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Syphilis diagnosis and management

The following tabs below provide information on the diagnosis and management of early syphilis and late syphilis.

For information on syphilis in pregnancy and HIV, see the following pages:

Further information

For further information on the diagnosis and management of syphilis contact Clinic 275.

Disclaimer

These guidelines are based on review of current literature, current recommendations of the United States Centers for Disease Control and Prevention, World Health Organization, the British Association for Sexual Health and HIV and local expert opinion.

They are written primarily for use by Clinic 275 staff and some flexibility is required in applying them to certain private practice situations.

Early syphilis

Last updated: June 2013

Diagnosis

Primary syphilis

The presence of a chancre plus confirmation using any of the following:

Microscopy

Definitive diagnosis involves demonstration of Treponema pallidum by dark field microscopy in primary chancres or lesions of secondary syphilis. There is no merit in performing this test on oral lesions because other treponemes microscopically indistinguishable from T. pallidum, occur in the mouth.

Nucleic Acid Amplification

Note: NAAT refers to Nucleic Acid Amplification Test, such as PCR

Direct detection of Treponema pallidum by PCR from a swab from the base of the lesion can be used for primary or secondary lesions.

Serologic

Serologic tests for syphilis are often positive during primary syphilis. The number of different treponemal and non treponemal serologic tests that are reactive and their strength of reactivity may depend on the duration of the primary chancre. Interpretation may be difficult and advice from an expert should be obtained.

Serologic tests for syphilis can take up to three months from infection to become reactive. Therefore, if initial investigation is negative and clinical suspicion is high, repeat serological tests no sooner than 1 month and no later than 3 months.

Negative serology at 3 months after exposure excludes syphilis.

Presumptive

A presumptive diagnosis can be made if a typical ulcer is associated with a consistent history of syphilis in sex partners and/or serologic pattern before or after treatment in the patient.

Secondary syphilis

Symptomatic patients

Typical lesions of secondary syphilis (rash, condylomata lata, alopecia) and a consistent serologic pattern before and/or after treatment, viz. a rising RPR titre before treatment (fourfold within 6 months) and a corresponding fall after treatment. In secondary syphilis the TPPA will be positive and the RPR will usually be 1:8 or greater.

Asymptomatic patients

An asymptomatic patient with a confirmed positive treponemal test (such as EIA, TPPA, TPHA or FTA-ABS) and one of the following:

  • negative serology within the previous 2 years
  • fourfold increase in RPR titre on subsequent testing
  • fourfold decline in RPR within twelve months after treatment.

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Treatment

Parenteral penicillin G is the preferred drug for treating all stages of syphilis. The dose and length of treatment depends on the stage and clinical manifestations of the disease.

Early syphilis (Primary, Secondary and Early Latent)

(Less than two years duration)

Benzathine penicillin G 1.8 g (2.4 million units) im as a single dose.

For patients who are allergic to penicillin, desensitisation to penicillin is the preferred management, especially in pregnancy. In patients allergic to penicillin who are not pregnant, in whom desensitisation is not feasible alternative treatments include Doxycycline 100 mg orally twice a day for 14 days OR Tetracycline HCl 500 mg orally four times a day for 14 days.

Health advice

Warn the patient about the possibility of a Jarisch-Herxheimer reaction and its management. The Jarisch-Herxheimer reaction is a short-lived self-limited reaction to treatment of treponemes during early syphilis, involving fevers and rigors, myalgias, headache and exacerbation of lesions of secondary syphilis, including the rash, occurring within several hours of the first injection. Management includes pre-emptive warning of the patient, antipyretics (for example, paracetamol 1 gm) and reassurance that the symptoms are self-resolving within 24 hours. In pregnancy a JHR may precipitate early labour or foetal distress but should not prevent or delay therapy. Patients over 20 weeks of pregnancy requiring treatment for early syphilis should be discussed with the attending Obstetrician prior to treatment.

Stress the importance of examining all contacts immediately. The patient should not have sex until treatment is completed (one week after the last injection), and sex partners have been examined (if possible).

It is undesirable for the patient (or a sex partner – as appropriate) to become pregnant until a good response to therapy has been demonstrated.

All patients are to be referred for contact tracing, and advised syphilis is a notifiable infection.

Follow up of early syphilis

A baseline RPR titre should be performed on the day of treatment.

Clinical assessment and sex partner review, +/- HIV testing, should be done at 4 weeks.

Clinical assessment and repeat syphilis serology (RPR) should be done at 1, 3, 6, and 12 months.

In very early syphilis, if the RPR is non-reactive on the day of treatment, one routine RPR follow up is required to confirm RPR remains non-reactive.

An RPR should be repeated at 1, 3, 6, and 12 months until serofast status is determined. A four fold drop is expected within 12 months from treatment of early syphilis.

A human immunodeficiency virus (HIV) test and clinical assessment should be done at 1 and 3 months.

Serofast status is defined as 2 identical RPR results three months apart with the assays performed in parallel.

The decision that follow up is complete is to be documented in the notes by a senior doctor.

Treatment failure or re-infection is likely if:

  • titres increase four fold
  • an initial titre above 1:32 fails to decline four fold within 12 to 24 months of therapy
  • signs or symptoms consistent with syphilis develop.

CSF examination should be considered and the patient retreated.

If a non-penicillin regimen was used, penicillin desensitisation and treatment with penicillin should be attempted.

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Late syphilis

Last updated: June 2013

Diagnosis

Late symptomatic syphilis is suggested when a positive treponemal test (RPR may be negative) occurs in association with typical neurologic or cardiovascular signs, or signs of late benign syphilis.

Late latent syphilis is characterised by a positive treponemal test (TPPA or FTA-ABS) and a negative or stable low titre RPR test. This same pattern may be due to adequately treated syphilis or a false positive treponemal test.

Neurosyphilis can occur at any stage of syphilis and is suggested by clinical presentation and positive serology. Asymptomatic neurosyphilis has also been documented.

CSF examination is indicated:

  • for patients with positive serology and signs of neurosyphilis
  • for patients who do not respond adequately or relapse after therapy, where reinfection has not occurred
  • for immunocompromised HIV positive patients who have syphilis.

The diagnosis is confirmed with a positive CSF VDRL. The disease is active if there are 5 or more mononuclear cells/mm3 and the CSF is not blood stained.

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Treatment

Parenteral penicillin G is the preferred drug for treating all stages of syphilis. The dose and length of treatment depends on the stage and clinical manifestations of the disease.

Late latent syphilis

A chest x-ray should be done and reviewed routinely prior to initiating treatment in late latent syphilis to exclude aortic abnormalities which may be exacerbated by treatment.

Thorough neurological and cardiovascular examination should be done prior to treatment. This should include but not be limited to gait, pupillary responses, cranial nerve examination, dorsal columns testing, reflexes, and signs of aortic valve incompetence including wide pulse pressure on BP, collapsing pulse, displaced apex and diastolic murmur.

RPR titre should be tested on the day of treatment.

Benzathine penicillin G 1.8 gm (2.4 million units) im weekly for 3 weeks

An interval of no more than 7 to 10 days between doses of penicillin is acceptable before restarting the entire sequence of injections. No late doses (doses given at more than seven days interval) are acceptable in pregnancy.

For non-pregnant patients allergic to penicillin, desensitisation to penicillin is the preferred management.

Alternative regimens include Doxycycline 100 mg orally twice a day for 28 days OR Tetracycline HCl 500 mg orally 4 times daily for 28 days.

Health advice

Late syphilis is essentially non-communicable and contact tracing is not indicated. The degree of certainty of the diagnosis, and uncertainty (but generally optimistic) of the prognosis should be discussed with the patient.

Follow-up late latent syphilis

If the RPR is non-reactive at treatment, one routine follow up serology is required at three months to confirm persisting non-reactivity.

Where initial RPR is reactive, repeat serology at 3, 6 and 12 months, until serofast status is determined.

The decision that follow up is complete is to be documented in the notes by a senior doctor.

If CSF has been examined and is abnormal, repeat at 6 monthly intervals until the cell count returns to normal.

A four-fold drop from pre-treatment RPR titre 12 to 24 months after treatment indicates cure of late latent syphilis.

Serofast status is defined as two identical RPR results 3 months apart with assays performed in parallel.

Treatment failure or re-infection is likely if:

  • titres increase four-fold
  • an initial titre above 1:32 fails to decline four-fold within 12 to 24 months of therapy
  • signs or symptoms consistent with syphilis develop.

Tertiary syphilis

Tertiary syphilis requires specialist review and treatment under consultant supervision. Assessment includes thorough neurological and cardiovascular examination, and CSF examination. The preferred regimen includes intravenous benzyl penicillin.

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