Overview
Syphilis is a sexually transmitted infection (STI) caused by the spirochaete Treponema pallidum. If untreated, an infection can persist for years and result in severe cardiovascular, neurological, and ocular complications.
Treponema pallidum invades via the mucous membranes or skin abrasions and can disseminate through the blood and lymphatics. Most cases are sexually transmitted during direct contact with an infectious lesion. Other routes of transmission include vertical transmission, sharing needles, and rarely, blood products and organ transplants.
Definitions
Early syphilis is the first 2 years post-infection and has 3 stages:
- Primary syphilis – a painless ulcer (chancre) at the infection site and local lymphadenopathy
- Secondary syphilis – systemic involvement with constitutional symptoms, generalised lymphadenopathy, skin changes, and oral lesions
- Early latent syphilis – when an infection is confirmed without any clinical features
Late syphilis is >2 years post-infection and has 2 stages:
- Late latent syphilis – when an infection is confirmed without any clinical features
- Tertiary syphilis – rare, but includes cardiovascular, skin, ocular, and neurological complications
Congenital syphilis describes an in utero syphilis infection with features including Hutchinson’s teeth, bone malformations, or mucocutaneous, ocular, and neurologic features.
Cardiovascular syphilis describes the cardiovascular features of syphilis, which can include aortic valve pathology and aortic aneurysms.
Neurosyphilis describes a syphilis infection of the central nervous system resulting in features including meningism, paresis, optic atrophy, Argyll-Robertson pupils, dementia, seizures, and tabes dorsalis.
Tabes dorsalis is a form of neurosyphilis characterised by the degeneration of the posterior spinal columns, roots, and ganglia of the spinal cord, which can cause features such as urinary incontinence, ataxia, hypotonia, and hyperreflexia.
Epidemiology
- In 2018, ~7500 diagnoses of syphilis were made in England
Risk Factors
Risk factors include:
- Unprotected sexual intercourse
- Multiple sexual partners
- Chemsex
- Transactional sex
- Needle-sharing
- Social vulnerability (e.g. homelessness, migrant or refugee status)
The risk of transmission is highest in primary and secondary syphilis.
Presentation
Primary syphilis
Features of primary syphilis emerge within 2-12 weeks:
- A chancre at the site of infection, which can ulcerate and appear ‘punched-out’
- They are highly infectious and tend to resolve spontaneously within 2 months
- Regional, non-tender lymphadenopathy
Secondary syphilis
Features of secondary syphilis occur as Treponema pallidum starts to disseminate and are seen 1-6 months later:
- Constitutional features – particularly fever and generalised lymphadenopathy
- Rash – localised/diffuse mucocutaneous on the trunk, palms, and soles, may be papular and/or pustular
- ‘Snail-track’ ulcers in the mouth
- Condylomata lata – painless, wart-like lesions in skin folds and the genitalia, highly infectious
Secondary syphilis can then resolve, resulting in early latent syphilis. This stage lasts up to 2 years.
Tertiary syphilis
After a latent period of 2-20 years, features of tertiary syphilis may emerge:
- Gummatous syphilis – granulomatous lesions on the skin, bones, mucous membranes, and organs
- Cardiovascular syphilis – aortic valve disease, aortic aneurysm,
Neurosyphilis can be divided into two forms:
- General paresis – also known as ‘general paresis of the insane’ or ‘paralytic dementia’:
- Due to chronic meningoencephalitis and cerebral atrophy
- Psychiatric features – confusion, hallucinations, cognitive impairment
- Neurologic features – seizures, tremors, hyperreflexia, plantar extensor response, Argyll-Robertson pupils
- Tabes dorsalis – also known as ‘syphilitic myelopathy’:
- Due to atrophy of the spinal cord dorsal columns and autonomic nerves as Treponema pallidum infects myelinated fibres:
- Sensory impairment – ataxia, paraesthesia/sensory loss, neuropathic pain,
- Other – reduced/absent reflexes, urinary incontinence, Argyll-Robertson pupils
Congenital syphilis
Features of congenital syphilis can include:
- Hutchinson’s teeth – blunted upper incisors
- Skin – rashes and condyloma lata, rhagades (fissures at the angles of the mouth)
- Saddle-shaped nose – due to nasal cartilage damage
- Clutton’s joints – symmetrical joint effusion and swelling, often in the knees
- Deafness and keratitis
Referral and Investigations
Referral
Refer people with suspected syphilis to a genitourinary medicine specialist for laboratory testing and sexual health screening.
Laboratory tests
Since Treponema pallidum cannot be grown on artificial media, its diagnosis is made using clinical features and serology.
Non-treponemal serological tests:
- Tests the amount of antibodies produced in response to cardiolipin
- They decline with treatment and can be used to monitor its effectiveness
- If treatment is successful, the amount of antibodies produced in response to cardiolipin decreases as Treponema pallidum is eradicated
- Non-specific as cardiolipins can be found in anti-phospholipid syndrome, systemic lupus erythematosus, tuberculosis, HIV, and pregnancy, which can cause false positives
- Examples include rapid plasma reagin (RPR) and venereal disease research laboratory (VDRL)
Treponemal-specific serological tests:
- Tests for the presence of treponemal antibodies, but can only report as positive (reactive) or negative (non-reactive) – they cannot measure their amounts or distinguish them
- This reports exposure to syphilis and remains positive for life regardless of treatment (due to immune memory):
- Therefore, a person who has/has had syphilis would have a positive/reactive result
- Examples include the Treponema pallidum haemagglutination assay (TPHA) or the Treponema pallidum particle agglutination assay (TPPA)
Therefore, overall, results can suggest:
- False positive (e.g. antiphospholipid syndrome): high non-treponemal tests + negative treponemal-specific test
- The high non-treponemal test suggests antibodies are being made to cardiolipin
- However, the negative treponemal-specific test suggests Treponema pallidum is not present, and they are being made in response to something else
- Acute syphilis: high non-treponemal tests + positive treponemal-specific test
- The high non-treponemal test suggests antibodies are being made to cardiolipin
- The positive treponemal-specific test suggests Treponema pallidum is present, and they are being made in response to it
- Never had syphilis: low non-treponemal tests + negative treponemal-specific test
- The low non-treponemal test suggests antibodies are not being made to cardiolipin
- However, the negative treponemal-specific test suggests Treponema pallidum is not present
- Successfully treated/previously treated syphilis: low non-treponemal tests + positive treponemal-specific test:
- The low non-treponemal test suggests antibodies are not being made to cardiolipin
- The positive treponemal-specific test suggests Treponema pallidum was present, so it has likely been eradicated
Management
Overview
Treatment involves the use of intramuscular benzathine penicillin or doxycycline. A fourfold decrease in non-treponemal test titres (or antibodies) suggests an adequate response.
The Jarisch-Herxheimer reaction may be seen as bacterial toxins are released as Treponema pallidum is killed. Features include fever, rash, and tachycardia without features of anaphylaxis. No treatment other than an antipyretic (i.e. paracetamol) is needed.
Prognosis
- Early treatment before complications develop can cure syphilis
- If untreated, around 1/3 of cases progress to late syphilis. Cardiovascular and neurological lesions can persist/progress despite treatment.
