Syphilis

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Introduction

Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. It can be transmitted sexually, during pregnancy and via blood transfusion. Syphilis can be classified as acquired or congenital.¹

Epidemiology

According to the World Health Organisation, an estimated 7.1 million adults between 15 and 49 years old acquired syphilis in 2020.²

Looking at the UK, data from 2022 showed there were 8,682 cases. This is a 15% increase from 2021, and the largest annual number since 1948.³

The number of cases of congenital syphilis is increasing in the UK. In 2019, there were a recorded 11 cases of congenital syphilis (compared to 3 cases in 2018, 6 cases in 2017, 5 cases in 2016 and 1 case in 2015).⁴

With syphilis infections rising, it is essential to be aware of the clinical presentation and management, as syphilis has a safe, effective and curative treatment. However, if left untreated, it can lead to severe, sometimes irreversible complications.

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Aetiology

Congenital syphilis

Mother-to-child transmission normally occurs via the placenta and rarely, if there is a genital lesion, via the birth canal. There are multiple adverse outcomes of untreated syphilis in pregnancy, including preterm labour, hydrops, low birth weight, foetal loss and congenital syphilis.¹

Most infants born with congenital syphilis are asymptomatic at birth. However, if untreated, clinical symptoms usually develop by three months of age. Symptoms are varied but commonly include hepatomegaly, jaundice, haemorrhagic rhinitis, generalised lymphadenopathy, and rash.⁵ 

There are also serious long-term complications of congenital syphilis, including frontal bossing, mulberry molars/Hutchinson’s incisors, intellectual disability and sensorineural deafness.⁶

Acquired syphilis

Acquired syphilis is transmitted sexually, through the sharing of needles and rarely through blood transfusion. If untreated, it can persist for years and progress through multiple stages:⁷

• Primary syphilis: onset is 9-90 days after exposure (mean 21 days) and presents with local infection. It usually self resolves over 3-10 weeks.
• Secondary syphilis: onset is 4-12 weeks after the initial infection and presents with generalised infection. If untreated, symptoms will slowly resolve over 3-12 weeks, but roughly 25% of cases will reoccur.
• Early latent syphilis: asymptomatic for less than 2 years
• Late latent syphilis: asymptomatic for more than 2 years
• Tertiary syphilis: onset is 15 to 49 years after initial infection, it is a rare but serious complication of syphilis infection. It can be divided into gummatous, neurological and cardiovascular syphilis.

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Risk factors

In the UK, syphilis disproportionally affects gay, bisexual and other men who have sex with men.¹

However, it is also important to be aware that syphilis cases have increased rapidly among heterosexual men and women, with data from England showing an increase of 20.1% and 33.3% from 2018 to 2019, respectively.⁸

Lifestyle and social risk factors include:⁷

• Unprotected sex: especially if with multiple or anonymous sexual partners
• Previous or current diagnosis of any sexually transmitted infection
• Needle-sharing

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Clinical features

Clinical features of syphilis vary depending on the stage of infection.

Primary syphilis

A lesion will form at the site of inoculation. A small, usually painless papule rapidly forms an ulcer called the chancre. The chancre is usually single, round, and painless, with a red margin and clear base. There will also be local lymphadenopathy. It should heal in 2-6 weeks.⁷

On occasion, the chancre can also present as painful, with multiple lesions and possibly purulent; these atypical features are more common with co-infection of HIV.⁷

Secondary syphilis

Secondary syphilis normally develops 4-8 weeks after the primary lesion. It is a symmetrical, non-itchy, maculopapular rash affecting the trunk, arms, legs, palms, soles, face and genitalia.

Secondary syphilis can also present with systemic symptoms such as fever, headache and lymphadenopathy. Around 5% of patients also develop symptoms of vasculitis.⁷

Some patients can also develop neurological complications as a presentation of secondary syphilis. This form of neurological syphilis can present with acute meningitis, cranial nerve palsies, uveitis, optic neuropathy and interstitial keratitis.⁶

Tertiary syphilis

Tertiary syphilis can be divided into three presentations.

Neurological syphilis

Neurological syphilis can be asymptomatic, which is defined as late syphilis with abnormal CSF findings but no neurological symptoms or signs.¹

Otherwise, clinical features include dorsal column loss, dementia and meningovascular involvement.⁷

Cardiovascular syphilis

Cardiovascular syphilis can cause aortitis and most commonly presents with aortic regurgitation, aortic aneurysm and angina.¹

Gummata syphilis

Gummata syphilis causes inflammatory fibrous nodules or plaques and most commonly affects the bone and skin.⁷

History

A full sexual history should be taken, including direct questioning for symptoms of syphilis. It is also important to explore whether the patient has had a previous diagnosis or treatment for syphilis, as well as their obstetric history.⁶

When discussing obstetric history, ask about syphilis screening tests, as during pregnancy, all women are offered a blood test for syphilis. Screening should be done during the first trimester, ideally by 10 weeks, to ensure treatment can be started as early as possible.⁹

Clinical examination

On examination, you should perform a genital examination and skin examination, including the eyes, mouth, scalp, palms and soles.

Also, consider neurological and cardiovascular examination if indicated from the history. During a cardiovascular examination, assess for signs of aortic regurgitation.⁶

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Differential diagnoses

As syphilis has a varied presentation, many conditions present with similar features, depending on the stage of syphilis.

Chancre (primary syphilis)

Differential diagnoses to consider will vary depending on the location of the chancre:⁷

• Genitalia: genital herpes, lymphogranuloma venereum (chlamydia trachomatis), Behcet’s syndrome (especially if there are ulcers on the genitals and mouth)
• Peri-anal area: herpes simplex infection, anal fissure or Crohn’s disease
• Cervix: cervical herpes or cervical erosions
• Oral mucosa: herpes simplex infection, aphthous stomatitis, Bechet’s syndrome, or a secondary infected traumatic lesion

Malignancy should be considered as a differential diagnoses for an ulcer in the genital area, on the cervix, peri-anal area or oral mucosa.

Maculopapular rash (secondary syphilis)

Differential diagnoses to consider include:⁷

• Primary HIV infection
• Rubella
• Scabies
• Guttate psoriasis
• Adverse drug reactions

Tertiary syphilis

Differentials for tertiary syphilis are broad due to its varied presentation. They could include:⁷

• Dementia
• Psychiatric conditions
• Chronic granulomatous lesions of tuberculosis
• Sarcoidosis

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Investigations

Bedside investigations

Relevant bedside investigations include:

• ECG: if suspecting cardiovascular syphilis

Laboratory investigations

Relevant laboratory investigations include:

• Direct tests for syphilis: dark field microscopy and PCR (only if chancre present)
• Full screening for other sexually transmitted infections: including swabs for chlamydia and gonorrhoea and blood tests for HIV and Hepatitis B and C
• Lumbar puncture: examination of cerebrospinal fluid is required for diagnosis of neurosyphilis/tertiary neurosyphilis
• Serological tests for syphilis

Imaging

Relevant imaging investigations include:

• Echocardiogram: if considering cardiovascular syphilis
• CT head or MRI brain: if considering neurosyphilis/tertiary neurosyphilis

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Diagnosis

Syphilis presents with a wide range of nonspecific symptoms, and some people may even be asymptomatic. As a result, diagnosis can often be delayed or missed.

Diagnosis can be made from direct tests for syphilis. These tests involve taking a swab from primary lesions; they include:⁷

• Dark field microscopy: has high specificity but low sensitivity, requires specialist equipment and training, and cannot be used for oral lesions
• PCR: can be used for all lesions

Serological testing

The diagnosis can also be made from serological testing, which is divided into treponemal and non-treponemal tests.

Treponemal tests

Treponemal tests include:

• Treponemal enzyme immunoassay (EIA)
• Treponemal chemiluminescent assay (CLIA)
• Treponema pallidum haemagglutination assay (TPHA)
• Treponema pallidum particle agglutination assay (TPPA)

It is recommended to use EIA or CLIA as the screening test of choice for syphilis. All positive tests must be confirmed with a different serological test (TPHA or TPPA).⁶

Non-treponemal tests

Non-treponemal tests include venereal disease reference laboratory (VDRL) or rapid plasma reagin (RPR). These can be used to monitor response to treatment.¹

Despite the above guidance, syphilis interpretation is challenging, and there are no hard or fast rules other than the initial screening test – the EIA often remains positive throughout life despite treatment.

The patient must know this in case they are tested elsewhere. To interpret serology, you need a detailed history from the patient, including the last STI screen and the serology from previous testing to compare results.

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Management

All people with suspected syphilis should be referred to a local specialist sexual health service.⁷

Medical management

Primary, secondary and early latent syphilis are treated with a single dose of IM penicillin.⁶

Late latent, cardiovascular and gummatous syphilis require IM penicillin weekly for three weeks. A 3 day course of steroids should be given with antibiotics for cardiovascular syphilis.⁶

Neurosyphilis, including when there is neurological/ophthalmic involvement in early syphilis, is treated with IM penicillin once daily for 14 days, alongside oral probenecid. A 3 day course of steroids should also be given for neurosyphilis.⁶

Treatment in pregnancy

In pregnancy, syphilis is again treated with penicillin. Treatment varies depending on the stage of syphilis and the trimester.

In early syphilis, the treatment is a single dose in the first and second trimesters or 2 doses if diagnosed in the third trimester. In late latent, cardiovascular, gummatous and neurosyphilis the first line treatment is the same during pregnancy as it is normally.⁶

Follow up

Following treatment it is recommended that patients are followed up clinically and with serological testing (RPR or VDRL) at three, six and twelve months. Follow up may then continue 6 monthly until serology has shown a sufficient response to treatment.⁶

Partner notification

Contact tracing is needed to limit ongoing transmission, prevent re-infection and ensure that contacts receive prompt treatment.⁷

Prevention

Prevention focuses on safer sex advice. This advice can include increased use of condoms and avoidance of drugs and alcohol when having sex.⁷

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Complications

If left untreated, the complications include presentations of tertiary syphilis: neurosyphilis, cardiovascular syphilis and gummatous syphilis.

Other complications of syphilis are adverse outcomes during pregnancy and facilitation of HIV transmission.⁷

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Key points

• Syphilis is an infectious disease caused by the spirochete bacterium treponema pallidum
• Syphilis has a wide and varied presentation, so if it is not considered as a diagnosis, it can be easily missed
• Syphilis has primary, secondary, and tertiary presentations
• Diagnosis is predominantly by serological testing
• Treatment is with penicillin, often a single dose, which is a safe and highly effective treatment
• If left untreated, tertiary syphilis can develop with significant complications

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Reviewer

Dr Ashley Jefferies

Community Sexual and Reproductive Health Registrar

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Editor

Dr Chris Jefferies

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References

1. Patient UK. Syphilis. 31 July 2022. Available from: [LINK]
2. World Health Organization. Syphilis. 31 May 2023. Available from: [LINK]
3. GOV.UK. Gonorrhoea and syphilis at record levels in 2022. 6 June 2023. Available from: [LINK]
4. NHS England. ISOSS syphilis report 2022. Available from: [LINK]
5. Hussain, S. A., & Vaidya, R. (2023). Congenital Syphilis. In StatPearls. StatPearls Publishing. Available from: [LINK]
6. BASHH. BASHH Syphilis Guidelines. December 2015. Available from: [LINK]
7. NICE. Syphilis. December 2019. Available from: [LINK]
8. GOV.UK. Tracking the syphilis epidemic in England: 2010 to 2019. February 2021. Available from: [LINK]
9. NHS. Screening for hepatitis B, HIV and syphilis. March 2021. Available from: [LINK]
10. Medecins sans frontieres. Endemic treponematoses. May 2018. Available from: [LINK]
11. Michael Marks, Anthony W Solomon, David C Mabey, Endemic treponemal diseases, Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 108, Issue 10, October 2014, Pages 601–607. Available from: [LINK]

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