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The Great
Imitator
Why a lecture on syphilis?
syphilis is an treatable disease
control of syphilis is vital because of its interactions
with HIV
Outline
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History
Microbiology
Epidemiology
Diagnosis
Pathophysiology
Clinical Manifestations
Treatment
Syphilis and HIV
Pre-Penicillin Era
• Highly prevalent in many
countries/societies in pre-penicillin era
• Dramatic drop in incidence/prevalence
after introduction of penicillin in mid1940s
Epidemiological Synergy
• HIV and syphilis co-facilitate
transmission of each other
 Despite CDC campaign to eradicate in 2000s total
cases per year continue to increase
 EPIDEMIOLOGY: Worldwide; primarily involving
young people between 20-35 years
 HOST RANGE: Humans
Microbiology
• Treponema pallidum, causative agent isolated
1905
• Family Spirochaetacaeae
Treponema
Gram-negative
have an outer membrane
motile
microaerophilic to anaerobic
found in the oral cavity, intestinal tract, genital
areas of man and some animals
The primary mode of transmission is
via sexual contact.
Syphilis is passed from person to person
through direct contact with a syphilis sore.
Sores occur mainly on the external
genitals, vagina, anus, or in the rectum.
Sores also can occur on the lips and in the
mouth.
blood transfusion
Syphilis is also transmitted
congenitally from an infected
mother to her infant.
Congenital Syphilis
• Syphilis is transmissible from mother
to infant
• Transmission usually occurs during
early stages, but may occur at any
stage in an untreated mother
Clinical Stages
• Syphilis is conventionally divided
into several stages:
–Primary
–Secondary
–Latent
–Late, or tertiary
Untreated, syphilis progresses
through a primary and secondary
stage before becoming latent.
Up to 1/3 of people with untreated
syphilis develop tertiary disease late
in life, primarily cardiovascular and
neurologic.
Natural History of Untreated
Syphilis
Pathophysiology
• Transmission, usually sexual, requires direct contact lesion,
incubation period 21 days
• PRIMARY: Initial lesion develops at site of transmission,
cellular response/perivascular infiltrate.
• SECONDARY: Treponemes disseminate, cleared by
macrophages.
• TERTIARY: Result of chronic inflammation, hypersensitivity
reaction and end organ damage
Primary syphilis
incubation period - 10-90 days(3weeks)
lesion at the site of inoculation –
chancre (hard chancre) lesion not infectious
lesion spontaneously disappears in 2-6 weeks
bacteria enter blood stream
Primary Syphilis
• Chancre appears within 3 weeks of infection
• Single painless papule at site of inoculation
distinct indurated borders and ulcerated
center
• Spontaneously heals
• Discreet, firm painless lympadenopathy
Primary syphilis
Secondary Syphilis
• Defined by disseminated symptoms and positive
serology
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Bilateral symmetric rash, palms/soles
Fever, sore throat, malaise
Arthalgias
Condyloma lata
• Usually 2-8 weeks after appearance of chancre.
• Even if untreated, eventually macrophage clearance
and treponemicidal complement leads to
resolution.
Rash is never vesicular except in congenital form
: rash-condyloma lata-generalized LAPpruritis
: mocus patch-ulcer-erosion
: chancre-rash-condyloma lata-mocus
patch
.: fever-malaise-pharyngitislaryngitis-anorexia –weight loss-arthralgia
: asymptomatic-symptomatic(headechmeningitis-meningismus)
(diplopia-decreased vision)
: tinnutis-vertigo-cranial nerve
involvement(2,8)
: GN-nephrotic syn.
: hepatitis
• Period of asymptomatic infection, however
serologic test continue to be positive.
– Early Latent: documented within one(4) year of
acquisition, very infectious.
– Late Latent: greater than 1(4) year since
transmission
Tertiary Syphilis
• 30% of untreated P&SS progresses to tertiary.
• Combination of treponemal invasion of end organs and
delayed type hypersensitivity response in skin, CVS, CNS.
• GUMMA: late benign granulomas to skin/viscera
• CVS: endarteritis obliterans to vaso vasorum
• Involvement may occur as soon as 1 yr post
acquisition.
• Asymptomatic: 15% of PS and 40% SS have abnormal
CSF findings
• Acute Meningitis: typical meningeal findings dx via
PCR, VDRL
• Meningovascular: diffuse inflammation/ syphilitic
endarteritis eventual vascular occlusion of cerebral
vessels.
– General paresis: chronic infection cerebral
cortex/meninges
– Tabes Dorsalis: demyelination of posterior
columns, dorsal roots, and dorsal root ganglia.
• Meningeal neurosyphilis
– includes acute syphilitic meningitis
– headache, fever, CSF abnormalities
• Meningovascular neurosyphilis
– “syphilitic stroke”
– hemiparesis, hemiplegia, aphasia,
seizure
• Parenchymatous neurosyphilis
– general paresis
– tabes dorsalis
Parenchymatous neurosyphilis
• General paresis (dementia paralytica)
– T. pallidum directly invades cerebrum
• memory loss, personality changes,
headache, delusions, seizure
– neurologic findings include:
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Argyll Robertson pupils
slurred speech
expressionless face
tremors
Parenchymatous neurosyphilis
• Tabes dorsalis
– occurs after long latent period
(20-25 yrs.)
• early features: lightning pains, paresthesias,
diminished DTRs, poor pupillary responses
• late features: ataxia, bladder and rectal
disturbances, Charcot joints, “visceral
crises”
– “tabetic facies” due to ptosis and
flabbiness of facial muscles
Tertiary syphilis
Syphlitic Aortic Aneurysm
Aortic Aneurysm
Ruptured Aortic Aneurysm
Tree-barking
Clot
Stenosis of Coronary Arteries
Charcot Joint
Gumma of Face
Gummas of the Nose
Gumma - Nose
Gmmas of Arm
Gummas - Arm
Ulcerating Gumma
• Late complications of syphilis
occurred in about 1/3 of patients in
the preantibiotic era
• Prompt penicillin therapy of early
disease not only prevents infection in
others, but also prevents late
complications
• Neurosyphilis may present and progress
rapidly in patients co-infected with HIV
perinatal death
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-premature delivery
-Low birth weigth
-congenital anomalies
Syphilis in newborns
Congenital syphilis:
- Transplacental:
beginning 9 - 10 weeks
analogous to secondary adquired syphilis
affects bone, brain, liver, lung
placenta: large and thickened, hypercellular villi, UC
abscess-like necrotic foci
- Vertical transmission:
more freq. primary and secondary.
Risk diminishes with after 4 years of infection
Clinical manifestations of early CS
• The earliest sign of CS is nasal discharge (snuffles) that occurs
1-2 weeks before the onset of the rash. Treponemes abound
in the discharge, providing a definitive means of diagnosis.
• Secondary lesions on face; they first appeared during the
fourth postnatal week.
• The vesiculobullous eruption, known as pemphigus
syphiliticus, is highly distinctive when present. When the
bullae rupture, they leave a macerated, dusky red surface that
readily dries and crusts
• Other stigmata seen before the age of 2 years
include maculopapular rash,
hepatosplenomegaly and jaundice.
Congenital syphilis. Diaphysitis with abundant callus formation secondary
to pathologic fractures through the metaphyseal lesions. The lesions healed,
and there were no sequelae
Laboratory Examination
• Since the treponeme is too small to be
visualized under light microscopy, oblique light
dark field microscopy is required to identify
organisms.
• Serology:
– Non-Treponemal: RPR, VDRL
– Treponemal Test: MHA-TP, FTA-ABS
Laboratory Diagnosis
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Blood serum for antibodies detection
a. Non-specific: non-treponemal tests (lipoidal
antibody)
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Rapid Plasma Reagin
RPR
Venereal Disease Reference Laboratory VDRL
Autamate reagin test ART
b. Specific: treponemal tests
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Treponema pallidum HemAgglutination assay TPHA
Treponema pallidum Particle Agglutination assay TPPA
FTA abs
DIAGNOSIS
• Diagnostic testing involves a two-step process, beginning
with a nonspecific test and concluding with a treponemespecific test for patients screening positive.
The non-treponemal screening tests include the VDRL (Venereal
Disease Research Laboratory), RPR (rapid plasma reagin), or
ART (automated reagin test). Nontreponemal test antibody
titers usually correlate with disease activity and should be
reported with a quantitative titer.
On the other hand, other disease states or physiologic states,
such as pregnancy, can yield false-positive results.
Because the current incidence of syphilis is so low, the
majority of positive screening tests are not due to
treponemal infection.
• The FTA-ABS test (Fluorescent Treponemal
Antibody Absorption Test) for syphilis is an
example of an indirect fluorescent antibody
procedure.
• This is a confirming test for syphilis
• In this test, killed T. pallidum,(the known
antigen), is fixed on a slide . The patient's
serum is added to the slide. If the patient has
syphilis, antibodies against the T. pallidum will
react with the antigen on the slide.
• Other spirochetal dis:
• Penicillin G, in benzathine, aqueous procaine, or
aqueous crystalline form, is the drug of choice for
treatment of all stages of syphilis, and is the only
effective treatment for the prevention of congenital
syphilis in pregnancy.
• Erythromycin may be curative in the mother, but may
not prevent congenital syphilis because of the
variability of transplacental passage of the antibiotic.
• Ceftriaxone may prove useful in adults as an
alternative regimen for patients who have penicillin
allergy
• azithromycin in the penicillin-allergic pregnant
woman has not been adequately evaluated.
– PCN G Benzathine single dose IM 2.4 million units IM – PCN procaine(2.4 million units IM daily +probencid
for 14 days)
– Ceftriaxon 250 IV_IM for 5 days
– Ceftriaxon 1 gr IM for 14 days
– Azithromycin 2 gr stat,1 gr daily for 8 days
– Doxycycline 100mg bid(15 days)
– Tetrasyclin 500 QID (15 days)
– Azithromycin 2 gr single dose
PCN G benzathine 2.4 m u IM weekly for
3 weeks.
PCN G IV 12-24 million units q 4hr for 14
days
(Congenital :PCN G IV(10 days) or procain
PCN).
• Within hours after treatment, patients
can develop an acute complication called
the Jarisch-Herxheimer reaction.
Symptoms include fever, chills, myalgias,
headache, tachycardia, hyperventilation,
vasodilation, and mild hypotension.
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• Although the reaction occurs in 10% to
25% of patients overall, it is most
common in the treatment of early
syphilis.
All children born to mothers who
were sero-positive during
pregnancy:
• A single intramuscular dose of
benzathine benzylpenicillin
50,000 IU/kg
: Re-evaluation after treatment at 3, 6
and 12 months of age.
: or >1yrs:3-6-12-24 m
until 5 yrs.
neurosyphilis should be evaluated
(clinical and CSF) every 6 months until CSF
clears.
– HIV pts have higher titers in early stage.
– Late stage HIV may have delayed or absent serologic response.
– Higher incidence of false reactive nontreponemal Ab test
HIV pts.
– High co-infection rate for HIV and syphilis.
– Early syphilis lesions may potentiate acquisition of HIV virus.
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More likely to present multiple or persistent chancres
Skin rash is more pronounced
More rapid progression to neurosyphilis
Gummas more common and typically involve the viscera
– Recommendations the same as HIV negative, but follow-up w
VDRL and RPR q 1,2,3.6,9,12 months.
THNAK YOU !