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Skin Thickness Score in Systemic Sclerosis

Skin Thickness Score in Systemic Sclerosis - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Questionnaires, Related


S k i n T h i c k n e s s S c o r e i n S y s t e m i c S c l e r o s i s : A n A s s e s s m e n t
o f l n t e r o b s e r v e r V a r i a b i l i t y i n 3 I n d e p e n d e n t S t u d i e s
i 1
I
l
P H I L I P J . C L E M E N T S , P E T E R A . L A C H E N B R U C H , J A M E S R . S E I B O L D , B E N N Y Z E E , V I R G I N I A D . S T E E N , ’
P A U L B R E N N A N , A L A N J . S I L M A N , N A N C Y A L L E G A R , J O H N V A R G A , M A R Y M A S S A , F R E D E R I C K M . W I G L E Y , ’
F R A N C E S I N G E N i l D , M I C H A E L W E I S M A N . B A R B A R A W H I T E , R I C H A R D W . M A R T I N , D E B O R A H M c C L O S K E Y ,
L A R R Y w . M O R E L A N D , M A U R E E N M A Y E S , E D W A R D v . L A L L Y , M A R Y U N A N U E , D A V I D H . C O L L I E R , I \
S T E V E N W E I N E R , A R T H U R W E I N S T E I N , T H O M A S A . M E D S G E R , J r , B R I A N A N D R E W S ,
M A R Y D I X O N , a n d D A N I E L E . F U R S T
A B S T R A C T . O b j e c t i v e . U s i n g d a t a f r o m 3 i n d e p e n d e n t s t u d i e s , t o q u a n t i f y t h e i n t e r o b s e r v e r r e l i a b i l i t y o f s e m i ›
q u a n t i t a t i v e s k i n s c o r i n g m e t h o d s ( t h e o r i g i n a l a n d t h e m o d i f i e d R o d n a n s k i n t h i c k n e s s s c o r e s ) u s e d
t o a s s e s s t h e d e g r e e a n d e x t e n t o f c u t a n e o u s t h i c k e n i n g i n s y s t e m i c s c l e r o s i s ( S S c ) .
M e t h o d . I n t e r o b s e r v e r v a r i a b i l i t y o f t h e o r i g i n a l R o d n a n s k i n t h i c k n e s s s c o r e m e t h o d ( c u t a n e o u s
t h i c k n e s s a s s e s s e d i n 2 6 b o d y s u r f a c e a r e a s u s i n g a 0 - 4 s c a l e ) w a s e v a l u a t e d i n o n e s t u d y . T h e m o d i f i e d
R o d n a n m e t h o d ( c u t a n e o u s t h i c k n e s s a s s e s s e d i n 1 7 b o d y s u r f a c e a r e a s u s i n g a 0 - 3 s c a l e ) w a s e v a l u a t e d
i n 2 s t u d i e s . I n a l l 3 s t u d i e s , e a c h p a t i e n t ’ s s k i n t h i c k n e s s w a s a s s e s s e d b y 6 o r 7 o b s e r v e r s i n a
b l i n d e d f a s h i o n .
R e s u l t s . T h e o v e r a l l w i t h i n p a t i e n t s t a n d a r d d e v i a t i o n s w e r e n o t s t a t i s t i c a l l y d i f f e r e n t i n a l l 3 s t u d i e s
( 5 . 4 , 4 . 6 a n d 4 . 6 ) i r r e s p e c t i v e o f t h e o v e r a l l m e a n s k i n t h i c k n e s s s c o r e s ( 2 6 . 6 , 1 8 . 3 a n d 1 7 . 7 ) . W i t h
t h e o r i g i n a l R o d n a n t e c h n i q u e , t h e w i t h i n p a t i e n t s t a n d a r d d e v i a t i o n t e n d e d t o b e h i g h e r i n p a t i e n t s
w i t h h i g h e r s k i n t h i c k n e s s s c o r e s . I n t h e 2 s t u d i e s w h i c h u s e d t h e m o d i f i e d t e c h n i q u e , n o s i g n i f i c a n t
d i f f e r e n c e s i n w i t h i n p a t i e n t s t a n d a r d d e v i a t i o n w e r e n o t e d b e t w e e n h i g h a n d l o w s k i n t h i c k n e s s s c o r e s .
C o n c l u s i o n s . T h r e e i n d e p e n d e n t s t u d i e s d e m o n s t r a t e t h a t t h e R o d n a n s k i n t h i c k n e s s s c o r i n g t e c h ›
n i q u e s a r e r e p r o d u c i b l e a m o n g d i f f e r e n t o b s e r v e r s ( t h e w i t h i n p a t i e n t s t a n d a r d d e v i a t i o n b e i n g c o n ›
s i s t e n t l y a b o u t 5 u n i t s ) . O u r d a t a p r o v i d e v a l u a b l e i n f o r m a t i o n n e e d e d f o r s a m p l e s i z e c a l c u l a t i o n s
f o r S S c t r i a l s i n w h i c h s k i n t h i c k n e s s s c o r e i s a n o u t c o m e v a r i a b l e . ( J R h e u m a t o l 1 9 9 3 ; 2 0 : 1 8 9 2 - 6 )
K e y I n d e x i n g T e r m s :
S C L E R O D E R M A S K I N S C O R E S K I N T H I C K N E S S
S y s t e m i c s c l e r o s i s ( S S C ) i s a c o n n e c t i v e t i s s u e d i s e a s e w h i c h
a f f e c t s s k i n , j o i n t s , a n d t e n d o n s a n d m a n y i n t e r n a l o r g a n s .
C u t a n e o u s t h i c k e n i n g i s a b s e n t i n o n l y 1 - 3 % o f p a t i e n t s i n
w h o m t h e d i a g n o s i s i s m a d e , b u t a l l o t h e r s h a v e v a r y i n g
d e g r e e s o f s k i n i n v o l v e m e n t
1

2
T h e n a t u r a l h i s t o r y o f s k i n
F r o m t h e D e p a r t m e n t s o f M e d i c i n e a n d B i o s t a t i s t i c s . U C L A S c h o o l o f
M e d i c i n e . L o s A n g e l e s , C A , U S A .
S u p p o r t e d i n p a r t b y a w a r d s f r o m U n i t e d S c ! e r o d e r m a F o u n d a t i o n ,
S c l e r o d e r m a F e d e r a t i o n , F D A O r p h a n D r u g P r o g r a m F D - R - 0 0 0 6 8 3 ,
A r t h r i t i s F o u n d a t i o n C l i n i c a l S c i e n c e G r a n t p r o g r a m , G C R C G r a n t
M o / R R 0 0 8 2 7 , N I H A R - 0 1 8 1 7 , N I H M u l t i p u r p o s e A r t h r i t i s C e n t e r
g r a n t P 6 0 - A R - 3 6 8 3 4 t o U C L A .
N . A l l e g a r , M D , F a c u l t y i n R e s i d e n c e , R o b e r t W o o d J o h n s o n M e d i c a l
S c h o o l ; B . A n d r e w s , M D , P h D , P r o f e s s o r o f M e d i c i n e , U n i 1 • e r s i t v o f
C a l i f o r n i a a t I r v i n e ; P . B r e n n a n , A R C E p i d e m i o l o g y U n i t , U n i v e r s i t v
o f M a n c h e s t e r ; P . J . C l e m e n t s , M D , P r o f e s s o r o f
M e d i c i n e / R h e u m a t o l o g y , U C L A S c h o o l o f M e d i c i n e ; D . H . C o l l i e r ,
M D , A s s o c i a t e P r o f e s s o r o f M e d i c i n e , C h i e f o f R h e u m a / O / o g v ,
U n i v e r s i t y o f C o l o r a d o H e a l t h S c i e n c e s C e n t e r ; M . D i x o n , R N , R H S ,
N u r s e , U n i v e r s i t y o f C a l i j i ; r n i a a l S a n D i e g o ( U C S D ) ; D . E . F u r s t ,
M D , C l i n i c a l P r o f e s s o r o f M e d i c i n e , V i r g i n i a M a s o n R e s e a r c h C e n t e r ;
F . I n g e n i t o , R N , A d u l t N u r s e P r a c t i t i o n e r , U n i v e r s i t y o f C o n n e c t i c u t
H e a l t h C e n t e r ; P . A . L a c h e n b r u c h , P h D , P r o f e s s o r o f B i o s t a t i s 1 i c s ,
U C L A : E . V . L a l l y , M D , D i r e c t o r , D i v i s i o n o f R h e u m a t o / o g y , R o g e r
W i l l i a m s M e d i c a l C e n t e r , B r o w n U n i v e r s i t y ; R . W . M a r t i n , M D ,
B u t t e r w o r l h H o s p i t a l , G r a n d R a p i d s , M l ; M . M a s s a , M D , A s s o c i a t e
P r o f e s s o r o f M e d i c i n e , S t r i t c h S c h o o l o f M e d i c i n e ; M . M a y e s , M D ,
i n v o l v e m e n t i n S S c h a s b e e n d e s c r i b e d a s o c c u r r i n g i n 3 c l i n ›
i c a l p h a s e s
1 4
: a n i n i t i a l p e r i o d o f p r o g r e s s i v e t h i c k e n i n g o f
t h e s k i n b y f l u i d a n d / o r c o l l a g e n ( p h a s e I ) , f o l l o w e d b y a
v a r i a b l e p e r i o d o f m i n i m a l c h a n g e o r p l a t e a u ( p h a s e I I ) a n d
l a t e r b y a p e r i o d o f s o f t e n i n g o r t h i n n i n g ( p h a s e I I I ) .
A s s i s t a n t P r o f e s s o r o f M e d i c i n e , W a v n e S t a t e U n i v e r s i t y ; D .
M c C / o s k e y , R N , C o o r d i n a t o r , S c l e r o d e r m a P r o g r a m , R o b e r t W o o d
J o h n s o n M e d i c a l S c h o o l ; T . A . M e d s g e r , J r . , M D , P r o f e s s o r o f
M e d i c i n e , U n i v e r s i t y o f P i f l s b u r g h S c h o o l o f M e d i c i n e ; L . W .
M o r e l a n d , M D , A s s i s t a n t P r o f i ’ . \ ’ s o r o f M e d i c i n e , U n i v e r s i f \ ’ o f A l a b a m a
a t B i r m i n g h a m ; B . W h i t e , M D , A s s o c i a t e P r o f e s s o r o f M e d i c i n e ,
U n i v e r s i t y o f M a r . v i a n d S c h o o l o f M e d i c i n e ; J . R . S e i b o l d , M D ,
A s s o c i a t e P r o f e s s o r o f M e d i c i n e , D i r e c t o r , C l i n i c a l R e s e a r c h C e n t e r ,
R o b e r t W o o d J o h n s o n M e d i c a l S c h o o l ; A . J . S i l m a n , M D , A R C
P r o f e s s o r i n R h e u m a t i c D i s e a s e E p i d e m i o l o g v , U n i v e r s i t y o f
M a n c h e s / e r ; V . S t e e n , M D , A s s o c i a l e P r o f e s s o r o f M e d i c i n e ,
U n i v e r s i t v o f P i u s h u r g h S c h o o l o f M e d i c i n e ; M . U n a n u e , M D ,
U n i v e r s i t y o f M i a m i S c h o o l 1 1 ( M e d i c i n e ; J . V a r g a , M D , A s s o c i a t e
P r o f e s s o r 1 1 ( M e d i c i n e , 7 7 w m a s J e f f e r s o n U n i v e r s i t y ; S . W e i n e r , M D ,
F A C P , A s s o c i a t e C l i n i c a l P r o f i ’ s s o r o f M e d i c i n e ! R h e u m a t o l o g v , U C L 4
S c h o o l o f M e d i c i n e ; A . W e i 1 1 . H e i n , M D , P r o f e s s o r o f ’ M e d i c i n e , N e w
Y o r k M e d i c a l C o l l e g e ; M . W e i s m a n . M D , P r o f e s s o r o f M e d i c i n e ,
U C S D M e d i c a l C e n t e r ; F . M . W i g l e v , M D , A s s o c i a t e P r o f e s s o r o f
M e d i c i n e , T h e J o h n s H o p k i n s U n i 1 • e r s i t v S c h o o l o f M e d i c i n e ; B . Z e e ,
P h D , C l i n i c a l T r i a l s G r o u p , N C J C , Q u e e n ’ s U n i v e r s i r y , K i n g s t o n , O N .
A d d r e s s r e p r i n l r e q u e s t s t o D r . P . C l e m e n / s , / 0 0 0 V e t e r a n A v e . , R m
3 2 - 4 8 , L o s A n g e l e s , C A 9 0 0 2 4 .
S u b m i t t e d F e b r u a r \ ’ 2 6 , 1 9 9 3 a c c e p t e d M a r c h 2 6 , 1 9 9 3 .
I
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- ~ - - - - . - . . . " ’ J , , , = , J i f R h . , , m , w f o g y 1 9 9 3 c 2 0 1 1 J

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For prognostic and classification purposes
1
-
4
patients with
SSc are often categorized on the basis of whether cutaneous
sclerosis affects skin proximal to ("diffuse" dSSc), or is
limited to areas distal to, the elbows, knees and clavicles
("limited" ISSc). Patients with limited cutaneous SSc fre›
quently have an indolent course with mild cutaneous thick›
ening of only the fingers, hands and/or face and mild visceral
involvement. In contrast, patients with diffuse cutaneous
thickening tend to have rapid progression of skin thickening
within the first 2-3 years, followed in many by gradual thin›
ning over subsequent years. Severe skin involvement has
been associated with a poor prognosis: patients with exten›
sive skin disease have decreased survival and a greater risk
of developing scleroderma renal crisis and/or severe SSc pul›
monary interstitial and myocardial disease
1 7

Objective variables that correlate with disease severity are
just now being developed. Several methodologies (i.e.,
devices for measuring distensibility of the skin, ultrasound
of the skin, photocopying of palmprints, measurement of
cutaneous hypoxia) have failed to provide a clinically useful
method for quantifying skin thickness
811
Rodnan first used
a semiquantitative method for determining the extent and
degree of skin thickening in systemic sclerosis in 1968 (un›
published). His original total skin score consisted of a 0-4
estimation of skin thickening by clinical palpation of 26 ana›
tomic areas for a maximum score of 104. He later demon›
strated that the clinical estimation of forearm skin thicken›
ing by palpation correlated with the weight of a uniform
diameter skin punch biopsyt
2
Recently the original Rodnan
total skin score has been simplified by decreasing the num›
ber of body areas examined and by making the grading scale
0-3 (modified Rodnan skin score). The original Rodnan to›
tal skin score and its recent modifications, are now being
used to document and follow the course of patients in the
clinic and in drug trials. Unfortunately there is as yet little
published data addressing the issue of the methods’ reliabil›
ity and reproducibility, both within and among investigators.
A one-day session was conducted in Pittsburgh in 1985
to determine interobserver reliability of the original Rodnan
method. lnterobserver reliability of the modified Rodnan
method was assessed by participants in a one-day session in
the United Kingdom (UK) in 1990 and by participants in a
large US multicenter controlled trial of penicillamine (DPEN)
who met at one of 4 locations in the United States in the sum›
mer of 1992. We now describe an analysis of these 3 studies,
1
which although conducted independently, employed similar
, skin scoring methodology to examine the reliability of the
Rodnan skin score technique.
MATERIALS AND METHODS
Skin assessments. The Pittsburgh study used the original Rodnan 0-4 scale
v. 10 assess cutaneous thickness (0 = normal skin thickness; I = slight but
definite thickening; 2 = mild-moderate thickening; 3 = moderately severe
thickening; and 4 = severe thickening) by clinical palpation of 26 surface
I areas of the body: face. anterior chest. abdomen, upper back, lower back,

II Clements, et al: Skin scoring in SSc
neck and (right and left separately) the fingers, dorsum of hands, forearms,
upper arms, shoulders, breasts, thighs, lower legs, dorsum of feet, and toes,
The scores from the individual areas were summed to produce the total skin
score, which could range from 0-104
1
2.
The modified Rodnan skin score technique used in the UK and the DPEN
portion of the studies
13
consisted of an evaluation of a patient’s skin thick›
ness rated by clinical palpation using a 0-3 scale (0 = normal skin thick›
ness; l = mild skin thickness; 2 = moderate skin thickness; and 3 = severe
skin thickness with inability to pinch the skin into a fold) for each of 17
surface anatomic areas of the body: face, anterior chest, abdomen, and (right
and left separately) the fingers, dorsum of hands, forearms, upper arms,
thighs, lower legs and dorsum of feet. These 17 body surface areas were
drawn from the previously described original 26u. The modified Rodnan
skin score was calculated by summing the scores from all 17 areas (range:
0-51).
Patients, All patients in these studies met the 1980 ARA classification criteria
for definite SSc
14
. Patients with SSc with varying degrees and extents of
skin thickening were examined. Although the majority of these subjects had
dSSc (cutaneous sclerosis proximal to elbows and knees and/or involving
the torso [anterior chest, abdomen]), some patients with ISSc (cutaneous
sclerosis limited to areas distal to the elbows and knees, with or without
facial involvement) also participated.
Study design. Skin induration (thickness) was assessed in a blinded ran›
domized rotation by multiple observers using the above mentioned scoring
techniques: A) In the Pittsburgh study, the original Rod nan method was
assessed in 15 patients at one sitting by 7 examiners assessing 26 body areas.
B) In the UK-Brennan study, the modified Rodnan skin score method was
assessed in 12 patients at one sitting by 6 examiners assessing 17 body areas.
A partial analysis of this study has been published
13
. C) In the DPEN study,
the modified Rodnan skin thickness score method was assessed in 5 or 6
patients by 6 or 7 examiners at each of 4 separate scoring sessions. They
examined 17 body areas. A total of 22 patients were examined by 23 ex›
aminers, With the exception of one examiner who attended 3 sessions and
3 examiners who each attended 2 sessions, each examiner attended only
one session.
Analysis. The amount of disagreement among examiners assessing patients
with a range of skin involvements was analyzed by calculating and pooling
the standard deviations (SD) of the skin thickness scores recorded on each
patient by the 6 or 7 examiners (within patient SD). The mean, within patient
SD and variance of all skin thickness score measurements on a single patient
were calculated. An overall mean skin thickness score for each of the 3 studies
was calculated by averaging the mean skin thickness scores of all the patients
examined in that study. The overall within patient SD for each study was
derived by calculating the square root of the sum of the variances divided
by the number of patients evaluated in the study. This overall within patient
SD provides a quantitative assessment of interobscrver disagreement. In
the DPEN study the results were corrected for multiple observations by
the 4 examiners who attended more than one session,
Data were also analyzed on the basis of whether patients had a high or
low skin thickness score: in the Pittsburgh study, patients with mean skin
thickness scores > 20 were classified as having high scores and those with
scores :’.’O 20 were classified as having low skin scores. In the DPEN
and UK studies, patients with skin thickness scores > 15 were classified
as having high scores and those with scores "’ 15 were classified as having
low scores.
RESULTS
The overall mean skin thickness scores for each of the 3
studies are shown in Table I. Also shown are the overall
within patient SD for each study. By obviating error intro›
duced by among patient variability, the calculation of within
patient SD (derived from the assessments on a single patient
1893

T a b l e 1 . O v e r a l l m e a n s a n d w i t h i n p a t i e n t S D f o r e a c h o f
t h e 3 s t u d i e s
S t u d y N o . P t s .
A . O r i g i n a l R o d n a n s k i n t h i c k n e s s s c o r e * *
P i t t s b u r g h 1 5
B . M o d i f i e d R o d n a n s k i n t h i c k n e s s s c o r e * *
U K ( B r e n n a n ) 1 2
O P E N 2 2
M e a n s W i t h i n P a t i e n t
2 6 . 6
1 8 . 3
1 7 . 7
S D *
– 5 . 4
– 4 . 6
– 4 . 6
* W i t h i n p a t i e n t S D = s q u a r e r o o t o f t h e s u m o f t h e v a r i a n c e s ( d e r i v e d
f r o m a s s e s s m e n t s o f s i n g l e p a t i e n t s b y m u l t i p l e o b s e r v e r s ) d i v i d e d b y t h e
n u m b e r o f p a t i e n t s .
* * P o s s i b l e r a n g e o f s k i n s c o r e s : O r i g i n a l R o d n a n = 0 - 1 0 4 ; m o d i f i e d
R o d n a n = 0 - 5 1 .
b y m u l t i p l e e x a m i n e r s ) p r o v i d e d t h e b e s t m e a s u r e o f i n t e r ›
o b s e r v e r v a r i a b i l i t y .
T h e i n t e r o b s e r v e r m e a n a n d w i t h i n p a t i e n t S D o f t h e s k i n
s c o r e s f o r e a c h p a t i e n t a r e d i s p l a y e d i n T a b l e s 2 - 4
( P i t t s b u r g h , U K - B r e n n a n a n d D P E N , r e s p e c t i v e l y ) . I n a d ›
d i t i o n , t h e o v e r a l l m e a n a n d w i t h i n p a t i e n t S D f o r t h e s u b ›
g r o u p s w i t h h i g h a n d l o w s k i n t h i c k n e s s s c o r e s a r e a l s o
s h o w n . T h e m e a n s o f t h e h i g h a n d l o w s c o r e g r o u p s i n a l l
3 s t u d i e s ( a l m o s t b y d e f i n i t i o n ) w e r e s i g n i f i c a n t l y d i f f e r e n t
( p < 0 . 0 0 1 ) . I n t h e 2 s t u d i e s u s i n g t h e m o d i f i e d R o d n a n
m e t h o d ( U K - B r e n n a n a n d D P E N s t u d i e s ) , t h e w i t h i n p a t i e n t
S D f o r t h e h i g h a n d t h e l o w s k i n t h i c k n e s s s c o r e g r o u p s w e r e
n o t s i g n i f i c a n t l y d i f f e r e n t . C o n v e r s e l y , t h e w i t h i n p a t i e n t S D
o f t h e h i g h a n d t h e l o w s k i n t h i c k n e s s s c o r e g r o u p s i n t h e
P i t t s b u r g h s t u d y , w h i c h u s e d t h e o r i g i n a l R o d n a n m e t h o d ,
w e r e m a r g i n a l l y d i f f e r e n t ( p < 0 . 0 4 , F - t e s t ) .
T a b l e 2 . l n t e r o b s e r v e r v a r i a b i l i t y i n t h e P i t t s b u r g h s t u d y ( 7
e x a m i n e r s a s s e s s i n g a s i n g l e p a t i e n t ) *
P a t i e n t N u m b e r M e a n W i t h i n P a t i e n t S D
A . H i g h s k i n t h i c k n e s s s c o r e s ( > 2 0 )
I 3 9 . 0 4 . 9
2 2 6 . 4 7 . 5
3 4 8 . 4 7 . 7
4 2 5 . 4 6 . 8
5 4 7 . 9 5 . 8
7 6 0 . 0 5 . 7
9 2 2 . 3 4 . 4
I O 3 6 . 6 5 . 1
1 3 2 0 . 7 4 . 9
M e a n 3 6 . 3 6 . 0
B . L o w s k i n t h i c k n e s s s c o r e s ( < 2 0 )
6 1 8 . 3 7 . 8
8 4 . 1 1 . 6
I I 9 . 4 2 . 8
1 2 8 . 7 2 . 9
1 4 1 7 . 1 3 . 1
1 5 1 4 . 9 5 . 5
M e a n 1 2 . 1 4 . 5 * *
* 2 6 b o d y s u r f a c e a r e a s e x a m i n e d , 0 - 4 s c a l e , p o s s i b l e r a n g e : 0 - 1 0 4 .
* * p < 0 . 0 4 , w i t h i n p a t i e n t S D ( l o w v s h i g h s k i n t h i c k n e s s s c o r e ) .
1 8 9 4
T a b l e 3 . I n t e r o b s e r v e r v a r i a b i l i t y i n t h e B r e n n a n - U K s t u d y
( 6 e x a m i n e r s a s s e s s i n g a s i n g l e p a t i e n t ) *
P a t i e n t N u m b e r M e a n W i t h i n P a t i e n t S D
A . H i g h s k i n t h i c k n e s s s c o r e s ( > 1 5 )
2 1 9 . 7 5 . 9
5 3 2 . 3 6 . 8
8 3 0 . 2 3 . 9
9 4 0 . 2 I . 9
I I 2 4 . 3 4 . 5
1 2 2 2 . 0 3 . 5
M e a n 2 8 . 1 4 . 7
B . L o w s k i n t h i c k n e s s s c o r e s ( < 1 5 )
I 9 . 5 5 . 0
3 6 . 7 3 . 1
4 1 0 . 5 6 . 3
6 4 . 8 2 . 9
7 6 . 8 2 . 5
I O 1 2 . 5 5 . 2
M e a n 8 . 5 4 . 4
* 1 7 b o d y s u r f a c e a r e a s e x a m i n e d , 0 - 3 s c a l e . p o s s i b l e r a n g e : 0 - 5 1 .
I
(
!
I
(
I
\
T a b l e 4 . I n t e r o b s e r v e r v a r i a b i l i t y i n t h e D P E N s t u d y ( 7 I
e x a m i n e r s a s s e s s i n g a s i n g l e p a t i e n t ) *
P a t i e n t N u m b e r M e a n W i t h i n P a t i e n t S D
A . H i g h s k i n t h i c k n e s s s c o r e s ( > 1 5 )
P l 1 6 . 3 4 . 5
P 2 1 9 . 4 3 . 6
P S 2 3 . 0 3 . 3
U l 1 5 . 6 4 . 5
U 2 1 6 . 9 4 . 8
U 3 3 3 . 7 5 . 5
U 4 2 0 . 3 4 . 8
u s 2 5 . 1 I . 9
U 6 2 0 . 9 2 . 0
N 2 3 0 . 9 5 . 7
N S 2 3 . 7 4 . 8
N J I 2 3 . 9 5 . 0
N J 2 2 0 . 0 5 . 9
N J 3 1 6 . 0 3 . 8
N J S 2 0 . 6 6 . 6
M e a n 2 1 . 7 4 . 6
B . L o w s k i n t h i c k n e s s s c o r e s ( < 1 5 )
P 3 1 1 . 6 9 . 5
P 4 1 4 . 3 4 . 7
N I * * 8 . 3 1 . 0
N 3 3 . 0 1 . 4
N 4 1 . 4 I . I
N J 4 1 2 . 0 4 . 0
N J 6 1 0 . 9 4 . 4
M e a n 8 . 8 4 . 7
* 1 7 b o d y s u r f a c e a r e a s e x a m i n e d , 0 - 3 s c a l e , p o s s i b l e r a n g e : 0 - 5 1 .
* * P a t i e n t e x a m i n e d b y 6 o b s e r v e r s .
D I S C U S S I O N
I n t h e p a s t , s t u d i e s a s s e s s i n g c u t a n e o u s i n v o l v e m e n t i n S S c
r e l i e d o n q u a l i t a t i v e d e s c r i p t i o n s o f t h e s k i n . S e v e r a l q u a n -
" ’ 1 " " ’ " " ’ " f R h , , , = < o f o g y 1 9 9 3 > 2 0 > I I l

titative methods have been proposed. Bluestonc used a suc›
tion cup to measure skin distensibility and explored photo-
\
copies of palmprints as means of quantifying skin discase
8
.
Roentgcnographic methods were proposed to determine skin
( thickness in relation to steroid induced cutaneous atrophy
9
t and some investigators used xeroradiography, ultrasound,
l and transcutaneous oxygen pressure measurements to quan-
1 titate skin thickness’!
11
. Although the initial descriptions of
these methods suggested they arc reliable, for various rea›
sons they have not been widely applied in clinical trials.
Since Rodnan ’s initial description of the total skin score
method utilizing clinical palpation to estimate skin thickness,
several variations of this technique for evaluating SSc skin
involvement semiquantitatively have been reported
7
". Be›
cause the modified Rodnan method (using a 0-3 scale) is
more easily learned and applied and because it eliminates
some difficult to evaluate areas (i.e., neck. shoulders. breasts,
upper and lower back, toes). it has become the preferred
method for evaluating skin thickness in SSc. Even so, only
one assessment of its intra and/or interobscrver variability
has been rcportcd
11
Brennan recently published a partial
analysis of a one-day session conducted in the UK designed
to evaluate interobservcr variability for the modified Rodnan
technique
11
Independently 2 groups in the United States
have also conducted similar sessions.
Since the patient remains constant when many examiners
assess the same patient on the same day, any variability in
the assessment is due primarily to the differences among ex›
t aminers. The calculation of the mean and within patient SD
(
for individual patients provides a readily applicable index
of interobserver (examiner) variability. The 3 studies sum-
J
marized here demonstrate independently that the overall
within patient SD (derived by multiple observers examining
the same patient) is about 5 skin thickness score units (Table
j 1). The within patient SD in the Pittsburgh study using the
(
original Rodnan method was slightly higher at 5.4 (but not
significantly) than that in the modified technique (at 4.6).
l
Possible reasons for this difference are the inclusion of less
experienced examiners (fellows, nurses), an increased num›
ber of body surface areas examined and a higher scaling
system.
Most of the examiners participating in these 3 studies were
experienced in palpation of skin in SSc. Several neophyte
examiners had SD that were higher (but not significantly)
than those of the more experienced examiners. It is very en-
, couraging, nevertheless, to note that regardless of the group
of examiners studied and whether they used the original or
the modified Rodnan method, the within patient SD remained
similar. This finding lends credence to the contention that,
( like joint tenderness and swelling scores in rheumatoid
( arthritis
16

17
, skin scores in SSc are reproducible, with an
acceptable degree of variability, among examiners at differ›
j ent institutions and in different countries.
I When patients were divided on the basis of high and low
r
Clements, et al: Skin scorini; in SSc
skin thickness scores. the within patient SD using the modi›
fied Rodnan method were virtually identical (Tables 3 and
4). For the original Rodnan method (Pittsburgh study),
however, the within patient SD were significantly different
(p <0.04), measuring 6.0 and 4.5 in the high and low
groups, respectively (Table 2). The above cited reasons (ex›
aminer experience, scaling system) could account for this
difference.
Interobserver reliability is often expressed as the coeffi›
cient of variation (within patient SD divided by the mean).
Because the skin thickness score mean is lower in patients
with limited skin thickening, the coefficient of variation is
higher in those individuals than in subjects with high skin
thickness scores. The coefficient of variation will, therefore,
not be as useful for understanding interobservcr variability
of skin thickness scores as the within patient SD itself.
The quantitation of interobserver reliability for skin scor›
ing is essential for determining sample sizes needed for SSc
drug trials in which change in skin thickness score is a
primary variable. Because patients with SSc with diffuse
cutaneous involvement have higher skin thickness scores than
those with limited cutaneous disease, the patients with dSSc
are more likely to show significant changes in skin thick›
ness in response to an effective therapy. For example (Table
5), the mean modified Rodnan skin thickness score for a
group of patients with dSSc is likely to be about 20 and the
interobserver within patient SD now known to be about 5.
Entry and final skin scores arc likely to be correlated, prob›
ably at the 0.5-0.7 level. From Table 5 we see that for an
effect size of 3 units (3 units more improvement in the treat›
ment than in the control group) and an assumed 0.6 correla›
tion between initial and final skin thickness score, we would
need 36 subjects in each group. Assuming an attrition rate
of 25-40% we would need to enter a total of 45-50 subjects
in each treatment arm to be assured that 36 subjects in each
arm would have complete data available for final analysis.
If the effect size is expected to be 5 units or 25 % (and there›
fore more clinically significant), then the number of subjects
needed would be less (i.e., 14 subjects would be needed in
each treatment group to demonstrate an effect size differ›
ence of 5 units plus an additional 3-4 patients needed to
replace patients lost by attrition). On the other hand, if the
Table 5. Estimation of the number of subjects required in
both treatment and control groups*
Differences Between Con›
trol and Treatment Groups
Unit Percent
3
5
10
15
25
50
Correlation Between Initial and
Final Skin Thickness Scores
0.5 0.6 0.7
45
17
5
36
14
4
7
II
3
* Assumptions: Mean skin thickness score = 20 units in both groups at
entry: interobserver within patient SD = 5 units: alpha = 0.05: power =
0.8: and a correlation between initial and final skin scores of0.5, 0.6, or 0.7.

p o w e r i s i n c r e a s e d t o 0 . 9 , t h e n u m b e r o f s u b j e c t s r e q u i r e d
i s i n c r e a s e d a c c o r d i n g l y . U s i n g t h e T a b l e 5 e x a m p l e , a b o u t
9 0 - 1 0 0 p a t i e n t s w i t h d S S c w o u l d b e r e q u i r e d t o a c h i e v e t h e
a i m o f s h o w i n g a 3 u n i t ( o r 1 5 % ) d i f f e r e n c e b e t w e e n t r e a t ›
m e n t a n d c o n t r o l g r o u p s a t t h e e n d o f t h e t r i a l . F e w r e p o r t ›
e d c l i n i c a l t r i a l s h a v e y e t a c h i e v e d t h i s s i z e . F u t u r e t h e r a p e u ›
t i c i n t e r v e n t i o n t r i a l s i n S S c m a y n e e d t o i n c l u d e l a r g e r n u m ›
b e r s o f p a t i e n t s i n o r d e r t o o b v i a t e a t y p e I I e r r o r . O u r s t u d y
p r o v i d e s v a l u a b l e i n f o r m a t i o n n e e d e d f o r t h e c a l c u l a t i o n o f
a p p r o p r i a t e s a m p l e s i z e s f o r c l i n i c a l t r i a l s i n p a t i e n t s w i t h
S S c i n w h i c h s k i n t h i c k n e s s s c o r e i s a p r i m a r y o u t c o m e
v a r i a b l e .
A C K N O W L E D G M E N T
W e w o u l d l i k e t o t h a n k J o h n H a r t e r , M D , w h o s e i n t e r e s t i n t h e c u t a n e o u s
a s p e c t s o f s c l e r o d e r m a s t i m u l a t e d u s t o p e r f o r m a n d c o m p l e t e t h i s a n a l y s i s .
R E F E R E N C E S
I . S e i b o l d J R : S c l e r o d e r m a . I n : K e l l e y W N . H a r r i s E D . R u d d y S .
S l e d g e C B , e d s . T e x t b o o k o f R h e u m a t o l o g y . P h i l a d e l p h i a : W B
S a u n d e r s 1 9 9 3 ; 1 1 1 3 - 4 3 .
2 . L e R o y E C , B l a c k C , F l e i s c h m a j e r R , e t a l : S c l e r o d e r m a
( S y s t e m i c S c l e r o s i s ) : C l a s s i f i c a t i o n , s u b s e t s a n d p a t h o g e n e s i s .
J R h e u m a t o l 1 9 8 8 ; 1 5 : 2 0 2 - 5 .
3 . M e d s g e r T A J r : P r o g r e s s i v e s y s t e m i c s c l e r o s i s . C l i n R h e u m D i s
1 9 8 3 ; 9 : 6 5 5 - 7 0 .
4 . S t e e n V D , M e d s g e r T A J r : E p i d e m i o l o g y a n d n a t u r a l h i s t o r y o f
s y s t e m i c s c l e r o s i s . R h e u m D i s C l i n N o r t h A m 1 9 9 0 ; 1 6 : 1 - 1 0 .
5 . C l e m e n t s P J , L a c h e n b r u c h P A , F u r s t D E , P a u l u s H E . S t e r z
M G : C a r d i a c s c o r e . A s e m i q u a n t i t a t i v e m e a s u r e o f c a r d i a c
i n v o l v e m e n t t h a t i m p r o v e s p r e d i c t i o n o f p r o g n o s i s i n s y s t e m i c
s c l e r o s i s . A r t h r i t i s R h e u m 1 9 9 1 ; 3 4 : 1 3 7 1 - 8 0 .
6 . S t e e n V D , M e d s g e r T A , O s i a l T A , Z i e g l e r G L , S h a p i r o A P ,
R o d n a n G P : F a c t o r s p r e d i c t i n g d e v e l o p m e n t o f r e n a l
i n v o l v e m e n t i n p r o g r e s s i v e s y s t e m i c s c l e r o s i s . A m J M e d
1 9 8 4 ; 7 6 : 7 7 9 - 8 6 .
1 8 9 6
7 . C l e m e n t s P J , L a c h e n b r u c h P A , N g S C . S i m m o n s M , S t e r z M ,
F u r s t D E : S k i n s c o r e . A s e m i q u a n t i t a t i v e m e a s u r e o f c u t a n e o u s
i n v o l v e m e n t t h a t i m p r o v e s p r e d i c t i o n o f p r o g n o s i s i n s y s t e m i c
s c l e r o s i s . A r t h r i t i s R h e u m 1 9 9 0 ; 3 3 : 1 2 5 6 - 6 3 .
8 . B l u e s t o n e R , G r a h a m R , H o l l o w a y V , H o l t P J L : T r e a t m e n t o f
s y s t e m i c s c l e r o s i s w i t h D - p e n i c i l l a m i n e : a n e w m e t h o d o f
o b s e r v i n g t h e e f f e c t s o f t r e a t m e n t . A n n R h e u m D i s
1 9 7 0 ; 2 9 : 1 5 3 - 9 .
9 . D y k e s P J , M a r k s R : M e a s u r e m e n t o f s k i n t h i c k n e s s : A
c o m p a r i s o n o f t w o i n v i v o t e c h n i q u e s w i t h a c o n v e n t i o n a l
h i s t o m e t r i c m e t h o d . J l n v e s t D e r m a t o l 1 9 7 7 ; 6 9 : 2 7 5 - 8 .
I O . M y e r s S L , C o h e n J S . S h e e t s P W , B i e s J R : B - m o d e u l t r a s o u n d
e v a l u a t i o n o f s k i n t h i c k n e s s i n p r o g r e s s i v e s y s t e m i c s c l e r o s i s .
J R h e u m a t o l 1 9 8 6 ; 1 3 : 5 7 7 - 8 0 .
1 1 . S i l v e r s t e i n J L , S t e e n V D , M e d s g c r T A J r . F a l a n g a V :
C u t a n e o u s h y p o x i a i n p a t i e n t s w i t h s y s t e m i c s c l e r o s i s
( s c l e r o d e r m a ) . A r c h D e r m a t o l 1 9 8 8 ; 1 2 4 : 1 3 7 9 - 8 2 .
1 2 . R o d n a n G P , L i p i n s k i E , L u k s i c k J : S k i n t h i c k n e s s a n d c o l l a g e n
c o n t e n t i n p r o g r e s s i v e s y s t e m i c s c l e r o s i s a n d l o c a l i z e d
s c l e r o d e r m a . A r t h r i t i s R h e u m 1 9 7 9 ; 2 2 : 1 3 0 - 4 0 .
1 3 . B r e n n a n P , S i l m a n A , B l a c k C , e t a l : R e l i a b i l i t y o f s k i n
i n v o l v e m e n t m e a s u r e s i n s c l e r o d e r m a . B r J R h e u m a t o l
1 9 9 2 ; 3 I : 4 5 7 - 6 0 .
1 4 . S u b c o m m i t t e e f o r S c l e r o d e r m a C r i t e r i a o f t h e A m e r i c a n
R h e u m a t i s m A s s o c i a t i o n D i a g n o s t i c a n d T h e r a p e u t i c C r i t e r i a
C o m m i t t e e : P r e l i m i n a r y c r i t e r i a f o r t h e c l a s s i f i c a t i o n o f
s y s t e m i c s c l e r o s i s ( s c l e r o d e r m a ) . A r t h r i t i s R h e u m
/ 9 8 0 ; 2 3 : 5 8 1 - 9 0 .
1 5 . K a h a l c h M B , S u t t a n y G L , S m i t h E A . H u f f s t u t t e r J E , L o a d h o l t
C B , L e R o y E C : A m o d i f i e d s c l e r o d e r m a s k i n s c o r i n g m e t h o d .
C l i n E x p R h e u m a t o l 1 9 8 6 ; 4 : 3 6 7 - 9 .
1 6 . R i t c h i e D M , B o y l e J A , M c i n n e s J M , e t a l : C l i n i c a l s t u d i e s
w i t h a n a r t i c u l a r i n d e x f o r t h e a s s e s s m e n t o f j o i n t t e n d e r n e s s i n
p a t i e n t s w i t h r h e u m a t o i d a r t h r i t i s . Q J M e d 1 9 6 8 ; 3 7 : 3 9 3 - 4 0 6 .
1 7 . E b e r l D R , F a s c h i n g V , R a h l f s V . S c h l e y e r I . W o l f R :
R e p e a t a b i l i t y a n d o b j e c t i v i t y o f v a r i o u s m e a s u r e m e n t s i n
r h e u m a t o i d a r t h r i t i s . A r t h r i t i s R h e u m 1 9 7 6 ; 1 9 : 1 2 7 8 - 8 6 .
I
l
I
j
T h ’ 1 " " ’ m ’ I < i f R h ’ ’ = l e f o g y 1 9 9 3 _ . 2 0 . . 1 1 l