Case Report: Suspected Infective Endocarditis in

DiGeorge Syndrome
Author: Juan José Sánchez
Case Report
A 13-year-old male, carrier of chromosome 22q11.2 deleton syndrome (DiGeore !yndrome, DG!", #ith
cardiac manifestaton of $etraloy of %allot ($o%" treated #ith correct&e s'reries, the last one #hich occ'rred
( #ee)s prior #ith p'lmonic &al&e replacement, presented to the emerency department #ith a 1-#ee)
history of fe&er 'p to 1*2.+,%, predominantly noct'rnal, accompanied -y malaise, chills, cold intolerance,
decreased le&el of act&ity, and enerali.ed #ea)ness. /atent denied #eiht loss and diaphoresis. 0edical
history #as sini1cant for an episode of -acteremia that occ'rred one year prior, #hich resol&ed a2er a lon
period of antmicro-ial therapy. /hysical e3aminaton #as sini1cant for a systolic m'rm'r, #ith mid-systolic
clic), -est a'sc'ltated at the le2 'pper parasternal -order, #hich had -een descri-ed on se&eral pre&io's
occasions. 4o Roth5s spots, 6sler5s nodes, 7ane#ay lesions, or splinter hemorrhaes #ere fo'nd. $he patent
#as sent to echocardioraphy to assess the possi-ility of infecto's endocardits (89".
:nli)e other specialtes, 9merency 0edicine is di;erent in the sense that patents #ill come in for a #ide
&ariety of primary complaints, that rane from common day-to-day illnesses to life-threatenin conditons. 8t is
the physician5s <o- to q'ic)ly assess these complaints and determine #hich ones req'ires immediate medical
a=enton. Rere=a-ly, the di;erence -et#een these t#o ends of the spectr'm is not al#ays so clearly de1ned.
$his happens to -e the case #ith 89.
8t is imperat&e to identfy and treat 89 in children, i&en its sini1cant mor-idity and mortality. 0ost children
#ith 89 #ill ha&e an ident1a-le ris) factor at the tme of dianosis. $he clinical presentaton of 89 in children is
&aria-le and may rane from lo#-rade fe&er and nonspeci1c complaints to a rapidly proressi&e f'lminant
disease #ith hih spi)in fe&ers and em-olic phenomena.
6nce a clinical s'spicion has -een a=ained, the ne3t step in manaement in&ol&es the 'se of ancillary tests,
partc'larly echocardioraphy, to dianose 89. Clinical de1nitons of 89 are important since 'nderdianosis can
lead to increased mor-idity and mortality, #hile o&erdianosis can res'lt in 'nnecessary antmicro-ial therapy
#ith e3cessi&e costs and dr'-related side e;ects.
8n this paper, the case of 13-year-old male, #ith an 'nderlyin imm'node1ciency, cardiac a-normality, 1-#ee)
history of fe&er, and no focal sins of infecton, is presented. %o'r recent artcles on the s'-<ect of 89 are
re&ie#ed, #ith emphasis on the de1niton, ris) factors, micro-ioloy, and dianostc approach. $he foc's of
this paper has -een redirected to -e=er encompass the aspects of conenital heart disease and
imm'nos'ppression on the s'-<ect of 89. 8t has also -een so'ht to do a enerali.ed o&er&ie# on the s'-<ects
of DG! and $o%.
6&er&ie# of DG! and $o%
Chromosome 22q11.2 deleton syndrome, or DG!, is a enetc disorder #ith a #ide &ariety of manifestatons.
$he 'nderlyin pathophysioloy in&ol&es a defect in the miraton of ne'ral crest cells a;ectn the third and
fo'rth -ranchial po'ches. Characteristc feat'res of DG! can -e remem-ered 'sin the mnemonic CA$C> 22,
#hich stands for? cardiac a-normalites, a-normal facies, thymic hypoplasia, cle2 palate, hypocalcemia and
hypoparathyroidism. 8mm'node1ciency and de&elopmental delay are common.
@$he dianosis of and e&al'aton for DG! sho'ld occ'r for any neonate #ith a conotr'ncal heart lesion,
hypocalcemia, andAor cle2 palate.B (!erooy, 2*13" Dianosis of DG! is made -y q'antfyin a mar)edly
red'ced n'm-er of CD3C $ lymphocytes in associaton #ith clinical 1ndins and demonstrated deleton of
chromosome 22q11.2.
8mm'node1ciency in patents #ith DG! can rane from @rec'rrent sinop'lmonary infectons (partal DG!" to
se&ere com-ined imm'node1ciency (complete DG!". $he se&erity of the imm'node1ciency is related to the
deree of the thymic hypoplasia.B (!erooy, 2*13"
Cardiac manifestatons of DG! 's'ally present as conotr'ncal heart defects. $hese defects are amon the
leadin ca'ses of cyanotc heart disease and incl'de tr'nc's arterios's, transpositon of arteries, and $o%.
Deca'se of parallel fetal circ'laton, these defects are #ell tolerated in 'tero. A;ected indi&id'als 's'ally
present #ith cyanosis #ithin the 1rst fe# days follo#in deli&ery.
$o% incl'des the follo#in feat'res? riht &entric'lar o'Elo# tract o-str'cton, &entric'lar septal defect (F!D",
de&iaton of the oriin of the aorta to the riht so that it o&erride the F!D, and concentric riht &entric'lar
hypertrophy. @$o% acco'nts for appro3imately 1*G of all cases of conenital heart disease and is one of the
most common cyanotc conenital heart defects.B (Doyle, 2*13"
@$he clinical presentaton of patents #ith $o% depends chieHy 'pon the deree of riht &entric'lar o'Elo#
o-str'cton.B (Doyle, 2*13" Children #ith se&ere o-str'cton typically present #ith profo'nd cyanosis #ithin
the 1rst fe# days follo#in deli&ery. Children #ith moderate and minimal o-str'cton may present #ith a
m'rm'r andAor heart fail're.
@Reparat&e s'rery is enerally performed in most patents #ith $o% #ithin the 1rst year of life as it has
impro&ed mortality and mor-idity.B (Doyle, 2*13" 8ntracardiac repair s'rery is recommended for all patents
#ith $6%. @Ion-term o'tcome of patents a2er $o% repair is e3cellent, #ith estmated 2*-year s'r&i&al rates of
o&er J*G.B (Doyle, 2*13" !tr'ct'ral cardiac complicatons follo#in repair may req'ire s'-seq'ent s'rical
inter&entons. 6ther common complicatons follo#in repair incl'de ne#-onset arrhythmias.
@$he dianosis of 89 is 's'ally -ased 'pon a constellaton of clinical 1ndins rather than a sinle de1nit&e test
res'lt.B (!e3ton, 2*12"
$he 1rst de1niton for 89 #as proposed -y /elleter and /etersdorf in 1JKK, and in&ol&ed the direct e3aminaton
of cardiac tss'e. Altho'h it #as hihly speci1c, it lac)ed sensit&ity and, f'rthermore, lac)ed practcality for
clinical 'se. A modi1ed de1niton -y &on Reyn and collea'es in 1J+1 intended to impro&e clinical 'tlity -y
incl'din criteria s'ch as persistent -acteremia, ne#-onset re'ritant heart m'rm'r, em-olic phenomena,
and &al&'lar heart disease. $his de1niton called for a fo'r-cateory classi1caton, #ith a de1nite 89 req'irin
con1rmaton thro'h direct patholoic e3aminaton.
!'-seq'ently, in 1JJ1, @in&estators from D')e :ni&ersity modi1ed the &on Reyn criteria to incl'de the role of
echocardioraphy in dianosis.B (!e3ton, 2*12" :sin the D')e de1niton, cases can -e classi1ed as de1nite,
possi-le, or re<ected.
89 is considered de1nitely present #ith any of the follo#in 1ndins?
• Direct e&idence of endocardits -ased 'pon histoloical 1ndins
• /osit&e Gram stain of specimens o-tained from s'rery or a'topsy
• $#o ma<or clinical criteria
• 6ne ma<or and any three minor clinical criteria
• %i&e minor clinical criteria
89 is considered possi-ly present #ith any of the follo#in 1ndins?
• 6ne ma<or and one minor clinical criteria
• $hree minor clinical criteria
0a<or clinical criteria incl'des? persistently posit&e -lood c'lt'res for typical oranisms ca'sin 89, &eetatons
on echocardioraphy, ne# re'ritant m'rm'r, and infecton #ith Co3iella -'rneti.
0inor clinical criteria incl'des? fe&er, &al&'lar heart disease or 8F dr' a-'se, em-olic phenomena (incl'din
7ane#ay lesions and splinter hemorrhaes", imm'noloic phenomena (s'ch as lomer'lonephrits, Roth5s spots
or 6sler5s nodes", and other posit&e -lood c'lt'res.
89 can -e re<ected #ith any of the follo#in 1ndins?
• A 1rm alternated dianosis
• Resol'ton of clinical manifestatons a2er fo'r days or less of antmicro-ial therapy
• 4o patholoical e&idence on s'rery or a'topsy a2er fo'r days or less of antmicro-ial therapy
• Clinical criteria for 89 not met
Ris) %actors
@0ost children #ith 89 ha&e an ident1a-le ris) factor for the disease.B (65Drien, 2*12"
Defore 1JK*, rhe'matc heart disease (R>D" #as the ma<or predisposin ris) factor for 89 in children. Lith the
ad&ent of -e=er dianostc modalites and prompt antmicro-ial therapy, the incidence of R>D has 'nderone
a s'-stantal decline. $his, com-ined #ith increased s'r&i&a-ility of children #ith conest&e heart disease, has
led to the appearance of ne# ris) factors for 89 and, as of today, the most common ident1a-le ris) factors are
pree3istn heart disease and ind#ellin central &eno's catheter (CFC".
@Children #ith comple3 cyanotc heart disease #ith palliat&e sh'nts, cond'its, or other prostheses ha&e the
reatest mor-idity and mortality from 89.B (65Drien, 2*12"
6ther ris) factors, #hich are rarely seen in the pediatric pop'laton, incl'de 8F dr' a-'se and deenerat&e
heart disease.
@Altho'h a &ariety of microoranisms can ca'se 89, streptococci and staphylococci species are the most
common pathoens associated #ith 89 in children.B (65Drien, 2*12" As noted in the Mids5 8npatent Data-ases
st'dy in 2**J, !taphylococc's a're's is the most common ca'sat&e aent of 89 in children, recorded in NKG of
cases. $he second most common micro-e is the Firidans ro'p streptococci, fo'nd in 2*G of cases. $he third
most common micro-e is coa'lase-neat&e staphylococci, fo'nd in 1OG of cases.
6ther common pathoens of 89 in children incl'de Gro'p A streptococci, Gro'p D streptococci, 9scherichia coli,
!treptococc's pne'moniae, and >aemophil's inH'
$his distri-'ton reatly di;ers from the ad'lt pop'laton, as noted -y 8nternatonal Colla-oraton on
9ndocardits-/rospect&e Cohort !t'dy in 2**N. Droadly spea)in, the etoloy of ca'sat&e oranisms of 89 in
ad'lts, as opposed to children, incl'des more ram-neat&e oranisms, s'ch as the m'ch p'-lici.ed >AC9M
oranisms, a n'm-er of fastdio's ram-neat&e -acilli. >AC9M stands for >aemophil's aphrophil's,
Actno-acill's actnomycetemcomitans, Cardio-acteri'm hominis, 9i)enella corrodens, and Minella )inae.
Gram-neat&e 89 is rare in children, e&en in those #ith a CFC. @$he lo# rate of ram-neat&e -acteria as a
ca'se of 89 may -e related in part to decreased adherence of these oranisms to heart &al&es.B (!e3ton, 2*12"
@>o#e&er, in neonates #ith 89, li)ely etoloic aents can incl'de Mle-siella pne'moniae and 9ntero-acter
species.B (65Drien, 2*12"
@%'nal endocardits is rare and is typically ca'sed -y Candida species.B (65Drien, 2*12" 6pport'nistc in&asi&e
f'nal infectons are more common in imm'nocompromised patents.
Dianostc Approach
@$he dianosis of 89 is 's'ally -ased 'pon a constellaton of history, clinical 1ndins, la-oratory st'dies
(partc'larly -lood c'lt'res", and echocardioraphy.B (!e3ton, 2*12"
D'rin the inital assessment of s'spected 89, a caref'l history sho'ld -e o-tained #ith special a=enton i&en
to @history of prior cardiac lesions and historical cl'es pointn to#ard a recent so'rce of -acteremia, s'ch as
ind#ellin CFC or 8F dr' a-'se.B (!e3ton, 2*12"
/hysical e3aminaton may incl'de e&idence of a ne# re'ritant m'rm'r, heart fail're, em-olic phenomena, or
imm'noloic phenomena. /eripheral c'taneo's lesions of 89 incl'de petechiae, splinter hemorrhaes, 7ane#ay
lesions, 6sler5s nodes, and Roth spots. 7ane#ay lesions are mac'lar, non painf'l, erythemato's lesions on the
palms and soles. 6sler5s nodes are painf'l, &iolaceo's nod'les fo'nd in the p'lp of the 1ners and toes. Roth
spots are hemorrhaic lesions of the retna.
As part of the inital e&al'aton of 89, all patents #ith s'spected 89 sho'ld 'ndero the follo#in st'dies? at
least three -lood c'lt'res from separate sites at di;erent moments in tme, an 9MG to e&al'ate the presence of
ischemia or infarcton, ne#-onset heart -loc) or cond'cton delay, and echocardioraphy.
@C'lt'res remain neat&e in 2 to NG of patents #ith 89. C'lt're-neat&e 89 sho'ld -e considered in patents
#ith neat&e -lood c'lt'res and persistent fe&er #ith one or more clinical 1ndins consistent #ith 89.B (!e3ton,
89 in children is a conditon associated #ith sini1cant mor-idity and mortality. A prompt dianosis and
antmicro-ial treatment has an e3cellent s'ccess rate #ith minimal complicatons.
$he most important ris) factors for 89 in children are pree3istn heart disease and ind#ellin CFC. Another
important ris) factor in children is R>D, specially in 'nderde&eloped natons.
89 sho'ld -e s'spected in any )id #ith associated ris) factors and a history of fe&er #itho't a clear foc's of
infecton. 0ost children #ith 89 ha&e at least one ident1a-le ris) factor at the tme of dianosis.
Lhen s'spectn 89, the inital e&al'aton sho'ld incl'de -lood c'lt'res and echocardioraphy. $hese t#o
st'dies #ill help ascertain most cases of 89 #ith a ood sensit&ity and sensi-ility, as descri-ed -y the D')e
dianostc criteria of 89.
$he most common ca'sat&e oranisms of 89 are staphylococci and streptococci. Certain patent pop'latons
are more s'scept-le to other micro-es. An important ro'p of oranisms ca'sin 89 in neonates is ram-
neat&e -acilli. 8n imm'nocompromised indi&id'als, f'nal 89 sho'ld -e considered.
Lor)s Cited
1. Doyle, $homas, 0D, Ann Ma&ana'h-0c>'h, 0D, and $homas /. Graham, 0D. P6&er&ie# of the
0anaement of $etraloy of %allot.P 9d. >eidy 0. Connolly, 0D, 7ohn M. $riedman, 0D, and 0elanie !.
Mim, 0D. :p$oDate. 4.p., 2 Apr. 2*13. Le-. 12 7'ly 2*13.
2. 65Drien, !haron, 0D. P8nfect&e 9ndocardits in Children.P 9d. Da&id R. %'lton, 0D, 0or&en !. 9d#ards,
0D, and 0elanie !. Mim, 0D. :p$oDate. 4.p., 2* Dec. 2*12. Le-. 12 7'ly 2*13.
3. !erooy, Christne 0., 0D. PDiGeore !yndrome? Clinical %eat'res and Dianosis.P 9d. 9. Richard
!tehm, 0D and 9li.a-eth $e/as, 0D. :p$oDate. 4.p., 11 7an. 2*13. Le-. 12 7'ly 2*13.
O. !e3ton, Daniel 7., 0D. PDianostc Approach to 8nfect&e 9ndocardits.P 9d. Catherine 0. 6=o, 0D and
9linor I. Daron, 0D. :p$oDate. 4.p., 1J 0ar. 2*12. Le-. 12 7'ly 2*13.
N. !e3ton, Daniel 7., 0D. P9pidemioloy, Ris) %actors and 0icro-ioloy of 8nfect&e 9ndocardits.P 9d.
!tephen D. Calder#ood, 0D and 9linor I. Daron, 0D. :p$oDate. 4.p., 13 7'ne 2*12. Le-. 12 7'ly 2*13.
(. !e3ton, Daniel 7., 0D. P8nfect&e 9ndocardits? >istorical and D')e Criteria.P 9d. !tephen D. Calder#ood,
0D and 9linor I. Daron, 0D. :p$oDate. 4.p., 1N 7'ne 2*12. Le-. 12 7'ly 2*13.

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