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Syphilis

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Syphilis\: infectious disease caused by T r e p o n e m a p a l l i d u m , transmitted sexually, via pregnancy, or blood transfusion;
classi
Epidemiology\: 7.1 million adults worldwide in 2020; UK had 8,682 cases in 2022 (15% increase from 2021); congenital syphilis
cases rising.
Congenital syphilis\: transmitted via placenta; asymptomatic at birth, symptoms by 3 months if untreated (e.g.
hepatomegaly, jaundice); long-term complications include intellectual disability and sensorineural deafness.
Acquired syphilis\: transmitted sexually, via needles, or blood transfusion; stages include primary, secondary, latent, and
tertiary syphilis.
Risk factors\: disproportionately a
men and women; unprotected sex, multiple partners, needle-sharing.
Clinical features\: primary (chancre, local lymphadenopathy), secondary (maculopapular rash, systemic symptoms), tertiary
(neurological, cardiovascular, gummatous syphilis).
Investigations\: dark
(treponemal and non-treponemal), imaging (echocardiogram, CT/MRI brain).
Diagnosis\: based on direct tests (dark
tests (VDRL, RPR) monitor treatment response.
Management\: IM penicillin for primary/secondary/early latent syphilis; weekly IM penicillin for three weeks for late
latent/cardiovascular/gummatous syphilis; daily IM penicillin for 14 days for neurosyphilis.
Follow up\: clinical and serological testing at 3, 6, and 12 months; partner noti
(e.g. condom use).
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A comprehensive topic overview

Introduction

Syphilis is an infectious disease caused by the spirochete bacterium T r e p o n e m a p a l l i d u m . It can be transmitted sexually,
during pregnancy and via blood transfusion. Syphilis can be classi
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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,
e
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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.
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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.
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There are also serious long-term complications of congenital syphilis, including frontal bossing, mulberry
molars/Hutchinson’s incisors, intellectual disability and sensorineural deafness.
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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\:
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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.

Risk factors

In the UK, syphilis disproportionally a
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.
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Lifestyle and social risk factors include\:
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Unprotected sex\: especially if with multiple or anonymous sexual partners
Previous or current diagnosis of any sexually transmitted infection
Needle-sharing

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.
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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.
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Secondary syphilis
Secondary syphilis normally develops 4-8 weeks after the primary lesion. It is a symmetrical, non-itchy, maculopapular
rash a
Secondary syphilis can also present with systemic symptoms such as fever, headache and lymphadenopathy. Around 5%
of patients also develop symptoms of vasculitis.
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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.
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Tertiary syphilis
Tertiary syphilis can be divided into three presentations.
Neurological syphilis
Neurological syphilis can be asymptomatic, which is de
neurological symptoms or signs.
1
Otherwise, clinical features include dorsal column loss, dementia and meningovascular involvement.
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Cardiovascular syphilis
Cardiovascular syphilis can cause aortitis and most commonly presents with aortic regurgitation, aortic aneurysm and
angina.
1
Gummata syphilis
Gummata syphilis causes in
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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.
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When discussing obstetric history, ask about syphilis screening tests, as during pregnancy, all women are o
test for syphilis. Screening should be done during the
as early as possible.
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Non-venereal Treponema pallidum
As previously mentioned, syphilis is caused by the bacterium T r e p o n e m a p a l l i d u m . There are a group of non-
venereal diseases caused by a subspecies of T r e p o n e m a p a l l i d u m . As a group they are referred to as non-venereal
T r e p o n e m a p a l l i d u m , and individually as yaws, pinta and bejel.
Non-veneral T r e p o n e m a p a l l i d u m (yaws, pinta, bejel) is endemic in some parts of the world. These infections are
closely related to syphilis, and current tests are unable to distinguish between them. Due to this, these patients
often undergo syphilis treatment and monitoring.
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When taking a history for a patient with suspected syphilis, it is important to document where the patient grew up, as
some patients may have had a previous infection of non-venereal T r e p o n e m a p a l l i d u m .
The geographic distribution of yaws, pinta and bejel include\:
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Yaws\: West Africa, South East Asia and the Paci
Pinta\: Latin America, in particular Mexico and Colombia
Bejel\: Semi-desert areas of the Middle East and Africa
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.
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Di

As syphilis has a varied presentation, many conditions present with similar features, depending on the stage of syphilis.
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Chancre (primary syphilis)
Di
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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 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 di
oral mucosa.
Maculopapular rash (secondary syphilis)
Di
7
Primary HIV infection
Rubella
Scabies
Guttate psoriasis
Adverse drug reactions
Tertiary syphilis
Di
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Dementia
Psychiatric conditions
Chronic granulomatous lesions of tuberculosis
Sarcoidosis

Investigations

Bedside investigations
Relevant bedside investigations include\:
ECG\: if suspecting cardiovascular syphilis
Laboratory investigations
Relevant laboratory investigations include\:
Direct tests for syphilis\: dark
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
Serological tests for syphilis
Imaging
Relevant imaging investigations include\:
Echocardiogram\: if considering cardiovascular syphilis
CT head or MRI brain\: if considering neurosyphilis/tertiary neurosyphilis

Diagnosis

Syphilis presents with a wide range of nonspeci
diagnosis can often be delayed or missed.
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Diagnosis can be made from direct tests for syphilis. These tests involve taking a swab from primary lesions; they include\:
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Dark
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 con
di
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.

Management

All people with suspected syphilis should be referred to a local specialist sexual health service.
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Medical management
Primary, secondary and early latent syphilis are treated with a single dose of IM penicillin.
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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
trimester. In late latent, cardiovascular, gummatous and neurosyphilis the
as it is normally.
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Jarisch-Herxheimer reaction
A Jarisch-Herxheimer reaction is a reaction to syphilis treatment. It is an acute febrile illness, presenting with
headache, myalgia, chills and rigours, which self-resolves within 24 hours. It is especially important when there is
neurological involvement and in pregnancy, as it can cause contractions, fetal heart rate abnormalities and stillbirth.
1
Follow up
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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 su
treatment.
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Partner noti
Contact tracing is needed to limit ongoing transmission, prevent re-infection and ensure that contacts receive prompt
treatment.
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Prevention
Prevention focuses on safer sex advice. This advice can include increased use of condoms and avoidance of drugs and
alcohol when having sex.
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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.
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References

Patient UK. S y p h i l i s . 31 July 2022. Available from\: [LINK]
World Health Organization. S y p h i l i s . 31 May 2023. Available from\: [LINK]
GOV.UK. G o n o r r h o e a a n d s y p h i l i s a t r e c o r d l e v e l s i n 2 0 2 2 . 6 June 2023. Available from\: [LINK]
NHS England. ISOSS syphilis report 2022. Available from\: [LINK]
Hussain, S. A., & Vaidya, R. (2023). C o n g e n i t a l S y p h i l i s . In StatPearls. StatPearls Publishing. Available from\: [LINK]
BASHH. B A S H H S y p h i l i s G u i d e l i n e s . December 2015. Available from\: [LINK]
NICE. S y p h i l i s . December 2019. Available from\: [LINK]
GOV.UK. T r a c k i n g t h e s y p h i l i s e p i d e m i c i n E n gl a n d \: 2 0 1 0 t o 2 0 1 9 . February 2021. Available from\: [LINK]
NHS. S c r e e n i n g f o r h e p a t i t i s B , H I V a n d s y p h i l i s . March 2021. Available from\: [LINK]
Medecins sans frontieres. E n d e m i c t r e p o n e m a t o s e s . May 2018. Available from\: [LINK]
Michael Marks, Anthony W Solomon, David C Mabey, E n d e m i c t r e p o n e m a l d i s e a s e s , T r a n s a c t i o n s o f T h e R o y a l S o c i e t y o f
T r o p i c a l M e d i c i n e a n d H y g i e n e , Volume 108, Issue 10, October 2014, Pages 601–607. Available from\: [LINK]

Reviewer

Dr Ashley Je
Community Sexual and Reproductive Health Registrar

Bacterial Vaginosis
Bartholin’s Cyst
Pelvic In

Test yourself

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