Other manifestations of Late Syphilis
 Begins early during the pathogenesis of syphilis
 Not apparent for years
Cardiovascular syphilis
 Attributable to endarteritis obliterans of the vasa
vasorum (which supply blood to large vessels)
 Results in
o Uncomplicated aortitis
o AR
o Saccular aneurysm
o Coronary ostial stenosis
 Symptoms appear 10-40 years after infection
 CXR: linear calcification of the ascending aorta 
asymptomatic syphilitic aortitis
 Syphilitic aneurysms
o usually saccular, occasionally fusiform
o does not lead to dissection
o 1:10 involves abdominal aorta
Late Benign Synphilis (gumma)
 Usually solitary
 Histology: granulomatous inflammation with
central necrosis
 T. pallidum sometimes recovered
 Most common sites:
o Skin, skeletal, mouth, URT, larynx, liver,
stomach
 Skin: painless and indurated nodular,
papulosquamous or ulcerative lesions. Usually
indolent
o Resemble chronic granulomatous diseases
(TB, sarcoidosis, leprosy, deep fungal
infections)
 Skeletal: long bones of legs ( most frequent)
o Radiograph: periostitis or destructive and
sclerosing oteitis
 Upper respiratory  perforation of nasal septum
or palate
 Diagnosis is confirmed with serologic tests and by
therapeutic trial
 TX: penicillin
Congenital Syphilis
 Any stage of pregnancy
 Onset: 4th months AOG (fetal immunologic
competence develops)
 Pathology depends on immune response of host
 Risk if untreated maternal infection: 75-95%
 35% - if >2 years duration
 Adequate treatment by 4th month
 In untreated:
o Fetal loss 40% (stillbirth > abortion)
o Premature
o Neonatal death
o Nonfatal congenital syphilis
 Fulminant congenital syphilis – clinically apparent
at birth; poor prognosis
 Routine serologic testing in early pregnancy:
prevention
 If high prevalence: rpt at 3rd trimester and at
delivery
 Early manifestations:
o First 2 years of life (2 and 10 weeks of
age)
o Infectious
o Resemble severe secondary in adult
 Late manifestations: after years and non-
infectious
 Residual stigmata
 Earliest sign: rhinitis or snuffles
 Followed by mucocutaneous lesions
o Bulla (syphilitic pemphigus)
o Vesicles
o Superficial desquamation
o Petechia
 Later
o Papulosquamous lesions
o Mucus patches
o Condylomata lata
 Early bone manifestations
o Osteochondritis
o Ostieits
o Periostosis
 Hepatosplenomegaly, lymphandenopathy, anemia,
thrombocytopwnia, leukocytosis
 Must be differentiated with: rubella, CMV, HSV,
toxo, and erythoblastosis fetalis
 Neonatal death due to:
o Pulmo hemo
o Secondary bacterial infection
o Severe hepatitis
 Late congenital syphilis
o 60% subclinical
o Interstitial keratisis common
o VIII nerve deafness
o Recurrent arthropathy
o Clutton’s joints: bilateral knee effusions
o Gummatous periositisL age 5-20
o Nonvenereal endemic syphilis:
destuructive lesions on palate and nasal
septum
 Stimata:
o Hutchinson’s teeth: central notched,
widely spaced, peg shaped upper central
incisors
o Mulberry molars: 6th year molars with
multiple poorly developed cusps
o Abnormal facies: frontal bossing, saddle
nose, poorly developed maxilla
o Saber shins: anterior tibial bowing (rare)
o Rhagades – linear scars at the angles of
the mouth and nose caused by secondary
bacterial infection of early face eruption
  Autoimmune disorders
Laboratory Exams  If with false +, syph excluded with a nonreactive
Demonstration of organism trep test
 Cannot be detected by culture
 Dark field microscopy of lesion exudates Acute false + (<6 months)
o Chancre in primary Recent viral illness or immunization 1-2%
o Condylomata lata in secondary Genital herpes 4
 Oral and anal lesions not recommended HIV 1-4
 Direct fluorescent antibody-TP Malaria 11
o Uses fluorescien conjugated polyclonal Parenteral drug use 20-25
antitreponemal antibody
Chronic (>6 months)
 PCR
Aging 9-11
 Silver stains
Autioimmune 1-20
 Immunofluorenscence and immunohistochemistry SLE 11-20
using mono- and polyclonal Ab RA 5
Parenteral drug use 20-25
Serologic tests
 Nontreponemal Evaluation for neurosyphilis
o Measure IgG and IgM directed against  Pleocytosis (>5 WBC/mm3)
cardiolipin-lecithin-cholesterol Ag  Increase CHON (>45mg/dL)
complex
 VDRL reactivity
o RPR – most widely used
 Csf exam recommended for:
 Automated or slide test o Any serologic + patient with neurologic
 Test of choice for rapid dx in signs and symptoms
clinic or office setting o Other late syphilis
o VDRL – standard for CSF
o Suspected tx failure
o RPR and VDRL equally sensitive
o HIV infected with untreated syph or
o For initial screening and quantification of
unknown duration or >1year
serum Ab o Early syph with HIV or >1:32 nontrep test
o VDRL reach 1:32 or higher in secondary
 CSF VDRL: highly specific but insensitive
o Adequate response to therapy: 4 fold fall
o Highest in meningovacular syph and
in titer (2 dilutions)
paresis
o VDRL do not sorrespond to RPR titers
o Lower in asymptomatic and tabes dorsalis
o May be unreactive in early syph
 Unabsorbed FTA more reactive in all stages
o Tests remain reactive after therapy
o But may reflect passive transfer of serum
 Treponemal
AB into CSF
o FTA-ABS and agglutination assays for Ab o Nonreactive test: rules out
to T. pallidum
o MHA-TP replaced by Serodia TP-PA test: Evaluation for syph in HIV patients
more sensitive for primary syph
 Highest risk: homosexually active men, developing
o All very specific: for confirmation of +
countries
non trep test
 Manifestations altered
o New: ELISA
 All trep and nontrep reactive during secondary Recommendations of TX of syphilis
syphilis
 3 uses: Stage of syphilis w/o pen allergy w/ pen allergy
o Testing of large number of sera for Primary, Pen G benzathine Tetracycline HCl
screening or diagnostic (RPT or VDRL) secondary or (single dose of (500mg PO qid) or
o Quantitative measurement of Ab titer to early latent 2.4 mU IM) doxycycline
assess the clinical activity of syph and (100mg PO bid)
monitor response to therapy (RPR or for 2 weeks
VDRL) Late latent (or Lumbar puncture Lumbar puncture
o Confirmation of the dx of syph w/ a + latend of CSF normal: Pen CSF normal or
nontrep Ab test or with a suspected clin uncertain G benzathine w/o HIV:
dx of syph (FTA-ABS or serodia) duration) (2.4mU IM weekly Tetracycline HCl
 IgM in neonates: Captia M test and 19s IgM FTA-ABS cardiovasc, for 3 weeks) (500mg PO qid) or
benign tertiary CSF abnormal: doxycycline
False positive serologic treat at neuroyph (100mg PO bid)
 Titers rarely exceed 1:8 for 4 weeks
 CSF abnormal: as  Must be warned of Jarisch-Herxheimer reaction:
neurosyph associated with premature contractions but rarely
Neurosyph Aqueous Pen G Desensitization results in premature delivery
(18-24 mU/d, and TX w/ Pen  After Tx, quantitative nontrep test repeated
given as q4h or monthly
continuous  If no decrease or rise in 3 months, repeat tx
infusion) for 10-
14 days Evaluation and management of Congenital Syphilis
Or  Newborn infants with positive tests:
Aqueous Pen G o Infected
Procaine (2.4 o Transplacental transfer of maternal IgG
mU/d IM) plus Ab
oral probenecid o Rising or persistent titers: indicate
(500mg qid), both infection
for 10-14 days
 Neonatal IgM: detected in cord or neonatal serum
Syphilis in According to Desensitization
with Captia-M or 19s IgM FTA-ABS
pregnancy stage and TX w/ Pen
 Asymptomatic infants born to adequately treated
mothers: monthly quantitative nontrep tests to
Treatment for acquired syphilis
appreciate decline in titers
 Killed with Pen G at low conc
 Long period of exposure is required with Pen bec  Infants should be treated at birth if:
of unusually slow rate of multiplication of o Seropositive mother has received pen
organism theraph in the 3rd trimester, Inadequate
 Tetracycline and erythromycin: large doses penicillin tx, Therapy with a drug other
 Sulfonamides and quinolones: inactive than penicillin
 Azithromycin: promising as oral agent o Increasing neutrophil count
 Pen G: must have serum levels of > pr equal to o Infant difficult to follow
0.03ug/dL for 7 days  CSF obtained as baseline values
 Tx: penicillin ( only recommended drug)
Patients with Early syphilis and their contacts
 Preventive tx recommended for seronegative w/o Jarisch-Herxheimer reaction
signs of syph who have been exposed w/in 3  Usually mild reaction
months  fever, chills, myalgia, headache, tachycardia,
 Prevention same with early syph tx increase RR, increase neutrophil count,
 Pen G Benzathine most widely used, but more vasodilation with mild hypotension
painful than procaine  usually follows treatment
 Single dose of 2.4U cure 95%  50% with primary syph
 Efficacy in secondary: lower  90% with secondary syph
 Ceftriaxone (1g/d IM or IV 8-10days) and  25% with early latent syph
azithromycin ( single oral dose 2g) may be  Defervescence within 12-24 hours
effective in early syph  Secondary syph: erythema and edema of
mucocutaneous lesions may increase
Late Latent and Late Syphilis  Symptom based therapy
 Clinical response to benign tertiary impressive
 Cardiovascular: not dramatic Follow-up evaluation of response to therapy
 AR and aortic aneurysm not reversed with Stage Tests When to Retreatment
antibiotic preform considered
if:
Neurosyphilis Primary Quantitative HIV 1. titer
 Pen G benzathine in up to 7.2 million units or or VDRL or RPR uninfected: 6 increases
50,000 in infants does not produce detectable secondar and 12 months 4fold
amounts in CSF and asymp neurosyoh may relapse y HIV infected: 2. titer fails
 IV Pen G recommended 3,6,9,12 to decline
months 4fold to
Syphilis in Pregnancy become
unreactive
 Nontrep test during 1st visit in 6
 Repeat at 3rd trimester and at delivery months
3. clinical
signs
 persist or
recur
Latent or Quantitative 6,12 and 24 1. titer
late VDRL or RPR months increases
4fold
2. initial
titer of
>1:32
fails to
decline
by 4fold
by
6months
3. new
clinical
signs
develop

Neurosyp 1. If 1. every 6 1. CSF cell

hilis pleocyto months count has
sis is until CSF not dec by
documen cell count 6months
ted is normal 2. CSF not
intitially, 2. until normal
rpt exam normal after 2
2. Monitor 3. at 6,12,18 years
decline and 24
in CSF months
CHON
and CSF
VDRL
3. Quantita
tive
VDRL or
RPR

 FTA-ABS tests remain positive despite treatment:

not recommended for following response to
therapy
 After tx, negative by 12 months
 If seropositive but asymptomatic after re-tx: no
ned to tx anymore
 Patients with late latent syph may have low titers
and not show 4 fold decrease in titer
 Neurosyph activity: correlates best with CSF
pleocytosis
 Most sensitive index of response to tx
 Falls to normal in 3 – 12 months in HIV
uninfected

Immunity and prevention of Syphilis

 Cellular immunity: important in healing of lesions