raynauds phenomenon and cold stress testing

7/30/2019 Raynauds Phenomenon and Cold Stress Testing

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Eur J Vasc Surg 8, 567-573 (1994)

R a y n a u d ' s P h e n o m e n o n a n d C o l d S tr e ss T e st in g : A N e w A p p r o a c hS a d h a n a N a i d u 2 , P a u l A . B a s k e r v i l l e 1 , D a v i d E . G o s s 3 a n d V . C o l i n R o b e r t s 2

D e p a r t m e n t o f 1 V a s cu l a r S u r g e r y a n d a D e p a r t m e n t o f M e d i c a l E n g i n e e r i n g a n d P h y s i c s , K i n g ' s C o l le g e H o s p i t a l,D e n m a r k H i l l L o n d o n S E 5 9 R S , U . K . a n d 3 V as c u la r L ab o r at o ry , D e p a r t m e n t o f M e d i c a l E n g i n e e r i n g a n d P h y s i c s,

K i n g ' s C o l le g e H o s p i t a l ( D u l w i c h ) , E a s t D u l w i c h G r o v e S E 2 2 8 P T , U . K .There are a num ber o f methods of evaluat ing digi tal blood f low in the vascular laboratory but none ful f i l ls the cri ter ia ofproviding a quick and reproducible diagnost ic tes t for Ra yna ud's phenomenon. W e present our experience w ith the use ofhigh frequen cy ul trasound to provide direct real time im aging of the digi tal arteries. U sing this m ethod and a s tandardisedcold chal lenge test, consis t ing o f exposure of the ha nd to a temperature o f lOC for 5 m inutes , i t is possible to dis t inguishpatients wi th Ray naud 's phenomenon from normal controls on the basis of extent of digi tal artery c losure. The mean fal lin digital artery diameter on cold challenge, expressed as a percentage of the original diameter, was 92.4% (s.D. = 16.4,S .E.M. = 2.1 ) in patients with R ayna ud's phenomenon as against 8 .7% (s .D. = 11.5, sx .M . = 2.5) in a group of normalvolunteers. U sing a 45% fall in d igital artery diam eter as the diagnostic cutoff point, the test has a specificity of 100%and a sensi t iv i ty of 96.6% in di f ferent iat ing pat ients w ith Ra ynau d's phenomenon from controls . I t is suggested that thetest could be used as objective confirmation of a clinical diagnosis and to assess the effica cy of therapeuticinterventions.Ke y W ords: Rayn aud's phenomenon; Digi tal blood f low; H igh frequency ul trasound; Digi tal arteries; Cold chal lenge.

I n t r o d u c t i o nThe diagnosis of Raynaud's phenomenon is largelybased on clinical criteria, often aided by question-naires seeking information on relevant risk factorsJ"2One of the main problems in evaluating digital bloodflow in patients with Raynaud's phenomenon hasbeen the episodic nature of the symptoms and signs.Different methods have been used to provoke anattack in a laboratory setting. These have includedlocal cooling of the hand or the digits by exposure tocold air, cold water or the use of digital cuffs perfusedwith cold water, 3'4's and general bo dy cooling usin gwater perfusable blankets 6 or thro ugh exposure to lo wambient temperatures. 7 Havi ng provo ked a vaso-spastic attack, the second problem that faces theinvestigator is the measurement and quantification ofthe digital arterial constriction.The "critical closing phenomenon" or spasticclosure of the digital arteries in response to pro-gressive cooling was first propo sed by Bur ton in 1951.sAltho ugh initially a subject of considerable debate, itPlease address all correspondence to: David Goss, Vascular Labo-rator~ Department of Medical Engineering & Physics, King'sCollege Hospital (Dulwich), East Dulwich Grove, SE22 8PT, U.K.

The patient group consisted of 60 patients, 40 withprimary Raynaud's Phenomenon (RP) and 20 patientswith secondary RP from the vascular clinic at King'sCollege Hospital. The diagnosis was bas ed on h istoryand clinical criteriaJ The control gr oup consisted of 22normal volunteers with no history of cold sensitivit~of which 18 were women and four were men (ratio4.5:1), with a mean age of 45.2 years (range 21 to 71years). The patient gro up co mprised 46 wome n an d 14men (ratio 3.3:1), wit h a me an age of 48.9 years (range15 to 79 years). Forty of the pati ents were classified as

is now considered to form the basis of the typicalRaynau d's attack. 9'm It has been demons trated tooccur using diverse methods such as digital ple-thysmography,11 digit systolic pres sures, 4"12 laser Dop-pler flowmetry13 and more recentl~ high frequencyult raso und. 14 The present repor t details ou r experi-ence with the use of high frequency ultrasound incharacterising digital artery responses to a standar-dised cold stress in patients with Rayn aud's phenome -non and in a group of normal controls.

S u b j e c ts a n d M e t h o d s

0950-821X/94/050567+07 $08"00/0 1994 W. B. Saunders CompanyLtd.


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568 S. Naidu e t a L

h a v i n g p r i m a r y R P a n d t h e r e m a i n i n g 2 0 a s s e c o n d a r yRP ( s ee Table 1 fo r sub jec t cha rac te r i s t i c s ) .

T h e s u b j e c t s w e r e r e s t e d f o r 1 5 m i n u t e s i n at h e r m a l l y n e u t r a l e n v i r o n m e n t m a i n t a i n e d a t a t e m -p e r a t u r e o f 2 5 C . T h e t es t w a s p e r f o r m e d b y p l a c i n gt h e h a n d o n a s p e c i a l l y c o n s t r u c t e d p e r s p e x p o s i t i o n -i n g r i g , w i t h t h e m i d d l e f i n g e r r e s t i n g o n t h e h o r -i z o n t a l s u p p o r t b a r ( F i g . 1 ) . M e a s u r e m e n t s w e r e m a d eu s i n g t h e D e r m a s c a n A h i g h f r e q u e n c y u l t r a s o u n ds y s t e m ( C o r t e x T e ch n o l o g y , D i a s t r o n L t d . H a m p s h i r e ) .T h e e q u i p m e n t u s e s a 20 M h z t r a n s d u c e r p r o b e w h i c hh a s a c a p t i v e w a t e r b a t h a t t h e f r o n t e n d t o s e r v e a s t h ec o u p l i n g m e d i u m . A s c r e e n d i s p l a y s t h e r e f l e c t e d A -l i n e u l t r a s o u n d e c h o e s i n r e a l t i m e a n d a f o o t s w i t c he n a b l e s t h e d i s p l a y t o b e fr o z e n . M e a s u r e m e n t c u r s o r sc a n b e p o s i t i o n e d o n s c r e e n a n d a l l o w f o r i n s t a n t -a n e o u s r e a d o u t s o f d i s t an c e s b e t w e e n e c h o e s o fi n t e r e s t . E c h o e s o r i g i n a t i n g f r o m t h e d i g i t a l a r t e r yw a l ls a r e r e c o g n i s e d b y t h e i r p u ls a t il e m o v e m e n t s a n dt h e i r s e p a r a t i o n b y a n e c h o f r e e i n t e r v a l r e p r e s e n t i n gb l o o d w i t h i n t h e a r t e r y .

T h e p r o b e c a n b e p o s i t i o n e d p e r p e n d i c u l a r t o t h elong ax i s o f t he d ig i t a l a r t e r )~ a t any po in t on th ec i r c u m f e r e n c e o f th e f i n g e r a n d f i x e d in p l a c e b ym e a n s o f a c l a m p a t t a c h e d t o t h e p e r s p e x r i g. T h ec l a m p e n a b l e s t h e p r o b e t o b e p o s i t i o n e d a g a i n s t t h ef i n g er w i th m i n i m u m p r e s s u re , t h e r e b y a v o i d i n ge r r o r s d u e t o d i s t o r t i o n o f t h e t i s s u e s b y u n d u ep r e s s u r e . T h e m o s t a c c u r a t e e s t i m a t e o f d i g i t a l a r t e r yd i a m e t e r i s o b t a i n e d w i t h t h e p r o b e p e r p e n d i c u l a r t othe long ax i s o f t he d ig i t a l a r t e ry (F ig . 1 ) .T h e m i d d l e f i n g e r w a s c h o s e n a s t h e r e p r e s e n t a -t i v e f i n g e r as m o s t o f o u r s u b j e c t s in t h e p a t i e n t g r o u ph a d b i l at e ra l a n d s y m m e t r i c a l s y m p t o m s a n d f o ra c c u r a t e c o m p a r i s o n i n t h e c o n t r o l g r o u p . H o w e v e rt h e t e c h n i q u e c a n b e e q u a l l y w e l l a p p l i e d t o a n y o f t h e

Table 1. Subject characteristicsAge, years(range) Male Fe m ale Total

Controls 45.2 (21-71) 4 18 22Patients with 48.9 (15-79) 14 46 60Raynaud'sPhenomenonPrimary Rayn aud's 46 (15-75) 6 34 40Second ary Rayna ud's 54.8 (35-79) 8 12 20

Systemic Sclerosis 49.9 (43-62) 1 6 7Rheum. Arthritis 53 (39-58) - - 4 4SLE 53 - - 1 1Peripheral Vasc. 70 (61-79) 2 - - 2DiseaseVibration White 57.5 (48-64) 4 - - 4FingerCervical Ribs 46 - - 1 1(bilateral)Beta blockers 62 1 - - 1

f i n g e r s , i n c l u d i n g t h e t h u m b , u n l e s s f i x e d d e f o r m i t i e so f t h e f i n g e r s d o n o t a l l o w t h e p r o b e t o b e p l a c e d a sd e s c r i b e d .

T w o s e t s o f d i g i t a l a r t e r y m e a s u r e m e n t s w e r et a k e n f o r e a c h s u b j e c t . A b a s e l i n e d i g i t a l a r t e r yd i a m e t e r ( D A D ) r e c o r d w a s m a d e a t r o o m t e m -p e r a t u r e . F o l l o w i n g t h i s , a s t a n d a r d i s e d c o l d c h a l -l e n g e w a s a d m i n i s t e r e d c o n s i s t in g o f i m m e r s i o n o f th eh a n d i n c o l d w a t e r a t a t e m p e r a t u r e o f 10 C f o r 5m i n u t e s . B o t h h a n d s w e r e a s s e ss e d a n d f o u r o b s e r v a -t i o n s w e r e t a k e n w i t h e a c h s e t o f m e a s u r e m e n t s . Am e a n v a l u e o f d i g i t a l a r t e r y d i a m e t e r w a s t h e nc a l c u la t e d f r o m t h e o b s e r v a t i o n s f r o m b o t h h a n d s i neach sub jec t . Resu l t s a re expres sed a s mean DAD (S .D .an d S .E .M.) and d ig i t a l a r t e ry re sp onse s to co ld s t re s sa r e e x p r e s s e d a s p e r c e n t a g e d e c r e a s e i n b a s e l i n e D A D .T h e d i f f e re n c e s b e t w e e n t h e g r o u p s w e r e a n a l y s e d f o rs t a t i s t i c a l s i g n i f i c a n c e u s i n g t h e M a n n - W h i t n e y Utes t .

Fig. 1. Measur ement of digital artery diam eter; finger positioned onthe perspex rig with probe held in place by clamp.

Results

T h e d i g i t a l a r t e r y d i a m e t e r s a n d t h e i r c h a n g e s i nr e s p o n s e t o c o l d s t r e s s w e r e r e c o r d e d i n 6 0 p a t i e n t sw i t h R a y n a u d ' s p h e n o m e n o n a n d 2 2 n o r m a l c o n t r ol s .T h e b a s e l in e D A D s a t r o o m t e m p e r a t u r e ( T ab l e 2 )w e r e s l i g h t ly h i g h e r i n t h e c o n t r o l g r o u p ( 1. 18 m m S.D .= 0 . 17 r a m ) a s c o m p a r e d t o t h e p a t i e n t g r o u p ( 1. 06

Eur J Vasc Sur g Vol 8, Septem ber 1994


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R a y n a u d ' s P h e n o m e n o n a n d C o l d S t r e s s T e s ti n g 5 6 9

T a b l e 2 . D i g i t a l A r t e r y D i a m e t e r s a n d c h a n g e s w i t h c o l d s t r e s s

Pa t i e n t s Pa t i e n t sw i t h w i t h C o n t r o lsC o n t r o ls P a t i en t s P r i m a r y R P S e c o n d a r y R P vs .(n = 22) (n = 60) (n = 40) (n = 20) Pat ients

p v a l u e s (M a n n -Wh i t n e y U Te s t )(*sign i f ican t )P r i m a r y R P P r i m a r y R P S e c o n d a r y R PVS. VS, VS.Se c o n d a ry R P a l l p a t i e n t s a l l p a t i e n t s

Base l ine DA D 1 .18 1 .06 1 .08at ro om S.D. = 0.17 S.D. = 0.26 S.D. = 0.27tem per atu re (ram) S.E.M. = 0 .04 S.E.M. = 0 .03 S.E.M. = 0.04D AD after 1 .07 0 .09 0 .09co ld stre ss S.D. = 0.15 S.D. = 0.21 S.D. = 0.20(ram ) S.E.M. = 0. 03 S.E.M. = 0. 03 S.E.M. = 0.03Perc ent d ro p 8 .7 92 .4 92 .9in D A D S.D. = 11.5 S.D. = 16.4 S.D. = 15.1S.E.M. = 2.5 S.E.M. = 2.1 S.E.M. = 2.4

1.03 0.01" 0.94 0.97 0.95S.D. = 0.23S.E.M. = 0.050.1 0


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5 7 0 S . N a i d u e t a L

T a b l e 3 . I n f l u e n c e o f s e x o n D A D r e s p o n s e s t o c o l d s tr e s sContro ls Pa t ien ts wi th RP p va lues (Mann-W hi tney U tes t )(n = 22) (n = 60) (* significant)

Con t ro ls P ts. wi th RP Con tro ls men Cntrl . wom enM e n W o m e n M e n W o m e n m e n vs . m en vs. vs. m e n vs. w o m e n(n = 4 ) (n = 18) (n = 14) (n = 46) wom en wom en wi th RP wi th RPBaseline DA D 1.16 1.18 1.22 1.01 0.7 6 0.009* 0.87 0.002*at ro om S.D. = 0.20 S.D. = 0.17 S.D. = 0.30 S.D. = 0.22tem pera ture (ram) S.E.M. = 0.1 0 S.E.M. = 0.0 4 S.E.M. = 0.0 8 S.E.M. = 0.03DA D afte r 0.12 0.44 0.003*co ld s t ress(mm)Perc ent dr op 0.07 0.49 0.003*i n D A D

1.18 1.04 0.18 0.07S.D. = 0.14 S.D. = 0.15 S.D. = 0.32 S.D. = 0.16S.E.M. = 0 .0 7 S.E.M. = 0. 03 S.E.M. = 0. 08 S.E.M. = 0.02-3 .4 t 11.4 87.9 93.7S.D. = 14.7 S.D. = 9.1 S.D. = 21.5 S.D. = 14.6S.E.M. = 7.4 S.E.M. = 2.2 S.E.M. = 5.8 S.E.M. = 2.2

< 0.0001"

< 0.0001"

(~- mea n change a f te r co ld s t ress was an inc rease in DAD)

0 . 1 0 m m (S .D . = 0 . 2 2 m m ) i n t h e l a t t e r . T h e c o l d s t r e s sr e s p o n s e s o f th e t w o g r o u p s w e r e n o t s i g n i f ic a n t lyd i f f e r e n t f r o m e a c h o t h e r a n d a l s o d i d n o t d i f f e r f r o mt h o s e o f t h e w h o l e p a t i e n t g r o u p ( p > 0 .0 5) .

W h i l e th e c o n t r o l a n d p a t i e n t g r o u p s w e r e f a i r l yw e l l m a t c h e d f o r ag e , t h e r e w a s a l a r g e r p r o p o r t i o n o fw o m e n i n t h e p a t i e n t g r o u p . T h e r e f o r e a f u r t h e rs u b g r o u p a n a l y s i s w a s p e r f o r m e d t o a s s es s th e i n f l u -e n c e o f s e x o n t h e d i g i t a l a r t e r y r e s p o n s e s ( T a bl e 3) .T h e r e w a s n o d i f f e re n c e b e t w e e n t h e D A D s o f m e na n d w o m e n i n th e c o n t r o l g r o u p ; e i t h e r a t r o o mt e m p e r a t u r e o r f o l l o w i n g a c o l d s tr e s s (p > 0 .0 5) .H o w e v e r i n t h e p a t i e n t g r o u p , w o m e n a p p e a r e d t oh a v e a s i g n if i c a n t l y s m a l l e r b a s e l in e D A D a s c o m -p a r e d t o m e n w i t h R P ( 1 .0 1 m m S .D . -- 0 .2 2 a s a g a i n s t1 . 22 m m S .D . = 0 . 1 8 m m ; p < 0 . 0 1 ) . T h i s d i f f e r e n c ed i s a p p e a r e d w h e n t h e r e s p o n s e s t o c o l d s t re s s w e r ec o m p a r e d , w i t h m e a n D A D s o f 0 .1 8 m m (S.D . = 0 . 32m m ) r e f l e c t i n g a 8 7 . 9 % ( S.D . = 2 1 . 5 % ) f a l l i n b a s e l i n eD A D i n m e n a n d m e a n D A D s o f 0 .0 7 m m (S.D . = 0 . 16r a m ) r e f l e c t i n g a f a l l o f 9 3 . 7 % (S .D . = 1 4 . 6 % ) o fb a s e l i n e v a l u e s i n w o m e n ( p > 0 .0 5) . T h e b a s e l i n eD A D s o f m e n w i t h R P d i d n o t d i f f e r s i g n i fi c a n t l y f r o me i t h e r m e n o r w o m e n c o n t r o l s (p > 0 .0 5) ; h o w e v e rb a s e l i n e D A D s o f w o m e n w i t h R P w e r e s i g n i f i c an t l yl o w e r t h a n b o t h m e n a n d w o m e n c o n t r o ls .I n a n a t t e m p t t o a s s e s s t h e i n f l u e n c e o f t h e b a s i cd i s e a s e p r o c e s s o n t h e b a s e l i n e D A D , t h e d i f f e r e n c e sb e t w e e n p a t i e n t s w i t h p r i m a r y a n d s e c o n d a r y R a y -n a u d ' s p h e n o m e n o n w e r e a n a l y s e d . W h i l e th e t w og r o u p s d i d n o t d i f f e r s i g n i f i c a n t l y a s a w h o l e , c e r t a i nd i f fe r e n ce s b e c a m e a p p a r e n t w h e n t h e s ex e s w e r es e p a r a t e d ( F ig . 3 ) B o t h m e n a n d w o m e n w i t h s e c o n -d a r y R P h a d s m a l l e r b a s e l i n e D A D s ( 1.1 m m , S .D . =0 .1 6 m m a n d 0 . 98 m m , S .D . = 0 . 2 7 m m r e s p e c t i v e l y ) a sc o m p a r e d w i t h m e n a n d w o m e n w i t h p r i m a r y R P

( 1 . 3 8 m m , S .D . = 0 . 3 9 a n d 1 . 0 2 m m , S . D. = 0 . 2 1 m mr e s p e c t i v e l y ) . W h e n s u b j e c t e d t o s t a t i st i c a l a n a l y s i sh o w e v e r , i t a p p e a r e d t h a t w o m e n w i t h p r i m a r y a n ds e c o n d a r y R P h a d s i g n i fi c a n t ly sm a l l e r b a se l i n e D A D sw h e n c o m p a r e d t o m e n w i t h p r i m a r y R P (p < 0 . 05 ),b u t n o t w h e n c o m p a r e d t o m e n w i t h s e c o n d a r y R P.A l t h o u g h m e n w i t h s e c o n d a r y R P h a d s m a l l e r m e a nD A D s t h a n t h o s e w i t h p r i m a r y R P th i s d i f fe r e n ce w a sn o t s i g n i f i c a n t (p > 0 . 0 5 ).

C o m p l e t e c l o s u re o f t h e d i g i t a l a r t e r y i n r e s p o n s et o c o l d s t r e s s w a s s e e n i n 48 p a t i e n t s ( 80 % ) , w i t h n op u l s a t i le s i g n a l d e t e c t e d o n s c a n n i n g . T h i s w a s a c c o m -p a n i e d b y s y m p t o m s a n d c o l o u r c h a n g e s t y p i c a l o f t h eR a y n a u d ' s a t t a c k . O f t h e r e m a i n d e r , 11 p a t i e n t s( 18 .3 % ) h a d s y m p t o m s s i m i l a r t o t h o s e t h a t o c c u r r e dd u r i n g a n a tt a ck , a l t h o u g h t h e i r m e a n D A D d e c r e a s ew a s 6 1 .8 % . T h e c o l d s t r e ss t es t d i d n o t p r o v o k es y m p t o m s i n o n l y o n e p a t ie n t . H i s m e a n D A Dd e c r e a s e w a s 3 6 . 2% . C o m p l e t e c l o s u r e o f t h e d i g i t a la r t e r y a s a c o l d s t re s s r e s p o n s e s e e m e d a s l i k e l y t oo c c u r i n p a t i e n t s w i t h p r i m a r y R a y n a u d ' s ( 8 0 % ) a s i nt h o s e w i t h s e c o n d a r y R a y n a u d ' s ( 80 % ).

I n n o n e o f t h e s u b j e c t s o f t h e c o n t r o l g r o u p w a st h e D A D d e c r e a s e g r e a te r t h a n 4 0% . A n i n t e r e s t i n gf i n d i n g th a t w a s o b s e r v e d i n th i s g r o u p w a s t h a t t w oc o n t r o l s h a d a n e t i n c r e a s e i n d i g i t a l a r t e r y d i a m e t e r i nr e s p o n s e t o c o l d s t r es s ( m e a n i n c r e a s e 1 5 % ).

W h e n w e s t u d i e d t h e c o l d s t re s s r e s p o n s e s o f t h et w o g r o u p s i n t e r m s o f a p e r c e n t a g e d e c r e a s e in D A Da c l ea r s e p a r a t i o n b e t w e e n t h e tw o g r o u p s w a se v i d e n t a t t h e l e v e l o f a 35 % d e c r e a s e i n D A D .H o w e v e r i n o r d e r t o i n c r ea s e t h e a p p l i c a b i l i t y o f t h es e l e c t e d c u t o f f p o i n t w e p l o t t e d t h e c o l d s t r e ssr e s p o n s e o f 11 c o n t r o l s a n d 3 0 p a t i e n t s ( 50 % o f e a c hg r o u p ) , s e l e c t e d i n a r a n d o m f a s h i o n ( F ig . 4 ). F r o m t h i sg r a p h , a c u t o f f p o i n t c o u l d b e o b t a i n e d a t a 45 %

Eur J V asc Surg V ol 8, Septemb er 199.4


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R a y n a u d ' s P h e n o m e n o n a n d C o l d S t r e s s T e s t in g 5 7 1

B a s e li n e D A D in cms4

I P < 0 . 0 5 ~ I

a p < 0 . 0 5 I

O

o 8 8

o 0M e n (n:6) Women (n:34) Men (n:8) Women (n:12)I 1 I IPrimary RP Secondary RP

Fig . 3 . Com par ison o f base l ine DAD accord ing to sex and e t io logy o f RP . Vert ica l ba rs ind ica te mean _+ S .D. Only s ign i f ican t p va lues a reshown.

+ 4 0 I I I I+ 2 0

02 04 06 080

10 012 0

Controls (n:ll )

O

O

P a t i e n t s (n:30) C o n t r o l s ( n : l 1 )O

Patients (n:30)

OOo o /x

/X/X A

Z~26)

P e r c e n t ch a n g e i n D A D

Fig . 4. Der iva t ion o f the d iagnos t ic cu to f f po in t . The le f t ha l f o f the f igu re rep resen ts the pe rcen tage d rop in DA D fo l lowing co ld s t ress in50% of rand om ly se lec ted con tro ls and pa t ien ts . The remain ing d a ta i s p lo t ted on the r igh t ha l f o f the f igu re .

d e c r e a s e i n D A D t h a t s e p a r a t e d t h e c o n t r o l s f r o m t h ep a t i e n t s . W h e n t h i s c u t o f f w a s a p p l i e d t o t h e r e m a i n -i n g d a t a , i t y i e l d e d a d i a g n o s t i c s p e c i f i c i ty of 10 0 % a n da s e n s i t i v i t y o f 96 .6 % i n d i s t i n g u i s h i n g t h e t w og r o u p s .

D i s c u s s i o nD u r i n g a t y p i c a l R a y n a u d ' s a t t a c k , t h e r e is c o m p l e t e

9 . 1 5 1 6c e s s a t i o n o f b l o o d f l o w i n t h e d i g i t a l a r t e r i e s ." 'H o w e v e r i t h a s b e e n d i f f ic u l t t o q u a n t i t a t e t h i s

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5 7 2 S. N a idu e t a L

response with most available methods. Singh e t a l . , 1 7in a group of patients with Raynaud's phenomenondemonstrated that progressive cooling of the fingerscaused digital vasospasm that was essentially com-plete in all patients at te mpera tures b elow 16C. Theclinical severity of the disease was found to correlatewith the temperature at which this critical closureoccurred. Practical difficulties were encountered withprogressive finger cooling to determine the point ofdigital vasospasm. Stepwise cooling of the han ds wit hrepeated immersion in cold water with several esti-mates of the digital artery diameters is required. Wetherefore evolved the concept of a standardised coldchallenge, consisting of exposure of the hand for astandard length of time to a temperature at whichdigital vasospasm is known to be complete in mostpatients with Raynaud's phenomenon. Standardisingthe cold stress has also allowed for comparison withnormal controls in whom the technique of progressivecooling does not have an end point as they do notexhibit complete vasospasm in response to cold.The cold stress test was successful in reproducingtypical symptoms in 80% of patients. This wasconfirmed on DAD estimation which demonstrated100% decrease or total digital arterial shut off. Oneobservation of interest was the fact that 18.3% of thepatients still had symptoms and signs of the typicalRaynaud's attack, even without complete digitalarter y closure (mean DAD decrease 61.8%). Weatt empt ed therefore, to relate the degree of vasospas mto the severity of the patients' clinical symptoms.However, although the patients whose DAD decreaseswere in the range of 40% to 50%, did admit to beingonly moderately symptomatic with their Raynaud's,there were several patients with such sympt oms in thegroup who had total arterial shutdown . In the patientswho showed incomplete digital vasospasm it ispossible that prolonging the duration of exposure tothe cold stress may convert the response to thecomplete digital arterial shut off characteristic of themajority of patients.

The baseline digital artery diameters were sig-nificantly smaller in the patient group as compared tothe control gro up (mean DAD: 1.06 mm as against 1.18mm; p < 0.05). When the results of the subgroupanalysis by sex were studied, it became apparent t hatthis difference was largely contributed by women withRP who had a mean baseline DAD of 1.01 mm. Incontrast men with RP had a mean baseline DAD of1.22 mm which was not significantly different eitherfrom men or wome n controls (p > 0.05). It may beargued that a smaller baseline DAD might predisposethe vessel to complete or near complete vasoconstric-tion in response to cold. However there was no

difference between the cold stress responses of menand women patients (p = 0.43).Baseline DADs were smaller in patients withseco ndar y RP (1.03 mm S.D. = 0.23) as comp are d tothose wi th p rim ary RP (1.08 mm S.D. = 0.27). Thisdifference however was not statistically significant (p> 0.05). Significant comparisons emerge d only onfurther subgroup analysis for sex when baselineDADs of men with primary RP were found to begreater than wom en with either primary or secondaryRP. It would seem therefore that the smaller baselineDADs observed in the patient group were moredirectly related to the sex of the patient t han the nat ureof the disease process. Smaller baseline DADs inwomen with secondary RP might be easily explainedconsider ing the effects of connective tissue disease ondigital arterial anatomy; especially as this groupconsisted almost entirely of patients with connectivetissue disease (11/12), 50% of whom had scleroderma.However the same observation in women with prim-ary RP does seem to suggest a possible hormonallymediated baseline vasoconstriction, existing even atroom temperature. In our study group, patients withsecondary Raynaud's constituted 33% of the totalwith a preponderance of women (ratio 3:2). Perhapsthe differences between the two groups ma y behighlighted by further studies that include morepatients, especially more men, with secondary RP.The diagnosis of Raynaud's phenomen on will to alarge extent remain clinical. However the character-isation of the digital artery response to a cold stress interms of a percentage drop from baseline values doesallow the separation of the patient group from normalcontrols. By ran dom ly selecting 50% of the data fromcontrols and from patients, it was possible to plotpercentage drop in baseline DADs. From this graph acutoff point of 45% was derived which separated theresponses of the control group from those of thepatient group. When this cutoff was applied as adiagnostic test to the rest of the data, it was possible todistinguish the patients from the controls with aspecificity of 100% and a sensitivity of 96.3%. The lessthan 100% sensitivity was accounted for by the singlepatient with 36% decrease in baseline DAD on coldstress, who felt that the cold stress test had notprovoked a typical Raynaud's "attack". While re-emphasising that the diagnosis of Raynaud's willremain clinical we suggest that the method ofmeasuring digital artery diameters using high fre-quency ultrasound together with a standardised coldstress test offers a direct, reproducible and non-invasive means of assessing the extent of vasospasmthat occurs in response to a cold challenge. Themethod also provides a useful objective parameter

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R a y n a u d ' s P h e n o m e n o n a n d C o l d S t r e s s T e s t in g 5 7 3

a g a i n s t w h i c h t o c o m p a r e t h e e f f e c ts o f v a r i o u st h e r a p e u t i c i n t e r v e n t i o n s .

AcknowledgementsT h e a u t h o r s w o u l d l i k e t o a c k n o w l e d g e t h e g e n e r o u s a s s i s ta n c eg i v e n b y t h e R a y n a u d ' s a n d S c l e r o d e r m a A s s o c i a ti o n .R e f e r e n c e s

1 ALLENE V a nd B ROWNGE . R a yna u d ' s d i s e a se : A c r i t ic a l r e v i e w ofmi n i ma l r e qu i s i t e s fo r d i a gnos i s . Am J Med Sc i 1 9 3 2 ; 1 8 3 :187-200.2 TAYLORW, PELMEARPL, (eds). Vibration White Finger in Industry.L ondon: Ac a de mi c P re s s , 1975 : xx i .3 L EWIS T . E xpe r i me n t s r e l a t e d t o t he pe r i ph e ra l m e c ha n i smi nv ol v e d i n t he spa sm odi c a r re s t o f c i r c u l a t i on in t he f i nge r s , av a r i e t y o f R a y n a u d ' s d i s ea s e . Heart 1929; 15: 7-101.4 NIELSENSL LASSENNA. C ol d s e ns i t i v i t y o f t he d i g i t a l a r t e r i e se v a l u a t e d b y m e a s u r e m e n t o f d i g i t a l b l o o d p r e s s u r e a f t e r l o c a lc oo l i ng . J Appl Physiol 1977; 43: 907-910.5 ARNEKLO-NOBINB, NIELSENSL , EKLOF B, LASSENN A . R e s e r p i n et r e a t m e n t o f R a y n a u d ' s d i s ea s e . Ann Surg 1978; 187: 12--16.6 NIE L SE N SL . R a y na ud ' s p he n om e no n a nd f i nge r sys t o l i c p re s -s u r e s d u r i n g c o o l i n g . Scand J Clin Lab Inves 1978; 38: 765-770.7 HOARE M, MILES C, GIRVANRr RAMSDENJ, NEEDHAM % PARDY B,NICOLArDES A. T he effec t of loca l co ol in g on dig i ta l sys tol icp r e s s u r e s i n p a t i e n t s w i t h R a y n a u d ' s s y n d r o m e . Br J Surg 1982;69 (Suppl . ) $27-$28.

8 BURTONA . O n t h e p h y s i c a l e q u i l i b r i u m o f s m a l l b l o o d v e s s e l s .Am J Physiol 1951; 164 : 319-329.9 BOLLINGERA L MAHLER F/ MEYER F. Velocity pa t t e rns i n na i l fo l dc a p il l ar i es in n o r m a l m e n a n d c a s e s w i t h R a y n a u d ' s d i s e a se a n da c roc ya nos i s . Bibl Anat 1977; 16: 142-148.10 KRAHENBUHL B, NIELSEN SL, LASSEN N A . C l o s u r e o f d i g i t a la r t e r i e s i n h i g h v a s c u l a r t o n e s t a t e s a s d e m o n s t r a t e d b ym e a s u r e m e n t o f s y s to l i c b l o o d p r e s s u r e i n t h e f i n g e r s. Scand JClin Lab Invest 1977; 37: 71-76.11 COFFMAN W,COHENR A . T o t a l a n d c a p i l la r y f i n g e r t ip b l o o d f l o wi n R a y n a u d 's p h e n o m e n o n . N Eng l J Med 1971; 285: 259-263.12 ROBERTS VC, COTTON LT. Func t iona l a ssess me nt of R ay nau d'ss y n d r o m e a n d i t s tr e a t m e n t w i t h p l a s m a e x c h a n g e . I n: P U EL P ,BOCCALON H I ENJALBERTA, (eds) . Haemodynamics of the Limbs.(Fourn i e , T ou l ouse ) 1981 , pp . 343-351 .13 ENGELHARTM r NIELSENHV, KIRSTENSEN K. Blood supply to thef i n g e r s d u r i n g a R a y n a u d ' s a t ta c k : A c o m p a r i s o n o f L a se rD o p p l e r F l o w m e t r y w i t h o t h e r t e c h n i q u e s . Clin Physiol 1985; 5:447-453.14 SINGH S, DE TRAFFORD C , Goss DE , BASKERVILLEPA , ROBERTS VC.U l t r a s o u n d i m a g i n g o f d i g i t a l a r t e r i e s . Clin Phys Physiol Meas1990; 11: 313-317.15 NIELSENSL . T he e v i de nc e fo r pe r i phe ra l a r t e r i a l va sospa sm: i t sc l i n i ca l i mpor t a nc e . Agressologie 1982; 23: 113-115.16 THULESrUSO. Pa t hophys i o l ogy o f c o l d s e ns i t i v i t y . In : C ooke E D,Ni c o l a i de s AN & Por t e r JM, ( e ds ) . Raynaud's Syndrome. M e d -Or i on Pub l i sh i ng C o . 1991 , pp . 22- -23 .17 S:N GH S, DE TRAEFORD , BASKERVILLEP A . D i g i t a l a r t e r y d o s i n gt e m p e r a t u r es : A n o b j e c ti v e i n d e x o f s e v e r i t y in R a y n a u d ' sp h e n o m e n o n . J Va sc Surg 1993; 27: 511-518.

Accep ted 24 January 1994

E ur J Va sc Su rg Vol 8, Se p t e m be r 1994

raynauds phenomenon and cold stress testing

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