doi 10 1016j jdermsci 2008 10 001 The SCINEXA A novel, validated score to simultaneously assess and differentiate between intrinsic and extrinsic skin ageing Andrea Vierkötter, Ulrich Ranft, Ursula.ádsadaSAD
Journal of Dermatological Science 53 (2009) 207–211 Contents lists available at ScienceDirect Journal of Dermatological Science journal homepage: www.intl.elsevierhealth.com/journals/jods The SCINEXA: A novel, validated score to simultaneously assess and differentiate between intrinsic and extrinsic skin ageing Andrea Vierkoătter, Ulrich Ranft, Ursula Kraămer, Dorothea Sugiri, Verena Reimann, Jean Krutmann * Institut fuăr Umweltmedizinische Forschung (IUF), Duăsseldorf, Germany A R T I C L E I N F O A B S T R A C T Article history: Received July 2008 Received in revised form 29 September 2008 Accepted October 2008 Background: Studies on the pathogenesis of skin ageing as well as efficacy testing of cosmetic and aesthetic measures to prevent or reverse skin ageing require – as an easy to use method – a validated noninvasive clinical score, which allows to simultaneously assess and differentiate between intrinsic (=chronological) and extrinsic (=photo-) skin ageing Such an ideal score, however, does currently not exist Objectives: We developed a novel skin ageing score ‘SCINEXA’ comprising items indicative of intrinsic and 18 items highly characteristic of extrinsic skin ageing These items were used to define an index (indexdiscr) that allowed differentiating between intrinsic versus extrinsic skin ageing In order to validate the ‘SCINEXA’, we asked whether it can be used to discriminate regular sunbed users, which have been chronically exposed to ultraviolet radiation and thus are prone to photoageing, from non-sunbed users, which were considered paradigmatic for intrinsic skin ageing Methods: For this purpose, 58 non-sunbed users and 16 regularly sunbed users were assessed In addition to the clinical examination of the 23 score items potential confounders were considered by questionnaire Results: By employing the indexdiscr, we were able to classify 92% of all study subjects correctly as sunbed or non-sunbed users Specifically, an index above was associated with sunbed use and thus extrinsic skin ageing, whereas an index below indicated intrinsic skin ageing Conclusion: The novel ‘SCINEXA’ is suitable for the simultaneous assessment of intrinsic and extrinsic skin ageing ß 2008 Japanese Society for Investigative Dermatology Published by Elsevier Ireland Ltd All rights reserved Keywords: SCINEXA Intrinsic and extrinsic skin ageing Sunbed use Introduction Increasing life expectancy and the resulting demographic consequences have made skin ageing a health topic that is of growing concern to the general population This is best illustrated by recent sale rates for cosmetic products which have been developed to prevent, slow down or even reverse the clinical signs of skin ageing Accordingly, in 2008 the skin care business has been a 15 billion US$ anti-ageing and rejuvenation industry with growth rates of more than 10% for cosmeceuticals [1] Many of these antiageing products contain molecules with defined biological activities and are claimed to modulate molecular processes involved in the pathogenesis of skin ageing Efficacy testing of such products is of outmost importance for consumers, dermatologists, cosmetic industry and regulatory institutions Although for the demonstration of molecular mechanisms, invasive test methods are clearly the gold standard, it has to be realized that * Corresponding author E-mail address: Krutmann@rz.uni-duesseldorf.de (J Krutmann) for obvious ethical reasons efficacy testing of the already large and still growing number of anti-ageing skin products has to be based on non-invasive methods In this regard, several skin ageing score have been developed which are mainly descriptive in nature, which may involve photographic grading scales and which can be used as global indicators of skin ageing [2], for the assessment of photoageing [3– 5] or of single clinical skin ageing signs [6,7] Skin ageing is, however, the consequence of intrinsic and extrinsic factors Intrinsic or chronological skin ageing and extrinsic skin ageing, which is primarily due to chronic exposure to ultraviolet (UV) radiation [8–10] and therefore is also called photoageing, can be distinguished histologically and clinically, involve distinct pathogenetic causes and mechanisms and their prevention is based on different principles [11–15] It is therefore surprising to see that no validated skin ageing scores exists that differentiates between these two different forms of skin ageing [2] Here we report on the development of an easy to use skin ageing score, the ‘SCINEXA’, which is based on the assessment of 18 skin symptoms which are highly characteristic of extrinsic skin ageing and skin symptoms which are indicative of intrinsic skin ageing 0923-1811/$30.00 ß 2008 Japanese Society for Investigative Dermatology Published by Elsevier Ireland Ltd All rights reserved doi:10.1016/j.jdermsci.2008.10.001 208 A Vierkoătter et al / Journal of Dermatological Science 53 (2009) 207–211 We have used this score to asses skin ageing in two groups of human volunteers: (i) regular sunbed users as a group that is paradigmatic for long-term, chronic exposure to UV radiation, and (ii) non (or rare) sunbed users, and we have found that by means of this new skin ageing score it is possible to discriminate these two groups Materials and methods 2.1 Study subjects We studied 74 volunteers from North Rhine Westphalia (NRW) in Germany in the age between 19 and 72 years One group (n = 58) had never used a sunbed before or had used it rarely (i.e no sunbed use for at least 18 months) This group will be referred to as nonsunbed users The second group (n = 16) consisted of volunteers, who used sunbeds once a week for at least 10 years This makes a sunbed user percentage of 21% in our study, which represents the sunbed user percentage of the German population of about 20% 2.2 ‘SCINEXA’: Score for Intrinsic and Extrinsic skin Ageing Skin ageing symptoms of study subjects were evaluated by a dermatologist using a newly developed skin ageing score called ‘SCINEXA’ This score contained items characteristic for intrinsic skin ageing and 18 items characteristic for extrinsic skin ageing (for details see Table 1) The complete skin was examined and the clinical signs of skin ageing were graded using ordinal scales as follows: (none), (mild), (moderate) and (severe) In addition, the items: sunburn freckles, lentigines solaris, cutis rhomboidalis nuchae, dryness, comedones and teleangiectasis were assessed on defined locations For the items: uneven pigmentation, cutis rhomboidalis nuchae, Favre racouchot, actinic precancerosis and the skin cancer types a binary scale ‘‘Yes’’ (present = 3) or ‘‘No’’ (absent = 0) was used The dermatologist evaluated the skin of the study subjects without knowing if they used sunbeds or not 2.3 Collection of individual data In order to discover possible confounders, the following individual data known to have an effect on skin ageing were collected by questionnaire: gender, chronological age, body mass index (BMI) [16], reactivity of the skin to sun exposure using Fitzpatrick’s level phototype classification (always burn and never tan, usually burn and tan with difficulty, sometimes mild burn and tan about the average, or rarely burn and tan with ease [17]), and smoking status [18] There was no difference in exposure to daily sunlight and job history in the both study groups 2.4 Statistical analysis Statistical analysis was done by using statistical software SAS 9.1 The relations between single items of the score with potential influencing factors were evaluated in two steps In a first step we used correlation analysis to assess the association of the potentially confounding factors: gender, age, BMI, sunbed use, skin phototype and smoking with single items of the score In a second step, the relationship between every single score item as dependent variable with relevant influencing factors (significant with p < 0.1 in the first step) as independent variables was analysed by applying logistic regression The independent variables were adjusted for each other and their relation with the score items was expressed as odds ratios (OR) with its confidence intervals (CI) and p-values Additionally two sub-scores were built: the extrinsic score defined as the sum of the 18 extrinsic score items (Se) and the intrinsic score defined as the sum of the intrinsic score items (Si) The associations between Se and Si and the relevant influencing factors were analysed by multiple linear regression and the results are presented as mutually adjusted standardised mean differences (MD ¼ ðbx Á Dxunit Þ=x) ¯ with their confidence intervals (CI) Table Skin ageing symptoms included in the skin ageing score ‘SCINEXA’ and number of study subjects (n, %) showing the respective skin ageing symptoms to different degrees other than Skin ageing score: SCINEXA Skin ageing symptoms Part: intrinsic skin ageing items Uneven pigmentation Fine wrinkles Lax appearance Reduced fat tissue Benign skin tumors Maximal achievable intrinsic score Part: extrinsic skin ageing items Sunburn freckles Lentigines solaris Pigment change Change of skin phototype Yellowness Pseudo scars Coarse wrinkles Elastosis Cutis rhomboidalis nuchae Favre racouchot Dryness Comedones Teleangiectasis Permanent erythema Actinic precancerosis Basal cell carcinoma Squamous cell carcinoma Malignant melanoma Maximal achievable extrinsic score 0/1/2/3: (none), (mild), (moderate), (severe); 0/3: No/Yes n (%) with symptom Location Shoulders Back of forearm Neck Face, back of forearms Periorbital Cheeks/nose Evaluation 0/3 0/1/2/3 0/1/2/3 0/1/2/3 0/1/2/3 15 69 56 31 26 (93.2) (75.6) (41.9) (35.1) (8.1) 0/1/2/3 0/1/2/3 0/1/2/3 0/1/2/3 0/1/2/3 0/1/2/3 0/1/2/3 0/1/2/3 0/3 0/3 0/1/2/3 0/1/2/3 0/1/2/3 0/1/2/3 0/3 0/3 0/3 0/3 54 38 38 24 19 21 28 21 47 57 44 15 1 (51.4) (51.4) (32.4) (25.7) (28.4) (37.8) (28.4) (63.5) (4.1) (0) (77.0) (5.4) (59.5) (20.3) (5.4) (1.4) (1.4) (1.4) A Vierkoătter et al / Journal of Dermatological Science 53 (2009) 207–211 Table Distribution of individual data: gender, chronological age, skin phototype (SPT), body mass index (BMI) and smoking status separated for the both study groups sunbed and non-sunbed users Individual data Group of non-sunbed users: (n = 58) Group of sunbed users: (n = 16) Gender Mean age 38 men; 20 women 41.5 Ỉ 15.9 men, women 45.9 Ỉ 16.5 Skin phototype (%): I II III IV 13 37 12 Body mass index (%): 18.5 18.5 < BMI < 25 25 BMI < 30 >30 27 24 Smoking status (%): Non-smokers Ex-smokers Current smokers 23 23 12 Finally we defined an index (indexdiscr) consisting of intrinsic and extrinsic elements to discriminate between sunbed users and non-sunbed users as follows: indexdiscr ẳ Se ỵ Si ỵ 209 Results In Table details of the newly developed skin ageing score ‘SCINEXA’ are presented (upper part: items characteristic for intrinsic skin ageing and lower part 18 items of extrinsic skin ageing) These items were chosen because they are thought to be specific for either intrinsic or extrinsic skin ageing and because the main parts are known to occur frequently In this table also the frequencies of study subjects with the skin ageing symptoms are given Nearly all study subjects had an ‘uneven pigmentation’ (93.2%) and the majority showed ‘fine wrinkles’ (75.6%) and ‘dryness’ (77.0%) None of the subjects had ‘Favre racouchot’ and for each skin cancer type there was in each case only one volunteer, who showed the respective skin cancer The distribution of gender, chronological age, BMI, sunbed use, skin phototype and smoking habits for both study groups are summarized in Table In order to analyse the impact of these potential confounders on the newly developed skin ageing score correlation analysis was conducted A significant effect was only determined for age and, most importantly, for sunbed use Accordingly, in Table the odds ratios for the association of each single skin ageing symptom with age and sunbed use are summarized The associations of age and sunbed use were additionally adjusted for each other In case there were significant interactions between age and sunbed use the odds ratios for age effects were listed separately for both groups and the odds ratios for sunbed effects were given separately for