Syphilis Flashcards
What causes Syphillis
Treponema pallidum spirochete bacterium
Symptoms of primary Syphilis
Painless ulcer on vulva / cervix Englarged groin / inguinal lymph nodes
Symptoms of secondary Syphilis
rash - Maculopapular (70%) papular (12%), macular (10%) rash can be on palms and soles - not usually itchy can cause alopecia generalised lymphadenopathy. mucous patches (buccal, lingual and genital) condylomata lata - warm, moist areas Less common: hepatitis; glomerulonephritis, splenomegaly, 1–2% develop neurological complications
Treatment of early Syphilis (primary, secondary and early latent)
Benzathine penicillin G IM 2.4 MU IM single dose
Treatment of Late latent, cardiovascular and gummatous syphilis
Benzathine penicillin G 2.4 MU IM weekly for 3 weeks (three doses)
Define late latent syphilis
Secondary syphilis resolves spontaneously and the disease enters an asymptomatic latent stage. Defined as early within two years, and late thereafter
Examination required for symptomatic late syphilis disease clinical examination
clinical examination as indicated, with attention to: - Skin - Musculoskeletal system (congenital) - Cardiovascular system (for signs of aortic regurgitation) - Nervous system (general paresis: dysarthria, hypotonia, intention tremor, and reflex abnormalities; Tabes dorsalis: pupil abnormalities, impaired reflexes, impaired vibration and joint position sense, sensory ataxia and optic atrophy)
Transmission route of syphilis
- direct contact with an infectious lesion - vertical transmission (trans-placental passage) during pregnancy rarer - Injecting drug use - blood transfusion outside of UK
What proportion of sexual contacts of infectious syphilis develop the disease
1/3 of sexual contacts of infectious syphilis will develop the disease (transmission rates of 10–60% are cited)
What is the usual site of entry for syphilis?
- typically genital in hetero-sexual patients - 1/3 of transmissions among MSM may be extra- genital = anal, rectal, oral
What proportion of syphilis is estimated to be acquired via oral sex?
approx 10% (one study)
At what stage of pregnancy is vertical transmission of syphilis most likely to occur?
T. pallidum readily crosses the placenta vertical transmission can occur at any stage of pregnancy.
transmission risk is greatest in early syphilis
more common in 2nd and 3rd T
rate of congenital syphilis
low 0.0025/ 1000 live births in 2011
Incubation period of syphilis
typically 21 days (range 9–90)
describe the classical chancre of syphilis
classically anogenital (penile, labial, cervical or peri-anal), single painless indurated clean base discharging clear serum
Appearance of a syphilitic chancre with HIV-1 co-infection
may be multiple, deeper persist into the secondary stage of disease
Timeframe for primary syphilitic chancre to resolve
ulcers resolve over 3–8 weeks
Timeframe for secondary syphilis development
typically 3m after infection
Impact of HIV-1 infection on mucocutaneous manifestations of secondary syphilis
No impact
1–2% of patients with secondary syphilis develop neurological complications These typically include…..
acute meningitis - (headache, neck stiffness, photophobia, nausea) cranial nerve palsies Eye involvement - uveitis, optic neuropathy, interstitial keratitis, retinal involvement
Duration of secondary syphilis resolving?
Secondary syphilis will resolve spontaneously in 3–12 weeks The the disease enters an asymptomatic latent stage.
what is the cut off between early and late latent syphilis?
Early latent syohilis is within two years Late latent is >2years thereafter
What % of patients develop a recurrence of secondary disease during the early latent stage?
approximately 25%
Time frame for developing tertiary syphilis?
around 20–40 years after initial infection
What proportion of patients develop tertiary syphilis?
1/3 of untreated patients
Types of tertiary syphilis?
- Gummatous disease (15%) - Cardiovascular (10%) - Late neurological complications (7%)
What is gummatous syphilis?
Granulomatous lesions with central necrosis Most often affect skin and bones. Rapidly resolve with treatment
Timeframe for developing gummatous tertiary syphilis?
Can occur within 2yr of latency Typically seen after 15 years
Timeframe for developing Cardiovascular tertiary syphilis
typically 15–30 years after infection
Proportion of patients who become symptomatic with cardiovascular tertiary syphilis
10%
Symptoms of cardiovascular tertiary syphilis
Aortitis - Ascending aorta - subsernal pain Aortic regurgitation Heart failure coronary ostial stenosis angina aneurysm.
Timeframe for developing Meningovascular syphilis
Typically 5–10 years after infection (may be earlier) Prodrome may occur in the weeks/months prior to stroke
Types of neuro-syphilis
Meningovascular Parenchymous - General paresis / Tabes dorsalis Asymptomatic
Symptoms of Meningovascular syphilis
Focal arteritis Infectious arteritis may result in ischaemic stroke (middle cerebral artery territory most commonly affected) Meningeal inflammation signs dependent on site of vascular insult Occasional prodrome; headache, emotional lability, insomnia
Symptoms of neurosyphilis causing general paresis
Progressive dementia Initial forgetfulness Personality change Seizures and hemiparesis may occur (late) Emotional lability Psychosis
Timeframe for developing neurosyphilis causing general paresis
10–25 years after infection
Cause of symptoms from neurosyphilis causing general paresis
cortical neuronal loss
Symptoms of neurosyphilis causing tabes dorsalis
lightning pains areflexia paraesthesia sensory ataxia Charcot’s joints mal perforans optic atrophy pupillary changes (Argyll Robertson pupil)
Timeframe for developing neurosyphilis causing tabes dorsalis
15–25 years after infection (longest of neurological complications)
Cause of symptoms from neurosyphilis causing tabes dorsalis
Inflammation of spinal dorsal column / nerve roots
Which symptoms of neurosyphilis are caused by the loss of the dorsal columns?
absent reflexes absent joint position sense absent vibration sense
what are the 2 divisions of congenital syphilis?
early (diagnosed in the first two years of life) late (presenting after two years)
In congenital what does the presence of signs at the time of delivery depend upon?
duration of maternal infection timing of treatment
What proportion of infants with congenital syphilis are asymptomatic at birth?
2/3
Common manifestations of early congenital syphilis?
40–60% have one of: - rash - haemorrhagic rhinitis - generalised lymphadenopathy - hepatosplenomegaly - skeletal abnormalities Other signs: condylomata lata, vesiculobullous lesions, osteochondritis, periostitis, pseudoparalysis, mucous patches, perioral fissures, non- immune hydrops, glomerulonephritis, neurological or ocular involvement, haemolysis, thrombocytopenia
Time cut off for early congenital syphilis
early congenital syphilis = diagnosed in the first two years of life
Time cut off for late congenital syphilis
late congenital syphilis = presenting after two years
Signs of Late congenital syphilis
interstitial keratitis Clutton’s joints Hutchinson’s incisors mulberry molars high palatal arch rhagades (peri-oral fissures) sensineural deafness frontal bossing short maxilla protuberance of mandible saddlenose deformity sterno-clavicular thickening paroxysmal cold haemoglobinuria neurological involvement (intellectual disability, cranial nerve palsies)
Cause of signs of Late congenital syphilis
A result of chronic and persistent inflammation resembling gummatous disease in adults
Endemic treponemes
yaws (T. pallidum pertenue) bejel ( T. pallidum endemicum) pinta (T. pallidum carateum)
Classificaftion of Treponemal antibody tests
Treponemal antibody tests classified into: - Non-specific tests (cardiolipin, lipoidal, reagin, non- treponemal): VDRL / RPR test. - Specific (treponemal) tests: EIA, CLIA, TPHA, TPPA, FTA-abs, T. pallidum immunoblot
What do most of the specific (treponemal) syphilis tests detect?
Most syphilis tests are based on recombinant treponemal antigens They detect treponemal IgG and IgM antibody
what is the VDRL test?
Venereal Diseases Research Laboratory (VDRL) carbon antigen test = non specific test anti-cardiolipin antibodies
What is the RPR Test?
rapid plasma reagin (RPR) = non specific test anti-cardiolipin and anti-lecithin antibodies - substances released by cells when they are damaged by T. pallidum
What is the EIA Test?
Treponemal enzyme immunoassay (EIA) Specific (treponemal) test - detect treponemal IgG and IgM antibody
What is the CLIA Test?
treponemal chemilumines- cent assay (CLIA) Specific (treponemal) test - detect treponemal IgG and IgM antibody
What is the TPHA Test?
Treponema pallidum haem- agglutination assay (TPHA) Specific (treponemal) test - detect treponemal IgG and IgM antibody
What is the TPPA Test?
Treponema pallidum particle agglutination assay (TPPA) Specific (treponemal) test - detect treponemal IgG and IgM antibody
What is the FTA-abs test?
fluorescent treponemal antibody absorption test (FTA-abs) Specific (treponemal) test - detect treponemal IgG and IgM antibody
what are the primary screening tests for syphilis?
Primary screening tests 1st = Treponemal test - TPPA or EIA/CLIA (preferably a test that detects both IgG and IgM
What test is required if primary syphilis is suspected?
Request an anti-treponemal IgM test if primary syphilis is suspected TPPA or EIA/CLIA
what are the confirmatory tests for syphilis?
Positive screening tests should be confirmed with a different treponemal test. Second specimen always tested to confirm +ve result And sample on day treatment commenced - for documenting peak RPR/VDRL
What test is used for assessing serological activity of syphilis
A quantitative RPR/VDRL - helps stage the infection and indicate need for treatment
What initial RPR level indicates active syphilis?
Initial RPR/VDRL titre >16 usually indicates active disease and the need for treatment, RPR titre <16 does not exclude active infection
What tests are used for for monitoring the effect of treatment on syphilis infection?
A quantitative RPR/VDRL for monitoring the serological response to treatment Specimen taken on the day treatment is started = accurate baseline
When is repeat syphilis screening recommended?
6 - 12 weeks after a single ‘high risk’ exposure If ongoing / frequent ‘high risk’ exposures - screening for all STIs including HIV + STS is recommended every three months
when should testing for syphilis be repeated in a patient with an ulcerative lesion that could be due to syphilis but the dark ground micro or PRC was negative
Two weeks after presentation
When may false negative syphilis serology occur?
Treponemal screening tests are negative before a chancre develops and may be for up to two weeks afterwards. A false-negative RPR/VDRL may occur in secondary or early latent syphilis due to the prozone phenomenon
What is the prozone phenomenon?
an immunologic phenomenon which causes a false negative syphilis result The effectiveness of antibodies to form immune complexes stops increasing with greater concentrations and decreases with extremely high concentrations
How can the prozone phenomenon be avoided
Any negative test on undiluted sera should be repeated on diluted sera
When may false positive syphilis serology occur?
Occasionally false-positive results occur with any of the serological tests for syphilis. False-positive reactivity is more likely in autoimmune disease, older age and injecting drug use.
Investigations if Neurosyphilis-syphilis is suspected after examination
CT or MRI lumbar puncture (only after CT or MR)
what microscopy method is used for syphilis
Dark ground microscopy - of exudates from suspicious lesions, or body fluids, e.g. nasal discharge.
For diagnosis of syphilis in a newborn infant what sample is recommended
Serological tests performed on infant’s blood NOT cord blood I If infant’s serum +ve perform treponemal IgM EIA, RPR/VDRL and TPPA tests on the infant and mother in parallel. Serological tests detecting IgG may be positive due to passive transfer of maternal antibodies whether or not the infant is infected.
In diagnosing syphilis in infants - what immunoglobulin type can be passively transferred from the mother
IgG Serological tests detecting IgG may be positive due to passive transfer of maternal antibodies whether or not the infant is infected.
What test results would indicate a diagnosis of congenital syphilis?
Positive IgM EIA test Positive RPR/VDRL test on CSF, A four-fold or greater difference of RPR/ VDRL titre or TPPA titre above that of the mother A four-fold or greater increase in RPR/VDRL or TPPA titre within 3 months of birth, A child >18 months with positive treponemal tests
What further investigations should be considered for infants with congenital syphilis?
FBC LFT, ALT/AST U+E Lumbar puncture for CSF: WCC, protein, VDRL or RPR, TPPA, X-rays of long bones - osteochondritis and periostitis Ophthalmic assessment - for interstitial keratitis HIV test Chest X-ray for cardiomegaly Cranial U/S scan Audiology for 8th nerve deafness
Why is a longer duration of treatment given in late syphilis?
Longer duration of treatment in late syphilis On the basis of more slowly dividing treponemes
Why is parenteral rather than oral treatment recommended for syphilis?
therapy is supervised bioavailability is guaranteed
When should steroid treatment be given alongside syphilis treatment?
steroid treatment be given alongside syphilis treatment for patients with Cardiovascular or neurological syphilis
Treatment regimen for neurosyphilis
procaine penicillin 2.4 g (2.4 MU) IM OD for 10–14 days OR benzylpenicillin 10.8–14.4 g daily, given as 1.8–2.4 g IV every 4 h for 14 days: AND probenecid 500 mg PO QDS for 10-14 days AND 40–60mg prednisolone OD for three days starting 24h before the antibiotics
What are the potential adverse pregnancy outcomes relating to syphilis?
fetal infection usually occurs in 2nd / 3rd trimesters
(But can occur as early as 8–9wk gest)
Polyhydramnios
Miscarriage / stillbirth
Pre-term labour
Fetal hydrops
placental oedema
Congential syphilis
Management of positive maternal treponemal serology
Urgent referral to GUM MDT - screening laboratory, midwifery, obstetric team, GUM and paediatrics. May be most appropriate that the HIV MDT manages cases of syphilis in pregnancy. Determine if syphilis treated prior to this pregnancy, inadequate previous treatment, reinfection or if this is a new diagnosis of early or late syphilis
Management of pregnant women where syphilis was cured prior to current pregnancy
RPR/VDRL titres checked at first antenatal booking appointment Repeat later in pregnancy if there is a risk of reinfection If RPR/VDRL excludes re-infection - no further treatment and no need for neonatal testing Re-treatment women with a history of syphilis if there is uncertainty about the adequacy of treatment or a four-fold drop in RPR/VDRL did not occur
When is referral to fetal medicine indicated for pregnant women with syphilis?
Refer women to fetal medicine if they are treated for syphilis at 26/40 or later. Esp if early syphilis Fetal assessment will help planning of antepartum care as well as neonatal treatment
What ultrasound features may suggest Fetal syphilis infection
Non- immune hydrops Hepatosplenomegaly
maternal antibiotic treatment regimen for syphilis in pregnancy
Up to 27+6 /40 - STAT benzathine penicillin G 2.4 MU
From 28/40 to term - Benzathine penicillin G 2.4 MU IM, on days 1 and 8
Due to physiological changes in pregnancy which alter drug pharmacokinetics and may reduce plasma concentrations. Close liaison with obstetrics, midwifery and paediatrics
Physical signs of early congenital syphilis?
Approximately 50% of neonates with congenital syphilis are normal on initial examination Jaundice Anaemia Generalised lymphadenopathy, Hepatosplenomegaly Non-immune hydrops, Pyrexia, Failure to move an extremity (pseudoparalysis of Parrot), Low birth weight Skin rash (usually maculo-papular); palms / soles red, mottled or swollen Condylomata lata Osteochondritis, periosteitis (elbows, knees, wrists) Ulceration of nasal mucosa, rhinitis
What is the risk of a Jarisch-Herxheimer reaction during pregnancy
Theoretical increased risk of spontaneous and iatrogenic pre-term delivery and fetal demise May experience uterine contractions - resolve within 24h. Seem secondary to development of fever. Decelerations may occur - usually resolve without early delivery being required
Management of the Jarisch-Herxheimer reaction in pregnancy
Supportive - As in the non-pregnant woman Antipyretics. No evidence that high-dose oral prednisolone reduces the occurrence of uterine contractions or fetal heart rate abnormalities
Maternal follow-up after syphilis treatment in pregnancy
May take several months to observe a four-fold drop in RPR/VDRL titre In many pregnancies labour occurs before these periods have elapsed. Women with late syphilis may have serofast RPR/VDRL titres = serological cure may not be demonstrable before birth
Non-penicillin alternatives for treating syphilis
Doxycycline 100mg PO BD 14 days Ceftriaxone 500mg IM daily10 days (if no anaphylaxis to penicillin) Azithromycin 2g PO STAT or Azithromycin 500mg OD 10/7 Erythromycin 500mg PO QDS 14 days
Non-penicillin alternatives for treating syphilis in pregnancy
Ceftriaxone 500mg IM OD 10/7 (if no anaphylaxis to penicillin)
Azithromycin 500mg OD 10/7 - uncertain placental penetration - treat baby with penicillin @ birth
Erythromycin 500mg PO QDS 14 days - uncertain placental penetration - treat baby with penicillin @ birth
De-sensitisation to penicillin with immediate subsequent penicillin treatment should be considered
Management of infants born to mothers with syphilis
Most infected neonates appear normal at birth
RPR/VDRL and IgM tests at birth
Then 3 monthly until negative.
If titres stay stable or increase - treated for congenital syphilis
Benzylpenicillin 25 mg/kg 12hrly IV for 7 days, then 8 hrly on days 8, 9 and 10 (total of 10 days)
How common is congenital syphilis?
Congenital syphilis is uncommon in the UK
Approximately 10 cases reported annually.
When do passively transferred maternal antibodies for syphilis decline?
Non-treponema antibodies decline by 3 months and are negative by 6 months
Treponemal antibodies are negative by 18 months
Management of an infant born to mothers treated for syphilis less than 4 weeks prior to delivery.
Treat infant
Benzyl penicillin sodium 25 mg/kg
12hrly IV for 7 days,
then 8 hrly on days 8, 9 and 10 (total of 10 days)
Management of an infant whose mother was treated for syphilis with a non-penicillin regimens.
Treat infant
Benzyl penicillin sodium 25 mg/kg
12hrly IV for 7 days,
then 8 hrly on days 8, 9 and 10 (total of 10 days)
Impact of HIV on syphilis treatment
HIV +ve patients may be at higher risk of treatment failure
HIV means the RPR may not drop as quickly and may become serofast at a higher point
Treatment regimen for
Late latent, cardiovascular and gummatous syphilis
Benzathine penicillin 2.4 MU IM weekly for 3 weeks = 3 doses
Why is IV treatment recommended for treating congenital syphilis?
In children IV therapy is preferable due to the pain associated with IM injections.
Advice for interruptions in treatment for congenital syphilis
If drug administration is interrupted for >1 day tat any point during the treatment then
Re-start the entire course
Advice for interruptions in treatment for late syphilis
If drug administration is interrupted for >1 day tat any point during the treatment then
Re-start the entire course
What is the Jarisch-Herxheimer reaction
Jarisch-Herxheimer reaction = An acute febrile illness headache, myalgia, chills, rigours
Resolves within 24 hours.
Common in early syphilis
Usually not clinically significant
unless neurological/ ophthalmic involvement or in pregnancy when it may cause fetal distress
management of the Jarisch-Herxheimer reaction
Antipyretics Reassurance.
although rare, why may the Jarisch-Herxheimer reaction be important in late syphilis
Jarisch-Herxheimer reaction is uncommon in late syphilis
BUT potentially life threatening if there is involvement of critical sites (e.g. coronary ostia, larynx and nervous system)
what is the recommended steroid regimen prior to treatment of cardiovascular or neurological syphilis
Prednisolone
40–60 mg daily for three days
started 24 h before the anti-treponemal antibiotics.
what is the procaine reaction
Procaine reaction = procaine psychosis / procaine mania / Hoigne’s syndrome
Characterised by fear of impending death
+/- hallucinations
+/- fits
Occurs immediately after injection lasts <20 minutes
What causes the procaine reaction
Inadvertent IV injection of procaine penicillin
Partner notification for patients with primary syphilis
PN for sexual partners in the last 3 months
As incubation period is up to 90 days.
Partner notification for patients with secondary syphilis
PN may have to extend to 2 years
Management of asymptomatic contacts of early syphilis
offer epidemiological treatment
OR
re-screening for syphilis 12 weeks after their last exposure
Follow up after treatment of syphilis
Follow-up is to detect possible re-infection and relapse.
non-treponemal titres should drop four-fold
Recommended follow-up with RPR is at 3, 6 and 12 months +/- every 6m if indicated until VDRL/RPR negative or serofast
How is syphilis treatment failure determined
Treatment failure is characterised by:
- Four-fold or greater increase in non-treponemal test titre.
- Recurrence of signs or symptoms
- Re-infection excluded
Management of individuals whose non-treponemal test titres do not decrease four-fold within 12 months of syphilis therapy
CSF examination
+ re-treatment If CSF is normal
- re-treatment with benzathine penicillin G - 2.4 MU IM, weekly, three doses
Window period for syphilis testing
12 weeks
what is the usual route of transmission for neonatal syphilis
Usually vertically transmitted
transplacental
most common in 2nd / 3rd T
what factors increase the risk of congenital syphilis
morther has early STS
mother has high titre RPR / VDRL
maternal co-infection with HIV
mother treated in the 4 weeks before delivery
presentations of congential syphilis
stillbirth
hydrops
nasal discharge / haemorrhagic rhinitis
nasal ulceration / chondritis / saddle nose
rashes
osteochondritis / periostitis
hepatosplenomegally
failure to thrive
generalised lymphadwnopathy
nephrotic syndrome / gleomerulonephrosis
meningitis
ocular involvement
haematological effects
alopecia
pneumonitis
pancreatitis
myocarditits
what is hutchinsons triad
interstitial keratitis
hutchinsons incisors
deafness
From congenital STS
Major criteria in Kaufman criteria for congenital STS
condylomata lata
osteochondritis / periostitis
haemorrhagic rhinitis
minor criteria in Kaufman criteria for congenital STS
fissures of lips
cutaenous lesions
mucous patches
hepatosplenomegally
lymphadenopathy
CNS signs
Haemolytic anaemia
Incfreased cells / protein in CSF
other than syphilis serology what additional investigations should be carried out for suspected congenital syphilis
FBC
LFT
U+E
CSF
X-ray of long bones
management of a neonate born to a mother correctly treated for STS earlier than 4 weeks before delivery
Infant serology at birth - NOT cord blood
if negative STS serology at birth and no symptoms = no further action needed
If +ve EIA @ birth, order RPR / TPPA / treponemal IgM EIA
serological tests detecgting IgG may be +ve due to passive maternal antibody transfer
repeat at 3, 6 and 12m
treatment of neonatal syphilis
Benzyl penicillin 60 - 90 mg / kg IV daily in divided doses – 30 mg/kg 12 hourly in the first seven days of life and 8 hourly thereafter for a further 3 days for a total of 10 days
tests at 1,2,3,6,12months until negative
what follow up is recommended after treatment of syphilis. What decline in bloods is expected
repeat bloods at 3, 6, 9 and 12m + additional 6monthly if req until RPR negative or serofast
RPR expected to fall at least 4x in 6months (if primary, secondary or early latent)
Late syphilis = no clear criterion, If RPR >32 at baseline, most fall a bit by 12m
after treatment of syphilis what serology results would raise suspicion of inadequate treatment or re-infaction
Failure to achieve 4x drop in RPR by 6m
Failure to achieve an 8x drop in RPR by 12m
A significant increase in RPR
Persisting RPR >16 is rarely seen in correctly treated syphilis
