Syphilis

Nisachon Tongtip,MD
Family medicine residency
Buriram hospital
 Syphilis
 Treponema pallidum
 Spirochete
 Systemic infection
 Natural reservoir : human
Routes of transmission
Sexual  Genital-genitalia, oral-genitalia
Skin  Non-intact skin
Maternal-fetal
Blood  incubation periods, early syphilis
component

Intubation periods
3 weeks (10-90 days)
 Stage of syphilis
Early syphilis Late syphilis
Latent
Primary Secondary Tertiary
Early latent Late latent
Chancre Mucocutaneous Asymptomatic Asymptomatic Gummas
(painless ulcer lesion & Cardiovascular
at site of generalized Late neuro-
inoculation) lymphadenopathy
syphilis
(parenchmatous)

Early neurosyphilis (asymptomatic neurosyphilis, syphilitic

meningitis, meningovascular syphilis)
Occular syphilis, otologic syphilis
Primary syphilis
Chancre Single painless papule at site of inoculation
Heterosexual men : penis
Homosexual men : anal canal, rectum, mouth,
external genitalia
Women : cervix, labia
Heals within 4-6 wks (2-12 wks)
Inguinal Appearing within 1 week of lesion onset
lymphadenopa Firm, nonsuppurative, painless
thy Persistent for months
DDx. Herpes simplex virus, chancroid, truamatic
injury, donovanosis, LGV
Secondary syphilis
Duration 4-10 wks of chancre onset (6-8 wks after
healing chancre onset)
Resolve spontaneously within 1-6 months
Constitutional 15-30% Sore throat
symptoms 5-8% Fever
2-20% Weight loss
25% Malaise
2-10% Anorexia
10% Headache
Secondary syphilis
Lymphadenopathy Firm, painless generalized lymphadenopathy
85% epitochlear
Skin rash Macular→Papule, pustule
Maculopapular
Papulosquamous : guttate psoriasis, pityriasis
rosea
Annular : Recurrent secondary syphilis
Pustular syphilides
Lues maligna : severe necrotic lesion in HIV
infection
Vesicular, bullous : only in congenital syphilis
Lues maligna
polymorphic, ulcerating, rupioid lesion
(heaped-up crusts)

Pustular syphilides Annular plaques

with slightly raised scaly borders
Secondary syphilis
Hair follicles 5% syphilitic patchy alopecia (moth-eaten
appearance)
Condyloma lata 10% papules progess to broad, wartlike,
moist, pink or gray-white patch
Intertriginous area : perianal, vulva, scrotum,
axillae, under breasts
Mucous patch 10-15% painless, silver membrane, superficial
mucosal erosion surrounded by red periphery
Secondary syphilis
Liver 50% hepatitis (↑ALP), asymptomatic
GI Hypertrophic gastritis, peptic ulcer
Patchy proctitis
Rectosigmoid mass
Musculoskeleto Arthritis
n Periostitis : tibia*, sternum, skull, ribs
Renal Nephropathy→proteinuria due to immune
complex deposition
Secondary syphilis
CNS 8-40% Early neurosyphilis
7-38% Asymptomatic neurosyphilis
1-2% Syphilitic meningitis
Meningovascular syphilis
Ocular syphilis Interstitial keratitis of cornea
Iritis
Uveitis : anterior*
Optic neuritis
Otologic syphilis Sensorineural hearing loss
Tinnitus, vertigo, disequilibrium
Tertiary syphilis
Gumma  Presenting after 5 yrs of onset
(late benign syphilis)  T.pallidum PCR
 Penicillin results in rapid solution
 DDx. : TB, sarcoidosis, tumor, Leprosy

Painless mass Ragged ulcer Hepar lobartum

Leathery fibrosis
Tertiary syphilis
Cardiovascular  Presenting 10-40 yrs after infection
syphilis  Uncomplicated aortitis : AR, saccular
aneurysm, coronary ostial stenosis

Tertiary syphilis
Late symptomatic  Parenchymatous syphilis
neuryosyphilis Tabes dorsalis, general paresis
Neurosyphilis
Asymptomatic neurosyphilis
 Lack of neurologic symptoms and signs
but CSF abnormalities at least one of the
following
 Mononuclear pleocytosis > 5 cell/µL
 Protein > 45 mg/dl
 Reactive CSF VDRL
Symptomatic neurosyphilis
Syphilitic meningitis Occurs <1 yr after infection
Meningismus with aseptic meningitis CSF
profile
Often presenting with uveitis, iritis, hearing
loss
Neurosyphilis
Symptomatic neurosyphilis
Meningovascular  Inflammatory vasculitis of small,
syphilis medium, or large vessels
 Most common involving the MCA
Stroke syndrome related with young adult
→ Menifesting after a subacute
encephalitic prodrome (headache, vertigo,
insomnia, psychological abnormalities)
→ Gradually progressive vascular
syndrome
Neurosyphilis
Symptomatic neurosyphilis
Parenchymatous ❶ General paresis
neurosyphilis  Appearing after 20 yrs after infection
 Chronic progression involving cerebral
cortex
Argyll Robert pupils Personalitiy Emotional lability, paranoia
Affect Carelessness in appearance
Reflect Hyperactive
Eye Small, irregular Argyll Robert pupils,
react to accommodation, not to light
Sensorium Illusion, delusion, hallucination
Intellect recent memory, capacity of
calculation, judgment, orientation,
insight
Speech Slurred
Neurosyphilis
Symptomatic neurosyphilis
Parenchymatous ❷ Tabes dorsalis (locomotor ataxia)
neurosyphilis  Appearing after 25-30 yrs after
infection
 Demyelinating with axon
degeneration of dorsal root ganglia, dorsal
root, posterior columns in spinal cord
Neurosyphilis
Symptomatic neurosyphilis
Parenchymatous ❷ Tabes dorsalis
neurosyphilis
Dorsal column degeneration
Orthopedic pain : Charcot’s joint
Reflexes decreased : Deep tendon
Shooting pain
Argyll Robertson pupils
Locomotor ataxia
Impaired proprioception
Syphilis
 Screening for syphilis
 All STD patients
 High risk for STD or requiring for screening STD ; HIV
 Sexual contact with a person who receives a diagnosis of early
syphilis
 First diagnosis of HIV infection→ annually follow up
 Multiple partners in some areas with high rates of syphilis
 MSM
 Cocaine user
 First ANC and GA 28 wks
 Women who had stillbirth after GA 20 wks
CDC criteria diagnosis for syphilis
Primary syphilis
Confirmed ①+ ② or ③
① ≥ 1 chancre
② T.pallidum in dark field or FTA-TP
microscopy
③ Positive T.pallidum DNA by PCR
Probable ①+ ② or ③
① ≥ 1 chancre
② Reactive nontreponemal test
③ Reactive treponemal test
CDC criteria diagnosis for syphilis
Secondary syphilis
Confirmed ①+ ② or ③ or ④
① ≥ 1 chancre
② T.pallidum in dark field or FTA-TP
microscopy
③ T.pallidum in silver stain, DFA-TP,
immunohistochemical method
④ Positive T.pallidum DNA by PCR
Probable ①+②
① Skin or mucosal lesion in secondary stage
② Reactive treponemal test or four-fold
rising in non-treponemal test titer ≤ 1 yr
CDC criteria diagnosis for syphilis
Early latent syphilis
Confirmed ①+ ② or ③ or ④ or ⑤
① Asymptomatic syphilis
② Seroconversion of non-treponemal test or
T.pallidum in dark field or four-fold rising in
non-treponemal test titer ≤ 1 yr
③ Sexual partner had early syphilis ≤ 1 yr
④ Positive T.pallidum DNA by PCR
⑤ Reactive non-treponemal and non-
treponemal test with sexual partner had
history of syphilis ≤ 1 yr
CDC criteria diagnosis for syphilis
Late latent syphilis
Confirmed ①+ ② or ③
① Asymptomatic syphilis
② Reactive non-treponemal and non-
treponemal test with evidence of T.pallidum
infection > 1 yr
③ Age or laboratory report wasn’t relate with
latent of uncertain duration
CDC criteria diagnosis for syphilis
Latent of uncertain duration
Confirmed ①+② +③
① Asymptomatic syphilis
② Reactive non-treponemal and non-
treponemal test without explicit
seroconversion
③ Age of 13-35 yrs with non-treponemal
titer ≥ 1:32
CDC criteria diagnosis for syphilis
Gumma and cardiovascular syphilis
Confirmed ①+ ② or ③
① Sign and symptom of gumma and
cardiovascular syphilis
② T.pallidum in silver stain, DFA-TP,
immunohistochemical method
③ Positive T.pallidum DNA by PCR
Probable ①+ ② or ③
① Sign and symptom of gumma and
cardiovascular syphilis
② Reactive treponemal and non-treponemal
test test
③ Asymptomatic neurosyphilis
CDC criteria diagnosis for syphilis
Neurosyphilis
Confirmed ①+② + ③ or ④ or ⑤
① Sign and symptom of neurosyphilis
② Reactive treponemal test
③ Reactive CSF VDRL
④ Positive CSF T.pallidum DNA by PCR
⑤ T.pallidum in silver stain, DFA-TP,
immunohistochemical method
Probable ①+②+③
① Skin or mucosal lesion in secondary stage
② Reactive treponemal test or four-fold
rising in non-treponemal test titer ≤ 1 yr
CDC criteria diagnosis for syphilis
Syphilitic stillbirth
Confirmed ①+②
① Women who had stillbirth after GA 20 wks
② Birth weigh > 500 g with untreated
maternal syphilis or incomplete treatment
course before birth
Investigations
Non-serologic test
Dark field  Identify spirochete in samples from moist
examination lesion
 Direct examination within 20 mins after
collect specimen
 Rarely available test
DFA-TP  Direct fluorescent antibody test
 Oral and anal sample
Tissue biopsy  Silver stain
 Immunohistochemical method
PCR  Polymerase chain reaction
 High sensitivity and specificity
 Non-commercial available
Investigations
Serologic test
Non-treponemal  Measure IgG and IgM directed against a
test cardiolipin-lecithin-cholesteral antigen
complex
 Non-specific for T.pallidum
 VDRL and RPR
VDRL  Venereal disease research laboratory
 Standard for examining CSF
 Quantitation of serum antibody : titer
RPR  Rapid plasma reagin
 False negative : prozone phenomenon
Investigations
Serologic test
Treponemal test  Measure Ab to native or recombinant
T.pallidum Ag
 VDRL and RPR
TPHA assay  T.pallidum agglutination
 High positive predictive value
 Remain reactive even after adequate treatment
TPPA assay  T.pallidum particle agglutination
Treponemal EIAs  Treponemal enzyme immunoassays
 False positive
Treponemal CIAs  Treponemal enzyme chemiluminescence
immunoassays
FTA-ABS test  Fluorescent treponemal antibody absorption
 Traditional sequence algorithm
Quantitative
RPR or VDRL or
other non-treponemal test

RPR or VDRL + RPR or VDRL -̶

TPHA or other
treponemal test

TPHA + TPHA ̶
Syphilis (past or Syphilis unlikely
present)
 Traditional sequence algorithm

Treponemal EIA or CIA

EIA or CIA + EIA or CIA ̶

Quantitative
RPR or VDRL or
other non-treponemal test

RPR or VDRL + RPR or VDRL ̶

Syphilis
(past or present) TPHA or
other treponemal test

TPHA + TPHA ̶
Possible syphilis Syphilis unlikely
(past or present) (High risk, retest in 1 mo.)
 Interpretation of serologic test
Treponemal test (TPHA, TPPA, FTA/ABS)
Non-reactive Reactive
 No syphilis diagnosis  Very early primary syphilis
 Incubating syphilis infection  Secondary syphilis with prozone
Non-treponemal test (VDRL,RPR)

 Very early primary syphilis phenomenon

Non-reactive

 Late untreated syphilis with

seroreversal of non-treponemal
test
 Treated syphilis
 False-negative non-treponemal
test
 False-positive treponemal test
 Biological false-positive  Positive syphilis diagnosis
Reactive

 False-negative treponemal  Lyme disease

test  Endemic nonsexually
tranmittted treponemal disease
(yaw, pinta, bejel)
 Indications for CSF examination
in all stage of syphilis
All patients
 Signs or symptom of CNS involvement
 Meningitis, hearing loss, cranial nerve dysfunction, altered
mental status
 Ophthalmic disease ; uveitis, iritis, pupillary abnormalities
 Ataxia, loss of vibration sense
 Active tertiary syphilis
 RPR or VDRL titer ≥ 1:32
 Suspected treatment failure*
Additional indication in HIV pateint
 CD4+ T cell count ≤ 350/µL
 Recommended by some experts for all HIV patient
Treatment of syphilis
Stage Recommended regimen Alternative regimen
Early syphilis  Benzathine penicillin G  Doxycycline 100 mg po
2.4 million units IM in a bid x 14 days
single dose  Tetracyline 500 mg po
qid x 14 days
 Ceftriaxone 1 g IV or IM
daily x 14 days
 Azithromycin 2 g po in
a single dose
Late syphilis  Benzathine penicillin G  Doxycycline 100 mg po
2.4 million units IM bid x 28 days
weekly for 3 wks  Tetracyline 500 mg po
qid x 28 days
Treatment of syphilis
Stage Recommended regimen Alternative regimen
Neurosyphilis  Aqueous crystalline  Desensitization +
CNS gumma penicillin G (18-24 million benzylpenicillin
Occular syphilis units/day) IV 3-4 million  Ceftriaxone 2 g IV or IM
Otologic syphilis units q 4 hr or continous daily x 10-14 days
infusion x 10-14 days  Experimental regimen
 Procaine penicillin G Doxycycline 200 mg po
2.4 million units IM daily bid x 28 days
+ Probenecid* 0.5 g po
qid x 10-14 days
*Severe sulfa allergy is contraindication in Probenecid
Syphilis treatment in pregnancy and HIV patient is according to stage
 Follow up evaluation of response to therapy
HIV HIV
Stage neg pos Treatment failure
Months
Primary 6 3  Persistent or recurrent sign and symptom
Secondary 12 6  Four-fold rising of VDRL or RPR and
9 persistent titer ≥ 2 wks
12  VDRL or RPR titer decline ≤ four-fold within
24 → 6 mo. in non-HIV patient
→ 12-24 mo. in HIV infection after therapy
Latent 6 6  Persistent or recurrent sign and symptom
Late 12 12  Four-fold rising of VDRL or RPR and
syphilis 24 18 persistent titer ≥ 2 wks
24  VDRL or RPR titer decline ≤ four-fold within
12-24 mo.
Management of sex partners
History of Recommendation for follow up sex partner
contact syphilis
Primary  Appearing symptom and next 3 mo.
Secondary  Appearing symptom and next 6 mo.
Early latent  Within 1 yr. before diagnosis
Late latent  All short term sex partners who had sex
within 1 yr.
 All long term sex partners who had sex before
diagnosis especially non-treponemal titer >1:32
Management of sex partners
History of contact
Serology Treatment
syphilis
Primary, secondary, Non-reactive Early syphilis regimen
early latent syphilis Asymptomatic
within 90 days before
diagnosis
Primary, secondary, Not available Early syphilis regimen
early latent syphilis Non-reactive None
> 90 days before
diagnosis Reactive According to stage
Late latent with non- Same with above
treponemal titer
>1:32
Long term Non-reactive None
relationship with late Reactive According to stage
latent syphilis