Article

Kawasaki Disease
1. Mary Beth F. Son , MD*
2. Jane W. Newburger , MD, MP
!
" Author A##iliation$
1.
*
Department of Pediatrics, National University Hospital, Singapore.
2.

Department of Cardiology, Cildren!s Hospital "oston, "oston, #$.

Author Di$clo$ure
Dr$ Son an% Newburger ha&e %i$clo$e% no #inancial relation$hi'$ rele&ant to thi$ article.
(hi$ co))entary %oe$ contain %i$cu$$ion o# una''ro&e%*in&e$tigati&e u$e o# a
co))ercial 'ro%uct*%e&ice.
Abbreviations
AA+
A)erican eart A$$ociation
ASA+
a$'irin
,A-+
coronary artery le$ion$
,.P+
,/reacti&e 'rotein
0B1+
0'$tein/Barr &iru$
0S.+
erythrocyte $e%i)entation rate
2123+
intra&enou$ i))unoglobulin
4D+
4awa$a5i %i$ea$e
-AD+
le#t anterior %e$cen%ing artery
.,A+
right coronary artery

Ne6t Section
Practice Gap
1. ,linician$ $houl% not %i$)i$$ the %iagno$i$ o# 4awa$a5i %i$ea$e 74D8 in chil%ren with
$y)'to)$ co))only attribute% to &iral illne$$. For e6a)'le, $e&ere hea%ache an%
'hoto'hobia $houl% $ignal the 'o$$ibility o# a$e'tic )eningiti$ e&en in the 're$ence o#
4D. An%, right u''er 9ua%rant 'ain )ay in%icate hy%ro'$ o# the gallbla%%er.
2. A challenging $ub$et o# 'atient$ who %o not )eet the cla$$ic ca$e %e#inition are $ai% to
ha&e inco)'lete 4D. Patient$ who ha&e inco)'lete 4D are )ore li5ely to be in#ant$ an%
ol%er chil%ren an%, a$ $uch, are al$o at higher ri$5 #or coronary artery le$ion$ 7,A-8. :#
note, in#ant$ younger than ; )onth$ o# age are at high ri$5 #or %e&elo')ent o# ,A-, yet
o#ten ha&e #ewer clinical #eature$ to #acilitate the %iagno$i$. For the$e rea$on$,
echocar%iogra'hy i$ reco))en%e% #or in#ant$ younger than age ; )onth$ with #e&er o#
unclear etiology 'er$i$ting #or < or )ore %ay$ an% ele&ate% in#la))atory )ar5er$.
Pre&iou$ Section Ne6t Section
Objectives
A#ter rea%ing thi$ article, rea%er$ $houl% be able to+
1. De$cribe the clinical )ani#e$tation$ o# 4awa$a5i %i$ea$e.
2. For)ulate a %i##erential %iagno$i$ #or 'atient$ with $u$'ecte% 4awa$a5i %i$ea$e.
=. De$cribe the laboratory &alue$ ty'ically $een in 4awa$a5i %i$ea$e.
>. Di$cu$$ the role o# echocar%iogra'hy in the )anage)ent o# 'atient$ who ha&e 4awa$a5i
%i$ea$e an% %e$cribe the car%iac co)'lication$ o# the %i$ea$e.
?. De#ine 'ri)ary treat)ent o# 4awa$a5i %i$ea$e with intra&enou$ i))unoglobulin an%
a$'irin.
Pre&iou$ Section Ne6t Section
Case Study
A =/year/ol% 're&iou$ly healthy i$'anic girl i$ brought to her 'e%iatrician@$ o##ice with a
hi$tory o# ; %ay$ o# #e&er. (he #e&er ha$ been 're$ent %aily an% ha$ been unre)itting, %e$'ite
a%)ini$tration o# anti'yretic )e%ication$. She ha$ been irritable with %ecrea$e% a''etite. er
)other notice% an erythe)atou$, non'ruritic ra$h co&ering her tor$o 1 %ay a#ter #e&er on$et. She
ha$ %e&elo'e% re% eye$ in the 'a$t 2 %ay$. She ha$ no $ibling$ an% atten%$ chil% care.
:n e6a)ination, the girl i$ #ebrile to =A.BC, an% tachycar%ic at 1>D beat$ 'er )inute. er bloo%
're$$ure while crying i$ 11D*;D )) g. er weight i$ 1>.? 5g. She ha$ conEuncti&al inEection
with li)bal $'aring an% without e6u%ate. er li'$ a''ear erythe)atou$ an% crac5e%, an% her
oro'haryn6 i$ %i##u$ely erythe)atou$ without e6u%ate. She %oe$ not ha&e $igni#icant cer&ical
chain ly)'ha%eno'athy. A 'oly)or'hou$ )aculo'a'ular ra$h co&er$ her tor$o an% e6tre)itie$.
(he %or$a o# her han%$ an% #eet a''ear $wollen.
She ha$ a total white bloo% cell count o# 1?,;DD*))
=
, a he)oglobin le&el o# B.A g*%-, an% a
'latelet count o# ;<D,DDD*))
=
. (he %i##erential count o# the white bloo% cell$ i$ A1F neutro'hil$
an% 1>F ly)'hocyte$. She ha$ )il% tran$a)initi$ with an alanine a)inotran$#era$e le&el o# ;A
G*-H her a$'artate a)inotran$#era$e le&el i$ nor)al. er ,/reacti&e 'rotein 7,.P8 le&el i$ B.A
)g*%- an% her erythrocyte $e%i)entation rate 70S.8 i$ ;? ))*hour. (here are 2? white cell$ 'er
high/'ower #iel% on urinaly$i$.
Pre&iou$ Section Ne6t Section
Overview
4awa$a5i %i$ea$e 74D8 i$ an acute #ebrile illne$$ o# chil%hoo% characteriIe% by &a$culiti$ o#
)e%iu)/$iIe%, e6tra'arenchy)al arterie$, with a 're%ilection #or coronary arterie$. 4D i$ the
lea%ing cau$e o# ac9uire% heart %i$ea$e in %e&elo'e% countrie$, although rheu)atic heart %i$ea$e
continue$ to %o)inate in the %e&elo'ing worl%. (he natural hi$tory an% treat)ent o# 4D are well
%e$cribe%, but it$ etiology re)ain$ ob$cure, ha)'ering e##ort$ to i%enti#y a $'eci#ic %iagno$tic
te$t an% targete% treat)ent$.
2n the ab$ence o# a $'eci#ic %iagno$tic te$t, 4D re)ain$ a %iagno$i$ ba$e% on clinical criteria. All
$ign$ an% $y)'to)$ o# 4D re$ol&e #ollowing the acute illne$$, but coronary artery le$ion$
7,A-$8 %e&elo' in =F to ?F o# chil%ren treate% with intra&enou$ i))unoglobulin 721238, an%
u' to 2?F o# untreate% chil%ren. 2t$ 'rogno$i$ i$ 're%icate% entirely on the 're$ence an% $e&erity
o# ,A-$, which can range #ro) )il% %ilation to giant aneury$)$ 7Fig 18. 2t i$ unclear i# chil%ren
who ha&e nor)al/a''earing coronary arterie$ %uring the acute 'ha$e o# the %i$ea$e will be at ri$5
#or en%othelial %y$#unction an% accelerate% athero$clero$i$ later in the li#e.
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Figure 1.
Selecti&e right coronary angiogra) %e)on$trating )ulti'le aneury$)$ in a chil% who ha$ 4D.
Pre&iou$ Section Ne6t Section
Epidemioloy
4D wa$ #ir$t %e$cribe% in 1B;< by a Ja'ane$e 'e%iatrician, Dr (o)i$a5u 4awa$a5i, a$ the
)ucocutaneou$ ly)'h no%e $yn%ro)e. 718 At that ti)e, the car%iac in&ol&e)ent o# 4D wa$ not
a''arent, nor wa$ e##ecti&e treat)ent %e$cribe%. Within a #ew year$, auto'$y ca$e$ o# 'atient$
who ha% 4D %e)on$trate% coronary artery aneury$)$ an% thro)bo$i$, an% the car%iac
co)'lication$ o# 4D beca)e e&i%ent. Since Dr 4awa$a5iJ$ initial re'ort, 4D ha$ been %e$cribe%
in chil%ren aroun% the worl%, an% in &irtually all race$H howe&er, Ja'ane$e chil%ren are at the
highe$t ri$5.
Since 1B<D, Ja'an ha$ collecte% e'i%e)iologic %ata about 4D nearly e&ery 2 year$ &ia
nationwi%e $ur&ey$. 2ntere$tingly, although the birth rate ha$ %ecline%, the nu)ber$ o# 'atient$
%iagno$e% with 4D an% the inci%ence rate in Ja'an ha&e ri$en ra'i%ly $ince the 1BBD$. (here
ha&e been three %ocu)ente% e'i%e)ic$ o# 4D in Ja'an, in 1B<B, 1BA2, an% 1BA;. 2n 2D1D, the
inci%ence rate o# 4D in Ja'an wa$ 2=B.; 'er 1DD,DDD chil%ren age D to > year$, which e6cee%$
the highe$t rate %uring any o# the e'i%e)ic$ an% i$ the highe$t rate recor%e%. (he rea$on #or the
linear increa$e in the inci%ence rate o# 4D in Ja'an i$ unclear. Si)ilar to 'rior $ur&ey$ in Ja'an,
the )o$t recent $ur&ey in 2DDBK2D1D #oun% that the inci%ence rate wa$ highe$t a)ong chil%ren
age ; to 11 )onth$ an% wa$ higher in boy$ than in girl$. A$ co)'are% with a $ur&ey 'er#or)e% in
1BBBK2DDD, the 'ro'ortion o# chil%ren with coronary artery %ilation an% aneury$)$ %ecrea$e%
#ro) ;F to =FH howe&er, the inci%ence o# giant aneury$)$ in 'atient$ who ha% 4D %i% not
%ecrea$e conco)itantly. 2n#ant$, 'articularly tho$e younger than ; )onth$, a$ well a$ chil%ren at
lea$t age ? year$ ha% an increa$e% relati&e ri$5 o# %e&elo'ing ,A-.
2n contra$t to Ja'an, ho$'italiIation rate$ a$$ociate% with 4D in the Gnite% State$ ha&e been
relati&ely $table o&er the 'a$t %eca%e. (he rate in 1BB< wa$ 1<.? 'er 1DD,DDD chil%ren younger
than age ? year$, an% in 2DD;, 2D.A 'er 1DD,DDD chil%ren younger than age ? year$. Mo$t
ho$'italiIation$ occurre% in chil%ren younger than age = year$. ,hil%ren o# A$ian*Paci#ic
2$lan%er %e$cent ha% the highe$t ho$'italiIation rate, %e)on$trating the li5ely role o# genetic$ in
the 'athogene$i$ o# 4D. An un%erlying genetic 're%i$'o$ition i$ $u''orte% #urther by the
#in%ing$ that $ibling$ o# chil%ren who ha&e 4D ha&e a 1D/#ol% increa$e% ri$5 #or the %i$ea$e, an%
the 'arent$ o# chil%ren who ha&e 4D in Ja'an to%ay are twice a$ li5ely, co)'are% with other
a%ult$, to ha&e ha% 4D when they were chil%ren.
.i$5 #actor$ #or 'oor coronary artery outco)e$ ha&e been $tu%ie% in $e&eral 'o'ulation$.
De)ogra'hic #actor$, $uch a$ young age, 'articularly younger than ; )onth$ an% ol%er than B
year$, )ale gen%er, A$ian an% Paci#ic 2$lan%er race, an% i$'anic ethnicity ha&e been a$$ociate%
with 'oor clinical outco)e$. -aboratory 'ara)eter$, $uch a$ neutro'hilia, thro)bocyto'enia,
hy'onatre)ia, ele&ate% ,.P, an% tran$a)initi$, ha&e all been a$$ociate% with 'oor re$'on$e to
2123 an% the %e&elo')ent o# ,A-. 728 0$$entially, 'atient$ with e&i%ence o# $igni#icant an%
wi%e$'rea% in#la))ation are at the highe$t ri$5.
Pre&iou$ Section Ne6t Section
Pat!oenesis
4DJ$ etiology re)ain$ un5nown. Many a$'ect$ o# 4D )i)ic in#ectiou$ 'roce$$e$, $uch a$ to6in/
)e%iate% illne$$e$ an% &iral illne$$e$. Sea$onal 'ea5$ ha&e occurre% in the Gnite% State$ an%
Ja'an, with increa$e% inci%ence in localiIe% area$, $ugge$ting a tran$)i$$ible &ector. .e$earcher$
ha&e loo5e% 'ain$ta5ingly an% un$ucce$$#ully #or an etiologic in#ectiou$ agent, inclu%ing
0'$tein/Barr &iru$ 70B18, a%eno&iru$, hu)an corona&iru$, hu)an boca&iru$, %ersinia
pse&dot&'erc&losis, her'e$ &iru$e$, an% other$.
(o6in$, $uch a$ tho$e 'ro%uce% by Stapylococc&s a&re&s an% Streptococc&s pyogenes, ha&e
been 'o$tulate% a$ the cau$ati&e agent$ o# 4D becau$e the ra$h can re$e)ble an erythro%er)a,
$i)ilar to the to6ic $hoc5 $yn%ro)e$ an% $ta'hylococcal $cal%e% $5in $yn%ro)e. A%%itionally,
the e##icacy o# treat)ent with 2123 coul% be e6'laine% by i))unoglobulin bin%ing o# the to6in$,
although antigen/in%e'en%ent )echani$)$ ha&e been 'o$tulate% a$ well. (o6in$ act a$
$u'erantigen$, which non$electi&ely acti&ate large nu)ber$ o# ( cell$, lea%ing to )a$$i&e
cyto5ine relea$e an% in#la))ation. Stu%ie$ loo5ing at the role o# $u'erantigen$ in 4D ha&e been
con#licting. S'eci#ically, i$olation o# $u'erantigen/'ro%ucing organi$)$, i$olation o#
$u'erantigen 'rotein$, an% the 're$ence o# an i))unologic $ignature o# $u'erantigen acti&ity
ha&e &arie% acro$$ $tu%ie$.
(o %ate, no uni9ue agent ha$ been 'ro&en to cau$e 4D. An alternati&e hy'othe$i$ 'o$it$ that
)any in#ectiou$ agent$ trigger a #inal co))on 'athway in genetically $u$ce'tible ho$t$, which i$
$u''orte% by the #in%ing that )any 'atient$ %iagno$e% a$ ha&ing 4D ha&e %ocu)ente%
conco)itant in#ection$. (he inter'lay o# in#ection an% &a$cular in#la))ation ha$ been %e$cribe%
in other #or)$ o# &a$culiti$, $uch a$ he'atiti$ B an% 'olyarteriti$ no%o$a, he'atiti$ , an%
cryoglobuline)ia, an% Stapylococc&s an% granulo)ato$i$ with 'olyangiti$ 7WegenerJ$8.
(here#ore, the hy'othe$i$ that in#ectiou$ agent$ )ay trigger the in#la))atory ca$ca%e in 4D ha$
#ace &ali%ity.
Both the innate an% a%a'ti&e ar)$ o# the i))une $y$te) ha&e been e&aluate% in the
'athogene$i$ o# 4D. (he innate i))une $y$te) inclu%e$ e'ithelial barrier$ an% 'hagocytic cell$
that 'ro&i%e 'rotection again$t in#ection, wherea$ the a%a'ti&e i))une re$'on$e i$ )e%iate% by
antigen/$'eci#ic ly)'hocyte$ $ti)ulate% by in#ectiou$ agent$. (here i$ e&i%ence that the innate
i))une $y$te) 'lay$ a $igni#icant role in the 'athogene$i$ o# 4D. :ne $tu%y re'orte% that
neutro'hil$ are i)'ortant actor$ in the initial attac5 on coronary artery wall$. 7=8 2n a )urine
)o%el o# coronary arteriti$ in%uce% by (acto'acill&s casei cell wall e6tract, (oll/li5e rece'tor 2
an% it$ %own$trea) a%a'tor 'rotein, MyDAA, are re9uire% #or the %e&elo')ent o# coronary artery
le$ion$, e$tabli$hing a role #or the innate i))une $y$te). 7>8 (wo recent $tu%ie$ %e)on$trate%
increa$e% e6're$$ion le&el$ o# innate i))unity/a$$ociate% gene$ %uring the acute 'ha$e o# 4D.
7?87;8
( cell$ al$o 'lay an i)'ortant role in 4D. ,DA" ( cell$ ha&e been #oun% in the coronary arterie$
#ro) auto'$y $'eci)en$. Stu%ie$ o# acute an% $ubacute $era in 'atient$ who ha&e 4D $howe% a
%ecrea$e in the 'o'ulation o# ( regulatory cell$ in the acute 'ha$e, with nor)aliIation #ollowing
treat)ent with 2123, in%icating that i)'aire% i))unoregulation ha$ a 'o$$ible role in the
%e&elo')ent o# 4D.
.ecent geno)e/wi%e a$$ociation $tu%ie$ ha&e %e$cribe% #unctional $ingle/nucleoti%e
'oly)or'hi$)$ in the )*P+C 7ino$itol 1,>,? tri'ho$'hate =/5ina$e ,8 gene that are a$$ociate%
with increa$e% ri$5$ #or $u$ce'tibility to 4D, )ore $e&ere coronary artery %i$ea$e, an% re$i$tance
to 2123. 7<8 )*P+C act$ a$ a negati&e regulator o# (/cell acti&ation through the
calcineurin*NFA( $ignaling 'athway, an% alteration$ in $ignaling )ay contribute to i))une
hy'erreacti&ity in 4D.
(o %ate, the role o# B cell$ in the 'athogene$i$ o# 4D ha$ not been clearly eluci%ate%.
2))unoglobulin A 'la$)a cell$ ha&e been #oun% in lung ti$$ue an% coronary arterie$ #ro) #atal
ca$e$ o# 4D, but the 'reci$e role o# the i))unoglobulin A 'la$)a cell$ re)ain$ to be
%eter)ine%. Further)ore, a recent $tu%y u$ing the )urine )o%el with (acto'acill&s casei cell
wall e6tractKin%uce% coronary arteriti$ in%icate% that B cell$ are not re9uire% #or %e&elo')ent o#
,A-$. 7A8
Pre&iou$ Section Ne6t Section
Clinical "ani#estations
,la$$ic clinical criteria with $u''orti&e clinical an% laboratory #in%ing$ are li$te% in (able 1. 7B8
With the e6ce'tion o# #e&er, the #eature$ o# 4D can #luctuate, an% a thorough )e%ical hi$tory i$
re9uire% to %eter)ine their 're$ence %uring the 'erio% o# illne$$. ,hil%ren who ha&e at lea$t >
%ay$ o# #e&er 7= %ay$ in e6'ert han%$8 an% > or ? o# the 'rinci'al criteria )eet the ca$e %e#inition
o# 4D. (he ca$e %e#inition al$o inclu%e$ chil%ren with #ewer than #our criteria i# they ha&e
coronary artery %i$ea$e.
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(able 1.
,linical an% -aboratory Feature$ o# 4awa$a5i Di$ea$e
(he hall)ar5 o# 4D i$ #e&er, ty'ically abo&e =BC,, which ha$ abru't on$et an% )ay not re)it
with anti'yretic )e%ication$. 2n the ab$ence o# treat)ent, #e&er ty'ically la$t$ 11 to 12 %ay$, with
rare ca$e$ o# 'rolonge% #e&er la$ting )ore than = wee5$. Although $o)e chil%ren treate% with
2123 e6'erience i))e%iate i)'ro&e)ent %uring the in#u$ion, other$ %e#er&e$ce 1 to 2 %ay$ a#ter
recei&ing 2123. A''ro6i)ately 1?F o# chil%ren treate% with 2123 ha&e 'er$i$tent or
recru%e$cent #e&er )ore than =; hour$ a#ter co)'letion o# the #ir$t 2123 in#u$ion.
More than BDF o# chil%ren who ha&e 4D %e&elo' bilateral, none6u%ati&e conEuncti&iti$ that
$'are$ the li)bu$ 7ie, with clearing aroun% the iri$ 7Fig 28. Anterior u&eiti$ al$o )ay be %etecte%
on $lit/la)' e6a)ination %uring the acute 'ha$e o# the %i$ea$e. :ro'haryngeal )ani#e$tation$ are
co))on an% inclu%e a %i##u$ely erythe)atou$ oro'haryn6, re% #i$$ure% li'$, an% a $trawberry
tongue 7Fig =8. Di$crete oral ulcer$ an% ton$illar e6u%ate$ are not $een ty'ically in 4D.
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Figure 2.
Bilateral none6u%ati&e li)bal $'aring conEuncti&iti$ i$ #oun% in u' to BDF o# chil%ren who ha&e
4D. ,ourte$y o# Annette -. Ba5er, NP.
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Figure =.
:ro'haryngeal change$, inclu%ing a $trawberry tongue, a$ 'icture%, are co))on in chil%ren who
ha&e 4D. ,ourte$y o# Annette -. Ba5er, NP.
4D ra$h u$ually a''ear$ within ? %ay$ o# #e&er on$et, an% o#ten $tart$ a$ %e$9ua)ation in the
'erineal area that e&ol&e$ into a %i##u$e, erythe)atou$, )aculo'a'ular ra$h. Morbilli#or) ra$he$,
erythe)a )ulti#or)a, an% erythro%er)a al$o can occur. Bullou$ or &e$icular le$ion$ $ugge$t an
alternati&e %iagno$i$.
,hil%ren a##licte% with 4D %e&elo' #ir) $welling o# the han%$ an% #eet, a$ well a$ erythe)a o#
the 'al)$ an% $ole$ in the acute 'ha$e o# the %i$ea$e. ,haracteri$tic, although not
'athogno)onic, 'eriungual 'eeling #ro) the #inger$ an% the toe$ 7Fig >8 begin$ 2 to = wee5$
a#ter the on$et o# the #e&er.
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Figure >.
Periungual 'eeling, #ir$t #ro) the #inger nailbe%$ an% then the toe$, i$ ty'ically $een 2 to = wee5$
a#ter on$et o# the #e&er. ,ourte$y o# Annette -. Ba5er, NP.
,er&ical ly)'h no%e enlarge)ent i$ the lea$t co))on criterion #oun% in 'atient$ who ha&e 4D.
(he enlarge)ent i$ u$ually unilateral, locate% in the anterior cer&ical chain, non#luctuant, an%
nonten%er. (he %ia)eter o# the in&ol&e% no%e $houl% be L1.? c). 2)aging ty'ically re&eal$ a
grou' o# )atte% no%e$ without ab$ce$$ #or)ation.
,hil%ren who ha&e 4D can ha&e a )yria% o# other $ign$ an% $y)'to)$, inclu%ing )yalgia$,
arthralgia$, an% arthriti$. Neurologic in&ol&e)ent can inclu%e $igni#icant irritability, li5ely
becau$e o# )eningeal in#la))ation, tran$ient #acial 'al$ie$, an% $en$orineural hearing lo$$.
3a$trointe$tinal co)'laint$ occur in u' to =DF o# 'atient$ an% inclu%e ab%o)inal 'ain, &o)iting,
%iarrhea, acalculou$ %i$tention o# the gallbla%%er 7hy%ro'$8, an% he'ato)egaly. .arely,
he)o'hagocytic ly)'hohi$tiocyto$i$, a li#e/threatening co)'lication in which acti&ate%
)acro'hage$ an% ( cell$ cau$e a cyto5ine $tor), can occur in 4D.
Pre&iou$ Section Ne6t Section
$ncomplete KD
A challenging $ub$et o# 'atient$ who %o not )eet the cla$$ic ca$e %e#inition are $ai% to ha&e
inco)'lete or aty'ical 4D. ,hil%ren who ha&e inco)'lete 4D %o not ha&e aty'ical #eature$H
rather, they ha&e $o)e o# the cla$$ic #eature$ o# 4D but not enough to )eet the ca$e %e#inition.
Patient$ who ha&e inco)'lete 4D are )ore li5ely to be in#ant$ an% ol%er chil%ren, an%, a$ $uch,
al$o are at higher ri$5 #or ,A-$.
,on$i%ering the car%iac con$e9uence$ o# #ailing to treat inco)'lete 4D an% the co)'arati&e
$a#ety o# 2123 treat)ent, the A)erican eart A$$ociation 7AA8 'ubli$he% an algorith) #or the
e&aluation an% treat)ent o# $u$'ecte% inco)'lete 4D to a$$i$t clinician$ 7Fig ?8. (he algorith)
u$e$ laboratory &alue$ an% echocar%iogra'hy in tho$e chil%ren who ha&e only a #ew clinical
#eature$ o# the %i$ea$e, an% al$o reco))en%$ con$ultation with a 4D e6'ert i# nee%e%.
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Figure ?.
0&aluation o# $u$'ecte% inco)'lete 4awa$a5i %i$ea$e 74D8. 718 2n the ab$ence o# gol% $tan%ar%
#or %iagno$i$, thi$ algorith) cannot be e&i%ence/ba$e% but rather re're$ent$ the in#or)e% o'inion
o# the e6'ert co))ittee. ,on$ultation with an e6'ert $houl% be $ought any ti)e a$$i$tance i$
nee%e%. 728 2n#ant$ M; )onth$ ol% on %ay L< o# #e&er without other e6'lanation $houl% un%ergo
laboratory te$ting an%, i# e&i%ence o# $y$te)ic in#la))ation i$ #oun%, echocar%iogra'hy, e&en i#
the in#ant$ ha&e no clinical criteria. 7=8 Patient characteri$tic$ $ugge$ting 4D are li$te% in (able
1. ,haracteri$tic$ $ugge$ting %i$ea$e other than 4D inclu%e e6u%ati&e conEuncti&iti$, e6u%ati&e
'haryngiti$, %i$crete intraoral le$ion$, bullou$ or &e$icular ra$h, or generaliIe% a%eno'athy.
,on$i%er alternati&e %iagno$e$ 7$ee (able 28. 7>8 Su''le)ental laboratory criteria inclu%e
albu)in M=.D g*%-, ane)ia #or age, ele&ation o# alanine a)inotran$#era$e, 'latelet$ a#ter < %ay$
L>?D,DDD*))
=
, white bloo% cell count L1?,DDD*))
=
, an% urine L1D white bloo% cell$*high/
'ower #iel%. 7?8 ,an treat be#ore 'er#or)ing echocar%iogra'hy. 7;8 0chocar%iogra'hy i$
con$i%ere% 'o$iti&e #or 'ur'o$e$ o# thi$ algorith) i# any o# = con%ition$ are )et+ , $core o# -AD
or .,A L2.?, coronary arterie$ )eet Ja'ane$e Mini$try o# ealth criteria #or aneury$)$, or L=
other $ugge$ti&e #eature$ e6i$t, inclu%ing 'eri&a$cular brightne$$, lac5 o# ta'ering, %ecrea$e% le#t
&entricular #unction, )itral regurgitation, 'ericar%ial e##u$ion, or , $core$ in -AD or .,A o# 2.D
to 2.?. 7<8 2# echocar%iogra'hy i$ 'o$iti&e, treat)ent $houl% be gi&en to chil%ren within 1D %ay$
o# #e&er on$et an% tho$e beyon% %ay 1D with clinical an% laboratory $ign$ 7,.P, 0S.8 o#
ongoing in#la))ation. 7A8 (y'ical 'eeling begin$ un%er nail be% o# #inger$ an% then toe$. Figure
an% legen% re'rinte% with 'er)i$$ion #ro) Newburger JW, (a5aha$hi M, 3erber MA, et al.
Diagno$i$, treat)ent, an% long/ter) )anage)ent o# 4awa$a5i %i$ea$e+ a $tate)ent #or health
'ro#e$$ional$ #ro) the ,o))ittee on .heu)atic Fe&er, 0n%ocar%iti$ an% 4awa$a5i Di$ea$e,
,ouncil on ,ar%io&a$cular Di$ea$e in the Noung, A)erican eart A$$ociation. Circ&lation.
2DD>H11D71<8+2<>A. ,.PO,/reacti&e 'roteinH echoOechocar%iogra'hyH 0S.Oerythrocyte
$e%i)entation rateH #*uO#ollow/u'H -ADOle#t anterior %e$cen%ing arteryH .,AOright coronary
artery.
A )ulticenter retro$'ecti&e $tu%y o# 'atient$ who ha&e 4D with aneury$)$ 're$enting be#ore
%ay 21 o# illne$$ #oun% that a''lication o# the AA algorith) woul% ha&e re$ulte% in re#erral o#
B<F o# 'atient$ #or 2123 treat)ent. 71D8 :# note, in#ant$ younger than age ; )onth$ are at high
ri$5 #or %e&elo')ent o# ,A-$, yet o#ten ha&e #ew clinical #eature$ to #acilitate the %iagno$i$. For
the$e rea$on$, it i$ reco))en%e% that in#ant$ younger than age ; )onth$ who ha&e ha% L< %ay$
o# #e&er o# unclear etiology an% ele&ate% in#la))atory )ar5er$ un%ergo echocar%iogra'hy.
Pre&iou$ Section Ne6t Section
Di##erential Dianosis
Becau$e 4D i$ a $el#/li)ite% #ebrile illne$$, in#ection$ %o)inate the li$t o# %i##erential %iagno$e$
7(able 28. Mea$le$, a%eno&iru$, entero&iru$, an% 0B1 can )i)ic the clinical 're$entation o# 4D.
Mea$le$ %oe$ not occur ty'ically in countrie$ with wi%e$'rea% &accinationH a tra&el or contact
hi$tory $houl% be $ought in ca$e$ in which coryIa an% cough are con$'icuou$. ,hil%ren who ha&e
a%eno&iral or entero&iral illne$$e$ ty'ically are le$$ ill co)'are% with chil%ren who ha&e 4D,
an% laboratory $tu%ie$ $how le$$ e&i%ence o# in#la))ation, with lower white bloo% cell count$
an% in#la))atory )ar5er$. White bloo% cell in%ice$ ty'ically re&eal ly)'hocyto$i$.
1iew thi$ table+
2n thi$ win%ow
2n a new win%ow
(able 2.
Di##erential Diagno$i$ o# 4awa$a5i Di$ea$e
0B1 i$ a$$ociate% co))only with an e6u%ati&e 'haryngiti$ an% %i##u$e ly)'ha%eno'athy,
neither o# which i$ $een ty'ically in 4D. (he conEuncti&iti$ an% ra$h o# 4D can be 9uite
'ro)inent an% )ay a''ear con$i$tent with Ste&en$/John$on $yn%ro)e. (he ab$ence o# other
clinical #eature$ o# 4D, or #in%ing$ o# $5in 'ain, $5in necro$i$, or bli$ter$, #a&or$ the %iagno$i$ o#
Ste&en$/John$on $yn%ro)e.
(o6in/)e%iate% $yn%ro)e$ triggere% by $ta'hylococcal or $tre'tococcal in#ection$ u$ually are
characteriIe% by &i$ceral organ in&ol&e)ent, inclu%ing renal in$u##iciency an% $igni#icant
he'atic %y$#unction that are 9uite unu$ual in 4D. y'oten$ion i$ al$o 9uite 'ro)inent in the
to6in/)e%iate% illne$$e$.
Scarlet #e&er can be e&aluate% with ra'i% $tre'tococcal antigen te$tingH #e&er cau$e% by grou' A
Streptococc&s i$ u$ually not a$$ociate% with conEuncti&iti$ an% u$ually i)'ro&e$ $igni#icantly
within 2> hour$ o# initiation o# antibiotic$. .oc5y Mountain $'otte% #e&er 're$enting with #e&er
an% ra$h can a''ear $i)ilar to 4D an% occur$ in $'eci#ic geogra'hic region$ in the Gnite% State$H
treat)ent #or thi$ 'otentially #atal in#ection $houl% not be withhel% while 4D i$ being
con$i%ere%.
Acro%ynia can cau$e irritability an% e6tre)ity change$ $i)ilar to 4DH an inge$tion hi$tory o#
)ercury $houl% be $ought i# the$e are 'ro)inent )ani#e$tation$. ,hil%ren who ha&e $y$te)ic/
on$et Eu&enile i%io'athic arthriti$ 're$ent with #e&er an% ra$h, an% coronary %ilation on
echocar%iogra'hy ha$ been %e$cribe% in thi$ 'o'ulationH howe&er, the ocular an% oro'haryngeal
$ign$ o# 4D are 9uite unu$ual in the $y$te)ic #or) o# arthriti$.
,onco)itant in#ection$ %o not 'reclu%e the %iagno$i$ o# 4D. 2n one $tu%y #ro) (oronto, o&er
=DF o# chil%ren who ha% ty'ical 4D ha% laboratory e&i%ence o# at lea$t one in#ection. 7118
Patient$ who ha&e 4D ha&e non$'eci#ic $y)'to)$ a$ well, $uch a$ hea%ache, ab%o)inal 'ain,
an% )alai$e. ,linician$ $houl% not %i$)i$$ the %iagno$i$ o# 4D in chil%ren who ha&e $y)'to)$
that are attribute% co))only to &iral illne$$e$.
Pre&iou$ Section Ne6t Section
Evaluation #or Suspected KD
%aboratory Studies
,hil%ren who ha&e 4D ty'ically ha&e leu5ocyto$i$ with a 're%o)inance o# neutro'hil$ an%
i))ature #or)$. Many o# the$e chil%ren ha&e a nor)ocytic nor)ochro)ic ane)ia, with the
a&erage he)atocrit at 're$entation being 2 SD$ below the nor) #or age. A $u%%en %ro' in
he)oglobin concentration #ollowing 2123 )ay be attributable to he)olytic ane)ia.
Platelet count$ u$ually are ele&ate% by the en% o# the #ir$t wee5 o# illne$$ 7>?D,DDD*))
=
8, an%
)ay e&ol&e into $igni#icant thro)bocyto$i$, with 'latelet count$ a&eraging <DD,DDD*))
=
by the
thir% wee5. Platelet count$ e6cee%ing 1 )illion*))
=
are not unco))on. .elati&ely lower
'latelet count$ at the ti)e o# 're$entation are a ri$5 #actor #or later %e&elo')ent o# ,A-, li5ely
re#lecting greater a%herence o# 'latelet$ to an acti&ate% en%otheliu). .arely, )ar5e%
thro)bocyto'enia at %iagno$i$ )ay be attributable to %i##u$e intra&a$cular coagulation.
2n#la))atory )ar5er$ are ele&ate% in nearly all ca$e$ o# 4D. (he 0S. an% ,.P $houl% be
a$$e$$e% at %iagno$i$. (he 0S. #ollowing treat)ent with 2123 o#ten i$ high, becau$e the 'rotein
loa% #ro) the in#u$ion ele&ate$ the 0S., ob$curing the e6tent o# %i$ea$e acti&ity. Nonethele$$,
)ea$ure)ent$ o# the 0S. can be hel'#ul in a$$e$$ing the %egree o# in#la))ation at %iagno$i$.
,.P le&el$ are una##ecte% by 2123 an% can be u$e% in both the acute an% $ubacute 'ha$e$ to
gauge the %egree o# in#la))ation.
(ran$a)ina$e$ are ele&ate% in a''ro6i)ately >DF o# 'atient$ with 4D, an% a )il%
hy'erbilirubine)ia can occur. Pla$)a ga))agluta)yl tran$'e'ti%a$e le&el$ are ele&ate% in
a''ro6i)ately two thir%$ o# 'atient$ who ha&e 4D. Sterile 'yuria 7ie, %i'$tic5 negati&e8 o# L12
white bloo% cell$*P- i$ 're$ent in a''ro6i)ately ADF o# 'atient$ who ha&e 4D. Such 'yuria )ay
be #oun% al$o in chil%ren who ha&e other #ebrile illne$$e$, but the )agnitu%e i$ greater in 'atient$
who ha&e 4D. 7128 :ther laboratory #in%ing$, $uch a$ hy'oalbu)ine)ia an% hy'onatre)ia,
re#lect )ore $e&ere illne$$ an% can be a$$ociate% with ca'illary lea5. -i'i% 'anel$ in 'atient$ who
ha&e 4D are )ar5e%ly altere%, with %ecrea$e% le&el$ o# total chole$terol, a$ well a$
a'oli'o'rotein A1 an% high/%en$ity li'o'rotein. Mar5er$ o# car%iac %a)age or %y$#unction, $uch
a$ tro'onin$ an% B/ty'e natriuretic 'e'ti%e, al$o )ay be ele&ate%, but are not obtaine% routinely.
Although laboratory $tu%ie$ are not a co)'onent o# the cla$$ic criteria #or 4D, they are inclu%e%
in the algorith) #or treat)ent o# $u$'ecte% inco)'lete 4D, becau$e )any o# the laboratory
abnor)alitie$ %e$cribe% 're&iou$ly are $een con$i$tently in 4D.
*e cild as ecocardiograpy performed. Her coronary artery dimensions are -itin normal
limits for age, '&t er left anterior descending artery does not taper normally. Her left
ventric&lar f&nction is normal, and no pericardial eff&sion is seen.
Cardiac $main
0chocar%iogra'hy i$ an e6cellent i)aging )o%ality #or e&aluating coronary artery %i)en$ion$,
)yocar%ial #unction, &al&e regurgitation, an% 'ericar%ial e##u$ion. (he 'roce%ure i$ nonin&a$i&e,
an% in e6'erience% han%$ ha$ high $en$iti&ity an% $'eci#icity #or %ilation in the 'ro6i)al
coronary arterie$. Se%ation o#ten i$ re9uire% in younger chil%ren to obtain o'ti)al i)age$. 2# the
%iagno$i$ i$ clear, treat)ent #or 4D $houl% not be withhel% while waiting to $che%ule or obtain
the re$ult$ o# echocar%iogra'hy. (wo/%i)en$ional echocar%iogra'hy $houl% be 'er#or)e% with
the highe$t/#re9uency 'robe a&ailable to 'ro%uce high/re$olution i)age$. Stan%ar% &iew$ #or
car%iac echocar%iogra'hy inclu%e 'ara$ternal, a'ical, $ubco$tal, an% $u'ra$ternal notch win%ow$.
Patient$ who ha&e %e#inite or $u$'ecte% 4D $houl% un%ergo a$$e$$)ent o# each coronary artery,
inclu%ing the le#t )ain coronary artery, le#t anterior %e$cen%ing artery 7-AD8, le#t circu)#le6
coronary artery, right coronary artery 7.,A8, an% 'o$terior %e$cen%ing coronary artery. (he
'ro6i)al -AD an% .,A are a##ecte% )o$t co))only by coronary artery aneury$)$.
,oronary arterie$ $houl% be e&aluate% with re$'ect to their $iIe an% a''earance. (he $iIe o# an
artery $houl% be )ea$ure% #ro) internal e%ge to internal e%ge, a&oi%ing area$ o# branching that
can be a$$ociate% with area$ o# natural %ilation. (he wi%ely u$e% Ja'ane$e Mini$try o# ealth
criteria cla$$i#y coronary artery $iIe$ accor%ing to age, with an internal lu)en %ia)eter greater
than = )) abnor)al in chil%ren le$$ than age ? year$, an% internal lu)en %ia)eter greater than >
)) abnor)al in chil%ren age L? year$. A%%itionally, artery $eg)ent$ that are L1.? ti)e$ larger
than the a%Eacent $ection an% tho$e $eg)ent$ ha&ing an irregular coronary lu)en al$o are
con$i%ere% abnor)al. Becau$e coronary artery %i)en$ion$ change with the $iIe o# the chil%,
bo%y $ur#ace areaKa%Eu$te% coronary %i)en$ion$ 7, $core$8 al$o $houl% be obtaine% #or the le#t
)ain coronary artery, -AD, an% .,A. (he other coronary arterie$ %o not ha&e e$tabli$he% ,
$core$, an% a$ $uch, the Ja'ane$e Mini$try o# ealth criteria )ay be a''lie% to tho$e $eg)ent$.
Aneury$)$ can be cla$$i#ie% a$ $)all 7Q? )) internal %ia)eter8, )e%iu) 7?KA )) internal
%ia)eter8, an% giant 7RA )) internal %ia)eter8 when u$ing ab$olute %i)en$ion$.
(he a''earance o# the coronary arterie$ i$ in#or)ati&e a$ well. 2n )o$t chil%ren who ha&e 4D,
coronary %ia)eter$ are greate$t on the #ir$t echocar%iogra'hy 'er#or)e% early in the %i$ea$e. 71=8
-arger ba$eline )ea$ure)ent$ 're%ict the %e&elo')ent o# wor$ening ,A-$ o&er the en$uing > to
; wee5$ in a $ub$et o# chil%ren. 2# coronary artery %i)en$ion$ are nor)al in the $ubacute 'erio%
7u' to ; wee5$8, it i$ highly unli5ely that the chil% will %e&elo' %ilatation o# coronary &e$$el$
therea#ter, unle$$ the %i$ea$e rela'$e$ or recur$.
2n a%%ition to %ocu)enting #in%ing$ in the coronary arterie$, echocar%iogra'hy 'ro&i%e$
a$$e$$)ent o# le#t &entricular an% &al&e #unction. -e#t &entricular $y$tolic %y$#unction 7ie,
eEection #raction R2 SD$ below nor)al8 occur$ in 2DF o# chil%ren who ha&e acute 4D.
i$tologic $tu%ie$ $ugge$t that )yocar%iti$ i$ uni&er$al in 'atient$ who ha&e 4D an% can be
$e&ere enough to 'ro%uce a clinical 'icture con$i$tent with $hoc5. (he )yocar%iti$ i)'ro&e$
ra'i%ly with a%)ini$tration o# 2123. (he 'ericar%iu) $houl% be a$$e$$e% with echocar%iogra'hy
#or e&i%ence o# e##u$ion. -a$t, although )itral regurgitation i$ $een in 2<F o# 'atient$ early in
the cour$e o# 4D, aortic regurgitation i$ le$$ co))on 71F8.
0chocar%iogra'hy $houl% be obtaine% at %iagno$i$, 1 to 2 wee5$ later, an% ; wee5$ 'o$t
%i$charge. ,hil%ren who ha&e 'er$i$tent or recru%e$cent #e&er or who ha&e 5nown ,A-$ nee%
)ore #re9uent )onitoring to in#or) treat)ent %eci$ion$, an% clo$e #ollow/u' with a 'e%iatric
car%iologi$t i$ e$$ential. AA reco))en%ation$ $ugge$t #ollow/u' echocar%iogra'hy at 1 year in
chil%ren who ne&er ha% coronary $e9uelaeH howe&er, echocar%iogra'hy $houl% be 'er#or)e%
)ore #re9uently a)ong tho$e who ha&e ,A-$.
Although echocar%iogra'hy i$ the 're#erre% )etho% o# &i$ualiIing the coronary arterie$ early
a#ter 4D, coronary angiogra'hy i$ u$e% in chil%ren who ha&e $igni#icant coronary artery
aneury$)$ u$ing techni9ue$ o# co)'ute% to)ogra'hy, )agnetic re$onance angiogra'hy, or
car%iac catheteriIation.
"ased on te clinical findings, te cild is diagnosed as aving +D and is prescri'ed ).)/ at 2
g01g and aspirin 2$S$3 45 to 155 mg01g per day divided every 6 o&rs.
&reatment
:nce the %iagno$i$ o# 4D i$ con#ir)e%, treat)ent with high/%o$e 2123 72 g*5g8 an% high/%o$e
ASA 7AD to 1DD )g*5g 'er %ay %i&i%e% into > %o$e$8 $houl% be in$titute% 'ro)'tly. 2%eally,
treat)ent i$ a%)ini$tere% within the #ir$t < %ay$ o# illne$$, an% by %ay 1D 7a$ %e#ine% by the #ir$t
%ay o# #e&er8 at the late$t. (reat)ent with 2123 a#ter %ay 1D o# illne$$ i$ re$er&e% #or tho$e with
ongoing #e&er an% e&i%ence o# $y$te)ic in#la))ation on laboratory $tu%ie$. (o a&oi% in#u$ion
reaction$, 're)e%ication with $tan%ar% %o$ing o# %i'henhy%ra)ine $houl% be con$i%ere%
$trongly. A%%itionally, 2123 $houl% be a%)ini$tere% $lowly, o&er A to 12 hour$, to a&oi%
he)o%yna)ic in$tability. 2123 can be a$$ociate% with low/gra%e #e&er$ within the #ir$t >A hour$
o# it$ a%)ini$tration. e)olytic reaction$ to 2123 are well %e$cribe%.
A''ro6i)ately 1?F o# chil%ren who ha&e 4D will ha&e recurrent or 'er$i$tent #e&er a#ter the
#ir$t %o$e o# 2123 an% are con$i%ere% re$i$tant to 2123 an% at higher ri$5 #or ,A-$. (he
treat)ent o# the$e chil%ren re)ain$ an area o# contro&er$y, becau$e $tu%ie$ to e&aluate treat)ent
$trategie$ #or 2123 re$i$tance are li)ite%. Mo$t clinician$ a%)ini$ter another %o$e o# 2123 72
g*5g8 >A hour$ a#ter the #ir$t %o$e i# #e&er 'er$i$t$ or i$ recru%e$cent.
Becau$e 4D i$ a &a$culiti$, cortico$teroi%$ ha&e un%ergone trial$ in 4D. Steroi%$ can be
a%)ini$tere% a$ S'ri)aryT thera'y when gi&en at the ti)e o# the #ir$t %o$e o# 2123, or a$
S$econ%aryT thera'y when gi&en #or 2123 re$i$tance. Further)ore, cortico$teroi%$ can be gi&en
in high/S'ul$eT %o$e$ o# =D )g*5g o# intra&enou$ )ethyl're%ni$olone, or in lower %o$e$ 7D.? to
2.D )g*5g 'er %ay8 o# 're%ni$olone orally.
(he u$e o# cortico$teroi%$ in 4D ha$ an intere$ting hi$tory, becau$e an early re'ort rai$e% the
'o$$ibility o# $teroi%$ wor$ening coronary artery %i$ea$eH howe&er, $ub$e9uent $tu%ie$ in%icate%
a li5ely bene#icial e##ect in chil%ren. Mo$t recently, a $tu%y by 4obaya$hi et al 71>8 in&ol&ing
high/ri$5 Ja'ane$e chil%ren $howe% that 'ri)ary thera'y with a co)bination o# cortico$teroi%$
7're%ni$olone 2 )g*5g 'er %ay8 an% 2123 'ro&i%e% 'rotection again$t 'oor coronary outco)e$.
owe&er, thi$ regi)en ha$ not been te$te% in non/Ja'ane$e 'o'ulation$, an% the 'rotocol
in&ol&e% a 'rolonge% cour$e o# intra&enou$ cortico$teroi% with conco)itant ho$'italiIation. (he
o'ti)al regi)en o# cortico$teroi%$ #or 2123 re$i$tance ha$ yet to be %eter)ine%, an% the lac5 o#
con$en$u$ ha$ #o$tere% con$i%erable 'ractice &ariation acro$$ center$.
:ther thera'ie$ u$e% in 2123 re$i$tance inclu%e in#li6i)ab, a tu)or necro$i$ #actor inhibitor 7?
)g*5g 'er %o$e8. .etro$'ecti&e %ata in%icate that in#li6i)ab )ay %ecrea$e the nu)ber o# %ay$ o#
#e&er, but )ay not alter coronary artery outco)e$. .e$ult$ o# a 'ro$'ecti&e trial u$ing in#li6i)ab
a$ 'ri)ary thera'y are awaite%. (here are re'ort$ #ro) Ja'an an% the Gnite% State$ that
calcineurin inhibitor$, $uch a$ cyclo$'orine A, )ay be e##ecti&e in 'atient$ with 2123 re$i$tance.
(here are &ery #ew in%ication$ #or ASA in chil%hoo% gi&en the ri$5 o# .eye $yn%ro)e, but 4D
re)ain$ one o# the). Stu%ie$ ha&e $hown that u$e o# ASA %oe$ not a##ect the %e&elo')ent o#
,A-$ 71?8H howe&er, all o# the )aEor clinical trial$ to $tu%y treat)ent o# 4D ha&e u$e% ASA.
G$e o# other non$teroi%al anti/in#la))atory %rug$, $uch a$ ibu'ro#en, ha$ not been $tu%ie%
recently. 2n treating 4D, ASA i$ gi&en at high 7anti/in#la))atory8 %o$e$ o# AD to 1DD )g*5g 'er
%ay, %i&i%e% into e&ery/;/hour %o$ing initially, #ollowe% by antithro)botic %o$e$ o# = to ? )g*5g
'er %ay in once/%aily %o$ing.
(here i$ 'ractice &ariation in %uration o# high/%o$e ASA a%)ini$tration. So)e 'ractitioner$ gi&e
high/%o$e ASA until 'atient$ are a#ebrile #or >A hour$, wherea$ other$ continue with high/%o$e
ASA #or 2 wee5$. -ow/%o$e ASA ty'ically i$ %i$continue% i# echocar%iogra'hy #in%ing$ are
nor)al at the ;/wee5 &i$it.
,hil%ren who ha&e 'er$i$tent ,A- at ; wee5$ are continue% on low/%o$e ASA, an% yearly
in#luenIa &accination$ are $trongly reco))en%e% in tho$e ca$e$ to %ecrea$e the ri$5 o# .eye
$yn%ro)e. Patient$ who are not #ully &accinate% $houl% recei&e i))uniIation$ accor%ing to the
gui%eline$ 'ut #orth in the A)erican Aca%e)y o# Pe%iatric$@ 7ed "oo1, which $tate that )ea$le$
an% &aricella/containing &accination$ are contrain%icate% #or 11 )onth$ a#ter a%)ini$tration o#
2123 #or 4D. 71;8
For tho$e 'atient$ who ha&e )o%erate to large aneury$)$, a $econ% anti'latelet agent )ay be
a%%e% to ASA. ,hil%ren who ha&e giant aneury$)$ re9uire anticoagulation with low/)olecular/
weight he'arin or war#arin, in a%%ition to ASA. Such regi)en$ are be$t i)'le)ente% with the
collaboration o# 'e%iatric he)atologi$t$ or coagulation $er&ice$.
(he role o# =/hy%ro6y/=/)ethylglutaryl coenIy)e A re%ucta$e inhibitor$ 7$tatin$8 in chil%ren
who ha&e 4D re)ain$ an area o# re$earch. Statin$ ha&e both chole$terol/lowering an%
i))uno)o%ulatory 'ro'ertie$. 2n a $)all $tu%y o# 11 chil%ren who ha% 4D an% ,A-$, u$e o# a
$tatin #or = )onth$ re$ulte% in i)'ro&e% #low/)e%iate% %ilation 7an in%ication o# en%othelial
health8 an% ,.P le&el$. 71<8 Although the$e re$ult$ are o# intere$t, larger/$cale clinical trial$ are
nee%e% be#ore one can reco))en% u$e o# $tatin$ in the earlie$t 'ha$e$ o# 4D. owe&er, the
thre$hol% #or u$e o# $tatin$ in chil%ren who ha&e aneury$)$ i$ lower becau$e o# %ata $ugge$ting
$u$ce'tibility o# the$e 'atient$ to athero$clero$i$.
*e patient tolerates er ).)/ inf&sion -ito&t complication and defervesces -itin te
s&'se8&ent 94 o&rs. Her tacycardia resolves. *e con:&nctival in:ection improves
significantly, as does te ras. Upon discarge, se is -ell appearing and prescri'ed $S$ 95.;
mg daily. Se is sced&led for an appointment in 2 -ee1s for ecocardiograpy and la'oratory
st&dies.
Pronosis and %on'&erm "anaement
(he 'rogno$i$ o# 4D relate$ entirely to the e6tent an% $e&erity o# car%iac %i$ea$e. With ti)ely
2123 treat)ent, the inci%ence o# ,A- in treate% chil%ren ha$ #allen to le$$ than ?F, an% only 1F
o# chil%ren %e&elo' giant aneury$)$. ,oronary aneury$)$ regre$$ to nor)al lu)en %ia)eter &ia
'roli#eration o# )yo#ibrobla$t$ in )ore than one hal# o# a##ecte% arterial $eg)ent$. owe&er,
en%othelial #unction i$ i)'aire% in the$e $eg)ent$ e&en a#ter regre$$ion. Steno$e$ at the 'ro6i)al
an% %i$tal en%$ o# aneury$)$ can %e&elo' o&er ti)e an% increa$e the ri$5 o# )yocar%ial i$che)ia.
Stenotic le$ion$ are )ore li5ely to #or) in giant aneury$)$, a$ co)'are% with $)aller le$ion$.
Manage)ent o# chil%ren who ha&e $igni#icant coronary artery %i$ea$e )ay re9uire a co)bination
o# beta/bloc5er$ to %ecrea$e o6i%ati&e $tre$$, a$ well a$ anticoagulation thera'y. (he$e chil%ren
are #ollowe% clo$ely with a$$e$$)ent o# coronary #unction 7eg, e6erci$e $tre$$ echocar%iogra'hy
in chil%ren ol% enough to run on a trea%)ill, %obuta)ine car%iac )agnetic re$onance i)aging #or
younger chil%ren8 an% $tructure 7echocar%iogra'hy, coronary angiogra'hy8.
2n tho$e who %e&elo' $y)'to)$ o# angina or #in%ing$ o# re&er$ible i$che)ia on $tre$$ te$ting,
'ercutaneou$ coronary inter&ention, #or e6a)'le with coronary $tent$, an% coronary artery
by'a$$ $urgery )ay be in%icate%. A recent re'ort #ro) Ja'an that #ollowe% 'atient$ who ha%
giant aneury$)$ into a%ulthoo% #oun% that long/ter) $ur&i&al i$ relati&ely goo% a)ong 'atient$
with giant aneury$)$, %e$'ite their nee% #or )ulti'le catheteriIation$ an% $urgerie$. 71A8
Mortality #ro) 4D i$ low 7QD.?F8, with the highe$t ri$5 occurring in the #ir$t year a#ter illne$$
on$et becau$e o# acute )yocar%ial in#arction a)ong 'atient$ who ha&e giant aneury$)$.
Sluggi$h bloo% #low through a %ilate% arterial $eg)ent an% acti&ation o# 'latelet$ an%
en%otheliu) contribute to the ri$5 #or )yocar%ial in#arction. ,hil%ren who ha&e )yocar%ial
in#arction )ay 're$ent with 'allor, &o)iting, an% ab%o)inal 'ainH ol%er chil%ren )ay co)'lain
o# che$t 'ain. .u'ture o# coronary artery aneury$)$ i$ &ery rare, an% generally occur$ within the
#ir$t #ew )onth$ o# illne$$. Se&ere )yocar%iti$ lea%ing to he)o%yna)ic co)'ro)i$e or
arrhyth)ia$ can lea% to %eath in the #ir$t wee5 o# illne$$.
Fortunately, )o$t chil%ren who ha&e 4D %o well a#ter a $ingle %o$e o# 2123, with ra'i% clinical
i)'ro&e)ent an% rea$$uring echocar%iogra'hic #in%ing$. (he ri$5 o# 're)ature athero$clero$i$
a)ong 'atient$ with alway$/nor)al coronary arterie$ will not be 5nown %e#initi&ely until large
cohort$ o# )i%%le/age% 'atient$ who ha&e 4D are a$$e)ble%. 2n the interi), all chil%ren with a
hi$tory o# 4D, e&en tho$e without a''arent coronary artery in&ol&e)ent, $houl% un%ergo
a$$e$$)ent o# ri$5 #actor$, $uch a$ hy'erli'i%e)ia an% hy'erten$ion, an% be coun$ele% regar%ing
a healthy li#e$tyle an% a&oi%ance o# )o%i#iable car%iac ri$5 #actor$, $uch a$ obe$ity, $)o5ing,
an% a $e%entary li#e$tyle.
Summary
Patient$ who ha&e acute 4awa$a5i %i$ea$e 74D8 $houl% be treate% 'ro)'tly with
intra&enou$ i))unoglobulin 721238 to 're&ent coronary artery abnor)alitie$ 7ba$e% on
$trong re$earch e&i%ence8. 71B8
Patient$ who ha&e 'er$i$tent or recru%e$cent #e&er #ollowing 'ri)ary thera'y with 2123
$houl% recei&e another %o$e o# 2123 at 2 g*5g 7ba$e% 'ri)arily on con$en$u$8. 7B8 :ther
$econ%ary thera'ie$ to con$i%er inclu%e cortico$teroi%$ 71>872D8 an% in#li6i)ab 7218
7ba$e% on $o)e re$earch e&i%ence8.
0chocar%iogra'hy i$ an e6cellent )o%ality #or a$$e$$ing coronary artery change$ in
chil%ren who ha&e early 4D 7ba$e% 'ri)arily on con$en$u$8.
2n 'atient$ who ha&e 4D an% alway$/nor)al coronary arterie$, 're&enti&e car%iology
coun$eling an% #ollow/u' are reco))en%e% until #urther $tu%ie$ %elineate the long/ter)
con$e9uence$ on en%othelial health 7B8 7ba$e% on $o)e re$earch e&i%ence a$ well a$
con$en$u$8.
2n 'atient$ who ha&e 4D an% coronary aneury$)$, car%iologic #ollow/u' i$ tailore% to the
%egree o# coronary artery in&ol&e)ent an% in&ol&e$ a$$e$$)ent o# coronary #unction an%
$tructure 7ba$e% on $trong re$earch e&i%ence8. 7B8
Pre&iou$ Section

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