Syphilis

Question 1

Syphilis pathogen

Answer 1

Treponema pallidum

Question 2

Association between HIV and syphilis

Answer 2

High rate of HIV coinfection among MSM with syphilis - 42% of MSM with syphilis also have HIV
Much lower coinfection rates in non MSM

Question 3

Transmission of syphilis

Answer 3

Direct contact with infectious lesion during sex
Infectious lesions:
- Primary chancre (highly infectious - around 30% transmission)
- Secondary syphilis: mucous patches and condyloma lata (less infectious)

Infection may occur wherever innoculation occurs e.g. lips lesisons, oral cavity, breasts, genitals

Question 4

Syphilis in pregnancy

Answer 4

T pallidum readily crosses placenta –> foetal infection

Question 5

Stages of syphilis infection & the importance of identifying stage

Answer 5

Syphilis is divided into early & late syphilis based on time since infection. Early syphilis is infection <2 years since diagnosis and late syphilis is infection >2 years since diagnosis. Patients may be latent at any time during early or late infection.

Syphilis is also divided into primary, secondary and tertiary syphilis based on symptomatology. Tertiary syphilis may only occur > 2 years. This may be interspersed with latent periods.

Important of identifying stage:

• Treatment implications
• Patients with late syphilis (>2 years) are considered non-infectious (do not have lesions that can transmit disease)

Note that some resources say 1 year for all of the above, rather than 2 years. ETG says 2 years.

Question 6

In what timeframe can you see the symptoms of tertiary syphilis, from the onset of primary infection?

Answer 6

Clinical symptoms of tertiary syphilis may occur at any time from 2 years - 30 years post initial infection

Question 7

Primary syphilis

• Initial manifestation
• Incubation time from exposure
• Lesion description
• Time to heal

Answer 7

• Primary syphilis = chancre
• Incubation roughly 3/52, range 3-90 days
• Typically painless papule –> ulcerates to produce classic chancre (1-2cm ulcer with raised, indurated margin). Assoc with mild-mod regional lymphadenopathy. Usually on genitalia but may be at other sites of inoculation. HIV patients may have multiple chancres.
• Heal spontaneously in 3-6/52 even without rx.

Question 8

Secondary syphilis

• Transition from primary syphilis
• Symptoms
• Time to recovery of symptoms

Answer 8

• Following chancre, syphilis quickly becomes systemic with widespread dissemination of T pallidum
• Symptoms: constitutional symptoms, pharyngitis, LOW, adenopathy. Most characteristic finding is RASH.
• Similar to primary syphilis, sx typically resolve spontaneously, even in the absence of therapy (except lues maligna). If untreated, may have sx of relapsing secondary syphilis for up to 5 years

Question 9

SKIN FINDINGS - secondary syphilis

• Classic rash
• Lues maligna?
• Other derm findings

Answer 9

Classic rash: Diffuse, systemic macular/papular rash involving entire trunk and extremities including palms & soles!!. May be pustular or nodular. Can also affected mucosal surfaces.

Lues maligna: Severe ulcerative form of secondary syphilis - primarily in severe immunocompromised patients - presents with non resolving severe ulcerative skin lesions.

Other findings: patchy alopecia

Question 10

GI FINDINGS - secondary syphilis

Answer 10

• Hepatitis: high ALP, other LFTs normal

- Ulcerations/infiltrations of GI tract

Question 11

Renal, MSK, neurologic findings - secondary syphilis

Answer 11

• Renal: albuminuria, nephrotic, or acute nephritis with HTN and acute renal failure. Resolution with rx.
• MSK; synovitis, osteitis, periostitis. Resolves with rx
• Neurologic/ocular (neurosyphilis): headache, meningitis, stroke, uveitis, etc. Investigate immediately.

Question 12

TERTIARY SYPHILIS

• Percentage of untreated primary/secondary syphilis that progress to tertiary syphilis
• Clinical manifestations
• Diagnosis

Answer 12

25-40% progress to late syphilis (1-30 years). May occur without clinical sx of primary or secondary.

Variable manifestations. Most common:

• CV syphilis: aortitis, aortic regurgitation
• Gummatous syphilis: rare granulomatous lesions in skin/bones and other organs
• CNS involvement: general paresis, tabes dorsalis

Diagnosis requires T pallidum in late syphilitic lesions by special stains (Warthin-Starry sliver/IF staining), PCR, etc.

Question 13

What is tertiary syphilis?

Answer 13

Late syphilis (>2 years) with symptomatic manifestations involving the CV system, CNS or gummatous disease

Question 14

Syphilis in patients with HIV? Manifestations and treatment

Answer 14

Similar manifestations, however patients with HIV are more likely to have multiple chancres and chancres present at the same time of secondary syphilis. Neurosyphilis also seen more commonly (any inkling of neurologic, ocular or otic involvement –> LP)

Treatment is the same, but frequency of monitoring after treatment should be more frequent (increased risk of treatment failure)

Test for syphilis in HIV positive patients upon diagnosis and yearly going forward

Question 15

Diagnostic testing for syphilis?

Answer 15

Diagnosis made using serology

Methods that detect the organism are not generally available (requires special equipment, organism difficult to detect)

Question 16

Syphilis in patients with HIV? Manifestations and treatment

Answer 16

Similar manifestations, however patients with HIV are more likely to have multiple chancres and chancres present at the same time of secondary syphilis. Neurosyphilis also seen more commonly (any inkling of neurologic, ocular or otic involvement –> LP)

Treatment is the same, but frequency of monitoring after treatment should be more frequent (increased risk of treatment failure)

Test for syphilis in HIV positive patients upon diagnosis and yearly going forward

Question 17

Diagnostic testing for syphilis? Which tests are used?

Answer 17

PRESUMPTIVE Diagnosis made using serology

Methods that detect the organism are not generally available (requires special equipment, organism difficult to detect) –> requires dark field microscopy. Also cannot be cultured in the lab.

Two types of serologic tests:

• Nontreponemal tests
• Treponemal tests

Use of only one test is insufficient –> serologic testing (esp non-treponemal) assoc. with false positives

Question 18

False positives and negatives in syphilis testing?

Answer 18

• False positives with serological testing (esp non-treponemal)
• False negatives given serology requires humoral response to infection –> false negative in early disease or advanced immunosuppression

Most patients have positive serology when presenting with the chancre - 20-30% still have a negative nontreponemal test. Repeat serology in 2-4 weeks (generally turns positive)

Question 19

What are non treponemal tests?

Answer 19

Tests for reagin antibodies. Based on the reactivity of the serum to a cardiolipin-cholesterol-lecithin antigen ….

Non-specific, but are cheap, easy and can be used to track response to therapy.

Examples include the rapid plasma reagin (RPR)!!
The amount of antibody present (IgM and IgG) generally reflects the activity of the infection. Reported as a titre e.g. 1:32 (detection of antibody in serum diluted 32-fold).

Successful therapy accelerates the pace of antibody decline (although titres tend to wane over time anyway).

Both false positives and negatives can occur.

Question 20

What are treponemal tests?

Answer 20

Traditionally more expensive and difficult, but new advances improving use.

Used to be used as only confirmatory of positive non-treponemal testing, but now used in initial screening.

Tests include:
T.pallidum enzyme immunoassay (TP-EIA)!!!!! and T. pallidum particle agglutination assay (TPPA)

Detect antibodies against specific treponemal antigens –> more specific than non-trep tests. Qualitative only and reported as reactive or non-reactive.

Question 21

What happens to treponemal tests if a patient has previously tested positive for syphilis?

Answer 21

Treponemal tests (EIA / TPPA) remain positive for life.

Question 22

Algorithm for screening for asymptomatic patients

Answer 22

TRADITIONALLY, perform RPR then EIA to confirm if RPR positive.

These days, also acceptable to do reverse order (EIA then RPR). This order picks up an extra group of patients: previously treated syphilis, very early syphilis, late or late latent syphilis whose RPR has become non-reactive over time

Either way:

• Both positive indicate latent syphilis
• If the results are discordant, repeat the second test in 2-4 weeks
• Positive EIA and negative RPR is expected in a patient with previous syphilis

Question 23

Testing for neurosyphilis?

Answer 23

Lumbar puncture

• CSF-VDRL (syphilis serology)
• CSF cell count, protein (elevation of both is non-specific)

No real gold standard CSF test

Question 24

Results of testing in a patient with previous syphilis?

Answer 24

• If a patient has a history of syphilis, and tests positive with both EIA and RPR, consider whether it is appropriate serology post treatment (e.g. titre still declining), inadequately treated infection, or new infection. Use previous RPR titres for clues.
• A new syphilis infection is diagnosed when RPR has a 4-fold or greater increase in titre from previous post-treatment test (provided same test used)

Question 25

What is a false positive result with testing?

Answer 25

A positive RPR and a negative EIA…

Particularly common during pregnancy or acute febrile illnesses

Question 26

Negative tests with a high degree of clinical suspicion?

And what is a prozone reaction?

Answer 26

If a patient is symptomatic w high degree of suspicion, and tests aren’t consistent with active infection, repeat in 2-4 weeks…. RPR may be negative in early infection

Prozone reaction: a second major cause of false negative RPRs. Really high antibody titres e.g. in 2ndary syphilis –> antibodies interfere with antigen agglutination –> can’t see the agglutination, false negative test

Question 27

How is latent syphilis diagnosed?

Answer 27

When a patient has no signs or symptoms of syphilis, but has serologic evidence of infection

Syphilis often follows a course with intermittent latent periods.

Early latent is when acquired in last 24 months (e.g. previous neg test or sexual debut)

Late latent - if not meeting above criteria

Question 28

Monitoring response to therapy…

Which tests, and what indicates an appropriate response?

Answer 28

Obtain a RPR titre JUST before treatment (can increase a lot in a short time)

Monitor clinically and serologically after treatment…

Appropriate response is a change of two dilutions in the RPR titre (AKA a four fold decline) e.g. from 1:16 to 1:4

Most will ‘serorevert’ over time AKA no more RPR. Some will ‘serofast’ AKA persistent small titre positive.

Question 29

Monitoring response to therapy….

Frequency of monitoring depending on stage of disease and HIV coinfection?

Answer 29

Non-HIV patients:
- Early: 6 and 12 months following rx, or if symptoms recur. Usually adequate response by 12/12

• Late syphilis: 6, 12 and 24 months. Usually adequate response by 24/12

Patients with HIV are monitored more frequently!!:
- Early syphilis: 3,6,9,12,24 months.. Usually adequate response 6-12 months

• Late syphilis: 6 month intervals for 24 months. Usually adequate response 12-24 months
• Neurosyphilis: usually 6 monthly until CSF tests negative (more complex than this). Usually adequate response 24 months

Question 30

Monitoring response to treatment… neurosyphilis

Answer 30

Undergo clinical and serologic monitoring at same frequency as normal

Question 31

Early syphilis: treatment

Answer 31

• Benzathine benzylpenicillin 2.4 million units IM single dose

OR

Procaine benzylpenicillin 1.5g IM daily for 10/7

Penicillin hypersensitivity: doxycycline for 2/52

Question 32

Late LATENT syphilis (>2 years duration or unknown duration): treatment

Answer 32

• Benzathine benzylpenicillin 2.4million units IM, once weekly for 3/52

OR

Procaine benzylpenicillin 1.5g IM daily for 15/7

Penicillin allergy: doxy for a month

Question 33

Tertiary syphilis: treatment

Answer 33

Tertiary syphilis is late syphilis with CV/CNS/gummatous involvement

Rx: Benzylpenicillin 1.8G IV 4 hourly for 15/7

Question 34

Manifestations of tabes dorsalis?

Answer 34

D - dorsal column degeneration
O - orthopaedic pain (charcot joints) 
 R - reflexes decreased (deep tendon)
S - shooting pain
A - argyll roberston pupils 
L - locomotor ataxia 
I - impaired proprioception
S - syphilis