Syphilis. 1Dr Frewan Neo

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CongenitalSyphilis

N.Frewan, PL2

Neonatology Divisio July 2008

%ntro"ution

.u$a!le ST caused !y theT$eponema pallidum o$)anism

199/ .omplete )enetic seuence

o #. palli"u$ was pu!lishedwhich helped unde$standin) thepatho)enesis o syphilis

Belon)s to 'Spi$ochaetaceae

amily*The )enus name, #repone$a, is

de$i(ed $om the #$ee2 te$m o$tu$nin) th$ead'

#repone$a Palli"u$

3otile

4t$emely astidiousSu$(i(e only !$ie6y outside

7ot culti(ated successully ona$ticial media

#rans$ission

Direct sexual contact with ulcerativelesions of skin or mucous membranes

Trans placental:

- Typically during second half of pregnancy- As early as 6 weeks of gestation- Pregnant with primary or secondary

syphilis are more likely to transmit the

disease than those with latent (notclinically apparent disease

Cannot be spread through contact with toilet seats, doorknobs, swimming pools, hot tubs,bathtubs, shared clothing, or eating utensils

Congenital syphilis

Se(e$e, disa!lin), and oten lie-

th$eatenin) inection seen ininants

8!out hal o all inected etusesdie sho$tly !eo$e o$ ate$ !i$th

%ni"ene&S

Despite the fact of being curable if

caught early! rising rates among

pregnant " in the #$ have recently %the number of infants born with

congenital syphilis

&')*&''+: overall incidence % ,)-

( $ex*Drug traffic

%ni"ene&S

&'': &./- of reported cases of 0$occurred because the mother receivedno1inade2uate penicillin tx before orduring pregnancy

According to the 0D0:

- 3+- of births are stillborn- 3+*,+- of the survivors will be infected- 4 &5- of these will subse2uently die

Reported cases for infants < 1 year of age andrates of 1ry & 2ry syphilis among women:

United States, 1997–2!

Rates for infants < 1 year of age: US, 1997–2! and the "ealthy #eople 21 target as

per S$% sr'eillance

ul-:00;

Pathophysiology CS

T$ans placental t$ansmission

T$ansmission $ate< ;0 - 100=

>ith ea$ly onset disease,maniestations $esult $omt$ans placental spi$ochetemiaand a$e analo)ous to seconda$y

sta)e o acui$ed syphilis.S does not ha(e a p$ima$y

Clinial 'ani(estations

"nt$a-ute$ine -?lacenta

-%etus

?ost-natal - 4a$ly

%ntra)uterine* Plaenta

The placenta is typically la$)e andedematous

.ha$acte$istic placental ndin)s include

- Hyd$ops placentalis- .h$onic (illitis

- ?e$i(illous !$ous p$olie$ation

-7o$mo!lastemia

- 7ec$oti@in) unisitis

- 8cute cho$ioamnionitis

- ?lasma cell deciduitis

%ntra)uterine* Fetus

epends on sta)e o de(elopmentat time o inection & du$ation ount$eated inection

"nitially cha$acte$i@ed !y placentalin(ol(ement and hepaticdysunction +eA)A, a!no$mal %T,ollowed !y amniotic 6uid

inection, hematolo)ica!no$malities, ascites, and hyd$ops

Still!i$th 7eonatal death

%ntra)uterine* Fetus

C:D wee2s )estation ;; = oetuses ha(e eithe$ con)enitalsyphilis o$ TA?allidum detected in

amniotic 6uid

"nt$aute$ine death :5 = o afected

?e$inatal mo$tality :5-E0 =, iunt$eated

Post)Natal

8mon) su$(i(o$s, maniestations !eendi(ided into

4a$ly sta)e F %i$st : yea$s

ate sta)e F 8te$ :yea$s

"n6ammato$y chan)es do not occu$ inthe etus until ate$ $st t$imeste$ Go$)ano)enesis is unafected

7e(e$theless, all o$)an systems may !ein(ol(ed

+arly CS) sy$pto$ati

ccu$s !etween 0 - : yea$s " asymptomatic

- "dentied on $outine p$enatalsc$eenin)

- " not identied and t$eated,these new!o$ns de(elop poo$

eedin) and $hino$$heaI 4a$liest si)ns o .S may !e poo$

eedin) and snuJes +iAeA,syphilitic $hinitis

Sy$pto$ati +arly CS

" Symptomatic

Ka$ia!le8ppea$ within 1st 5 wee2s o lieStill!o$n ?$ematu$e

%ailu$e to )ain wei)ht o$ %TT%e(e$ "$$ita!ilitySe(e$e con)enital pneumonia

Sy$pto$ati +arly CS

3ost st$i2in) lesions afect themucocutaneous tissues and !ones

- 3ucous patches

- Lhinitis FsnuJe

- .ondylomatous lesions

I I hi)hly cha$acte$istic eatu$es omucous mem!$ane in(ol(ement in.S

Sy$pto$ati +arly CS

SnuJes G %ollowed uic2ly !ydifuse maculopapula$desuamati(e $ash that in(ol(esetensi(e slou)hin) o theepithelium, on the palms & solesand a$ound the mouth & anus

>hen ch$onic G 'Saddle 7ose* esions & nasal 6uid hi)hly

inectious

Sy$pto$ati +arly CS

Bullous s2in disease 2nown as'pemphi)us syphiliticus*

M 4a$ly $ash -- small !liste$s onthe palms and soles G Nlce$ated

M ate$ $ash -- coppe$-colo$ed,6at o$ !umpy $ash on the ace,

palms, and soles

Sy$pto$ati +arly CS

the$ ea$ly maniestations

include hepatosplenome)aly+100=, Oaundice, anemia

3etaphyseal dyst$ophy andpe$iostitis oten a$e noted on$adio)$aphs at !i$th PQ?seudopa$alysis

.on)enital syphilis ea$ly

.on)enital syphilis - ea$lye(idence o inection - !ullae and

(esicula$ $ash

3ultiple, punched out, pale, !liste$edlesions, with associated desuamation

o palms & planta$s

"nt$ao$al mucous patches & acials2in lesions

Seconda$y lesions on eet Lesions frst appeared during 4th week

Late)onset CS

e(elop $om sca$$in) $elatedto ea$ly inection

.an !e p$e(ented !y t$eatmentwithin $st E months

.an appea$ as late as D0 yea$sate$

Late)onset CS

3aniestations include neu$osyphilisand in(ol(ement o teeth, !ones,eyes, and /th c$anial ne$(e

4A)A %$ontal !ossin), sho$t mailla,hi)h palatal a$ch, Hutchinson t$iad,

saddle nose, and pe$io$al ssu$e+Lha)ades F !acte$ial inection os2in lesions

Hutchinson t$iad

1A eaness +10 D0 yea$s

:A Hutchinsons teeth F

cent$ally notched, widely-spaced pe)-shaped uppe$cent$al inciso$s

EA "nte$stitial Ue$atitis G!lindness +5-:0 yea$s

Notched incisors known asHutchinson’s teeth

3o$i!und new!o$n with .S

$al s2in lesions and saddle nose

3etaphyseal osteomyelitis

3etaphyseal osteomyelitisLadiolucent distal $adius & ulna with cuppin)

distal ulna

steochond$itis o emu$ &ti!ia

1 ld .l i l >i ! V i

1-m-old A .lassical >im!e$)e$Vs si)n odest$ucti(e metaphysitis in(ol(in) medial

aspects o distal emo$a and p$oimal ti!ae

'Sa!e$ shins* F

Sa!e$ shins Fsteope$iostitis Ti!ia

"nte$stitial 2e$atitis

Possi-le Co$pliations

Blindness

eaness

%acial deo$mity

7eu$olo)ical p$o!lems

eniti(e dia)nosis

1A By di$ect (isuali@ation ospi$ochetes usin) da$2eldmic$oscopy

:A $ di$ect 6uo$escent anti!ody testso lesion eudate o$ tissue+?lacentaN.

-Helpful early in the disease, prior to development of seroreactivity

Serologi tests

- ?$esumpti(e dia)nosis can !e madeusin)

- 7ont$eponemal + %alse P in medical

conditions- T$eponemal +%alseP in othe$

spi$ochetal iseases

G So use o only one type is insuWcient

- " nont$eponemal test is PGcon$mato$y testin) is pe$o$medwith a specic t$eponemal test

Nontrepone$al test

KL +Kene$eal iseaseLesea$ch a!o$ato$y

L?L +Lapid plasma $ea)in

8LT +8utomated $ea)in test)

Nontrepone$al test

- Nsed o$ sc$eenin) +sensiti(e !ut notspecic

- "nepensi(e, pe$o$med $apidly, and

p$o(ide uantitati(e $esultsG helpul indicato$s o disease acti(ity &

monito$ t$eatment $esponse- 3easu$es 8! di$ected a)ainst lipoidal

8) $om TA ?allidum, 8! inte$actionwith host tissues o$ !oth

- 7onspecic 8! de(elop D-/ wee2sollowin) inection

Nontrepone$al test

False negative

- Early primary S-

atent ac!uired S- ate CS- Prozone phenomenon

False "ositive- #iral infection $ E%#,

Hepatitis, #aricela,&easles)

- ymphoma- '%- &alaria- Endocarditis- C' diseases- "regnancy- (# drugs- harton *elly

contamination in cordsamples

Nontrepone$al test

8ny $eacti(e 7T test must !e con$med!y T$eponemal test to eclude alsepositi(e

T$eatment should not !e delayed isymptomatic o$ at hi)h $is2 o inection

3onito$

- Sustained D old X7T test tite$ ate$

t$eatmentG 8deuate t$eatment

- Sustained Y Le-inection o$ $elapse

N t l t t

Nontrepone$al test New-orn Dile$$a

Testin) o new!o$n oten is p$o!lematic!ecause ")# anti!ody may !e a $e6ectiono mate$nal $athe$ than inant inection

Nnless 7T tite$ is much hi)he$ in !a!ythan in mothe$ G u se$olo)y o(e$ 1st ;

months o lie, when mate$nal ")# is lost,would !e $eui$ed to ma2e a dia)nosis

i.e. Loosing preious ti$e in treat$ent initiation

#repone$al Spei #est

T pallidum immobiliation (TP;

<luorescent treponemal antibodyabsorption (<TA*A=$

8icrohemagglutination assay forantibodies to T pallidum (8>A*TP)

#repone$al Spei #est

0onfirm ? nontreponemal reaginic test

@emain positive for life

i.e. @esult do not correlate with disease

activity and tests are not 2uantified

<alse ? reactions:

Bther spirochetal diseases (e.g.! yaws!

pinta! leptospirosis! rat*bite fever!

relapsing fever! Cyme disease

Cere-rospinal Flui"

Cere-rospinal Flui" nalysis

0$< D@C

0ould be negative and still develop signs

of neurosyphilis Therefore! all those

with presumptive 0$ should be treated

A non2uantitative D@C test is the only

serologic test that should be performed

on 0$<

+ther test like F'-%S are less specific on CSF samples

.S cha$acte$i@ed !y anemia,th$om!ocytopenia, and eithe$

leu2openia o$ leu2ocytosis

4(idence o .oom!s-ne)ati(e

hemolytic anemia o$ aleu2emoid $eaction may !ep$esent

%$aging Stu"ies

- Syphilitic pneumonia iscommon in .S - %lufy difuse inlt$ate

'pneumonia al!a*

%$aging Stu"ies

on) !one $adio)$aphy

– 95= o symptomatic inants and:0= o asymptomatic

– 3ultiple sites o osteochond$itis atw$ists, el!ows, an2les and 2nees

and pe$iostitis o lon) !ones– The lowe$ et$emities almost

always afected

%$aging Stu"ies

7eu$o$adio)$aphy

- %indin)s nonspecic

- 3ay mimic he$pes simple(i$us

- 3L" may $e(eal ce$e!$al

hype$t$ophy andhype$intensity in the tempo$allo!es

CDCNew-orn +valuation

The dia)nosis o .S iscomplicated !y the t$ans

placental t$anse$ o mate$nalnont$eponemal andt$eponemal ")# 8!s to etus

I 3a2in) inte$p$etation o$eacti(e se$olo)ic tests o$ .SdiWcult

4(aluation should include

1A 3ate$nal H syphilis includin) t type& adeuacy !eo$e and du$in) thep$e)nancy

:A ?4 o new!o$n

EA [uantitati(e 7T & T tests

DA .B., lon) !one -$ays, .S% +KL, cellcount, p$otein, and .ZL ando$ %T

5A ?atholo)ic eamination o placenta o$um!ilical co$d usin) specic 6uo$escentantit$eponemal anti!ody stainin)

8 p$esumpti(e dia)nosis, which $esultsin t, is made i !a!y has P se$olo)ictest

and any o ollowin)1A .ompati!le ndin)s on ?4

:A .S% a!nA +P KL, Y >B., o$ Yp$otein

EA steitis on -$ay lon) !ones

DA ?lacentitis5A 7T test D C than mate$nal

;A ?ositi(e %T8-8BS-19S ")3 anti!ody

#reat$ent

"K ?enicillin # is the d$u) o choiceo$ all sta)es o syphilis includin) .S

"nants

- 100,000 - 150,000 N2)d "K [1: \dA then [ / to complete 10 days

- $ ?$ocaine ?enicillin # 50,000N2)d "3 once o$ 10 days +adequateCSF conc. may not be achieved)

#reat$ent

"ndications

1A " new!o$n meets any o c$ite$ia

:A " mothe$ was t$eated ] D wee2sp$io$ to deli(e$y

EA " mothe$ t$eated with othe$ than

penicillinDA " mate$nal tite$s su))est

inadeuate $esponse to t$eatment!eo$e o$ ea$ly in p$e)nancy

Syphilis %n Pregnany

"n communities in which $is2 o$ .S ishi)h G se$olo)ic testin) and a seualhisto$y also should !e o!tained at :/

wee2s )estation and at deli(e$y

T$eat all p$e)nant patients withpenicillin, $e)a$dless o the sta)e op$e)nancy

Syphilis %n Pregnany

E doses o !en@athine penicillin

+:AD million N "3 at 1-wee2inte$(als

7o p$o(en alte$nati(e t$eatment o$patient alle$)ic to penicillin

iAeA 4$yth$omycin o$ patient alle$)ic topenicillin is not $elia!le t$eatment o$etus

%n(ants During the First 'onth o(Li(

The ollowin) scena$ios

desc$i!e the e(aluation andt$eatment o inants o$con)enital syphilis

Senario %n(ants with proven or highly pro-a-le "isease

%n(ants with proven or highly pro-a-le "isease

8!no$mal ?4 consistent with.S

Se$um uantitati(e 7T tite$D C mothe$s tite$ o$

P da$2eld o$ 6A a!A test o!ody 6uids

Senario %n(ants with proven or highly pro-a-le "isease

%n(ants with proven or highly pro-a-le "isease

1eo$$en"e"+valuation

.S% analysis o$KL, cell count &p$otein

.B. wA difA& ?count

the$ tests asclinically indicated+ lon)-!one -$ays,.ZL, %T, HNS,ophthalmolo)ic

eam, and B84L

1eo$$en"e"1egi$ens

8ueous c$ystallinepenicillin #50,000 N2)dose "K[ 1: h$sA $st \ and [ / h$sthe$eate$ o$ a total

o 10 daysL

?$ocaine penicillin #50,000 units2)dose"3 in a sin)le dailydose o$ 10 days

Senario 2N l P+ 3 titi N# tit 6

Nor$al P+ 3 seru$ 4uantitive N# titer 5 6 7

$aternal titer

3othe$ not inadeuatelyt$eated, o$ no documentation

3othe$ was t$eated withe$yth$omycin o$ othe$nonpenicillin $e)imen o$

3othe$ $ecei(ed t$eatment ]D wee2s !eo$e deli(e$y

Senario 2

Senario 2Nor$al P+ 3 seru$ 4uantitive N# titer 5 6 7

$aternal titer

.S% analysis o$KL, cell count,and p$otein

.B. wA difA and?T count

on)-!one Z-$ays

1eo$$en"e"1egi$ens

Aqueous crst! penici""in #

50$000 u!%kg%dose &' ( 1)hrs during the 1st * +,Land ( hrs therea.ter .ora tota" o. 10 das

, rocaine penici""in #

50$000 units%kg%dose &2 ina sing"e dai" dose .or 10das

, enathine penici""in #

50$000 units%kg%dose &2 ina sing"e dose

Senario

Senario Nor$al P+ 3 seru$ 4uantitive N# titer 5 6 7

$aternal titer

3othe$ was t$eated du$in)p$e)nancy, tA was app$op$iate o$the sta)e o inection, andt$eatment was administe$ed C Dwee2s !eo$e deli(e$y^AA and

3othe$ has no e(idence o$einection o$ $elapse

Senario

Senario Nor$al P+ 3 seru$ 4uantitive N# titer 5 6 7

$aternal titer

1eo$$en"e" +valuation

7o e(aluation$eui$ed

1eo$$en"e"1egi$en

_Ben@athine

penicillin # 50$000units%kg%dose &2 in asing"e dose

Senario 6

$aternal titer

3othe$s t$eatment was adeuate!eo$e p$e)nancy^A and

3othe$s 7T tite$ $emained lowand sta!le !eo$e, du$in)

p$e)nancy and at deli(e$y +KL]1:` L?L ]1D

Senario 6

$aternal titer

7o e(aluation$eui$ed

1eo$$en"e" 1egi$en

7o t$eatment$eui$ed

9utloo! :Prognosis;

"nected ea$ly in p$e)nancy I still!o$n

T$eatment o epectant mothe$ X $is2 o

Ba!ies who !ecome inected whenpassin) th$ou)h !i$th canal ha(e !ette$

outloo2

eath $om .S is usually th$ou)hpulmona$y hemo$$ha)e

References

www!cdc!go%67+%67A76%fgs!gi.

,eriew o. 7,8H in.ections9 :aren ; <ohnson$ 2+!=ptodate )00>

;ar" congenita" sphi"is9 A?eeta 6ingh$ 26 26c$@:aren 6uther"and$ N 6cN$ onita Lee$ 2+ 26c-puB?ed

8ongenita" sphi"is re-e?erging!6i??s &$ routet N!

Syphilis. 1Dr Frewan Neo

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