Joris A.C. Verkouteren

Epidemiology of basal cell carcinoma: scholarly review

Basal cell carcinoma (BCC) is the most common cancer in white‐skinned individuals with increasing incidence rates worldwide. Patients with BCC place a large burden on healthcare systems, because of the high incidence and the increased risk of synchronous and metachronous BCCs and other ultraviolet radiation (UVR) related skin cancers (i.e. field cancerization). As a result, the disability‐adjusted life years and healthcare costs have risen significantly in recent decades. BCC is a complex disease, in which the interplay between UVR, phenotype (UVR‐sensitive) and genotype (somatic mutations and germline mutations/polymorphisms) fulfils a key role in the aetiopathogenesis. Prevention programmes with continual refinements and improvements could be of major importance in tackling the growing skin cancer problem. To provide the most appropriate BCC care, physicians should engage in shared decision‐making and choose their treatments wisely.

Predicting the Risk of a Second Basal Cell Carcinoma

A third of basal cell carcinoma (BCC) patients will develop subsequent BCCs. We aimed to develop a simple model to predict the absolute risk of a second BCC. We observed 14,628 participants of Northern European ancestry from a prospective population-based cohort study. BCCs were identified using a linkage with the Dutch Pathology Registry (Pathological Anatomy National Automated Archive). Predictors for a second BCC included 13 phenotypic, lifestyle, and tumor-specific characteristics. The prediction model was based on the Fine and Gray regression model to account for the competing risk of death from other causes. Among 1,077 participants with at least one BCC, 293 developed a second BCC at a median of 3 years. Several well-known risk factors for a first BCC were not prognostic for a second BCC, whereas having more than one initial BCC was the strongest predictor. Discriminative ability at 3 years was reasonable (bootstrap validated c-index=0.65). Three groups were created, with 7, 12, and 28% risk of a second BCC within 3 years. We conclude that a combination of readily available clinical characteristics can reasonably identify patients at high risk of a second BCC. External validation and extension with stronger predictors is desirable to further improve risk prediction.

Atopic dermatitis is not associated with actinic keratosis: cross-sectional results from the Rotterdam study

Epidermal barrier impairment and an altered immune system in atopic dermatitis (AD) may predispose to ultraviolet‐induced DNA damage.

Perceived skin colour seems a swift, valid and reliable measurement

DEAR EDITOR, Skin colour is an important trait in dermatological research because it modifies the risk of many skin diseases. In clinical practice dermatologists evaluate skin colour by a quick visual assessment of the sun-unexposed skin. Because visual assessment might be subjective, Fitzpatrick proposed a sun-sensitivity skin-type (Fitzpatrick skin type, FST) classification as a better alternative to quantify skin colour. However, this self-reported skin type might change in time and could be biased because light-skinned individuals tend to overestimate their skin colour. Alternatively, a spectrophotometer measures skin colour objectively, but might be influenced by the seasonal variations and colour inequalities. Visual assessment of perceived skin colour (PSC) allows physicians to combine different clues besides the colour (such as freckles), and to exclude tanning influences, into one skin-colour category. PSC has been used in several studies, but it has not yet been validated. We investigated the reliability of physicians’ perception of skin colour, and how PSC relates to the widely used FST and to unexposed skin colour quantified by a spectrophotometer. This study included adult volunteers visiting the dermatology department of Erasmus MC Rotterdam, the Netherlands, in December 2014 (exclusion criteria: albinism and erythroderma). A sample-size calculation showed 80% power to detect an inter-rater correlation of 0 8 with a maximum deviation of 0 1 when 80 participants were included. The local medical ethics committee approved this study and all participants signed informed consent. Skin colour was assessed using a six-point scale: 1 very white, 2 white, 3 white to olive, 4 light brown, 5 brown and 6 dark brown to black. Three physicians (L.C.J., M.A.H. and J.A.C.V.) independently graded the colour of sun-unexposed skin of the upper body (abdomen and inner upper arm) of each participant, without discussing their assessments. The agreement in grading was tested using the intraclass correlation coefficient (ICC; two-way-mixed, single measures). Subsequently, skin colour was measured as colour saturation at the inner upper arm using a spectrophotometer (CM-600d; Konica-Minolta, Osaka, Japan), and the FST was assessed by combining the answers to the questions: ‘What is your skin colour?’ (type I–IV white, type V brown, type VI black) and, ‘If white, how does your unprotected skin react to sunlight?’ (type I always burns and never tans, type II usually burns and afterwards lightly tans, type III sometimes burns and always tans, type IV never burns and tans deeply). Spearman’s q was used to test the correlation of the spectrophotometer skin colour with PSC and FST. We studied 117 individuals (mean age 45 7 18 6 years, 31% men) of different ancestry. The mean PSC of the three graders included 28 individuals (24%) as very white, 58 (50%) white, 14 (12%) white to olive, six (5%) light brown, 11 (9%) brown and none dark brown to black. The three physicians showed an excellent agreement in grading (ICCabsolute agreement = 0 90). In 114 individuals (three answered ‘unknown’) the self-reported FST included 14 individuals (12%) of type I, 46 (40%) type II, 28 (25%) type III, four (4%) type IV, 22 (19%) type V and none type VI. Colour saturation of unexposed skin ranged from 0 17 (very white) to 0 45 (dark) and was highly correlated with mean PSC (q = 0 82, Fig. 1a, and less so with FST (q = 0 63, Fig. 1b). The FST was generally higher than the mean PSC (mean difference = 0 5, P < 0 001; Fig. 2), but consistency between PSC and FST was still high (ICCconsistency = 0 82). Five individuals were white or white to olive according to the physicians but judged themselves as brown. However, none of the individuals with light brown or brown PSC judged their own skin as white (Fig. 2). After excluding these five individuals, the consistency between PSC and FST increased to an ICC of 0 86. Comparing PSC in younger (≤ 45 years, n = 60) vs. older (> 45 years, n = 57) individuals, a similar agreement between the three physicians was seen (ICCabsolute agreement young = 0 89, ICC old = 0 90). However, the correlation between the mean PSC and the FST was higher in the younger individuals (ICCconsistency young = 0 89, ICC old = 0 76). To assess differences in sun reaction between the present and the teenage years, we asked the volunteers whether their answers to the FST questions would have been different for their teens. Seven individuals reported a higher FST in the past and 11 a lower FST. Most individuals with a higher FST in the past were aged < 45 years (six of seven), and most individuals with a lower FST in the past would have had an FST of I in their teens (seven of 11). Our results show that physician assessment of skin colour is reliable, because minimal interobserver variability was observed. The self-reported FST is higher than the PSC, but largely consistent with it. However, the spectrophotometer colour saturation correlated less with the FST than with the PSC. This suggests that PSC is a mix between true colour (spectrophotometer) and sun sensitivity (FST). Moreover, our data confirm that light-skinned individuals tend to overestimate

Non-melanoma skin cancer: The hygiene hypothesis

Protection against ultra violet radiation-induced DNA-damage in the skin is not only provided by the pigmentary system. The epidermal barrier consisting of stratum corneum keratinocytes, filaggrin and other proteins is an additional component of the UV-shield. Disruption of the epidermal barrier through frequent body cleansing with soaps and cosmetics may increase the risk of non-melanoma skin cancer.

Dermatological screening of a middle‐aged and elderly population: the Rotterdam Study

DEAR EDITOR, The prevalence of several skin diseases increases with age, partly due to age-related physiopathological alterations. The global burden of disease project (GBD) presented a comprehensive overview of the burden due to skin diseases across different age groups. However, the point prevalences of many common skin diseases, especially in older people and noninstitutionalized settings, are still unknown. In this study, we estimated the point prevalence and ageand sex-adjusted standardized prevalence rates of common inflammatory and (pre)malignant skin diseases in a cross-sectional study in a middle-aged to elderly population (Appendix S1; see Supporting Information). In 2010, full body skin examinations (FBSEs) were introduced in the Rotterdam Study, a prospective populationbased cohort study of people aged ≥ 45 years. Since the start of study, in 1989, all citizens of Ommoord (a district of Rotterdam) were invited to participate, with an overall response of 72% during three invitation cycles. The study design and follow-up are detailed in Hofman et al. At FBSE, all participants were aged ≥ 50 years. The FBSEs were carried out by dermatology-trained physicians who checked for common skin diseases, including (pre)malignancies, eczema, psoriasis, seborrhoeic dermatitis and clinical signs of venous insufficiency (Appendix S2; see Supporting Information). Ageand sex-adjusted standardized prevalence rates (PR) were calculated per 100 000 persons aged ≥ 50 years and standardized to the Revised European Standard Population (Appendix S3; see Supporting Information). In total, 5365 participants (median age 67 2 years; interquartile range 61 6–74 8) were examined. The ageand sex-adjusted prevalence of skin diseases are presented in Table 1. Xerosis cutis was present in 66% of participants. Premalignant and malignant skin diseases were very common, comprising 48% of all identified skin diseases (Fig. S1; see Supporting Information). Actinic keratosis (AK) was found in 1399 (26 1%) participants; 234 (4 4%) showed one or more cutaneous malignancies. Basal cell carcinomas (BCCs) were most common but melanomas, squamous cell carcinomas (SCCs) and mycosis fungoides were also diagnosed (Table 1). Seborrhoeic dermatitis was the most common nonmalignant disorder, with a standardized prevalence rate of 17 685 per 100 000 men and 9588 per 100 000 women. Skin disorders are often not identified, or neglected. In this cohort, we found a high prevalence of (pre)malignant disorders. About a quarter of participants were diagnosed with AK, a potential precursor of SCC. The point prevalence of SCCs is lower than expected compared with melanomas. This could be because melanomas more often develop on less visible body sites and are often subclinical, contrasting with SCC. Therefore, melanomas are more likely to be detected during screening. About one in 25 participants was diagnosed with at least one cutaneous malignancy. This high prevalence suggests that primary care practitioners should be more alert to detect suspicious skin lesions in the middle-aged and elderly population. The U.S. Preventive Services Task Force recently concluded that there is insufficient evidence for skin cancer screening in asymptomatic adults. However, screening via self-examination, case finding by physicians or screening of high-risk subgroups were considered. The German skin screening programme showed that screening of all adults had a limited impact on melanoma-related mortality. However, the lower number needed to treat in elderly patients, and the higher skin cancer prevalence in men, suggest that elderly men are potentially a target group for skin screening. Also, skin cancer awareness campaigns should not be restricted to melanomas but should include keratinocytic cancers given their prevalence and associated disease burden. Although most prevalent diseases identified in this study (e.g. seborrhoeic dermatitis, psoriasis, venous disease and eczema) have low mortality rates, they can severely affect quality of life. Simple measures such as education on general skin care (e.g. using mild cleansers instead of water and soap in xerosis cutis) might be a fast and easy way to manage some of these conditions. Also, treatment of varicose veins in patients with oedema or skin changes might reduce symptoms and prevent the development of venous leg ulcers. Most skin diseases may only cause a relatively small burden on the individual patient level, but due to the high prevalence, the societal burden is substantial. As stated in a recent report from the World Health Organization on ageing and health, changes in health care will be needed to adapt to the continuing increase in life expectancy and the subsequent higher proportion of the elderly population living with comorbidity, including skin diseases. The high prevalence of skin malignancies found in this population-based screening indicate that the total burden of skin diseases is beyond the recent estimates presented by the GBD project. Therefore, the diagnosis, prevention and treatment of skin disease should get sufficient priority in general healthcare education and policies.

Occurrence of metachronous basal cell carcinomas: a prognostic model

A third of patients with a first basal cell carcinoma (BCC) will develop subsequent (metachronous) BCCs.

Cohort studies (and skin cancer) never come alone.

A previous keratinocyte carcinoma is probably the strongest predictor of developing new keratinocyte carcinomas, which makes these patients an interesting population for prevention interventions. Investing in large cohort studies and consortia might increase the validity of observational findings and should stimulate scientists to investigate the underlying mechanisms in detail.