Revised Cutaneous Lupus erythematosus Disease Area and Severity Index (RCLASI): a modified outcome instrument for cutaneous lupus erythematosus

CLINICAL AND LABORATORY INVESTIGATIONS

BJD

British Journal of Dermatology

Revised Cutaneous Lupus Erythematosus Disease Area andSeverity Index (RCLASI): a modified outcome instrument forcutaneous lupus erythematosusA. Kuhn, S. Amler,* S. Beissert, M. Bohm, R. Brehler, J. Ehrchen, S. Grundmann, M. Haust,� V. Ruland,M. Schiller, P. Schulz,� S. Stander, C. Sauerland,* T.A. Luger and G. Bonsmann

Department of Dermatology, University of Munster, Von-Esmarch-Strasse 58, D-48149 Munster, Germany

*Department of Medical Informatics and Biomathematics, University of Munster, Munster, Germany

�Department of Dermatology, University of Dusseldorf, Dusseldorf, Germany

�Department of Dermatology, Fachklinik Bad Bentheim, Bad Bentheim, Germany

CorrespondenceAnnegret Kuhn.

E-mail: [email protected]

Accepted for publication30 March 2010

Key wordsactivity, cutaneous lupus erythematosus, damage,

score, severity of illness index

Conflicts of interestThe authors declare no conflict of interest.

DOI 10.1111/j.1365-2133.2010.09799.x

Summary

Background In 2005, a scoring system (CLASI, Cutaneous Lupus Erythematosus Dis-ease Area and Severity Index) was developed for patients with cutaneous lupuserythematosus (CLE) to assess disease ‘activity’ and ‘damage’. However, theCLASI does not give an accurate assessment of the severity in all disease subtypes.Objectives The main objective of this study was to analyse critically the includedparameters of the CLASI and to revise the activity and damage score taking intoaccount various clinical features of the different subtypes of CLE. The revisedCLASI (RCLASI) was also validated for use in clinical trials.Patients and methods A RCLASI was designed with regard to the anatomical region(i.e. face, chest, arms) and morphological aspects (i.e. erythema, scaling ⁄hyper-keratosis, oedema ⁄ infiltration, scarring ⁄atrophy) of skin lesions and evaluated bynine dermatologists who scored 12 patients with different subtypes of CLE toestimate inter- and intrarater reliability.Results Reliability studies demonstrated an intraclass correlation coefficient (ICC)for an inter-rater reliability of 0Æ89 for the activity score [95% confidence interval(CI) 0Æ79–0Æ96] and of 0Æ79 for the damage score (95% CI 0Æ62–0Æ92). The ICCfor intrarater reliability for the activity score was 0Æ92 (95% CI 0Æ89–0Æ95) andthe ICC for the damage score was 0Æ95 (95% CI 0Æ92–0Æ98).Conclusions In the present study, a RCLASI was developed by experts, and reliabilitystudies supported the validity and applicability of the revised scoring instrumentfor CLE. Thus, the RCLASI is a valuable instrument in multicentre studies and forthe clinical evaluation of activity and damage in different disease subtypes.

Lupus erythematosus (LE) is an inflammatory autoimmune

disorder comprising a broad spectrum of cutaneous and sys-

temic manifestations. For the evaluation of disease activity via

scoring methods in patients with systemic LE (SLE), several

disease activity scores [British Isles Lupus Assessment Group

(BILAG) index; European Consensus Lupus Activity Measure-

ment (ECLAM); Systemic Lupus Erythematosus Disease Activity

Index (SLEDAI)] have been established.1,2 These disease activ-

ity scores include some dermatological criteria, such as butter-

fly rash, generalized erythema and oral ulcers; however, they

are not sensitive enough for the precise evaluation of disease

activity in the various subtypes of cutaneous LE (CLE), e.g.

acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE)

and intermittent CLE (ICLE).3,4 Therefore, the CLASI (Cutane-

ous Lupus Erythematosus Disease Area and Severity Index)

scoring system has been developed specifically for patients

with CLE taking into account both the anatomical region

(e.g. face, chest, arms) and morphological aspects of skin

lesions.5 Activity is scored on the basis of erythema, scale ⁄hyperkeratosis, mucous membrane involvement, acute hair

loss and nonscarring alopecia. Damage is scored in terms of

dyspigmentation and scarring, including scarring alopecia.

Moreover, patients are asked whether dyspigmentation due to

CLE lesions usually remains visible for more than 12 months,

which is taken to be permanent. The total scores are calculated

by simple addition based on the extent of the symptoms,

which is documented according to the worst affected lesion

within a specific anatomical area. The CLASI has been

� 2010 The Authors

Journal Compilation � 2010 British Association of Dermatologists • British Journal of Dermatology 2010 163, pp83–92 83

validated in nine patients.5,6 In addition, the clinical respon-

siveness of the instrument was assessed in patients with CLE

from baseline until day 56 after starting a new standard of

care therapy7 or during prospective clinical studies to assess

the efficacy of a therapeutic strategy.8,9 However, clinical

responsiveness still needs to be evaluated in a prospective ran-

domized placebo-controlled trial.

The CLASI is the first validated instrument to measure dis-

ease activity and damage in patients with CLE, but it does not

give an accurate assessment of the severity of all CLE lesions.

Therefore, we optimized the compilation of parameters for

the evaluation of the various CLE subtypes by increasing the

accuracy of existing parameters, such as scaling ⁄hypertrophy

and dyspigmentation, and by adding several new parameters,

such as oedema ⁄ infiltration and subcutaneous nodule ⁄plaque.

In the present study, we also validated this revised scoring

system, named RCLASI, and estimated inter- and intrarater

reliability for use in clinical trials.

Patients and methods

Revised Cutaneous Lupus Erythematosus Disease Area

and Severity Index

The RCLASI is designed to score the activity and damage of the

disease separately, taking into account both anatomical region

(e.g. face, chest, arms) and morphological aspects (erythema,

scaling ⁄hyperkeratosis, oedema ⁄ infiltration, subcutaneous nod-

ule ⁄plaque, dyspigmentation, scarring ⁄atrophy) of skin lesions

(Appendix 1). The activity was scored on the basis of ery-

thema, scaling ⁄hyperkeratosis, oedema ⁄ infiltration, subcutane-

ous nodule ⁄plaque, mucous membrane lesions, nonscarring

alopecia and ‘lupus hair’. Erythema was scored from 0 to 3

points, while scaling ⁄hyperkeratosis, oedema ⁄ infiltration, sub-

cutaneous nodules ⁄plaques can be scored from 0 to 2 points at

each anatomical region (scalp, ears, nose and ⁄or malar area,

lips, rest of the face, V-area of the neck, posterior neck and ⁄or

shoulders, chest, abdomen, back ⁄buttocks, arms, hands, legs,

feet). The intermediate sum of the activity score was calculated

by simple addition of the points. Mucous membrane lesions

were scored with 0 or 1 point for erythematous lesions and

keratotic lesions and from 0 to 2 points for erosion ⁄ulceration

on three sites of involvement (buccal mucosa, hard and soft

palate, other mucous membranes). Finally, nonscarring alope-

cia was rated from 0 to 3 points, and ‘lupus hair’ was rated

with 0 or 3 points (absent, present). The total activity score

was calculated again by simple addition of all subtotals.

Damage was scored on the basis of dyspigmentation and

scarring ⁄atrophy that were both scored from 0 to 2 points at

every anatomical region (see above). In addition, scarring alo-

pecia was scored from 0 to 6 points, modified after Olsen

et al.10 Here, the scalp is divided into four areas by distinction

between right and left side and frontal and occipital part. Every

area has a different dimension and was, therefore, weighted

differently (from 18% to 40%). The percentage of scarring

alopecia was then estimated in each area. This value was multi-

plied by the percentage of the scalp surface area (from 0Æ18 to

0Æ40), the calculated value was weighted with a scale, giving 0

(absent) to 6 points (75–100% scarring alopecia). In all cases,

‘a ⁄b’ are simply defining specific morphological terms and

have no influence on the calculation of the total scores (e.g.

1a = 1 point, 2a = 2 points). The total damage score was

calculated by simple addition of the subtotals.

Assessment of inter- and intrarater reliability

Inter-rater reliability was assessed by a group of 11 physicians

(seven board-certified dermatologists and four second- or

third-year residents in dermatology training) and one student.

Their mean age was 39Æ3 (range 20–59) years. Seven of the

group were male and five were female. They were recruited

from the Departments of Dermatology at the Universities of

Dusseldorf, Osnabruck and Munster, Germany. They scored a

group of 12 patients according to a predefined protocol in

two sessions. In the first session, 12 patients were scored by

11 dermatologists and one student in a randomized order,

followed by a second session in which the same 12 patients

were rated again by the same physicians and the student in a

new randomized order. In the final analysis, the evaluations of

nine investigators were included. The student’s data were

eliminated, as we wanted to include only the data of experi-

enced raters. Furthermore, the scoring of two board-certified

dermatologists who evaluated the most severely affected LE-

specific skin lesion using a different strategy in each round

was excluded from the analysis.

All physicians recorded the time they needed for filling out

the RCLASI for each patient. The scoring time of one of the

physicians is partly missing due to a malfunction of the stop-

watch and, therefore, the time of this physician was com-

pletely excluded from the final analysis. To assess intrarater

reliability, all physicians scored all CLE patients. These patients

represented a wide range of activity levels (mean scores 4Æ3–

30Æ3) and damage levels (mean score 0Æ4–14Æ1) (Table 1).

Assessment of content validity

The RCLASI was designed by A. Kuhn and G. Bonsmann, who

have considerable expertise in relation to patients with auto-

immune diseases, in particular those with CLE. Comments and

suggestions from colleagues from different departments of

dermatology were included. Additionally, a questionnaire for

critical assessment of the RCLASI by the investigators was

composed for the assessment of the RCLASI in order to estab-

lish areas for improvement, mostly concerning the feasibility

of the instrument.

Patients

Twelve patients (10 female, two male) from the Department

of Dermatology, University of Munster, Germany, with CLE

were included in the study. The mean age of the patients with

CLE at the time of the study was 40Æ0 ± 13Æ3 (range 21–68)


Journal Compilation � 2010 British Association of Dermatologists • British Journal of Dermatology 2010 163, pp83–92

84 Revised CLASI for cutaneous lupus erythematosus, A. Kuhn et al.

years. The diagnosis and classification of CLE were based on

clinical and histological criteria as well as on serological ab-

normalities according to the Dusseldorf Classification 2004.4

Patients with the following subtypes of CLE were included in

the study: one with ACLE (and additional SCLE lesions), two

with SCLE, seven with CCLE [five patients with discoid lupus

erythematosus (DLE), two patients with LE panniculitis] and

two with ICLE (one with additional DLE lesions). The study

was approved by the ethical committee of the University of

Munster, Germany, and was conducted according to the ethi-

cal guidelines at our institution and the Helsinki Declaration.

Statistical methods ⁄hypothesis

To estimate inter- and intrarater reliability, we validated the

RCLASI based on two directly calculated separate subscale

scores for activity and damage. For the assessment of inter-rater

reliability, the intraclass correlation coefficient (ICC) for abso-

lute agreement among raters was applied. To measure associa-

tions between pairs of raters, we used Spearman’s rank

correlations. In addition, the ANOVA was performed to test for

significant differences in overall clinical scores among the

patients as well as among the raters. By means of these inter-

rater reliability analyses, we tested for general ‘rater effects’. To

study whether the raters’ scores over all patients were in accor-

dance between the first and second ratings, we estimated sum-

mary statistics and the agreement between both sessions in

order to assess the intrarater reliability. Therefore, we calcu-

lated the ICCs as mentioned above. Furthermore, regression

analyses, specified by Spearman rank correlations, were per-

formed in order to measure the association between the two

sessions. Comparisons between the first and second rating were

performed using the Wilcoxon rank test. For both inter-rater

and intrarater reliability the following ICC interpretation scale

was determined: an ICC of 0Æ5–0Æ7 was considered minimally

acceptable, whereas an ICC above 0Æ81 was considered to be

almost perfect.11 Twelve patients were evaluated by nine raters,

to detect an intraclass correlation based on a null hypothesis of

an ICC of 0Æ7 and an alternative hypothesis of an ICC unrelated

to 0Æ7 using an F-test. Considering the intrinsic weakness of

the simple linear correlation as a measure of agreement, we

refer to its common use as a measure of intra- and inter-rater

reliability.12 Secondly, we compared the scoring time over all

raters from first rating to second rating using the Wilcoxon

rank test. Any two-sided P-value < 0Æ05 was considered to

reflect statistical significance. All analyses were performed

using SPSS version 15.0 (SPSS Inc., Chicago, IL, U.S.A.).

Results

Patients

The twelve patients with different subtypes of CLE represented

a full range of skin lesions with different levels of activity and

damage, based initially on clinical impression and subse-

quently confirmed by application of a RCLASI. The mean

activity score ranged from 4Æ3 to 30Æ3 and the mean damage

score ranged from 0Æ4 to 14Æ1 (Table 1).

Activity and damage scores

The RCLASI was evaluated by nine dermatologists who scored

12 patients with different subtypes of CLE in two ratings. The

highest activity score over all physicians was found in two

patients with SCLE (mean ± SD; rating 1: 29Æ4 ± 5Æ3; rating

2: 29Æ3 ± 5Æ5) followed by a single patient with ACLE

(25Æ0 ± 5Æ3; 22Æ9 ± 7Æ4). Patients with ICLE (n = 2) had an

activity score of 18Æ8 ± 5Æ7 in the first rating and 18Æ7 ± 6Æ1

Table 1 List of participating patients

Patient

Age

(years) Sex Subtype Positive antibodies and other laboratory parameters

Activity score,

mean (SD)

Damage score,

mean (SD)

1 28 F ACLE/SCLEa ANA, Ro ⁄SSA, La ⁄SSB, Sm, RNP, C3 fl, C4 fl 23Æ94 (5Æ47) 1Æ06 (2Æ98)2 55 M SCLE ANA, Ro ⁄SSA, C3 fl, C4 fl, C1q fl, CRP ›, proteinuria 28Æ44 (5Æ38) 0Æ72 (1Æ00)

3 48 F SCLEa ANA, Ro ⁄SSA, La ⁄SSB, leucopenia 30Æ33 (4Æ04) 1Æ78 (3Æ44)4 25 F CCLE ANA, dsDNA, Sm, RNP, C3 fl, C4 fl, proteinuria 5Æ00 (1Æ79) 14Æ06 (2Æ65)

5 21 F CCLE ANA 5Æ17 (1Æ54) 4Æ17 (1Æ30)6 42 F CCLEa ANA, dsDNA, Ro ⁄SSA, Sm, cardiolipin, C3 fl, C4 fl,

ESR ›, CRP ›, leucopenia

14Æ61 (2Æ97) 11Æ67 (3Æ94)

7 35 M CCLE None 14Æ28 (2Æ27) 1Æ17 (0Æ90)

8 42 F CCLE None 8Æ83 (2Æ21) 2Æ50 (1Æ54)9 31 F CCLE None 7Æ78 (3Æ10) 4Æ06 (1Æ74)

10 68 F CCLE None 4Æ33 (1Æ77) 2Æ11 (2Æ30)11 44 F ICLE ANA, Ro ⁄SSA 23Æ44 (3Æ45) 0Æ44 (0Æ85)

12 41 F ICLE/CCLE ANA, Ro ⁄SSA, histone 14Æ11 (2Æ50) 1Æ39 (2Æ20)

ACLE, acute cutaneous lupus erythematosus; ANA, antinuclear antibodies; CCLE, chronic cutaneous lupus erythematosus; ICLE, intermittentcutaneous lupus erythematosus; SCLE, subacute cutaneous lupus erythematosus; fl, decreased; ›, increased; ESR, erythrocyte sedimentation

rate; CRP, C-reactive protein.aIn the context of systemic lupus erythematosus.



Revised CLASI for cutaneous lupus erythematosus, A. Kuhn et al. 85

in the second rating. Patients with CCLE (n = 7) had the low-

est activity score of 8Æ6 ± 4Æ9 and 8Æ5 ± 4Æ6, respectively. The

damage score was equally low in patients with ACLE, SCLE

and ICLE in both ratings (rating 1: 1Æ1 ± 3Æ0, 1Æ1 ± 2Æ3,

1Æ1 ± 2Æ0, respectively; rating 2: 1Æ0 ± 3Æ0, 1Æ4 ± 3Æ0, 0Æ7 ±

1Æ6, respectively). The damage score of patients with CCLE

was clearly higher in both rounds (5Æ4 ± 5Æ0 and 5Æ9 ± 5Æ5,

respectively) (Fig. 1). Senior physicians and residents did not

yield significantly different measurement results, which indi-

cates that different levels of experience do not lead to differ-

ences in the scoring of patients and that the criteria are

obviously distinguishable (Fig. 2).

Inter-rater agreement

In this study, the inter-rater reliability of the different derma-

tologists assessing the RCLASI was high. With the Spearman’s

rank correlation coefficient (rsp), we compared a pair of raters

ICLECCLESCLEACLE

Act

ivity

sco

re

40

30

20

10

0

Round 2Round 1

ICLECCLESCLEACLE

*

* ** *

*

***

Dam

age

scor

e

20

15

10

5

0

Round 2Round 1(a) (b)

Fig 1. Box plot analysis of the total activity (a) and damage (b) Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index scores

between the four cutaneous lupus erythematosus (CLE) subtypes for both ratings. Box area, 50% of data [i.e. lines in box denote medians, bars

include at most 1.5 of interquartile distance, difference between first and third quartiles of data, circles indicate values out of the 1.5-fold box area

(outliers), whereas asterisks indicate values out of the 3-fold box area (extreme outliers)]. ACLE, acute CLE; SCLE, subacute CLE; CCLE, chronic

CLE; ICLE, intermittent CLE.

AssistantSenior

Act

ivity

sco

re

40

30

20

10

0

Round 2Round 1

Round 2Round 1

AssistantSenior

Dam

age

scor

e

20

15

10

5

0

(a) (b)

Fig 2. Box plot analysis of the total activity (a) and damage (b) Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index scores

for both ratings given by senior and assistant physicians. Box area, 50% of data [i.e. lines in box denotes medians, bars include at most 1.5 of

interquartile distance, difference between first and third quartiles of data, circles indicate values out of the 1.5-fold box area (outliers), whereas

asterisks indicate values out of the 3-fold box area (extreme outliers)].

Table 2 Results of reliability testing

F-test Rater (n) Patients (n)

Inter-rater reliability ICCActivity 0Æ89 95% CI 0Æ79–0Æ96 < 0Æ001 9 12

Damage 0Æ79 95% CI 0Æ62–0Æ92 < 0Æ001 9 12Intra rater reliability ICC

Activity 0Æ92 95% CI 0Æ89–0Æ95 < 0Æ001 9 12Damage 0Æ95 95% CI 0Æ92–0Æ98 < 0Æ001 9 12

CI, confidence interval; ICC, intraclass correlation coefficient.




based on the scores, to assess the relationship between two

raters’ rankings on the same set of patients. Identical measure-

ments will result in a Spearman correlation coefficient (rsp) of

rsp = 1Æ00. The rsp between pairs of raters ranged for the

activity subscale from 0Æ82 to 0Æ99 in round 1 and from 0Æ74

to 0Æ98 in round 2; for the damage subscale, the rsp between

pairs of raters ranged from 0Æ23 to 0Æ93 in round 1 and from

0Æ24 to 0Æ94 in round 2, demonstrating that the relative order

of the patients based on the raters’ scores is consistent

between raters. In addition to high consistency among raters,

the agreement among the raters’ scores for a given patient

was also high. The ICC was r = 0Æ89 [95% confidence interval

(CI) 0Æ79–0Æ96] for the activity scale and r = 0Æ79 (95% CI

0Æ62–0Æ92) for the damage scale (Table 2). In addition, the

ANOVA results showed significant differences in overall scores

among the patients (activity score F-test: round 1 = 65Æ17,

P < 0Æ001; round 2 = 54Æ56, P < 0Æ001; damage score F-test:

round 1 = 34Æ50, P < 0Æ001; round 2 = 42Æ82, P < 0Æ001),

demonstrating that an individual score for each patient could

be evaluated.

Intrarater reliability

Both, the activity and the damage scores demonstrated high

intrarater reliability. The ICC was r = 0Æ92 (95% CI 0Æ89–0Æ95)

for the activity score and r = 0Æ95 (95% CI 0Æ92–0Æ98) for the

damage score (Table 2). The ICC of every physician exceeded

0Æ7, which means the data were at least ‘substantial’ (Fig. 3).12

The intercept and slope of the regression equation relating first

scores to second scores showed small differences for both sub-

scales (intercepts of 0Æ99 for activity and 0Æ09 for damage) and

a slope close to 1 (b = 0Æ92 for activity and b = 1Æ04 for dam-

age) for predicting the second rating based on the result of the

first rating (Fig. 4). Both scales also demonstrated high consist-

ency throughout, regarding the relative order of the patients at

first and second rating; there were no outliers.

The differences in the mean activity score between first and

second rating of all investigators ranged from 0 to 4Æ2 points

of the 13Æ4–17Æ6 point total scores, but the mean difference

between the first and second rating for the activity subscale

was only 0Æ29 points on average and was not statistically

significant (t = 0Æ78; P = 0Æ436). Slightly lower ratings were

given on the second rating by 41% of the nine raters. No

significant differences between the first and the second rating

were found. The differences in the mean damage score

between ratings of all investigators were even smaller and

ranged from 0Æ1 to 1Æ7 points of the 1Æ9–6Æ3 point total

scores. The mean difference between the first and second rat-

ing for the damage subscale was only 0Æ24 points on average

and was not statistically significant (t = )1Æ58; P = 0Æ118).

Slightly higher ratings were given on the second rating by

27% of the nine raters.

0·9

1·0

0·6

0·7

0·8

0·4

0·5ICC

0·1

0·2

0·3

A B C D E F G H

Investigators

0·0I

Activity scoreDamage score

Fig 3. Intra rater reliability. The intrarater intraclass correlation

coefficient (ICC) is an instrument to measure the intrarater reliability

for the activity and damage subscales. Circles denote the ICCs to

illustrate the intrarater reliability between first and second rating for

all investigators, A–I. Error bars represent the 95% confidence interval

(CI) of each ICC. The dotted lines represent ICC 0.7 and 0.9, which

are taken to be ‘almost perfect’ reliability and ‘perfect’ reliability,

respectively, after Landis and Koch.11

40

Activity

30

10

20

2nd

Rou

nd

400 10 20 300

1st Round

20

Damage

15

5

10

2nd

Rou

nd

00

5 10 15 20

1st Round

(a) (b)

Fig 4. (a, b) Prediction of the second rating based on the results of the first rating. The intercept and slope of the regression equation relating first

scores to second scores show small differences for both subscales (intercepts of 0.99 for activity and 0.09 for damage) and a slope close to 1

(b = 0.92 for activity and b = 1.04 for damage).




Time of investigation

The time needed to conduct the patient assessment with the

RCLASI ranged from 181Æ3 s to 260Æ0 s in the first rating and

from 129Æ6 s to 181Æ3 s in the second rating. The mean time

of assessment of all physicians decreased significantly

(P < 0Æ001) from 225Æ9 ± 80Æ70 s in the first rating to

160Æ2 ± 61Æ6 s in the second rating (Fig. 5).

Critical assessment of the Revised Cutaneous Lupus

Erythematosus Disease Area and Severity Index by the

investigators

After finalizing the validation of the RCLASI, all investigators

received a questionnaire to evaluate whether the RCLASI is

feasible and well structured in its design and, if not, which

changes are suggested. Fifty per cent of the investigators sta-

ted that the sites of involvement (e.g. scalp, face, chest)

included in the first part of the RCLASI present an optimal

selection. In contrast, 25% criticized that there were too

many sites of involvement, and 25% found it difficult to dis-

tinguish between single sites of involvement (Table 3). The

majority (73%) of the investigators considered the choice of

the different skin lesions (e.g. erythema, scaling, dyspigmen-

tation) as optimal in the RCLASI. In addition, a large propor-

tion of the investigators were content with the sites of

involvement (e.g. buccal, hard and soft palate) and the types

(e.g. erythematous and keratotic) of mucous membrane

lesions (100% and 90%, respectively). More than half of the

investigators (64%) evaluated the different types of nonscar-

ring alopecia (diffuse alopecia and lupus hair) as optimal.

The new method of calculating the score of scarring alopecia

was accepted by 70% of the investigators; only 10% found it

too difficult, and 20% would like to have a more precise

method. None of the investigators had any problems finding

the ‘most severely affected LE-specific lesion’. However, 36%

concluded that the criteria for ‘most severely’ are not well

defined, and 64% stated that the ‘most severely affected LE-

specific lesion’ cannot clearly be defined in a larger and ⁄or

symmetrical area with several skin lesions. Finally, we asked

whether training on the RCLASI would help to fill out the

scoring system and 31% of the investigators answered ‘yes’;

however, 31% also mentioned that it would probably not be

feasible in an international analysis.

Discussion

In our opinion, the CLASI, as the only existing evaluation tool

for activity and damage of disease in patients with CLE, is a

good instrument to measure disease severity.5–7,13 Nevertheless,

the CLASI does not give an accurate assessment of the disease

severity in all CLE subtypes (D. Bein et al., manuscript submit-

ted). For example, most patients present with lesions showing

oedema at an early stage of the disease, regardless of the CLE

subtype; moreover, oedema is one of the most prominent fea-

tures of lupus erythematosus tumidus (LET).14 Thus, oedema is

an important criterion that is not included in the activity score

of the CLASI, which can possibly result in a nonoptimal evalu-

ation of these patients. Furthermore, the efficacy of a therapeutic

agent on oedema cannot be evaluated in a clinical trial. To ana-

lyse the four subtypes of CLE precisely, we modified and

expanded the CLASI in several points. In order to validate the

revised version of this scoring instrument for disease activity

and damage in patients with CLE, we assessed the RCLASI for

content validity, inter-rater validity, intrarater validity and prac-

tical applicability. The score proved to be valid and well applica-

ble, verifying it as especially relevant for multicentre studies,

which form the basis of any therapeutic evaluation for CLE.

Because specific lesions of ACLE and DLE in the area of the

lips could not be listed in the original CLASI, we added this

site of involvement in the RCLASI. To distinguish between

superficial SCLE scaling (psoriasiform ⁄papulosquamous) and

DLE firm adherent scaling (follicular plugging), we separated

both lesions and assigned each lesion 1 point for the activity

score. Furthermore, we changed the heading of the column

‘scale ⁄hypertrophy’, which is listed in the CLASI, to ‘scal-

ing ⁄hyperkeratosis’ as well as the unspecific term ‘verru-

cous ⁄hypertrophic’ to the correct descriptive morphological

term of ‘verrucous hyperkeratosis’. While the CLASI activity

score consists of the erythema and the scale ⁄hypertrophy

scores only, the activity score of the RCLASI includes two

additional sections, namely the oedema ⁄ infiltration score and

the score for subcutaneous nodules ⁄plaques. The oedema ⁄infiltration score is necessary to include early evolving lesions

of ACLE, SCLE and DLE; moreover, it is the most important

criterion to assess LET.15 Therefore, this parameter is essential

for equally recording the activity in all CLE subtypes with one

500

400

300

200

Tim

e (s

)

100

0

Round 1 Round 2

Fig 5. Time of investigation. The variation over time for all

investigators needed to conduct the patient assessment with a Revised

Cutaneous Lupus Erythematosus Disease Area and Severity Index in

two different ratings. Box area, 50% of data [i.e. lines in box denote

medians, bars include at most 1.5 of interquartile distance, difference

between first and third quartiles of data, circles indicate values out of

the 1.5-fold box area (outliers), whereas asterisks indicate values out

of the 3-fold box area (extreme outliers)].




instrument. In addition, the subcutaneous nodules ⁄plaques

score allows for the collection of data in patients with clini-

cally active LE panniculitis and is, therefore, also required to

score activity.

The dyspigmentation score of the CLASI was originally

divided only into the criteria ‘absent’ and ‘present’, giving 0

points for absent and 2 points for present. To distinguish

between, for example, SCLE dyspigmentation (only hypo-

pigmentation) and DLE dyspigmentation (hypo- and hyper-

pigmentation), two criteria were established in the RCLASI,

giving 1 point each for hypopigmentation or hyperpigmenta-

tion. With this differentiation, the simultaneous appearance of

hypo- and hyperpigmentation is assessed with two points.

Moreover, the CLASI criteria of ‘scarring ⁄atrophy ⁄panniculitis’

that is subdivided into ‘absent’, ‘scarring’ and ‘severely atro-

phic scarring or panniculitis’ was changed to ‘scarring ⁄atro-

phy’, because panniculitis is a more histological than a clinical

criterion. Furthermore, the subdivision of the scarring ⁄atrophy

score was changed to ‘initial scarring’ being evaluated with 1

point, and ‘severe firm ⁄atrophic ⁄vermicular scarring’ being

evaluated with 2 points to separate early scarring from

chronic, atrophic and ⁄or vermicular scarring DLE lesions.

Finally, we added the criterion ‘lipatrophy’ to include the pos-

sibility of assessing the typical damage of a burned-out stage

in LE panniculitis, which was also rated with 2 points.

The section ‘mucous membrane’ was comprehensively

changed in the RCLASI. We think it is essential to differentiate

between lesion and ulceration and to give more weight to

ulceration than to lesions. The statement by the patient that

mucous membranes are involved should not be the premise

for examining it, as stated in the CLASI; therefore, we deleted

the sentence ‘examine if patient confirms involvement’. The

differentiation between various sites of involvement, such as

‘buccal mucosa’, ‘hard and soft palate’ and ‘other mucous

membranes’ is important as erosions and ulcerations in SLE

more frequently affect the hard and soft palate in contrast to

discoid lesions at the buccal mucosa in DLE.

In the CLASI, alopecia is measured by giving 1 point for

recent hair loss within the last 30 days as reported by the

patient. We deleted this paragraph as a time specification

reported by patients is difficult to judge and include in an objec-

tive score. Moreover, we modified the heading of the section on

Table 3 Questionnaire for critical assessment of the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) by theinvestigatorsa

(%)

Please evaluate the sites of involvement of skin lesions in the RCLASI (e.g. scalp, face, chest)Optimal 50

Not enough sites 0Too many sites 25

Sites are not well distinguishable 25Right and left site (symmetrical appearance) should be separated 0

Please evaluate the skin lesions in the RCLASI (e.g. erythema, scaling, dyspigmentation)Optimal 73

Not enough skin lesions 0Too many skin lesions 9

Skin changes are not distinguishable 18Please evaluate the site of involvement of mucous membrane lesions in the RCLASI

Optimal 100Not enough sites 0

Too many sites 0

Please evaluate the mucous membrane lesions in the RCLASIOptimal 90

Not enough lesions 10Too many lesions 0

Please evaluate the different types of nonscarring alopecia in the RCLASIOptimal 64

Differentiation into ‘diffuse alopecia’ and ‘lupus-hair’ is too specific 9The criteria are not distinguishable (e.g. slight vs. severe diffuse) 27

Please evaluate the method of scoring for scarring alopeciaOptimal 70

Too difficult 10Too imprecise 20

Please evaluate the method of scoring the ‘most severely affected LE-specific lesion’It is not problematic to find the ‘most severely affected LE-specific lesion’ 0

Criteria for ‘most severely’ are not well-defined 36In a larger ⁄ symmetric area with several skin lesions the ‘most severely affected LE-specific lesion’ can not clearly be defined 64

aSeveral answers were possible within one question.




alopecia, which is not clinically scarred, into diffuse alopecia

and also changed the scoring system as, in our opinion, non-

scarring alopecia does not present with hair loss in one or more

than one quadrant. In addition, we added a new paragraph

named ‘lupus hair’, or ‘wooly hair’, a typical sign in patients

with active disease of primarily SLE, which is characterized by

thin, weakened, brittle hairs, especially at the anterior hair-

line.16 This hair easily fragments and becomes unruly, giving a

characteristic appearance. If ‘lupus hair’ is present, the activity

score is increased by 3 points; if it is absent, no point is added.

The scarring of the scalp was formerly measured within the

CLASI by dividing the scalp into four quadrants and giving

points to the number of quadrants that were affected even if

there is only one lesion within the quadrant. This way of

weighting the scarring of the scalp leads to a high damage score,

even if there are only a few small lesions spread over the whole

scalp. We modified this measurement after an assessment guide-

line developed for alopecia areata by Olsen et al.10 The scalp is

divided into the left and the right areas as well as into the top

and back areas. Every area has a different dimension and will,

therefore, be weighted differently (from 18% to 40%). The per-

centage of scarring alopecia can now be estimated in each area.

This value is multiplied by the percentage of the scalp surface

area (from 0Æ18 to 0Æ40). These calculated values can be

weighted with a scale, giving 0 (absent) to 6 points (75–100%

scarring alopecia).

In summary, the RCLASI provides a clinically meaningful

tool to assess disease activity and damage in patients with CLE

and further refinements by other groups should contribute to

the utility of this instrument. Due to the lack of an accurate

assessment of disease severity in all CLE subtypes, a revision

of the CLASI with a critical analysis of the included parameters

was performed. The reliability studies in this manuscript sup-

port the validity and applicability of the RCLASI confirming

that it is a valuable instrument for multicentre studies and for

the evaluation of activity and damage in CLE.

What’s already known about this topic?

• In 2005, the CLASI (Cutaneous Lupus Erythematosus

Disease Area and Severity Index) scoring system was

developed to evaluate activity and damage of the dis-

ease; however, the CLASI does not provide accurate

assessment in all disease subtypes.

What does this study add?

• The revised CLASI (RCLASI), which was validated in the

present study, includes several new and adjusted parame-

ters. It provides a clinically meaningful tool to assess the

disease activity and damage in patients with CLE.

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Revised Cutaneous Lupus erythematosus Disease Area and Severity Index (RCLASI): a modified outcome instrument for cutaneous lupus erythematosus