invited to participate in a postal survey. The questions regarded demographics, vitiligo characteristics, phototherapy history, skin cancer risk factors and the number of skin cancers experienced during the patient’s lifetime. Patients were asked to have their partner fill in a control questionnaire. All skin cancers were validated by a pathology report. In total 2635 invitations were sent and 1307 eligible questionnaires were returned (50%). Multivariate logistic regression models were used to quantify adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between vitiligo and lifetime prevalences of melanoma and NMSC. Results Adjusted for confounders, patients with vitiligo had a threefold lower probability of developing melanoma (adjusted OR 0·32; 95% CI 0·12–0·88) and NMSC (adjusted OR 0·28; 95% CI 0·16–0·50). Subgroup analyses of patients treated with narrowband ultraviolet (UV) B, and psoralen and UVA did not show dose‐related trends of increased age‐adjusted lifetime prevalence of melanoma or NMSC. Conclusions Our findings suggest that patients with vitiligo have a decreased risk of both melanoma and NMSC.     

P-cadherin expression in Merkel cell carcinomas is associated with prolonged recurrence-free survival

Background Merkel cell carcinoma (MCC) is a highly aggressive skin cancer, associated with advanced age, immunosuppression and Merkel cell polyomavirus (MCV) infections. As development and progression of cancer can be promoted by changes in cell adhesion proteins, we have previously analysed homo‐ and heterotypic cell–cell contacts of normal Merkel cells and MCCs and obtained indications for cadherin switching. Objectives To examine the prevalence and prognostic relevance of E‐, N‐ and P‐cadherin in MCCs. Methods Paraffin‐embedded MCC samples (n = 148) from 106 different patients were analysed by double‐label immunostaining and immunofluorescence microscopy. MCV status was determined by real‐time polymerase chain reaction. The cadherin repertoire and MCV status were correlated to clinical data, including tumour stage and recurrence‐free survival. Results Ninety‐one per cent of all MCC were positive for N‐cadherin whereas only 61·6% and 70·3% expressed E‐ and P‐cadherin, respectively. P‐cadherin was significantly more frequent in primary tumours than in lymph node metastases (81·9% vs. 40·9%, P = 0·0002). Patients with P‐cadherin‐positive primary tumours were in earlier tumour stages at initial diagnosis (P = 0·0046). Both in log‐rank tests (P = 0·0474) and in multiple Cox regression analysis including age, sex, immunosuppression, stage at initial diagnosis and MCV status (hazard ratio 0·193, P = 0·0373), patients with P‐cadherin‐positive primary MCCs had significantly prolonged recurrence‐free survival (mean 25·2 vs. 10·6 months; median 9·0 vs. 4·0 months). MCV DNA was detected in 78·2% of all MCC, more frequently in P‐cadherin‐positive MCC (P = 0·0008). Conclusion P‐cadherin expression in MCCs predicts prolonged recurrence‐free survival and may therefore indicate favourable prognosis.     

Does it look like melanoma? A pilot study of the effect of sunless tanning on dermoscopy of pigmented skin lesions

Background Dermoscopy has led to an improvement in diagnosing malignant melanoma (MM). Sunless tanning agents containing dihydroxyacetone (DHA) could lead to a decrease in ultraviolet exposure, decreasing the risk of MM. Importantly, DHA has been reported to change dermoscopic features and could thus endanger diagnostic improvement in dermoscopy. Objectives To investigate whether the use of DHA can lead to changes that simulate a real, clinically relevant dermoscopic change, suggesting malignant transformation either in facial solar lentigo/initial seborrhoeic keratosis (SL/ISK) or in naevi on the body. Methods Seven patients with 25 pigmented skin lesions (PSLs) were photographed, resulting in 38 dermoscopic images. Photographs were taken before, 1 week after and 1–2 months after the use of DHA. Two dermatologists separately evaluated the PSLs and their dermoscopic features. For lesions on the body Menzies’ method was used, and for facial lesions the criteria defined by Stolz et al. were used. Results In facial PSLs equivocal lesions were registered by both evaluators significantly more often after DHA use than before (42% vs. 12%, P = 0·021 and 69% vs. 19%, P = 0·001). Furthermore, follicular pigmentation that partly mimics that of lentigo maligna was also seen significantly more often after DHA use than before (81% vs. 12%, P < 0·001 and 69% vs. 15%, P < 0·001) and in these instances the evaluators recommended a biopsy. Equivocal lesions in naevi on the body were not significantly increased after DHA use. Conclusions Dermoscopists that come across unclear dermoscopic findings, especially in facial PSL, should ask patients about the use of DHA.     

Prospective study of skin surgery in smokers vs. nonsmokers

Background Smoking may increase complications following minor surgery leading many clinicians to urge patients to refrain from smoking before and after surgery. Objective To study the association between smoking and complications following skin surgery. Methods In a 5‐year prospective observational study 7224 lesions were excised on 4197 patients. Patients were not instructed regarding smoking. All complications were recorded. Results A total of 439 smokers (10·5%) underwent 646 procedures (9%), 3758 nonsmokers (89·5%) underwent 6578 procedures (91%). Smokers were younger (55 ± 16 years) than nonsmokers (66 ± 17 years) (P < 0·001). Infection incidence was not significantly different, 1·9% (12/646) in smokers compared with 2·2% (146/6578) in nonsmokers (P = 0·55). There were two bleeds with smokers (0·3%) vs. 50 in nonsmokers (0·8%) (P = 0·2). The incidence of wound dehiscence in nonsmokers (three) was not different from nonsmokers (21) (P = 0·54). However, the incidence of scar contour distortion in smokers (three) was greater than in nonsmokers (two) (odds ratio 15·3; 95% confidence interval 2·5–92). Total complication incidence was similar, 3·6% in smokers vs. 4·0% in nonsmokers (P = 0·58). Out of 2371 flaps there were 14 (0·6%) cases of end‐flap necrosis but smokers were not at increased risk. The case–control analysis compared each smoker with two nonsmokers matched for age, sex, postal code and outdoor occupational exposure. This again demonstrated no difference in infection, scar complication, bleed, dehiscence, end‐flap necrosis or total complication incidence. Conclusions Smokers and nonsmokers suffer skin surgery complications similarly. The increased risk of contour distortion identified was difficult to interpret. Advice to cease smoking in the short term to improve outcomes with skin cancer surgery is not supported by these data.