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De elopmen o a clinical-
de moscopic model o he
diagnosis o u ica ial asculi is
B. Ga cía-Ga cía
1*, J. Aubán-pa ien e1, p. Munguía-calzada1, B. Vi anco2, G. A genziano3 &
. Vázquez-López1
he clinical c i e ia o he diagnosis o u ica ial asculi is lack accu acy, acco ding o p e ious s udies.
he aim o he s udy was o assess he accu acy o a clinical and a clinical-de moscopic model o he
di e en ial diagnosis o ch onic spon aneous u ica ia (CSU) and u ica ial asculi is (UV). De moscopic
images o lesions wi h his opa hologically con i med diagnosis o CSU and UV we e e alua ed o he
p esence o selec ed c i e ia (pu pu ic pa ches/globules (PG) and ed linea essels). Clinical c i e ia o
CSU and UV we e also egis e ed. Uni a ia e and adjus ed odds a ios we e calcula ed. Mul i a ia e
eg ession analyses we e conduc ed sepa a ely o clinical a iables (clinical diagnos ic model) and
o bo h clinical and de moscopic a iables (clinical-de moscopic diagnos ic model). 108 pa ien s wi h
CSU and 27 pa ien s wi h UV we e included in he s udy. The clinical-de moscopic model no ably
showed highe diagnos ic sensi i i y han he clinical app oach (63% s. 44%). De moscopic pu pu ic
pa ches/globules (PG) was he a iable ha be e disc imina ed UV, inc easing by 19- old he odds o
his diagnosis. In conclusion, de moscopy helps he clinical disc imina ion be ween CSU and UV. The
isualiza ion o de moscopic pG may con ibu e o op imize decisions ega ding biopsy in pa ien s wi h
u ica ial ashes.
U ica ial asculi is (UV) is a clinicopa hologic en i y cha ac e ized by u ica ial lesions disclosing his opa ho-
logically leukocy oclas ic asculi is, mainly o pos capilla y enules1,2. Recognizing UV is c ucial gi en a possible
associa ion wi h sys emic ea u es. UV is classi ied in o hypocomplemen emic (HUV) and no mocomplemen -
emic (NUV). HUV is a a e sys emic asculi is, showing u ica ial lesions and sys emic mani es a ions, such as
a h i is/a h algia, glome uloneph i is, u ei is, ecu en abdominal pain o ch onic obs uc i e pulmona y dis-
ease. Mo e han hal o pa ien s ha e associa ed an i-C1q an ibodies2. In con as , NUV, is a skin-limi ed ascu-
li is1,2. UV may be associa ed o au oimmune connec i e issue diseases, in ec ions, d ugs o neoplasia, al hough
mos o he cases a e idiopa hic3,4. UV is a a e condi ion, clinically o e lapping wi h he mo e common ch onic
spon aneous u ica ia (CSU). I is no ewo hy ha lesions o CSU and UV may be isually indis inguishable, and
o en ep esen a eal diagnos ic challenge o he clinician5.
A de ini i e diagnosis o UV equi es a skin biopsy, which is pe o med when UV is suspec ed due o he
p esence o ou classic clinical c i e ia: pe sis ence o indi idual lesions, las ing mo e han 24 hou s; p esence o
ende ness o a pain ul/bu ning sensa ion; pu pu a o dusky discolo a ion o he skin and esolu ion o lesions
wi h esidual hype pigmen a ion6. The accu acy o his clinical app oach has been ques ioned, as some s udies
ha e demons a ed absence o hese ea u es in a signi ican p opo ion o pa ien s wi h UV4–9. Fu he mo e,
e en he need o a eassessmen o diagnos ic c i e ia o UV has been sugges ed5. The alue o de moscopy, a
low-cos and apid skin examina ion echnique, o clinically disc imina ing common u ica ia and UV has been
p oposed bu in a ew small-sized s udies10,11. De moscopy o CSU ypically e eal a ed ne wo k o linea essels,
co ela ing wi h ansien asodila a ion o ho izon al subpapilla y plexus10,11. In con as , u ica ial lesions o
UV cha ac e is ically de elop de moscopic i egula / ound small pu pu ic pa ches /globules (PG), de i ed om
pe i ascula haemo hage associa ed wi h in lamma o y pu pu a10,11. We assessed and compa e he ein o he
i s ime he accu acy o bo h a clinical and a clinical-de moscopic model o disc imina ing u ica ial asculi is
and ch onic spon aneous u ica ia.
1Depa men o De ma ology, Cen al Uni e si y Hospi al o As u ias, O iedo, Spain. 2Depa men o Pa hology,
Cen al Uni e si y Hospi al o As u ias, O iedo, Spain. 3De ma ology Uni , Uni e si y o Campania, Naples, I aly.
*email: [email p o ec ed]
open
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The aim o his s udy was o in es iga e he alue o de moscopy o he di e en ial diagnosis o u ica i o m
ashes o CSU and UV, and o e alua e he accu acy o a clinical-de moscopic diagnos ic model e sus a clinical
app oach o disc imina ing bo h diseases.
Pa ien s, Me hods and De ini ions
This was a e ospec i e, cha e iew, single cen e s udy de eloped om 2003 h ough 2014 a he depa -
men o De ma ology o a e ia y eaching uni e si y hospi al (Cen al Uni e si y Hospi al o As u ias -HUCA-)
in no he n Spain. The s udy was app o ed by he E hical Commi ee o Regional Clinical Resea ch o he
P incipali y o As u ias. All esea ch was pe o med in acco dance wi h ele an guidelines/ egula ions and
in o med consen was ob ained om all pa icipan s. Inclusion c i e ia we e a clinical diagnosis o an u ica ial
ash o a leas 6 weeks o e olu ion (ch onic spon aneous u ica ia o u ica ial asculi is), comple e in o ma ion
ega ding clinical and de moscopic ea u es ga he ed du ing he medical in e iew and physical examina ion
and a his opa hologic con i ma o y s udy. Exclusion c i e ia we e: child en, lack o pa ien ´s consen , diagnosis
o o he e y hema ous-pu pu ic and pe sis en ashes (e y hema mul i o me, capilla i is, lymphocy ic ascu-
li is, pu pu ic pi y iasis osea and insec bi es) o absence o complemen a y da a. De moscopic examina ion
p eceded biopsy, and bo h we e pe o med on he same u ica i o m lesions. Since asculi is is a dynamic p ocess,
and he mos cha ac e is ic his ological ea u es de elop in mo e ecen lesions (neu ophils, haemo hage, and
leukocy oclasia)21, biopsies we e aken om lesions less han 24 hou s old. The lowe leg loca ion was excluded
in o de o a oid his ological changes caused by enous s asis. Clinical c i e ia we e egis e ed on s anda dized
ques ionnai es including: du a ion and pe sis ence (mo e o less han 24 hou s) o u ica i o m indi idual lesions;
symp oms (p u i us, pain o bu ning sensa ion). Clinical lesions we e desc ibed as wheals ( ansien ); papules/
plaques (long las ing o unde ined); e y hema and pu pu ic a eas we e addi ionally disc imina ed by diascopy.
Clinical a iables assessed and selec ed o subsequen analysis in ou s udy we e he classical clinical signs o UV:
pe sis ence (u ica i o m lesions las ing mo e han 24 hou s as e e ed by he pa ien s), pain/bu ning sensa ion
(as i was e e ed by he pa ien s) and pu pu a/ esidual hype pigmen a ion. Resul s o labo a o y examina ions
we e no e alua ed gi en he clinical-de moscopic na u e o he s udy.
Lesions we e examined wi h a 10× manual de moscope (Del a 10; Heine Op o echnik, He sching, Ge many,
and la e , De mli e II P o HR,3Gen Inc, CA, USA). Lesions we e pho og aphed wi h a digi al de moscopic cam-
e a (De mapho pho og aphic equipmen -Heine Op o echnik- and la e De mli e Fo o Sys em). A p elimina y
s udy was conduc ed in o de o e alua e whe he Del a 10 and De mli e II P o HR could gi e di e en de mo-
scopic obse a ions in his se ing, bu no di e ences we e ound and consequen ly he de moscopic obse a ions
we e conside ed as a single da a se . The de moscopic p ocedu e was applied aking in o accoun ha essels
ecogni ion is he basis o de moscopy o u ica ial ashes10–14. Because essels a e isualized due o he ed blood
cells ul illing and passing h ough hem, de moscopy was ealized in a wo-s eps p ocedu e: (a) non-con ac
de moscopy (a oiding p essu e), allowing ecogni ion o bo h ascula and pu pu ic ea u es; (b) de moscopy
applied o e diascopy (applying a glass p essu e o e he lesion), blanching essels meanwhile pu pu ic ea u es
pe sis s.
Pa ien s who bo h ga e and signed an in o med consen o pe o m a skin biopsy we e ec ui ed h ough-
ou he s udy pe iod om a single ou pa ien de ma ology o ice. De moscopic examina ion and pho og aphs
p eceded biopsy. The e ospec i e sco ing o de moscopic s uc u es, pe o med on de moscopic images by
wo expe ienced de ma ologis s, included he ollowing s uc u es, acco ding o p e ious s udies:10–14 (1)
De moscopic ascula ea u es: (a) Round essels (co ela ing wi h papilla y essels): do ed o globula , acco d-
ing o hei size; b) Linea essels (co ela ing wi h ho izon al subpapilla y essels): simple, a bo i o m, and
ne wo k s uc u es, wi h a de ined/blu ed con ou . (2) De moscopic pu pu ic indings: (a) La ge homoge-
neous, s uc u eless pu pu a (mo e equen ly associa ed o non-in lamma o y o ms o de mal haemo hage
such as auma ic, senile o s e oid pu pu a); b) I egula / ound small pu pu ic pa ches/globules (PG): pe i as-
cula haemo hage, ela ed o pu pu ic in lamma o y p ocesses (pigmen ed pu pu ic de ma oses, a h opods
eac ions, i al and d ugs eac ions, leukocy oclas ic asculi is, in ec i e o ganisms). PG a e blu ed and appea
i s wi hin a pu pu ic and la e wi hin an o ange-b own backg ound, which may obscu e PG i i is p omi-
nen o when issue nec osis appea s. (c) Black/pu pu ic spo s (subco neal and subungual pu pu a); (3) o he
de moscopic s uc u es: haemo hagic c us s; e osions/exco ia ions. In o de o ob ain a simple and easible
clinical-de moscopic model o disc imina ing CSU and UV, and acco ding o p e ious s udies which include ou
p e ious expe ience10–14, we inally selec ed and sco ed only wo de moscopic ea u es: pu pu ic pa ches/globules
(PG) and ed linea essels.
His ological c i e ia o diagnosis o UV we e: pe i ascula and in e s i ial neu ophilic in il a e; signs o
ka yo hexis (nuclea dus ); ex a asa ed e y h ocy es and deposi ion o ib in in he essels. His ological c i e ia
o diagnosis o CSU we e supe icial and deep pe i ascula and in e s i ial in il a e o lymphocy es, neu ophils
and eosinophils de oid o ka yo hexis and ascula ib in deposi ion.
S a is ical analysis. S a is ical analysis was pe o med using SPSS so wa e (IBM Co p. Release 2013.
IBM SPSS S a is ics o Windows, e sion 21.0. A monk, NY: IBM Co p). Uni a ia e and mul i a ia e anal-
yses we e conduc ed by logis ic eg ession. C ude odds a io (OR), adjus ed OR and he co esponding 95%
con idence in e al (CI) and p- alue we e ob ained o e e y clinical and de moscopic a iable. Mul i a ia e
analysis was conduc ed sepa a ely o clinical a iables and subsequen ly o bo h clinical and de moscopic a -
iables al oge he . Goodness o i o he mul i a ia e analyses was examined by adjus ed R2, likelihood a io es
and co ec classi ica ion pe cen age. Speci ici y, sensi i i y, posi i e p edic i e alue (PPV) and nega i e p e-
dic i e alue (NPV) we e ex ac ed om classi ica ion ables o bo h diagnos ic models ( he clinical and he
clinical-de moscopic) acco ding o s anda d o mulas. We conside ed s a is ically signi ican a 2-sided p- alue
o 0.05.
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Resul s
In all, 135 pa ien s wi h u ica i o m ashes and ul illing all inclusion c i e ia we e inally ec ui ed (84 emale,
51 male; mean age 50 yea s; ange 20–79 yea s). O hose, 108 (80%) pa ien s had CSU and 27 (20%) had UV.
Desc ip i e esul s o clinical signs, symp oms and de moscopic ea u es o bo h his ological g oups a e quo ed
in Table1.
As ega ds de moscopic indings, ed linea essels we e obse ed in he majo i y o bo h CSU and UV
pa ien s (85% and 74% espec i ely) bu PG we e highly disc imina i e, being p esen in mos o he pa ien s
wi h UV (n = 19, 70.4%) bu only in a mino i y o pa ien s wi h CSU (n = 11; 10.2%) (Fig.1). Uni a ia e analysis
yielded s a is ical signi icance o wo clinical a iables (pe sis ence o lesions, and pu pu a/ esidual hype pig-
men a ion) and one de moscopic ea u e (PG), inc easing he likelihood o UV by 7- old, 9- old and 21- old
espec i ely (Table1).
A mul i a ia e eg ession analysis o a clinical model (whe e only clinical a iables we e en e ed), main ained
he signi icance o pe sis ence (OR: 4.97; 95% CI 1.85–13.35) and pu pu a/ esidual hype pigmen a ion (OR
6.34; 95% CI 2.19–18.36) (Table2). Finally, he mul i a ia e eg ession analysis o a clinical-de moscopic model
(based on bo h clinical and de moscopic a iables), showed ha de moscopic PG we e an independen posi i e
p edic o o UV. Only one clinical a iable -pe sis ence o lesions- main ained signi icance. This inal model
e ealed a 19- old inc ease in he odds o UV when de moscopic PG we e p esen and a 6- old inc ease o pe -
sis ence o lesions, when he diagnosis o UV was compa ed wi h CSU (Table2). Goodness o i was examined
by co ec classi ica ion pe cen age (88.9%), adjus ed R2 (0.503) and a signi ican likelihood a io es (p < 0.05).
In e es ingly, i was ema kable ha sensi i i y was no ably highe o he clinical-de moscopic app oach han o
he clinical model (63% s. 44%) (Table3).
Discussion
De moscopy is a non-in asi e skin magni ica ion echnique, which allows a eal in i o subclinical explo a ion o
he skin. De moscopy imp o es and comple es clinical examina ion by e ealing mo phologic s uc u es sca cely
isible o in isible on he s anda d naked-eye physical examina ion, enhancing he mos basic o diagnos ic unc-
ions in de ma ology: he isual inspec ion15. De moscopy has a well demons a ed alue in he diagnosis o skin
umou s, especially melanoma, bu also o many non- umo al de ma osis, such as in ec ions and in es a ions,
hai o nail diseases and in lamma o y skin condi ions15–17. In addi ion, nail old de moscopy may be applied
o he sc eening o suspec ed connec i e issue diseases ins ead o classic capilla oscopy18. In ac , his aluable
low-cos de ice has e en been conside ed o ha e in de ma ology a ole simila o he s e hoscope o gene al
p ac i ione s19.
The alue o de moscopy o he di e en ial diagnosis be ween common u ica ia and u ica ial asculi is
has been p oposed bu in small se ies10,11. In he p esen s udy, we con i m his in a la ge se ies o pa ien s,
adding o he i s ime he e alua ion o a clinical-de moscopic model e sus a clinical model o di e en i-
a ing CSU and UV. I is ou p emise ha de moscopic indings should always be in e p e ed wi hin he o e all
clinical con ex o he pa ien , and in eg a ed wi h his o y and s anda d clinical examina ion. Consequen ly, we
de eloped a clinical-de moscopic diagnos ic model ins ead o a pu e de moscopic model o di e en ia ing bo h
diseases. Ou obse a ions mainly e ealed ha sensi i i y o di e en ia ing UV om CSU is imp o ed when a
clinical-de moscopic model is applied in compa ison wi h a clinical model (63% s 44%).
The applica ion o a clinical model o di e en ia ing common u ica ia and UV is he gold s anda d a he
p esen ime. The classical clinical signs (u ica i o m lesions las ing mo e han 24 hou s, pain/ bu ning sensa ion,
pu pu a/ esidual hype pigmen a ion) help o suspec UV, and es ablish whe he a biopsy is needed ( o con i m
a UV diagnosis) o no (in case o common u ica ia). Ne e heless, he e a e s udies epo ing a lack o e icacy
o his clinical model, aking in o accoun he a iable equencies o hese clinical signs (Table4)4–9. In a s udy
including 47 pa ien s wi h biopsy p o en UV, Tosoni e al. ound ha mos o hem did no show he classic
clinical ea u es o UV: only 57% o pa ien s e e ed lesions las ing mo e han 24 hou s and pain was epo ed in
only 8,6%. Consequen ly, hey sugges ed he need o a eassessmen o he diagnos ic c i e ia o UV5. Addi ional
s a egies ha e included ou lining he con ou o he lesions o e alua ing he e en ual pe sis ence o indi idual
lesions and pe o ming a biopsy acco ding o he esponse o he ea men wi h o al an ihis amines ins ead o
conside ing he clinical ea u es4,5. These me hods imply he cons o being ime and cos -consuming and in asi e,
in case o pe o ming ou ine biopsies. His opa hologically, he essen ial c i e ia o he diagnosis o UV is he
p esence o ka yo hexis (nuclea dus ), joined by ex a asa ed e y h ocy es and, a ime, by ib in deposi s wi hin
P edic o Ch onic spon aneous
u ica ia (n = 108) n (%) U ica ial asculi is
(n = 27) n (%) p- alue OR 95% CI
Pe sis ence (wheals ˃24 hou s) 28 (25.9) 19 (70.4) <0.001 6.79 2.67–17.22
Pain/Bu ning 17 (15.7) 7 (25.9) 0.216 1.87 0.69–5.12
Pu pu a/ esidual hype pigmen a ion 10 (9.3) 13 (48.1) <0.001 9.10 3.36–24.65
DC ed linea essels 92 (85.2) 20 (74.1) 0.17 0.50 0.18–1.37
DC pu pu ic pa ches/globules (PG) 11 (10.2) 19 (70.4) <0.001 20.94 7.44–58.96
Table 1. F equencies and uni a ia e analysis o he i e clinical and de moscopic a iables assessed in ou
ch onic spon aneous u ica ia and u ica ial asculi is pa ien s. S a is ically signi ican alues a e shown in bold.
DC: de moscopic.
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Figu e 1. Clinical, his ological and de moscopic ea u es o ch onic spon aneous u ica ia (pa ien 1) and
u ica ial asculi is (pa ien s 2 and 3). Pa ien 1. 1 A: Mul iple wheals on he legs o a woman wi h an u ica ial
ash. 1B: edema in papilla y and uppe e icula de mis and a mixed in lamma o y in il a e cons i u ed by
lymphocy es, eosinophils and occasional neu ophils (H&E, o iginal magni ica ion ×20). 1 C: de moscopic
well-de ined ne wo k o ed lines. Pu pu ic pa ches a e absen . Pa ien 2. 2 A: pe sis en isola ed and con luen
e y hema o-edema ous u ica ial papules and plaques loca ed on a leg. 2B: A p edominan ly neu ophilic
in lamma o y in il a e a ec ing he ascula walls and associa ed wi h blood ex a asa ion and nuclea dus
(ka yo hexis) (H&E, o iginal magni ica ion x40). 2 C: de moscopic small i egula pu pu ic pa ches and ed
lines. Pa ien 3. 3 A: u ica ial e y hema ous papules and plaques loca ed on he unk. 3B, 3 C: di e en deg ees
o de moscopic blu ed small pu pu ic pa ches and ed lines on an e y hema ous backg ound. 3D: de moscopy
o a esidual, long las ing lesion disclosing a yellow/o ange esidual discolo a ion.
Diagnos ic model P edic o p- alue OR 95% CI
Clinical model Pe sis ence (wheals ˃24 hou s) <0.001 4.97 1.85–13.35
Pu pu a/ esidual hype pigmen a ion <0.001 6.34 2.19–18.36
Clinical-de moscopic model
DC pu pu ic pa ches/globules (PG) <0.001 19.42 5.79–65.15
DC ed linea essels 0.011 0.13 0.03–0.63
Pe sis ence (wheals ˃24 hou s) 0.006 5.65 1.64–19.44
Table 2. Diagnos ic models (clinical and clinical-de moscopic) o di e en ial diagnosis o ch onic
spon aneous u ica ia and u ica ial asculi is. Mul i a ia e analysis wi h only clinical a iables en e ed (clinical
model) and all a iables (clinical-de moscopic model): adjus ed clinical and clinical-de moscopic p edic o s o
u ica ia asculi is om 135 pa ien s.
Diagnos ic models Sensi i i y (%) Speci ici y (%) PPV
(%) NPV (%) Co ec
diagnosis (%)
Clinical 44.4 97.2 80 87.5 86.7
Clinical-de moscopic 63 95.4 77.3 91.2 88.9
Table 3. Sensi i i y, Speci ici y, Posi i e P edic i e Value (PPV) and Nega i e P edic i e Value (NPV) o bo h
diagnos ic models, ob ained by mul i a ia e logis ic eg ession analysis.
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walls o essels6,20,21. Vascula ib inoid nec osis is conside ed a e o absen in UV. Biopsy iming (op imally
wi hin he i s 24–48 hou s) is impo an o achie e a cha ac e is ic pic u e o UV20,21.
Ou obse a ions showed ha lesions pe sis ence and pu pu a/ esidual hype pigmen a ion we e he mos
equen clinical a iables in UV pa ien s, in line wi h p e ious in es iga ions (Table4). Bo h a iables yielded
s a is ical signi icance, inc easing he likelihood o UV by 7- old and 9- old espec i ely. In con as , pain/bu n-
ing sensa ion was only e e ed by 26% o pa ien s, and did no each signi icance. Conside ing only hese clinical
a iables, he global accu acy o he clinical diagnos ic model o disc imina ing UV and CSU was 87%, wi h
97% speci ici y o CSU, bu wi h only a low 44% sensi i i y o UV. In e es ingly, when de moscopy was added
o he pa ien e alua ion, he clinical-de moscopic model inc eased sensi i i y o 63%, while main aining accu-
acy (89%), hus ou lining he ole o de moscopy in imp o ing he co ec non-in asi e diagnosis o UV. This
imp o emen was mainly achie ed by he de ec ion o subclinical pu pu ic pa ches/globules (PG) ha became
isible by he use o de moscopy. Taking in o accoun ha he deg ee o de mal haemo hage in UV lesions is
a iable, anging om e iden o unappa en pu pu a, iden i ica ion o de moscopic PG may be especially use ul
o hose UV lesions wi h minimal clinical pu pu ic a eas. Indeed, he p esence o de moscopic PG was he mos
aluable c i e ia o disc imina ing CSU and UV by mul i a ia e analysis (19- old inc ease in he odds o UV),
while clinical pe sis ence o lesions inc eased i by 6- old. Al hough we did no in es iga e his opic, i is also o
in e es ha ha PG migh be p esen e en in ea ly UV lesions11.
Unde de moscopy, he wheals o CU mainly e ealed ed linea essels, which co ela e wi h ec a ic, ho i-
zon ally o ien ed, subpapilla y essels, and e lec a p ocess o ansien asodila a ion o de mal capilla ies. They
we e obscu ed when p ominen oedema was p esen (nega i e a eas). Pu pu ic s uc u es o pa ches we e a e in
CSU and mus be di e en ia ed om e osions/c us s and om ed ound essels ( e ical papilla y essels) which
appea as ed do s wi h a clea con ou , loca ed along linea essels, and disappea ing a e diascopy14. U ica ial
lesions o UV also e ealed linea essels bu , in con as o CSU, hey equen ly showed blu ed i egula / ound
pu pu ic s uc u es (PG) wi hin a pu pu ic (ea ly s age) o o ange-b own (la e s age) backg ound. Limi a ions o
ou s udy include he e ospec i e design and he numbe o pa ien s e alua ed.
In conclusion, de moscopy helps he clinical disc imina ion be ween ch onic spon aneous u ica ia and u i-
ca ial asculi is by imp o ing he sensi i i y o he s anda d clinical examina ion ( isual inspec ion). De moscopy
enhances isualiza ion o subclinical pu pu ic pa ches, which a e highly indica i e o an unde lying asculi is
when con on ed wi h common u ica ia. This echnique may con ibu e o op imize decisions ega ding biopsy
in pa ien s wi h u ica ial ashes, so commonly a ended in daily clinical p ac ice.
Recei ed: 17 No embe 2019; Accep ed: 16 Ma ch 2020;
Published: xx xx xxxx
Re e ences
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Li e a u e: Au ho , yea o
publica ion and e e ence. UV
pa ien s N Pe sis ence (wheals
˃24 hou s) N (%) Pain/bu ning N (%) Pu pu a/ esidual
hype pigmen a ion N (%)
Meh egan e al.672 46 (63.8) 23 (31.9) 25 (34.7)
Lee e al.822 22 (100) 10 (45.5) (pain)
15 (68.2) (bu ning) 18 (81.8)
Dincy e al.468 61 (89.7) 22 (32.3) 17 (25)
Tosoni e al.547 20 (42.6) 4 (8.6) (pain)
6 (12.8) (bu ning) 3 (6.4)
Kul hanan e al.764 60 (93.8) 28 (43.8) (pain)
12 (18.8) (bu ning) 53 (82.8)
Mo eno e al.915 14 (93.3) 2 (13.3) 9 (60)
Ga cia e al. (p esen s udy) 27 19 (70.4) 7 (25.9) 13 (48.1)
Table 4. Clinical c i e ia o u ica ial asculi is (p opo ion o pa ien s) acco ding o li e a u e and ou s udy.
UV: u ica ial asculi is.

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Acknowledgemen s
S a is ical analysis and in e p e a ion we e comple ed wi h he assis ance o he Scien i ic and Technical Se ices
(s a is ical consul ancy uni ) om he Uni e si y o O iedo.
Au ho con ibu ions
B.G.G., G.A. and F.V.L. w o e he main manusc ip ex . J.A.P., P.M.C. and B.V. p epa ed igu es and ables. All
au ho s e iewed he manusc ip .
compe ing in e es s
The au ho s decla e no compe ing in e es s.
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