Syphilis

Introduction

Syphilis (aka venereal disease or venereal syphilis) is a contagious (usually sexually transmitted) disease caused by the spirochaete bacterium – treponema pallidum.
Transmission is either by sexual contact, or congenital via spread from the mother in utero. As such, syphilis is often classified as acquired or congenital. 

• Congenital syphilis is associated with stillbirth and increased childhood morbidity and mortality

T. pallidum enters the blood stream via mucous membranes or abraded skin and enters the bloodstream and lymphatics. It has an incubation period of about 3 weeks.
It can cause many complications, and death.

• All genital ulcers should be considered syphilis until proven otherwise!

Syphilis is often found alongside HIV. It is thought that syphilis increases the risk of HIV transmission.

• All newly diagnosed syphilis patients should have HIV screening, and those with HIV should have regular screening for syphilis

Syphilis causes different specific phases of infection. After the initial primary syphilis symptoms, 75% of patients will enter an asymptomatic latent phase – hence the need for screening of at risk populations.

Treatment is typically with a single stat dose of 1.8mg benzathine penicillin IM. Late syphilis will require longer courses (typically up to 3 weeks). Resistance is very uncommon. Alternative effective treatments include azithromycin and doxycycline, although it is recommended that those with penicillin allergy first undergo desensitization rather than use an alternative drug.

Syphilis is believed to have been brought back from the New World by sailors on the first voyage of Christopher Columbus to the Caribbean in 1492/93.

Epidemiology

• About 5,000 cases per year in the UK
• Rates are rising particularly quickly in men who have sex with men (MSM)

The number of cases in the UK is on the increase. In recent years there have been particular outbreaks in certain cities in the UK.
Over the last 5 years, rates have increased by:

• 200% in heterosexual men
• 1500% in MSM
• 25% in women

In Australia, there are outbreaks in Aboriginal populations in WA, QLD, NT and SA.

Presentation

About 50% of patients will have no symptoms at all and will only be diagnosed on serological testing.

Primary syphilis – Usually, a painless, solitary ulcer – chancre

• All genital ulcers are syphilis until proven otherwise!
• Not all cases cause an ulcer
• Some ulcers may go unnoticed – e.g. if on the anus, cervix or in the mouth
• 30% of cases have multiple ulcers

Secondary syphilis – a rash which typically affects the trunk, face, palms and soles
Tertiary / Late syphilis – the solitary ‘gumma nodule’

• This is a non-cancerous granuloma, whch can occur in any tissue of the body, typically, skin, bones, testes, mucosa.

Stages of syphilis

The bacterium enters through any abrasion or graze in squamous or columnar epithelium.
Infection of non-genital sites is rare, but possible.

Primary syphilis

An ulcer at the site of the original infection. This is usually the genitals (typically, penis, vagina, or rectum), but can be any point of contact.

• The incubation period is 9-90 days, but typically 2-3 weeks
• Often beings as a painless hard macule, and develops into a painless ulcer known as a chancre
  • Usually solitary (70%) of cases
  • Often unnoticed, especially if in the mouth or around anus
  • Sometimes the chancre may be “atypical”
    • Multiple
    • Painful
    • Purulent (produces pus)
  • In men typically found on the penis. In MSM may be found in the anus and in the mouth
  • In women, they can found on the external genitalia, or rarely internally
    • Common extra-genital sites include the mouth, lips, fingers and buttocks
• Typically persists for 4-6 weeks before healing spontaneously
• Usually also involves a local painless lymphadenopathy
• Patients often otherwise asymptomatic
• EXTREMELY INFECTIOUS!

Secondary syphilis

Secondary syphilis affects about 25% of infected untreated patients. Typical symptoms include fever, rash, malaise, headache and lymphadenopathy.

• The other 75% of patients enter a latent asymptomatic phase – which in 50% of these patients persists for life (I.e. they have no further symptoms)

Occurs 4-8 weeks after the chancre has healed (can be up to 6 months later). Consists of a rash of the trunk, palms, soles and sometimes face. The rash and any papules present are highly infectious. The rash can be confused with pityriasis roses, psoriasis or drug eruptions.

There may also be:

• Malaise / fever
• Sore throat
• Arthralgia
• Lymphadenopathy
• Alopecia
• Condylomata lata
  • These are number moist papules found around the genital region
• Ulcers of the palate and buccal region
• Snail track ulcers – found in the mouth and genitalia.
• Rare:
  • Meningism
  • Nephrosis
  • Uveitis
• Secondary syphilis is the most infectious phase!

Latent syphilis

A state of being infected with treponema pallidum but without clinical signs or symptoms. It occurs after the signs of primary and secondary syphilis have subsided (or were not noticed). Patients are not infective during this period. 

• Early latent syphilis – two years since the initial infection
• Late latent syphilis – >2 years since the initial infection

The differentiation between early and late syphilis is important, as it has implications for treatment. Those with early latent syphilis can be treated with a single IM dose of benzathine penicillin, those with late latent syphilis require more doses of therapy.

• In real-life situations, knowing when the initial infection occurred can be difficult, and thus in these cases it should be assumed that the disease Is late latent syphilis.

Tertiary syphilis

Usually occurs after a latency period of >2 years. Typically it occurs several years after the primary infection, but it can be 10+ years later.

Can cause a very wide range of non-specific symptoms and thus may not been easily recognised.

• Syphilis should be considered as a differential in any patient present with cardiological or neurological symptoms – especially where the symptoms are unexplained

It is only rarely seen – possibly because many patients may end up being treated when they receive antibiotics for other indications and thus never knew they had syphilis.

There is the appearance of gummas:

• Soft granulomas. Affect any tissue.
• The result of the inability of the immune system to clear the infection
• The gummas induce a state of chronic inflammation

Late stage syphilis. Can result in many complications:

• Cardiovascular:
  • Ascending aortic aneurysm
  • Aortic regurgitation
• Neurosyphilis:
  • Meningovascular
  • Tabes dorsalis refers to neurological disease where the functions of the dorsal column are lost due to syphilis
    • Sensory ataxia
    • Shooting pains
    • Takes 15-25 years to develop after infection
  • Dementia
• Cranial nerve palsies
• Stroke
  • General Paresis of insane (GPI)
• Dementia
• Psychoses – can be fatal if untreated, can be reversed with treatment
• Degeneration of sensory neurons
• Sensory ataxia
• Sensory loss – legs, nose, chest
• Lightning pains
• Gastric crisis
• Loss of reflexes
• Argyll – Robertson Pupils – bilateral, pupils constrict excessively when accommodating (focussing on near object), but DO NOT constrict in response to bright light.
  • Aka Prostitiues pupils – like prostitutes, they accommodate, but they don’t react!

Investigations

Screening

• Recommended for men who has sex with men (MSM) at least annually, up to x4 per year
• HIV positive MSM – 4x per year
• Routine antenatal screening
• Routine immigration screening
• Routine sexual health check

Upon diagnosis of syphilis screen for STIs including HIP, Hep B and Hep C

Clinica indications in symptomatic patients include:

• Genital ulcers
• MSM with any genital symptoms or any rash
• Any rash of the palms or soles, which is persistent
• PUO
• Persistent lymphadenopathy
• Alopecia
• Unexplained liver disturbance

Specific tests for presence of treponema

These tests are unable to distinguish between syphilis and other treponema diseases (e.g. yaws) – however the other treponema diseases are rare.

• Treponemal enzyme immunoassay (EIA)
  • IgM or IgG tests avilable
  • IgG becomes positive 5 weeks after infection
  • Request “EIA IgM” or often just “syphilis serology”
  • This IgM test remains positive for life after infection, and thus does not confirm active infection
  • If positive, diagnosis usually confirmed with a cardiolipin antibody (RPR) test – which is much less specific – but confirms active infection
• T. pallidum chemiluminescant assay (CLIA)
• Several other types of test exists for detecting syphilis Ig – such as TPPA, TPHA tests

Tests should be repeated at 12 weeks if the initial test is negative and there is a strong clinical suspicion of syphilis.

Cardiolipin antibody

• Not very specific
• Sometimes referred to as VDRL – Venereal disease reference laboratory or RPR – rapid plasmin reagin
• Gives a specific titre result
• Easiest to detect in primary syphilis, levels decrease as disease progresses
• Test will be negative after treatment
• Mainly used to monitor the progress of treatment

Detecting T. Pallidum

• It may be possible to directly detect the T. Pallidum bacteria in some circumstances
• This is not routinely performed
• Biopsy from lymph nodes and swabs from skin lesions in early syphilis
  • May be performed to confirm early syphilis where serology could still be negative
• Can be detected with:
  • Dark Field Microscopy
  • PCR
  • Direct fluorescent antibody test (DFA)

Management

• Patients should be referred to a sexual health clinic
• Contract tracing
• Patients who contract syphilis are at risk of re-infection. Opportunity should be taken to provide safe sex advice
• Offer screening for other STIs – particularly HIV
• Advise no sexual contact for 7 days after treatment

Medical management

• Primary syphilis
  • 1.8g benzathine penicillin IM STAT dose
  • Alternatives
    • Azithromycin 2g PO STAT
    • Doxycycline 100mg BD for 2 weeks
    • It is recommended that those with penicillin allergy first undergo desensitization rather than use an alternative drug.
  • BENZATHENE PENICILLIN is NOT the same as benzylpenicillin – it has an especially long half life and lasts in the blood stream for several weeks – hence why only a one off dose is required. It has a consistently like toothpaste, and is often injected into the buttocks (half of the dose into each buttock). It is a painful injection.
• Late syphilis
  • Benzathine penicillin 1.8g IM weekly for three weeks
• Neurosyphilis
  • Procaine penicillin 1.5g IM daily for 14 days
  • PLUS
  • Oral probenecid 500mg QID

Procaine penicillin – can cause an unusual reaction with a feel of impending doom and hallucinations. Usually only lasts about 30 minutes. Warn patients this can occur.

Jarisch-Herxheimer reaction

• A reaction to treatment that can occur with early syhpilis
• Usually occurs 6-12 hours after onset of treatment
• Causes fevers, headaches, myalgias
• Usually resolved within 24 hours
• Rarely is life-threatening
• Management supportively with paracetamol and rest
• Important in pregnancy
  • Occurs in about 40% of cases treated during pregnancy
  • Can cause fetal distress and premature labour
• Uncommon in late syphilis
• No evidence that the use of steroids reduce morbidity or mortality associated with Jarisch-Herxheimer reaction

Intrauterine syphilis

• 70-100% of infants of infected mothers will contract syphilis
• 25% of pregnancies in women with untreated syphilis will result in miscarriage or stillbirth
• A further 10% result in neonatal death
• In children born to infected mothers, infection can either present:
  • Early – <2 years age
  • Late – >2 years ago
• IgG tests in neonates can be positive from maternal antibodies
• Positive IgM testing indicates a congenital infection
  • Tests can be negative in infants that are infected late in pregnancy and should be repeated at 3 months of age
• Management
  • All pregnant women should be screened for syphilis
  • Any woman with positive serology should be referred to a sexual health specialist urgently
  • Older siblings should be screened
  • Sexual partner should be screened
  • Babies born to mother who have been treated during pregnancy should be screened with IgM testing at birth and at 3 months
  • Treatment in pregnancy is the same as the general population – 1.8g stat of benzathine penicillin IM
    • HOWEVER – pregnant women require close FU and specialist involvement to ensure the infection has been effectively treated
    • Also be aware of the increased risk of the Jarish-Herxheimer reaction as above

References

• Syphilis – Australian STI guidelines
• Syphilis – patient.info
• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.

Read more about our sources

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