Journal of Dermatological Science 53 (2009) 207–211

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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 Vierkötter, Ulrich Ranft, Ursula Krämer, Dorothea Sugiri, Verena Reimann, Jean Krutmann *
Institut für Umweltmedizinische Forschung (IUF), Düsseldorf, Germany

A R T I C L E I N F O A B S T R A C T

Article history: Background: Studies on the pathogenesis of skin ageing as well as efficacy testing of cosmetic and
Received 7 July 2008 aesthetic measures to prevent or reverse skin ageing require – as an easy to use method – a validated non-
Received in revised form 29 September 2008 invasive clinical score, which allows to simultaneously assess and differentiate between intrinsic
Accepted 6 October 2008
(=chronological) and extrinsic (=photo-) skin ageing. Such an ideal score, however, does currently not
exist.
Keywords: Objectives: We developed a novel skin ageing score ‘SCINEXA’ comprising 5 items indicative of intrinsic
SCINEXA
and 18 items highly characteristic of extrinsic skin ageing. These items were used to define an index
Intrinsic and extrinsic skin ageing
(indexdiscr) that allowed differentiating between intrinsic versus extrinsic skin ageing. In order to validate
Sunbed use
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 2 was associated with sunbed use and thus extrinsic
skin ageing, whereas an index below 2 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.

1. 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 anti-
ageing 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, dermatol-
ogists, 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 patho-
genetic 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 5 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. Vierkötter 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.
2. 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 non-
sunbed 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 5 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: 0 (none), 1 (mild), 2 (moderate) and 3 (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 4 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 vari-
ables 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 5 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  Dxunit Þ=x̄) with their confidence intervals (CI).

Table 1
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 0.

Skin ageing score: SCINEXA n (%) with symptom

Skin ageing symptoms Location Evaluation

1. Part: intrinsic skin ageing items Uneven pigmentation 0/3 69 (93.2)

Fine wrinkles 0/1/2/3 56 (75.6)
Lax appearance 0/1/2/3 31 (41.9)
Reduced fat tissue 0/1/2/3 26 (35.1)
Benign skin tumors 0/1/2/3 6 (8.1)
Maximal achievable intrinsic score 15

2. Part: extrinsic skin ageing items Sunburn freckles Shoulders 0/1/2/3 38 (51.4)
Lentigines solaris Back of forearm 0/1/2/3 38 (51.4)
Pigment change 0/1/2/3 24 (32.4)
Change of skin phototype 0/1/2/3 19 (25.7)
Yellowness 0/1/2/3 21 (28.4)
Pseudo scars 0/1/2/3 28 (37.8)
Coarse wrinkles 0/1/2/3 21 (28.4)
Elastosis 0/1/2/3 47 (63.5)
Cutis rhomboidalis nuchae Neck 0/3 3 (4.1)
Favre racouchot 0/3 0 (0)
Dryness Face, back of forearms 0/1/2/3 57 (77.0)
Comedones Periorbital 0/1/2/3 4 (5.4)
Teleangiectasis Cheeks/nose 0/1/2/3 44 (59.5)
Permanent erythema 0/1/2/3 15 (20.3)
Actinic precancerosis 0/3 4 (5.4)
Basal cell carcinoma 0/3 1 (1.4)
Squamous cell carcinoma 0/3 1 (1.4)
Malignant melanoma 0/3 1 (1.4)
Maximal achievable extrinsic score 54

0/1/2/3: 0 (none), 1 (mild), 2 (moderate), 3 (severe); 0/3: No/Yes.

 A. Vierkötter et al. / Journal of Dermatological Science 53 (2009) 207–211 209

Table 2 3. Results
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. In Table 1 details of the newly developed skin ageing score
‘SCINEXA’ are presented (upper part: 5 items characteristic for
Individual data Group of Group of
intrinsic skin ageing and lower part 18 items of extrinsic skin
non-sunbed sunbed users:
users: (n = 58) (n = 16) ageing). These items were chosen because they are thought to be
specific for either intrinsic or extrinsic skin ageing and because the
Gender 38 men; 20 women 9 men, 7 women
main parts are known to occur frequently. In this table also the
Mean age 41.5  15.9 45.9  16.5
frequencies of study subjects with the skin ageing symptoms are
Skin phototype (%): given. Nearly all study subjects had an ‘uneven pigmentation’
I 1 1
(93.2%) and the majority showed ‘fine wrinkles’ (75.6%) and
II 13 2
III 37 12 ‘dryness’ (77.0%). None of the subjects had ‘Favre racouchot’ and for
IV 7 1 each skin cancer type there was in each case only one volunteer,
Body mass index (%):
who showed the respective skin cancer.
18.5 0 0 The distribution of gender, chronological age, BMI, sunbed use,
18.5 < BMI < 25 27 9 skin phototype and smoking habits for both study groups are
25 BMI < 30 24 6 summarized in Table 2. In order to analyse the impact of these
>30 7 1
potential confounders on the newly developed skin ageing score
Smoking status (%): correlation analysis was conducted. A significant effect was only
Non-smokers 23 5 determined for age and, most importantly, for sunbed use.
Ex-smokers 23 6
Accordingly, in Table 3 the odds ratios for the association of each
Current smokers 12 5
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
Finally we defined an index (indexdiscr) consisting of intrinsic interactions between age and sunbed use the odds ratios for age
and extrinsic elements to discriminate between sunbed users and effects were listed separately for both groups and the odds ratios
non-sunbed users as follows: for sunbed effects were given separately for <45 years and 45
years. For age, the prevalence of almost all skin ageing symptoms
Se þ 1 significantly increased. Regular sunbed use was associated with an
indexdiscr ¼
Si þ 1 even higher prevalence of the vast majority of extrinsic skin ageing

Table 3
Odds ratios (OR) with confidence intervals (CI) for the associations of skin ageing symptoms ((A) intrinsic items and (B) extrinsic items) with age (per age decade) and sunbed
use adjusted for each other.

Skin ageing symptoms OR (CI) for age OR (CI) for sunbed use

1. Intrinsic skin ageing items Uneven pigmentation 1.25 (0.68–2.31) 0.34 (0.1–2.34)
Fine wrinkles Rarely sunbed use: 7.26 (3.58–14.69)*** <45 years: 1.36 (0.21–8.62)
Regularly sunbed use: 2.72 (1.14–6.48)* 45 years: 0.11 (0.02–0.71)*
Lax appearance 3.15 (2.01–4.92)*** 0.04 (0.01–0.28)***
Reduced fat tissue 4.23 (2.35–7.61)*** 0.05 (0.01–0.37)**
benign skin tumors 1.59 (0.87–2.92) n.e.

Skin ageing symptoms OR (CI) for age OR (CI) for sunbed use
***
2. Extrinsic skin ageing items Sunburn freckles Rarely sunbed use: 1.93 (1.34–2.78) <45 years: 5.53 (1.04–29.40)*
Regularly sunbed use: 1.07 (0.62–1.88) 45 years: 1.19 (0.3–5.01)
Lentigines solaris 3.21 (2.10–4.89)*** 9.38 (2.74–32.15)***
Pigment change 3.28 (1.93–5.55)*** 25.39 (5.68–113.53)***
Skin type change 2.26 (1.39–3.66)*** 40.37 (8.93–182.46)***
Yellowness 4.18 (1.88–9.30)*** 657.54 (20.06–999)***
Coarse wrinkles 2.17 (1.36–3.46)** 40.89 (9.04–185.04)***
Elastosis 2.34 (1.66–3.30)*** 20.87 (5.72–76.22)***
Dryness 2.24 (1.59–3.16)*** 8.60 (2.53–29.28)***
Comedones 5.72 (0.98–33.50)(*) n.e.
Teleangiectasis 2.10 (1.53–2.89)*** 1.62 (0.56–4.62)
Pseudo scars 3.04 (1.9–4.86)*** 12.32 (3.26–46.50)***
Permanent erythema 1.73 (1.14–2.62)** 3.44 (0.97–12.21)(*)
Cutis rhomboidales nuchae 5.73 (0.87–37.73) 0.83 (0.05–15.09)
Actinic precancerosis 1.09 (0.56–2.13) 12.69 (1.20–133.90)*
Basal cell carcinoma 0.73 (0.17–3.04) n.e.
Squamous cell carcinoma 0.73 (0.17–3.04) n.e.
Malignant melanoma 1.09 (0.31–3.85) n.e.

OR: odds ratio; CI: confidence interval; n.e.: not evaluable.

(*)
p  0.1.
*
p  0.05.
**
p  0.01.
***
p  0.001.
210 A. Vierkötter et al. / Journal of Dermatological Science 53 (2009) 207–211

Fig. 1. Relation of the intrinsic (Si) and extrinsic skin ageing score (Se) with age and sunbed use adjusted for each other.

symptoms (Table 3B), but with a decrease in most of the intrinsic
skin ageing items (Table 3A). The associations between the sum of
intrinsic skin ageing score items (Si) and the sum of extrinsic skin
ageing score items (Se) with age and sunbed use are summarized in
Fig. 1. The association of the intrinsic and extrinsic score with age
are similar (intrinsic score: MD = 0.22 (CI: 0.18–0.27) and extrinsic
score: MD = 0.34 (CI: 0.25–0.43)). It should be noted that for
sunbed users there is a very strong positive association with the
extrinsic score (MD = 1.33 (CI: 0.98–1.69)) and a negative
association with the intrinsic score (MD = 0.36 (CI: 0.54 to
0.18).
In Fig. 2 the indexdiscr for sunbed versus non-sunbed users is
given separately for subjects <45 years of age and 45 years. It
appears that the indexdiscr still increases with age for non-sunbed
users, but not for sunbed users. Furthermore there is a clear
differentiation between the two study groups at an indexdiscr of 2.
Almost all non-sunbed users have an index <2, whereas sunbed
users have an index 2. In Table 4 the precise classification of each
study subject as sunbed user or non-sunbed user is presented
using an indexdiscr level of 2 as the cutting point. Only 2 out of 16
sunbed users and 4 out of 58 non-sunbed users were misclassified.
Hence, by means of the SCINEXA, 91.9% of the study subjects could
be classified correctly as sunbed or non-sunbed users.
4. Discussion
We have developed and validated a novel skin ageing score
which allows to discriminate between intrinsic versus extrinsic
skin ageing. This score that we have termed ‘SCINEXA’ represents
an easy to use, non-invasive and sensitive tool for the simultaneous
assessment of intrinsic and extrinsic skin ageing. We expect that
the ‘SCINEXA’ will greatly facilitate the efficacy testing of most
types of cosmetic, cosmeceuticals and aesthetic measures which
are directed at the prevention or reversal of intrinsic and/or
extrinsic skin ageing. In addition, this score may prove useful in
studies on the different pathogenetic background of intrinsic
versus extrinsic skin ageing. Accordingly, by means of this score we
have recently obtained evidence that – in addition to chronic UV
irradiation – exposure to ambient particle pollution from traffic
related sources significantly contributes to extrinsic skin ageing
[19].
The ‘SCINEXA’ was validated by assessing intrinsic versus
extrinsic skin ageing in a collective of 74 subjects which comprised
regular sunbed users and non-sunbed users. In accordance with
the existing literature we have assumed that regular sunbed use
for more than 10 years will cause extrinsic skin ageing [20,21],
whereas non-sunbed users will show more signs of intrinsic skin
ageing. By means of the ‘SCINEXA’ we were indeed able to classify
92% of these subjects correctly according to their sunbed use

Table 4
Classification of the study subjects of the sunbed user groups according to their
indexdiscr. Number of individuals correctly classified are bold.

indexdiscr Sunbed user groups Total

Non-sunbed users Sunbed users

<45 years 45 years All <45 years 45 years All

<2 27 27 54 2 0 2 56
2 1 3 4 6 8 14 18
Fig. 2. Index (=indexdiscr) for sunbed and non-sunbed users for <45 years and 45 Total 28 30 58 8 8 16 74
years.
 A. Vierkötter et al. / Journal of Dermatological Science 53 (2009) 207–211
habits. This clear differentiation was made possible by means of
the indexdiscr which was defined as the ratio of the extrinsic skin
ageing score and the intrinsic skin ageing score. A misclassification
occurred only for 2 out of 16 regular sunbed users younger than 45
years and 4 out of 58 of older (45 years) non-sunbed users. We
believe that in the first case the misclassification may be due to the
fact that the sunbed-induced skin damage in young regular sunbed
users is perhaps less advanced, so that they have indexdiscr values
at the borderline of 2. In the latter case other confounding factors,
which are not related to sunbed use, may have caused extrinsic
skin ageing. Overall these results further support the notion that
regular sunbed use causes extrinsic skin ageing.
In this study we observed that intrinsic (=chronological) skin
ageing as well as extrinsic skin ageing increase with age. This result
is expected and reflects the age-dependent cumulative effect of
environmental factors on human skin. It also emphasizes that
intrinsic and extrinsic skin ageing are not completely independent
from each other.
Besides age sunbed use was the only other factor with a positive
associationwiththeextrinsicskinageingscore.In particular,the odds
ratios for the association between extrinsic skin ageing items and
sunbed use were much higher than those for a 10 year increase in age.
The only exceptions werecomedones and teleangiectasis.Chronic UV
exposure is a triggering factor for the formation of comedones and
teleangiectasis but the pathogenetic basis includes intrinsic factors
such as genetic, endocrine and infectious determinants.
Interestingly, chronic sunbed users showed a decrease in the
intrinsic skin ageing score. This decrease is most likely due to the
superposition of extrinsic skin ageing factors, e.g. coarse wrinkles
superpose fine wrinkles, and therefore the intrinsic skin ageing
symptoms seem to decrease. This observation also points to a
limitation of the ‘SCINEXA’, because it can not be used to measure
intrinsic skin ageing in severely photoaged skin.
In the present study, no confounding effects were observed for
BMI, skin phototype or smoking habits, all of which are known to
significantly affect either extrinsic or intrinsic skin ageing. In this
regard it is important to note that the collective used in this study
was small and only chosen according to their sunbed user habits. As
previously mentioned, chronic UV exposure and thus regular sunbed
use is a very strong influencing factor on extrinsic skin ageing, which
has therefore been termed photoageing, and smaller effects by other
factors might not be detectable in such a small and preselected study
group. Clearly, the ‘SCINEXA’ needs to be further validated in larger
collectives with a more balanced graduation of environmental
factors other than UV exposure. Indeed, in an independent study the
‘SCINEXA’ has proven to be useful for identifying exposure to
ambient particle pollution from traffic related sources as a UV-
independent factor causing extrinsic skin ageing [19].
211
Acknowledgements
This study has been supported by the Deutsche Forschungsge-
meinschaft (DFG), Collaborative Research Center (SFB) 728, TP C1.
We would like to thank Dr. M. Matsui (Estee Lauder Inc.) for
critically reading the manuscript.
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