Syphilis is a sexually transmitted disease caused by the spirochaetal bacterium Treponema pallidum which enters the body through a break in the skin or mucous membranes following contact with an individual with early (primary or secondary) syphilis. Congenital infection may occur through maternal transmission during pregnancy.

Historically, syphilis has been a highly stigmatised disease, due to its association and proliferative spread through prostitution. Untreated syphilis can cause considerable morbidity such as cardiovascular and neurological disease.

Nowadays, the majority of patients present with a painless anogenital ulcer and are treated appropriately without progression from primary to secondary syphilis.


  • Incidence: 10.00 cases per 100,000 person-years
  • Peak incidence: 30-40 years
  • Sex ratio: more common in males 8:1
Condition Relative
Genital herpes30.00
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+


Syphilis is caused by sexual transmission of the spirochetal bacterium Treponema pallidum via areas of minor abrasion at genital skin or mucous membrane site. Humans are the only natural host of this bacterium.

  • The risk of transmission after sexual contact with someone with primary or secondary syphilis is between 30-60%.
  • Other forms of transmission may occur through:
    • Blood transfusion or sharing needles
    • Transplacental transmission from mother to foetus resulting in congenital syphilis syndrome.

Risk factors for transmission include:
  • Men who have sex with men (MSM)
  • HIV infection
    • Approximately 42% of MSM with primary and secondary syphilis are HIV infected compared to 8% of men who have sex with women and 4% of women
    • 1 in 20 MSM were diagnosed with HIV infection within 1 year of HIV coinfection
  • IV drug use


Treponema pallidum initiates infection via microscopic abrasions allowing access to subcutaneous tissues.
  • Evasion of early host defences allows the bacterium to establish the initial ulcerative lesion that characterises primary syphilis, the chancre
    • The primary ulcer contains the Treponema pallidum bacterium
    • Initial infiltration of the lesion is with polymorphonuclear leukocyte
    • Infiltration appears to coincide with the resolution of the primary chancre which occurs over 3-6 weeks

Secondary syphilis is caused by the haematogenous spread of the bacterium resulting in endarteritis obliterans.
  • Immune complexes of antibodies, spirochetal components and complement are present in arterial walls
  • Mucocutaneous lesions in secondary syphilis also contain treponemes
  • Resolution is likely due to macrophage driven and cell-mediated immunity.

Approximately 15-40% of patients with untreated secondary syphilis progress to late syphilis involving
  • Neurosyphilis
    • Chronic inflammation of the meninges due to the presence of treponemes
    • Parenchymal involvement of the spinal cord results in tabes dorsalis, predominantly due to dorsal column loss
    • Parenchymal involvement with neuronal loss will result in general paresis.
  • Gummatous syphilis
    • Characterised pathologically by the presence of granulomas, consistent with a cellular hypersensitivity reaction
  • Cardiovascular syphilis
    • A consequence of vasculitis of the vasa vasorum
    • Lymphocytes and plasma cells infiltrate blood vessels and perivascular tissues
    • Occlusion of the aortic vasa vasorum causes necrosis of the tunica media and weakening of the aortic wall leading to aortic aneurysms.
    • Narrowing of the coronary ostia typically results in aortic regurgitation.

Clinical features

Early syphilis is defined as the first 2 years after infection and includes 3 stages:

(1) Primary syphilis is how the majority of patients will present
  • It is characterised by:
    • A painless chancre, which is a highly infectious, hard anogenital ulcer
    • Local lymphadenopathy
  • The chancre forms at the site of entry of bacterium and develops about 3 weeks post exposure
  • The chancre may be hidden within the vagina or rectum
  • The chancre heals within approximately 3 to 6 weeks

(2) Secondary syphilis (6 weeks - 6 months post infection) is systemic involvement and might present with a wide range of clinical features:
  • Symmetrical maculopapular rash , typically on the trunk, face, palms or soles
    • 90% have some skin involvement
    • Might be scaly
  • Constitutional symptoms including fever, malaise, myalgia, fatigue, and arthralgia (25%)
  • Lymphadenopathy
  • Tonsillitis
  • Condylomata lata (flat papules around/ beyond the genitals)
  • Oral snail-track ulcers
  • Alopecia
  • Hepatitis (33%)
  • Hepatosplenomegaly
  • Rhinitis
  • Uveitis
  • Optic neuritis
  • Meningism (1-2%)
  • Glomerulonephritis
  • Periosteitis

(3) Early latent syphilis is confirmed infection in the absence of any current clinical features.

If left untreated, early syphilis might progress to tertiary or late syphilis (defined as more than 2 years after infection).
  • This is described further within the complications section, as only 15-30% of untreated patients will go on to develop the complications of tertiary syphilis.
  • In the late stage, the disease may damage the brain, nerves, eyes, heart, blood vessels, liver, bones, and joints
  • These problems may occur many years after the original, untreated infection.


A diagnosis of syphilis should be suspected in any patient presenting with any anogenital ulcer or sore.

In early disease, where the majority of patients present, examination should include:
  • Genital examination: looking for a chancre
  • Skin examination including mouth, palms and soles
  • Neurological examination: looking for signs of neurological disease
    • In particularly: signs of meningitis, stroke and cranial nerve lesions
  • Eye examination: looking for signs of ocular disease

Referral to genito-urinary medicine (GUM) specialist for laboratory investigations (such as dark-field microscopy and serology) and a full sexual health screen (including HIV testing) should be performed.

Diagnosis in the specialist setting is dependent on:
  • Positive serological treponeme specific antibody testing (which will remain positive for life)
  • Positive non-treponeme specific antibody testing (to confirm active infection).

Any suspected neurological involvement should be investigated with a lumbar puncture and cerebrospinal fluid analysis.

After confirmation of infection, contact tracing is required to prevent ongoing transmission of the infection and screening for other sexually transmitted infections should be undertaken.

Differential diagnosis

Syphilis is often referred to as the 'great imitator' due to its ability to mimic many other diseases, particularly those that present with anogenital ulcers or sores. Due to this, any anogenital sore or ulcer should be suspected syphilis until proven otherwise.

The two main differentials are:
  • Chancroid : most common cause of genital ulcers worldwide
    • Similarities: initially painless papule
    • Differences: recent travel to subtropical or tropical areas, develops into a tender and painful ragged deep ulcer or pustule after several weeks, accompanied by inguinal lymphadenopathy that may suppurate
  • Genital herpes
    • Similarities: anogenital sore or blister, localised lymphadenopathy
    • Differences: typically painful, one or more sore(s) around genitals and mouth, lymphadenopathy is usually tender,
    • Herpes and syphilis are notoriously difficult to distinguish and a herpes virus PCR should be performed

Other differentials that should be considered include:
  • Primary HIV infection
    • Similarities: maculopapular rash, may present with a genital ulcer
  • Psoriasis
    • Similarities: maculopapular rash
  • Alopecia areata
    • Similarities: alopecia
  • Oral cancer
    • Similarities: snail tract lesions
  • More unusual causes of genital ulcers: lymphogranuloma venereum, granuloma inguinale, candidiasis, trauma, Reiter’s syndrome, Behçet’s syndrome, fixed-drug eruption, and scabies


  • Early syphilis occurs before 2 years of infection
    • Primary syphilis is characterised by generalised lymphadenopathy and a chancre
    • Secondary syphilis occur 3-12 weeks after appearance of the initial chancre and is characterised by systemic features, skin lesions, alopecia, and mucous patches
    • Early latent syphilis is serological confirmation of infection in the absence of clinical features

  • Tertiary or late syphilis occurs after 2 years of infection (typically 15-40 years)
    • Tertiary syphilis may present with gummatous syphilis, cardiovascular syphilis or neurosyphilis
    • Tertiary latent syphilis is serological confirmation of infection in the absence of clinical features


NICE guidelines recommend all patients with suspected syphilis should be referred to a genito-urinary medicine (GUM) clinic or other specialist local sexual health service.
  • Currently recommended first-line treatments for syphilis (including parenteral benzathine and procaine penicillin) are not readily available for use in primary care.

(1) Explanation of the condition, risk factors, methods of prevention and complications should be provided for the patient

(2) Avoidance of all sexual contact until either
  • Diagnosis is excluded OR
  • Successful treatment has been confirmed
(3) Contact tracing and partner notification should be discussed at diagnosis

(4) Consideration of testing for HIV infection in addition to full sexual health screen
  • Co-infection leads to higher risk of treatment failure
If diagnosis is confirmed:
(5) Benzathine benzylpenicillin 1.8g IM 2-3 doses, 1 week apart
  • Alternative: Doxycycline 100mg/12h
    • 14 days for early syphilis
    • 28 days for late syphilis
  • In pregnancy: Erythromycin 500mg/6h PO
(6) Follow up at 3, 6, and 12 months in specialist GUM clinic


Around 30% of patients who are untreated or have the failure of treatment of primary or secondary syphilis progress to late tertiary symptomatic syphilis.

Late syphilis typically follow at least a 2 year latency period, where patients are non infectious. Patients may present with
  • Gummas (16% of untreated patients): granulomas in skin, mucosa, bone, joints, and viscera such as the lung and testis
    • These granulomatous rubbery lesions have a necrotic centre and may gradually replace normal tissue.
  • Cardiovascular disease (10% of untreated patients): ascending aortic aneurysm or aortic regurgitation
  • Neurosyphilis (6% of untreated patients): might present in three separate ways
    • Meningovascular : cranial nerve palsies e.g. decreased vision, stroke
    • General paresis of insane : dementia, psychosis
    • Tabes dorsalis : loss of proprioception, vibration sense, incontinence and ataxia

Screening and prevention

Any anogenital ulcer or sore should be investigated as suspected syphilis until proven otherwise.

Preventative measures include:
  • Increased use of condoms
  • Avoidance of drugs and alcohol when having sex
  • Risk reduction counselling and regular syphilis screening for people at high risk
    • Available through GUM
  • Early recognition of clinical features of syphilis, prompt treatment and prophylactic treatment of exposed contacts

All pregnant females are screened for syphilis as part of routine antenatal care.