Syphilis is a bacterial sexually transmitted infection caused by the spirochete Treponema pallidum. The past high incidence rate of syphilis declined dramatically following World War II, and the introduction of penicillin. During the 1990s, syphilis primarily occurred among heterosexual men and women of racial and ethnic minority groups; however, cases have recently increased among men who have sex with men and people with HIV/AIDS in major cities of the US, UK, Canada, Europe and Australia. In Australia in 2011, there were 1,233 new cases of syphilis which had been diagnosed within two years of contracting the infection.

Syphilis is transmitted from person to person by direct contact with a syphilitic skin sore (known as a chancre), which occurs mainly on the external genitals, vagina, anus, in the rectum, and sometimes on the lips and in the mouth. Syphilis has a widely variable course and clinical presentation that can mimic other conditions. Fortunately, the causative organism Treponema pallidum remains highly susceptible to antibiotics; therefore late manifestations are no longer commonly seen.

The incubation period for primary syphilis is two to three weeks after exposure. Primary chancre occurs at the site of inoculation. These lesions are painless, indurated, and are 1-2cm in diameter. They may become painful, there may be multiple chancres, and they may be secondarily infected. The lesions may exude serous fluid, but not blood. Regional lymph nodes usually become enlarged; they may feel rubbery and are generally painless. The lesions heal spontaneously in three to six weeks, leaving a scar. Primary syphilis may be mistakenly diagnosed as herpes or anal fistula (if in the anal region).

Secondary syphilis occurs when the infection becomes systemic, usually within six to twelve weeks after the primary chancre appears. Secondary syphilitic lesions are variable in their manifestations however they are most commonly macular, discrete, reddish brown, less than 5mm in diameter, often scale and may coalesce to produce larger lesions. The rash is extensive and occurs symmetrically on the trunk and extremities, especially palms and soles. They are generally painless and not itchy.

Other skin findings include patchy alopecia and condylomata lata, which are highly contagious grey-white wart-like painless lesions that develop in warm moist areas such as the perineum and under the breasts. Systemic symptoms are common in the secondary stage: generalised lymphadenopathy, fever, headache, loss of appetite, nausea and fatigue.

Other manifestations are ocular lesions (e.g. anterior uveitis, optic neuritis, and retinitis), hepatomegaly, nephritis and asymptomatic meningitis. Immune reaction is at its peak and antibody titres are high, but the secondary stage is self-limiting and patients progress to the latent stages.

Early latent syphilis occurs when the features of secondary syphilis have resolved but patients remain seroactive. This stage lasts for two years after infection. Some patients experience recurrence of the infectious skin lesions of secondary syphilis during this period.

Late latent syphilis is latent syphilis of more than two years, or of indeterminate duration, in the absence of tertiary syphilis. About two-thirds of untreated latent syphilis patients remain asymptomatic, and the rest go on to develop tertiary syphilis.

There are three types of presentations for late or tertiary syphilis: gummatous or benign tertiary syphilis, neurosyphilis and cardiovascular syphilis. These conditions may occur between two and forty years after the primary stage, however they are now very rare due to the widespread use of antibiotics. Gummatous or benign tertiary syphilis usually develops within three to ten years of infection. Gummas are soft fibrous inflammatory nodules or plaques that may cause local destruction of tissue. They may affect any organ of the body; but most commonly the liver, bone, skin or spleen.

Early neurosyphilis is most often asymptomatic, but may present with meningitis, headache, and blurry vision. It occurs within the first year after initial infection and resolves, regardless of treatment.

Late neurosyphilis is considered as a tertiary manifestation of syphilis but the appearance of neuropsychiatric signs and symptoms can occur at any time after infection. Late neurosyphilis is then further subdivided into meningovascular (focal cerebral ischaemia and infarction leading to movement disorders), parenchymal (development of psychosis, dementia, irritability and hyperreflexia) and Tabes dorsalis (lightning-like pain in the legs, sensory ataxia and bowel or bladder dysfunction).

Cardiovascular syphilis occurs at least ten years after infection. It is most commonly manifested as aortic aneurysm, aortic regurgitation and angina.

Management

The management of syphilis has been simplified in recent years, however other sexually transmissible infections may also be present. Penicillin remains the preferred antibiotic for treating all stages of syphilis and during pregnancy. Benzathine penicillin, procaine penicillin and benzylpenicillin are narrow-spectrum penicillins and are all indicated for syphilis. The regimens are described in Table 1.

Table 1. Penicillin treatment for different stages of syphilis.

Penicillin Indication Doses Precautions
Benzathine penicillin Early (primary, secondary and latent) IM 1.8g (2.4 million units) as a single dose Deep IM injection only, in the upper outer quadrant of the buttock or mid-lateral aspect of the thigh. Avoid major nerves and blood vessels due to severe neurovascular damage.
Aspirate before injecting the dose. Give doses >900mg as two injections at separate sites.
Late latent (with/without neurosyphilis) IM 1.8g (2.4 million units) once a week for three doses
Procaine penicillin Early (primary, secondary and latent <2 years duration) IM 1.5g (1.5 million units) once daily for 10 days Deep IM injection only. Avoid major nerves and blood vessels. Give doses >1.5g as two injections at separate sites.
Late latent (absence of neurosyphilis) IM 1.5g (1.5 million units) once daily for 15 days
Benzylpenicillin Tertiary (including neurosyphilis) IV 1.8g (3 million units) every four hours for 15 days

Intramuscular (IM) benzathine and procaine penicillins are absorbed slowly into the circulation and hydrolysed to benzylpenicillin. These long-acting preparations are used because of the long division time of the organism (30-33 hours). Benzathine penicillin is preferred when treating syphilis as fewer doses are required.

Pregnant patients who are allergic to penicillin should be hospitalised and desensitised to penicillin. Other patients with a history of penicillin hypersensitivity may choose desensitisation (recommended) or a second-line option; the first alternative is oral doxycycline 100mg 12-hourly for 14 days (28 days for late latent syphilis).

Azithromycin 2g as a single oral dose is effective in primary, secondary or early latent syphilis but it should be used with caution due to the potential of resistance. Azithromycin should not be used to treat pregnant women or late latent syphilis. Ceftriaxone 1g IM or IV (intravenously) once daily for 10-14 days has been used successfully in treating early syphilis, and 2g IM or IV once a day for 14 days in late or tertiary syphilis. It should be noted that cross reactivity between penicillins and cephalosporins may be possible.

Jarisch-Herxheimer reaction (JHR) typically manifests as malaise, fever, headache, sweating, rigours, anxiety or a temporary exacerbation of the syphilitic lesions. It happens most frequently in the early stages of syphilis, especially the secondary stage, within 6-12 hours after treatment. It is an immunological response to the release of inflammatory molecules by the ruptured spirochetes. Corticosteroid is given with antibiotic treatment in pregnant women and in cases with neurological or cardiovascular involvement (i.e. 20mg prednisone or prednisolone every 12 hours for three doses) to reduce the likelihood of JHR.

All sexual partners should be evaluated and treated if infected. The look-back periods to trace and notify contacts for various stages of syphilis are:

  • Primary syphilis: three months prior to onset of symptoms
  • Secondary and early latent syphilis: two years
  • Late latent, tertiary, neuro and cardiovascular syphilis: lifelong

Casual contacts may be difficult to trace, therefore health education and condom promotion is vital to reduce future risk of sexually transmitted infections.

References:

  1. Antibiotic Expert Group. Syphilis (Treponema pallidum). In: Therapeutic Guidelines: Antibiotic Version 14. Melbourne: Therapeutic Guidelines Limited; 2010.
  2. Centers for Disease Control and Prevention. Syphilis – CDC Fact Sheet. Atlanta, GA: U.S. Department of Health and Human Services; 2014.
  3. Euerle B. Syphilis Treatment and Management. New York: Medscape; 2012.
  4. McCutchan JA. Syphilis. In: Porter R et al. Merck manual of diagnosis and therapy<?i>. 19th ed. Whitehouse Station, N.J.: Merck Research Laboratories; 2010.
  5. Pink B. Sexually transmissible infections. In: Australian Social Trends. Cat. no. 4102.0 Canberra: Australian Bureau of Statistics; 2012.
  6. Penicillins. In: Australian Medicines Handbook 2014 (online). Adelaide: Australian Medicines Handbook Pty Ltd; 2014 July. Available from: http://www.amh.net.au.
  7. Sukthankar A. Syphilis. Medicine 2010. 38(5): 263–6.

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