Syphilis

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Venereal syphilis is a contagious, systemic disease caused by Treponema pallidum. T. pallidum enters via abraded skin or intact mucous membrane and distributes via the bloodstream and lymphatics after an incubation period of around 3 weeks.

  • Early syphilis causes significant morbidity and is an important facilitator of HIV transmission.
  • All patients diagnosed with syphilis must be tested for HIV and those having follow-up for HIV must have regular screening for syphilis.
  • Congenital syphilis is a major cause of stillbirth, childhood morbidity, and mortality worldwide.[1] 
  • Syphilis is classified as acquired or congenital.

Acquired syphilis[2] 

  • Primary syphilis: incubation period 2-3 weeks (range 9-90 days): local infection.
  • Secondary syphilis: incubation period 6-12 weeks (range 1-6 months): generalised infection.
  • Early latent syphilis: asymptomatic syphilis of less than 2 years' duration.
  • Late latent syphilis: asymptomatic syphilis of 2 years' duration or longer.
  • Late symptomatic syphilis (tertiary syphilis): cardiovascular syphilis, neurosyphilis, gummatous syphilis.

Congenital syphilis

  • Early congenital syphilis occurs within the first 2 years of life.
  • Late congenital syphilis emerges in children older than 2 years.

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    • In 2012, there were 2,978 cases of infectious syphilis diagnosed in genitourinary medicine (GUM) clinics in England (an increase of 1% over the previous year). 79% of male attendees were men who had sex with men.[3]
    • In the years between 2003 to 2012 diagnoses of infectious syphilis (primary, secondary and early latent) made at GUM clinics in England increased by 61% in men but decreased in women by 16%.[4]
    • The total number of diagnoses is the highest since the mid-1950s. The typical patient is a white man who has sex with men and is co-infected with HIV. There is a separate subgroup of often socially vulnerable heterosexuals under the age of 19. Other factors driving the current epidemic are the use of recreational drugs associated with an increase in high-risk sexual practices and the influx of infected individuals from eastern Europe.[4]
    • The tertiary stage is now rarely seen in the UK, possibly because those affected many years ago have received antibiotics for other infections in the intervening time.

Primary syphilis

  • The primary lesion develops at the site of infection, which heals in 2-6 weeks.
  • The small, painless papule rapidly forms an ulcer (the chancre). The chancre is usually single, round or oval, painless, surrounded by a bright red margin, indurated with a clean base, and discharging clear serum.
  • Chancres may be atypical - eg, multiple, painful, purulent, destructive and may be extragenital.
  • They are usually found in heterosexual men on the coronary sulcus, the glans and inner surface of the prepuce but may appear on the shaft and beyond. In homosexual men, they are usually found in the anal canal and, less frequently, in the mouth and genitalia. In women, they are found on the vulva, labia and, much less frequently, on the cervix.
  • Extragenital sites are the lips, mouth, buttocks and fingers.
  • There are enlarged regional lymph nodes that are painless, discrete, firm and not fixed to surrounding tissues.

Secondary syphilis

  • Secondary syphilis often appears 6 weeks after the beginning of the primary lesion but may overlap or not appear for several months.
  • Multisystem involvement occurs within the first 2 years of infection.
  • Systemic symptoms are mild or absent, but include nighttime headaches, malaise, slight fever and aches.
  • A generalised polymorphic rash often affects the palms, soles and face. The rash is classically non-itchy; however, it may be itchy, especially in dark-skinned patients. It is associated with generalised painless lymphadenopathy.
  • Papules enlarge into condylomata lata (pink or grey discs) in moist warm areas. Papule lesions disappear spontaneously.
  • There may also be mucocutaneous lesions.
  • Less common presentations include patchy alopecia, anterior uveitis, meningitis, cranial nerve palsies, hepatitis, splenomegaly, periostitis and glomerulonephritis.
  • In 80% of cases, patients enter the latent asymptomatic stage which for over half of them persists for life. In about 20% of patients, an infectious relapse occurs during the next year.

Early latent syphilis

  • Characterised by positive serological tests for syphilis with no clinical evidence of treponemal infection within the first two years of infection.

Late latent syphilis

  • Infection of more than two years' duration diagnosed on serological testing with no symptoms or signs of late manifestations of syphilis.
  • Studies of cohorts of untreated patients suggest that symptomatic late syphilis is found in up to 40% of individuals with late T. pallidum infection.

Tertiary syphilis

This consists of three major clinical manifestations, which may coexist:

  • Neurological syphilis:
    • Asymptomatic neurosyphilis: late syphilis with abnormal cerebrospinal fluid (CSF) examination but with no associated neurological symptoms or signs.
    • Symptomatic neurosyphilis: the most common presentations are dorsal column loss (tabes dorsalis), dementia (general paralysis of the insane) and meningovascular involvement.
  • Cardiovascular syphilis:
    • Characterised by an aortitis, which usually involves the aortic root but may affect other parts of the aorta, usually spreading distally from the aortic root.
    • The most frequent clinical manifestations are aortic regurgitation, aortic aneurysm and angina.
  • Gummata:
    • Inflammatory fibrous nodules or plaques, which may be locally destructive.
    • Can occur in any organ but most commonly affect bone and skin.

Primary syphilis

Differentials of chancre include:

  • Herpetic ulcers (especially chronic mucocutaneous anogenital herpes occurring with HIV infection).
  • Chancroid.
  • Lymphogranuloma venereum.
  • Donovanosis.

Secondary syphilis

Differentials of the rash include:

Tertiary syphilis

As the presentation is variable so the differential diagnoses are extensive but syphilis should be considered in anyone presenting with cardiac or neurological signs or symptoms. The history and examination should help guide the likelihood of tertiary syphilis as a cause.

Investigations must include a screen for all sexually transmitted infections as well as investigation for other possible diagnoses. All patients with neurological signs or symptoms and those who fail treatment should have a lumbar puncture. Likewise, neurological imaging may be appropriate. Similarly, cardiac investigations may also be indicated - eg, ECG and echocardiogram.

Specific treponemal tests include[5]

  • Treponemal enzyme immunoassay (EIA) - can be for immunoglobulin M (IgM) for early infection or immunoglobulin G (IgG) (the latter becomes positive at 5 weeks) or both. Check both for screening.
  • T. pallidum chemiluminescent assay.
  • T. pallidum haemagglutination assay (TPHA).
  • T. pallidum particle agglutination assay (TPPA).
  • Fluorescent treponemal antibody absorbed test (FTA-abs).
  • T. pallidum recombinant antigen line immunoassay.

All the above tests can be used for screening but the recommendations are to request EIA IgM for primary syphilis.[5] All of these will also be positive in secondary and early latent syphilis. They will also be unable to differentiate between other treponemal diseases - eg, yaws. All positive tests should then be confirmed by using a different test.[5]

Cardiolipin or non-treponemal tests[5]

  • Venereal disease reference laboratory (VDRL) or rapid plasmin reagin (RPR) - quantitative VDRL can be used as an indication of the stage of syphilis and is also used for monitoring treatment.[6] 
  • Provides a titre, thus an indication of disease activity.
  • Perform VDRL/RPR when treponemal tests are positive.
  • False negatives may occur in secondary or early latent syphilis - thus, there may be a need to repeat.

Demonstration of T. pallidum

  • From lesions or infected lymph nodes in early syphilis.
  • Dark field microscopy.
  • Direct fluorescent antibody (DFA) test.
  • PCR.
  • Treatment should be within a sexual health clinic, with enquiries about sexual contacts.
  • Patients who acquire syphilis are at significant risk of re-infection, and should therefore be regularly screened for syphilis and given sexual health promotion. All patients should be offered screening for other sexually transmitted infections, including HIV.

Drugs

Recommended regimes for adults:[2]

  • Primary, secondary, early latent syphilis: benzathine penicillin 2.4 mega units (intramuscular (IM), single dose) is first-line and oral azithromycin single dose is second-line.[5] Azithromycin has been shown to be as effective as benzathine penicillin in treating early syphilis.[7] Alternatives that have been used include procaine penicillin 600,000 units (IM, once daily for 10 days) or doxycycline 100 mg (twice daily for 14 days).
  • Late latent syphilis: benzathine penicillin weekly for three weeks is first-line; the exception being neurosyphilis where procaine penicillin with oral probenecid remains first-line.
  • Neurosyphilis: procaine penicillin 2.4 units once daily (IM, for 17 days) with oral probenecid 500 mg four times a day. Alternatively, doxycycline 200 mg twice daily for 28 days.
  • Pregnancy:
    • Treatment depends upon which trimester the presentation is in: first and second trimesters: give single dose benzathine penicillin; third trimester two doses of benzathine penicillin one week apart. For late syphilis treat as for non-pregnancy (avoiding tetracyclines). Alternatives include ceftriaxone 500 mg IM for 10 days.[5]

Jarisch-Herxheimer reaction

  • This is a reaction to treatment.[5]
  • It is an acute febrile illness with headache, myalgia, chills and rigors and resolves within 24 hours.
  • It is common in early syphilis but is usually not important unless there is neurological or ophthalmic involvement or in pregnancy when it may cause fetal distress and premature labour.
  • It is uncommon in late syphilis but may be life-threatening.
  • In non-pregnant women, treatment is with prednisolone and antipyretics. In pregnant women, there is no evidence that treatment with steroids will reduce complications.[8] 
  • Treatment of asymptomatic contacts.
  • Use of condoms.
  • All pregnant women in the UK are offered syphilis screening.[9] 
  • In pregnant women with untreated early syphilis, 70-100% of infants will be infected, with stillbirths in up to one third of cases.[5]
  • Diagnosis:
    • Early (first two years): rash including condylomata lata, vesiculobullous lesions, snuffles, haemorrhagic rhinitis, osteochondritis, periostitis, pseudoparalysis, mucous patches, perioral fissures, hepatosplenomegaly, generalised lymphadenopathy, glomerulonephritis, neurological or ocular involvement, haemolysis, thrombocytopenia.
    • Late, including stigmata: interstitial keratitis, Clutton's joints (arthritis of the knees), Hutchinson's incisors, mulberry molars, high palatal arch, rhagades, deafness, frontal bossing, short maxilla, protuberance of mandible, saddle nose deformity, sternoclavicular thickening, paroxysmal cold haemoglobinuria, neurological or gummatous involvement.
  • Investigations:
    • Serological tests that detect IgG may be positive due to passive transfer of maternal antibodies.[10] 
    • A positive anti-treponemal EIA IgM is indicative of congenital infection.
    • Serological tests may be negative in infants infected in late pregnancy and should be repeated.
  • Treatment:
    • Refer all pregnant women with syphilis to fetal medicine specialists.[5]
    • Intravenous benzylpenicillin for the first ten days of life.
    • Older siblings should be screened for congenital syphilis.
    • Congenital syphilis diagnosed in an older child or in adulthood should be managed as for late syphilis.
    • Parents, all siblings and any sexual partner should be screened for syphilis.

Further reading & references

  • Sexually Transmitted Infections in Primary Care; Royal College of General Practitioners and British Association for Sexual Health and HIV (Apr 2013)
  • Jinno S, Anker B, Kaur P, et al; Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging Era of universal antiretroviral therapy use. BMC Infect Dis. 2013 Dec 26;13:605. doi: 10.1186/1471-2334-13-605.
  • Rathod S, Shah B; Early prenatal syphilis. Indian Dermatol Online J. 2010 Jul;1(1):39-41. doi: 10.4103/2229-5178.73259.
  1. Blencowe H, Cousens S, Kamb M, et al; Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality. BMC Public Health. 2011 Apr 13;11 Suppl 3:S9. doi: 10.1186/1471-2458-11-S3-S9.
  2. French P; Syphilis. BMJ. 2007 Jan 20;334(7585):143-7.
  3. Health Protection Report, Public Health England, Volume 7 Number 23 Published on: 7 June 2013
  4. Recent epidemiology of infectious syphilis and congenital syphilis; Health Protection Agency, 2013
  5. Management of syphilis; British Association for Sexual Health and HIV (2008)
  6. Ratnam S; The laboratory diagnosis of syphilis. Can J Infect Dis Med Microbiol. 2005 Jan;16(1):45-51.
  7. Hook EW 3rd, Behets F, Van Damme K, et al; A phase III equivalence trial of azithromycin versus benzathine penicillin for J Infect Dis. 2010 Jun 1;201(11):1729-35.
  8. Update on management of syphilis in pregnancy CEG Statement; British Association for Sexual Health and HIV (BASHH), August 2011
  9. The UK NSC policy on Syphilis screening in pregnancy; UK National Screening Committee, 2013
  10. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children: Syphilis; Cliinical Guidelines Portal, 2013

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Colin Tidy
Current Version:
Peer Reviewer:
Dr Adrian Bonsall
Document ID:
2829 (v24)
Last Checked:
23/01/2014
Next Review:
22/01/2019