Syphilis Flashcards
What organism causes syphilis
Trepnema pallidum sub species pallidum
What type of organism is treponema pallidum?
Spirochete bacterium
Spirochete - describe what it is?
Di-derm (double membrane) bacteria
Spiral
Flagella than periplasmic space inner to outer membrane
Asexual - reproduces through transverse binary fission
What modes of transmission are there for syphilis?
Direct contact with infectious lesion
Vertical transmission - transplacental passage
What proportion of contacts with syphilis will develop disease?
1/3
Which anatomical site is implicated in syphilis infection?
Genital-genital contact (main mode for heterosexual) In MSM: Anal Oral Rectal
At what stage of syphilis disease is vertical transmission highest risk?
Early disease
RPR greater than or equal 8
What demographic typically get syphilis infection?
MSM
25-34 yr olds
Chancre - describe how it develops
T. pallidum INVADE through the mucosal surface or abraded skin
DIVIDE at the point of entry to produce the CHANCRE
What is the incubation period for primary syphilis?
typically 21 days (range 9–90)
dependent on infectious dose - larger doses resulting in ulcers more quickly
What is the characteristic presentation of primary syphilis?
single papule
moderate regional lymphadenopathy
papule subsequently ulcerates to produce a chancre
classically anogenital (penile, labial, cervical
or peri-anal)
single
painless
indurated
clean base discharging clear serum but not pus
Why can you not rely on the classic presentation of primary syphilis for all diagnoses?
chancres may also be: multiple painful purulent destructive extra-genital (most frequently oral) and may cause the syphilitic balanitis of Follman
Typically how long until a chancre resolves without treatment?
3-8 weeks
What proportion of untreated primary syphilis will go onto symptomatic secondary syphilis?
25%
Secondary syphilis - describe the features?
multi-system
widespread mucocutaneous rash
generalised lymphadenopathy
What organ dysfunction can occur in secondary syphilis?
hepatitis
glomerulonephritis
splenomegaly
neurological
What causes the glomerulonephritis in secondary syphilis?
mediated by antibody-treponeme complex deposition
What proportion of people will develop neurological complications from syphilis?
1-2%
What is the typical presentation of the mucocutaneous rash in secondary syphilis?
Maculopapular 50-70%
Secondary syphilis - neurological complications?
Acute meningitis
Cranial nerve palsy
Which cranial nerves are typically implicated in syphilis infection?
8th nerve - hearing loss and tinnitus
Optice nerve - optic neuropathy
What complications of the eye occur in syphilis infection?
uveitis (most commonly posterior)
optic neuropathy
interstitial keratitis
retinal involvement
What is the definition of early latent syphilis disease?
Asymptomatic syphilis acquired <2 years
What is the definition of late latent syphilis disease?
Asymptomatic syphilis acquired >2 years
What proportion of patients will develop a recurrence of secondary disease during the early latent phase?
25%
Symptomatic late syphilis disease aka tertiary disease occurs when?
20-40years after initial infection
What proportion of untreated patients will develop tertiary syphilis?
1/3
What categories of tertiary syphilis are there?
Gummatous disease
Cardiovascular
Late neurological
Why is tertiary syphilis now rarely seen?
Use of treponemocidal antibiotics for other indications eg. penicillins
What are the clinical manifestations of gummatous syphilis?
Inflammatory granulomatous destructive lesions; can occur in any organ but most commonly affect bone and skin
What are the clinical manifestations of cardiovascular syphilis?
Aortitis (usually ascending aorta)
Rarely other sites affected - coronary Ostia
What are the clinical manifestations of neurological late syphilis?
Mengingovascular
General paresis - Cortical neuronal loss
Tabes dorsalis
Nerve damage IRREVERSIBLE
Meningovascular syphilis - onset, presentation
5-10 yrs
infectious arteritis –> ischaemic stroke (MCA territory most common)
May be associated with PRODROME weeks/months before stroke - headache, emotional lability, insomnia
General paresis (tertiary syphilis) - onset, presentation
10-2 yrs
Progressive dementing illness due to cortisol neuronal loss
Prodrome of forgetfulness and personality change
Seizures and hemiparesis may occur
Tabes dorsalis - onset, presentation
15-25 yrs
SENSORY ATAXIA and lighting PAINS
PUPILLARY abnormalities common (Argyll-Robertson)
DORSAL COLUMN LOSS (absent reflexes, joint position
and vibration sense)
How is congenital syphilis categorised?
Early <2yr old
Late >2yr old
What are the common presentation of EARLY congenital syphilis?
rash haemorrhagic rhinitis generalised lymphadenopathy hepatosplenomegaly skeletal abnormalities
What are the common presentation of LATE congenital syphilis?
Signs develop as a result of chronic and persistent inflammation resembling gummatous disease -EYES - BONE DEFORMITY - SENSORINEURAL DEAFNESS - INTELLECTUAL DISABILITY - CRANIAL NERVE PALSY ( see BASHH for specific condition)
What methods can be used to identify syphilis infection from clinical lesions?
Dark ground microscopy
Polymerase chain reaction (PCR)
When should dark microscopy NOT be used to identify syphilis infection?
oral lesions due to the presence of commensal treponemes
What is the limitation of treponemal antibody tests?
cannot differentiate syph- ilis from the endemic treponematoses
Which treponemal antibody tests are NON-SPECIFIC?
Venereal Diseases Research Laboratory (VDRL) carbon antigen test/RPR test
Which treponemal antibody tests are SPECIFIC?
treponemal enzyme immunoassay (EIA)
treponemal chemiluminescent assay (CLIA)
Treponema pallidum haemagglutination assay (TPHA)
Treponema pallidum particle agglutination assay (TPPA)
What are the preferred components of a primary screening test for syphilis?
preferably a test that detects both IgG and IgM
Treponemal EIA/CLIA
TPPA
When should a RPR/VDRL be performed in syphilis infection, and why?
when treponemal tests indicate syphilis
to help stage the infection
What does An initial RPR/VDRL titre of >16 usually indicate?
Active disease and need for treatment
Following a negative syphilis screen, when should it be repeated?
6 and 12 weeks after a single ‘high risk’ exposure
3 monthly for individuals at ongoing risk due to frequent ‘high risk’ exposures
2 weeks after negative PCR for ulcer that could be due to syphilis
If performing CSF sampling what is important to avoid when collecting sample?
vital CSF is not macroscopically contaminated with blood
Wat would you expect the white cell count to be in the CSF of individuals who have symptomatic
neurosyphilis?
RAISED
>5cells/mm
How long should a person abstain from sex following treatment for syphilis?
Very little evidence:
until lesions healed
at least 2 weeks following completion of treatment
How long should therapeutic levels of antibiotics remain in system for treatment of syphilis?
at least 7 days
to cover a number of divisions of treponemes
How might you alter the treatment schedule for late syphilis, and why?
Longer duration
more slowly dividing treponemes
some treponemes may be ‘resting’ or dividing very slowly
Why is penicillin the main treatment approach for syphilis?
Clinical data are lacking on antimicrobials other than penicillin
Why is parenteral rather than oral the treatment of Choice in syphilis?
supervised and bioavailability is guaranteed
Why is erythromycin not appropriate for treatment of syphilis?
does not penetrate the CSF or placental barrier well
When might azithromycin be considered for treatment of syphilis?
Early syphilis
STAT 2gram
Why do we typically avoid azithromycin for syphilis?
MACROLIDE RESISTANCE leading to treatment failure
What percentage of people with untreated syphilis AVOID late complications?
60%
Benzathine penicillin G and standard regimens of procaine penicillin G do not achieve
treponemicidal levels in CSF, why does neurosyphilis not arise following treatment of early syphilis?
Likely host immune responses in early syphilis play an essential part in clearing infection in CSF
What additional agent should be added alongside the antibiotic when treating cardiovascular or neurological syphilis?
Steroid
Neurosyphilis - treatment, duration
Procaine penicillin 2.4g IM DAILY for 10-14 days
AND
probenecid 500mg oral QDS
When does foetal infection typically occur?
Late in pregnancy
but has been seen as early as 8-9 weeks gestation
How might maternal syphilis infection impact on pregnancy?
polyhydramnios miscarriage pre-term labour still- birth hydrops
If a woman is treated for syphilis in third trimester, what must be considered following first dose of penicillin, and why?
Repeat IM penicillin 1 week after initial injection
pharmacokinetics in pregnancy may cause reduced plasma penicillin concentrations
What is the rate of Jarisch-Herxheimer reaction following treatment for syphilis?
40%
What might a pregnant woman experience with a Jarisch-Herxheimer reaction following treatment for syphilis?
Uterine contractions - resolve 24hrs
Decelerations
When do maternal treponemal antibodies start to decline in the neonate?
18 months
How often does a neonate need syphilis serology checked if mother treated/diagnosed with syphilis in pregnancy?
at birth and then 3 monthly until negative
When should treatment of the neonate be considered in syphilis infection?
If clinical signs of syphilis
serology titres do not fall or increase
Incubating syphilis/epidemiological treatment?
Benzathine penicillin G 2.4 MU IM single dose Doxycycline 100 mg PO twice daily 14 days
Azithromycin 2 g PO stat
Early syphilis - treatment?
Benzathine penicillin G 2.4 MU IM single dose
Early syphilis - treatment alternatives?
Procaine penicillin G 600,000 units IM daily10 days Doxycycline 100 mg PO BD 14 days
Ceftriaxone 500 mg IM daily 10 days
Amoxycillin 2 g PO TDS AND probenecid 500 mg PO QDS for 28 days
Ceftriaxone 2g IM or IV for 10–14 days
Amoxycillin 500 mg PO QDS 500 mg QDS 14 days
Azithromycin 2 gram STAT or 500 mg daily 10 days Erythromycin 500 mg PO QDS 14 days
Late latent, cardiovascular and gummatous syphilis - treatment options?
Benzathine penicillin 2.4 MU IM weekly for three weeks (three doses)
Doxycycline 100 mg PO BD for 28 days
Amoxycillin 2g PO TDS AND probenecid 500mg
QDS for 28 days1
What additional treatment must be given for cardiovascular and neuro-syphilis?
Steroids prednisolone 40-60mg 3 days, 24 hours before antibiotics
Neurosyphilis including neurological/ophthalmic involvement in early syphilis - treatment?
Procaine penicillin 1.8 MU–2.4 MU
OD plus probenecid 500mg PO QDS for 14 days
Describe the differences between regimens of doxycycline for early, late and neurological/opthalmic syphilis?
EARLY - doxycycline 100mg FOURTEEN days
LATE doxycycline 100mg TWENTY EIGHT days
NEURO - doxycycline 200mg 28 days
If giving oral amoxicillin for syphilis treatment what else needs to be administered?
Probenicid
When should probenecid be given alongside procaine penicillin in syphilis treatment?
Neurosyphilis including neurological/ophthalmic involvement in early syphilis
Which antimicrobial is NOT used in pregnancy for syphilis treatment?
Doxycycline
If treatment for late or congenital syphilis is interrupted, how long can this be for before entire course must be repeated?
1 day maximum
What is procaine psychosis/mania/Hoigne’s syndrome?
fear of impending death
hallucinations or fits immediately after injec- tion
lasts less than 20 minutes
Why might procaine psychosis occur?
inadvertent IV injection of procaine penicillin
Is the any benefit of steroids for the Jarisch-Herxheimer reaction?
no evidence that the use of steroids prevents these serious conse- quences
Why are steroids used in the treatment of syphilis?
severe clinical deterioration in early syphilis with optic neuritis and uveitis has been reported following treatment, it is hypothesised that steroids may reduce this risk
What is the risk of sexual transmission in late latent syphilis?
usually unable to trans- mit the infection
What is the risk of vertical transmission in late latent syphilis?
Can occur for many years during initial infection but Reduces with time
How often should syphilis serology be repeated following treatment?
3, 6, 12 months then 6 monthly thereafter until negative or serofast
When should re-infection or treatment failure be considered when interpreting syphilis serology?
sustain four-fold or greater increases in VDRL or RPR titre
What reduction in VDRL or RPR titre suggests effective treatment of syphilis?
decrease four-fold within 12 months
