Changes

March 2025 — reviewed. A literature search was conducted in January 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic.

Update

Goals

To support primary healthcare professionals to:

• Recognize the presenting features of syphilis in primary care.
• Refer all people with suspected syphilis to a genito-urinary medicine (GUM) clinic.
• Seek specialist advice about appropriate investigations, interpretation of results and further management of people who decline referral to a GUM clinic.

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

NICE quality standards

Sexual health

• People are asked about their sexual history at key points of contact.
• People identified as being at risk of sexually transmitted infections have a discussion about prevention and testing.
• Local authorities provide a range of condom distribution schemes tailored to the needs of their populations.
• People contacting a sexual health service about a sexually transmitted infection are offered an appointment that is within 2 working days.
• Men who have sex with men have repeat testing every 3 months if they are at increased risk of sexually transmitted infections.
• People diagnosed with a sexually transmitted infection are supported to notify their partners.

[NICE, 2022]

What is it?

• Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum — untreated infection can persist for years and result in severe cardiovascular, ocular and neurological complications. 
• Syphilis is catagorized as either:
  • Acquired
    • Sexually transmitted during direct contact with an infectious lesion (usually involving the genital, rectal, or oral mucous surfaces).
      • This is the most common route of transmission. 
      • T. pallidum invades through mucous membranes or abraded skin at the point of contact with an infectious lesion. The spirochetes multiply locally and then are disseminated through the vasculature and lymphatic system.
      • The incubation period is around 21 days but can range from 9–90 days depending on the infectious dose.
    • Transmitted through sharing of needles in injecting drug users.
    • More rarely, transmitted through blood products or organ transplants — screening of donations is mandatory in the UK.
  • Congenital
    • Vertical transmission from mother to child during pregnancy (congenital syphilis) — serological screening for syphilis is part of routine antenatal care in the UK.
• Early syphilis (defined as within two years after infection) includes three stages:
  • Primary syphilis — characterized by a painless ulcer (chancre) at the site of infection (most commonly the genital area) and local lymphadenopathy.
  • Secondary syphilis — multisystem involvement due to bacteriaemia, which can present with a wide range of clinical features including:
    • Skin and hair changes such as a maculopapular rash, condylomata lata (moist wart-like lesions), and patchy alopecia.
    • Oral lesions (snail tract lesions).
    • Generalized lymphadenopathy.
    • Low-grade fever, headache, and malaise.
  • Early latent syphilis — confirmed infection in the absence of any current clinical features.
• Late syphilis (defined as more than two years after infection) includes two stages:
  • Late latent syphilis — confirmed infection in the absence of any current clinical features.
  • Tertiary syphilis — occurs in approximately one-third of untreated people 20–40 years after initial infection. May present with cardiac disease (for example aortic aneurysm), cutaneous disease (for example gummatous lesions), and/or neurological disease (for example tabes dorsalis and general paresis).

[Janier, 2021; Peeling, 2023; BASHH, 2024]

What are the risk factors?

• Factors associated with increased risk of syphilis infection include:
  • Unprotected sex.
  • Male sex, especially men who have sex with men (MSM).
    • In MSM this includes risk compensation related to pre-exposure prophylaxis for HIV — associated with a higher incidence of unprotected sex.
  • Multiple or anonymous sexual partners.
  • Transactional sex (for example commercial sex work or exchange of sex for drugs).
  • Previous or current diagnosis of any sexually transmitted infection.
  • Social vulnerability such as poverty; homelessness; or migrant or refugee status.
  • Illicit drug use.
  • HIV infection.
  • Syphilis during pregnancy (risk for congenital syphilis)
• Transmission rates of syphilis through sexual contact (genital or extra-genital) range from 10–60%. The risk of transmission is highest in primary and secondary syphilis.

[Janier, 2021; BMJ Best Practice, 2023; Peeling, 2023; ECDC, 2025]

How common is it?

• Globally — the World Health Organisation (WHO) estimated that globally in 2022 [WHO, 2024a; WHO, 2024b]: 
  • In people aged 15–49 years of age:
    • There were 8 million new cases of syphilis — an incidence rate of 2 per 1000 females and 2 per 1000 males.
    • There were 24 million prevalent cases of syphilis — a prevalence of 0.6% in females and 0.6% in males.
  • There were 700,000 maternal syphilis cases, which resulted in 390,000 adverse pregnancy outcomes, including stillbirths, neonatal deaths, preterm births, and infected infants.
    • Congenital syphilis is the second leading cause of preventable stillbirth globally, preceded only by malaria.
• UK — the prevalence of syphilis in the UK has continued to increase in recent years [UKHSA, 2024].
  • Between 2013 and 2019, infectious syphilis diagnosis increased by 140% (3345 to 8040 cases). Cases declined in 2020/2021 due to COVID-19 related disruption in diagnosis but rose to 8693 cases in 2022.
  • In 2023, 12,588 new diagnoses of syphilis were made: 9513 diagnoses of infectious syphilis, and 3075 diagnoses of 'other acquired syphilis', including neurosyphilis, cardiovascular syphilis, and other late or latent syphilis (asymptomatic and non-infectious, but requiring treatment).
    • The number of diagnoses of infectious syphilis was highest among gay, bisexual, and other men who have sex with men (GBMSM) (76%), an increase of 173% between 2013 and 2023.
      • Rates of syphilis diagnoses are higher in GBMSM living with HIV, but the proportion of infectious syphilis diagnoses among GBMSM living with HIV decreased from 39% (924 of 2,390) to 26% (1,670 of 6,527) between 2013 and 2023.
      • Most new diagnoses (53%) among GBMSM occurred in London. Outside of London, diagnoses occurred in the South East, and urban areas of the Midlands and the North of England.
    • The number of diagnoses of infectious syphilis among heterosexuals also rose between 2013 and 2023, with an increase of 203% in women who have sex with men and 126% in men who have sex with women.
    • Diagnoses of infectious syphilis continued to occur disproportionately in socioeconomically deprived areas, with approximately 40% of diagnoses among heterosexual individuals were in those living in the most socioeconomically deprived quintile areas.
      • 61% of diagnoses made in GBMSM were in those living in the two most deprived quintiles.
  • The rate of women who screened positive for syphilis during antenatal care increased by 18% from 1.39 per 1,000 women tested in the screening year 2017 to 2018, to 1.64 per 1000 women tested in the screening year 2021 to 2022.

What is the prognosis?

• Syphilis can be cured if treated with appropriate antibiotics before complications develop.
• If left untreated after the appearance of the initial chancre:
  • 25% of people will develop signs of secondary syphilis within 3–10 weeks.
  • Around one-third of cases will progress to later stages of disease after 20–40 years, which can result in severe, sometimes irreversible, cardiovascular, neurological, and ocular complications. 
• Treatment in late syphilis aims to prevent progression of the disease, but some Treponema spirochetes can persist.
  • Cardiovascular and neurological lesions which develop as a result of syphilis may continue to progress despite treatment.
  • Gummatous lesions resolve rapidly with appropriate syphilis treatment.
• Co-infection with HIV may increase the likelihood of reinfection with syphilis and the likelihood and severity of ocular and neurosyphilis in late syphilis.

[BMJ Best Practice, 2023; Peeling, 2023; BASHH, 2024]

What are the complications?

Untreated syphilis infection can result in serious complications, including:

• Neurosyphilis — neurological involvement can occur at any stage of syphilis infection and affect the meninges, cerebral arteries, cranial nerves, eyes, brain, and spinal cord parenchyma.
  • Early neurosyphilis usually involves the meninges and blood vessels and can result in:
    • Meningitis, cranial nerve defects, and infarction.
    • Auditory or ocular abnormalities such as hearing loss, uveitis, optic neuropathy, interstitial keratitis, and retinal problems — permanent visual loss may occur.
  • Late neurosyphilis usually involves the brain and spinal cord and includes:
    • General paresis — cortical neuronal loss with a gradual decline in memory and cognitive function; hemiparesis and seizures may also occur.
    • Tabes dorsalis — progressive degeneration and inflammation of the spinal dorsal column/dorsal spinal nerve roots leading to ataxia, lancinating pain, paraesthesiae, Charcot’s spine and joints, and pupillary irregularities (Argyll-Robertson pupil).
  • Cardiovascular syphilis — chronic syphilis infection can lead to aortic aneurysm, aortic regurgitation, angina, and heart failure.
  • Gummatous syphilis (granulomatous lesions with a necrotic centre) — can occur anywhere but most often affect the skin and bones.
• Psychological and social complications
  • Sexually transmitted infections (STIs) have been associated with stigma, shame, loss of self-worth, relationship disruption, and domestic violence.
• Syphilis infection in pregnancy
  • Untreated syphilis infection in pregnancy is associated with multiple adverse outcomes including hydrops foetalis, preterm labour, low birth weight, foetal loss, and congenital syphilis in the newborn.
• HIV infection
  • Untreated syphilis infection can facilitate HIV transmission.

[Clement, 2014; Nyatsanza, 2016; WHO, 2016; O’Byrne, 2019; PHE, 2019; Janier, 2021; BMJ Best Practice, 2023; Peeling, 2023; ECDC, 2025]

When should I suspect syphilis?

• Syphilis can present with a wide range of nonspecific symptoms — in some people infection may be asymptomatic. As a result, diagnosis can be delayed or missed.
• Suspect syphilis if there is a history or presence of any of the following, especially if there are any risk factors: 
  • Genital lesion(s) — the characteristic feature of primary syphilis is a solitary, painless, indurated, ano-genital (penile, labial, cervical, or perianal) ulcer (chancre) with a clean base and sharp border, which discharges clear serum.
    • Lesions may present atypically and be painful, multiple, purulent, or extra-genital (most frequently oral).
    • Associated regional lymphadenopathy is common.
  • A widespread mucocutaneous rash — May be maculopapular, papular, macular, and occasionally ulceronodular. Rash typically involves the palms of the hands and soles of the feet.
  • Moist wart-like lesions (condylomata lata) — usually develop at moist areas, most commonly the perineum and anus.
  • Patchy lesions on the oral mucosa (‘snail tract’ lesions).
  • Generalized lymphadenopathy.
  • Unexplained neurological or ophthalmological symptoms.
• The presence of:
  • Chancre may indicate primary syphilis — for more information, see the section on primary syphilis. 
  • A mucocutaneous rash, condylomata lata, oral lesions, generalized lymphadenopathy, unexplained neurological or ophthalmological symptoms may indicate secondary syphilis — for more information, see the section on secondary syphilis. 
• Tertiary syphilis rarely presents in primary care — this may be partly due to widespread use of treponemicidal antibiotics for other infections.
  • Clinical features of tertiary syphilis are varied, non-specific and can include cardiovascular, neurological, ocular and cutaneous symptoms and signs — for more information see the section on Tertiary syphilis. 

How should I assess a person with suspected syphilis?

Take a history and ask about:

• Symptoms of syphilis.
• Risk factors.
• A full sexual history
  • Primary syphilis – to include all sexual partners in the last 3 months.
  • Secondary and early latent syphilis – to include all partners in the last 2 years.
  • Late syphilis – according to history and previous treponemal serology, lifetime partners and possibly children.
• Past medical history including previously diagnosed sexually transmitted infections and treatment, including previous syphilis testing with consideration of the screening tests used at the time.
• Potential of previous non-venereal T. pallidum infection (such as childhood skin infections and previous residency in an endemic country).
• If appropriate, a full obstetric history including adverse pregnancy outcomes, which may relate to syphilis infection, and identification of live births and children who may have late congenital disease.

Examine the person

• In early disease, examination may include: 
  • Genital examination — looking for chancre.
  • Skin examination including mouth, scalp, palms and soles — looking for skin lesions such as maculopapular rash, mucous patches or condylomata lata. 
  • Neurological examination — looking for neurological signs (including meningitis, stroke and cranial nerve lesions).
  • Eye examination — looking for signs of ocular disease.
• In symptomatic late disease, examination may include:
  • Skin examination — looking for signs such as gumma. 
  • Cardiovascular system — looking for signs of cardiovascular disease including aortic regurgitation.
  • Nervous system — looking for signs of tabes dorsalis or general paresis. 
  • Eye examination — looking for signs of ocular disease. 

Refer for investigations

• Refer to a genito-urinary medicine (GUM) specialist for laboratory investigations (such as dark-field microscopy and serology) and a full sexual health screen (including HIV testing).
  • For more information on specialist investigations for the diagnosis of syphilis see the Section on Laboratory diagnosis. 

What else might it be?

Many conditions can present with features similar to those associated with the different stages of syphilis:

• Primary syphilis
  • Chancre — the differential diagnosis for ulceration affecting the:
    • Genital area includes genital herpes, balanitis, secondary infected traumatic lesions, lymphogranuloma venereum (Chlamydia trachomatis), Behçet’s syndrome (especially in the presence of mouth ulcers), genital cancer, chancroid (Haemophilus ducreyi), and granuloma inguinale.
    • Peri-anal area includes herpes simplex infection, anal fissure, Crohn's disease, and anal cancer.
    • Cervix includes cervical herpes, cervical erosions, and cervical cancer.
    • Oral mucosa includes herpes simplex infection, aphthous stomatitis, Behçet’s syndrome (especially in the presence of genital ulcers), secondary infected traumatic lesions, pemphigus, pemphigoid, drug reactions, and oral cancer.
  • Regional lymphadenopathy:
    • The differential diagnosis of regional and generalized lymphadenopathy is broad and can include infectious causes, systemic diseases, and malignancy.
    • Lymphadenopathy in syphilis is typically non-tender.

• Secondary syphilis
  • Maculopapular rash — the differential diagnosis includes:
    • Other infections such as primary HIV infection, rubella, scabies, or measles.
    • Dermatological conditions such as guttate psoriasis, pityriasis rosea, and eczema.
    • Drug eruptions.
  • Condylomata lata — the differential diagnosis includes:
    • Human papillomavirus, molluscum contagiosum, or haemorrhoids (in the anal area).
  • Patchy alopecia — the differential diagnosis includes:
    • Conditions such as alopecia areata, scarring alopecia, and tinea capitis.
  • Patchy lesions on the oral mucosa ('snail tract lesions'):
    • The differential diagnosis includes conditions such as oral cancer or aphthous ulcers.
    • If ulcers are present on the tonsils it can be difficult to differentiate from infectious mononucleosis, especially in the presence of a rash precipitated by administration of ampicillin or amoxicillin.
  • Regional or generalized lymphadenopathy:
    • The differential diagnosis of regional and generalized lymphadenopathy is broad and can include infectious causes, systemic diseases, and malignancy.
    • Lymphadenopathy in syphilis is typically non-tender.
• Tertiary syphilis
  • Symptoms associated with tertiary syphilis are highly variable and non-specific.
  • The differential diagnosis is broad and includes dementia, psychiatric conditions, diseases that affect mobility, and chronic granulomatous lesions of tuberculosis, sarcoidosis, or leprosy.

Scenario: Management of suspected syphilis

From age 16 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of syphilis.

Search dates

November 2019 - January 2025

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 11th December 2019). These were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S6    S1 OR S2 OR S3 OR S4 OR S5 
S5    AB treponema pallidum OR TI treponema pallidum 
S4    (MH "Treponema pallidum") 
S3    AB chancre OR TI chancre 
S2    AB syphilis OR TI syphilis 
S1    (MH "Syphilis+") 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.