Syphilis is caused by the Treponema. pallidum spirochete.
Primary syphilis may develop within several weeks of exposure and manifests as one or more painless, indurated, superficial ulcerations (chancre).
Secondary syphilis develops 4-10 wks after the chancre resolves and may produce a rash, mucocutaneous lesions, adenopathy, and constitutional sx.
Tertiary syphilis follows between 1 and 20 yrs after infection, and includes cardiovascular, gummatous, and neurologic disease (general paresis, tabes dorsalis, or menignovascular syphilis)
HIV coinfection is high. Rule this out.
Lab:
Primary syphilis, dark-field microscopy of the lesion exudates show organisms. A nontreponemal serologic test (RPR or VDRL) should be performed with a treponemal specific test (FTA-ABS, or T. pallidum particle agglutination)
Secondary syphilis dx is made on basis of serologic tests and clinical illness.
Latent syphilis is a serologic diagnosis in the absence of sx - early latent syphilis is serologically positive for < 1 year, and late latent syphilis is serologically positive for > 1 year.
Syphilis Tx:
Early syphilis: pts who are seroneg. and without si of syphilis, but who have been exposed to infection within previous 3 mo.
Latent syphilis: serological tests for syphilis +ve plus normal CSF plus asymptomatic.
Early latent: <1 y post inf. in untreated Pt.
Primary, secondary, or early latent < 1 year: Benzathine PCN G, 2.4 million units IM single dose. PCN allergic, nonpregnant: Doxycycline, 100 mg PO bid x 14 d; tetracycline, 500 mg PO qid x 14 d.
Late latent: >1 y or more post inf. in untreated Pt.
Tx of late latent, cardiovascular or benign 3° syphilis with normal CSF:
Pen G benzathine 2.4 MU IM weekly x 3 weeks. For PCN allergic pts: Tetracycline 500 mg PO qid or Doxycycline 100 mg PO bid x 4 weeks
1°, 2°, or early latent syphilis: Pen G benzathine, give single dose of 2.4 MU IM (1.2 in each butt) cures 95% of cases.
Examine CSF from HIV-seropositive individuals with syphilis. If +ve Rx as in neurosyphilis
Aqueous pen G (procaine) 2.4 MU IM + probenicid 500 mg PO qid x 10 - 14 days; or
Aqueous pen-G 3 - 4 MU IV q4h x 10 - 14 days (total: 18 - 24 MU/d).
For Pts. allergic to PCNs: Patients must be desensitized to PCN, as neurosyphilis is only effectively treated with PCN. Tetracycline 500 mg PO qid or Doxycyline 100 mg PO bid x 2 weeks
Followup evaluation of responses to Tx in syphilis
Monitor VDRL and RPR titers: 1, 3, 6, and 12 mo after Rx.
In HIV + syphilis, VDRL and RPR titers: 1, 2, 3, 6, 9, & 12 mo.
Successful Tx: VDRL titers slowly declines, become negative in 12 mo.
If VDRL titer fails to fall at least 4 folds, within 12 mo, or if VDRL titer increase 4 fold, or clinical features persist, or recur: Retreat.
If CSF is abnormal, treat as in neurosyphilis.
If Pt stays sero +ve after Rx for neurosyphilis but asymptomatic, no further Rx is reqd.
The most sensitive index of response to Rx in neurosyphilis is degree of CSF pleocytosis.
ASx NS: No neurologic sx and si, but CSF abnl, including mononuclear pleocytosis, increased protein conc, or a reactive VDRL slide test. Seen in 1/4 of Pts with untreated latent syphilis. NS is associated with a RPR titer of >1:32 or more, regardless of clinical stage or HIV infection status.
Patient's with HIV and syphilis of >1 year's duration should undergo a lumbar puncture, for CSF studies, especially if the RPR titer if greater or equal to 1:32 and CD4 <350/uL
Neurosyphilis Tx:
Neurosyphilis is only effectively treated with penicillin.
Penicillin G 4 million units IV q.4 h. for 14 days. Follow up with benzathine penicillin 2.4 million units IM q. every week for 3 weeks.
Follow up response to treatment done with RPR. Check at 3-month, 6-
month, and 1-year after successful treatment RPR and VDRL should become negative by 1 year. Same non-treponemal test may be used in followup, as were used in original setting.
Pregnancy: PCN only recommended Tx. Desensitize Pt if needed.
Here are some examples of common serologic patterns and their interpretation:
EIA reactive, RPR reactive, TP-PA reactive
This is consistent with syphilis infection. If the patient has previously received treatment and the RPR titre is declining, it may be consistent with treated syphilis.
EIA reactive, RPR reactive, TP-PA non-reactive, OR
EIA reactive, RPR non-reactive, TP-PA non-reactive
The treponemal tests do not agree. This may be due to early infection where TP-PA has not yet developed, prior syphilis (treated or untreated), or potentially a false positive EIA. This patient should be re-tested in 2 weeks.
EIA reactive, RPR non-reactive, TP-PA reactive
Remember that treponemal tests will generally stay positive for life, so if the patient has previously been treated for syphilis, this is the expected serologic result. If the patient has never been treated, this could also be consistent with late latent syphilis, as RPR titers decline over time, with or without treatment. Confirming treatment history in this situation is essential to avoid overtreatment.
The combination of a reactive treponemal test plus RPR 1:8 should be treated as active syphilis until proven otherwise, particularly if there is no documented prior treatment with a corresponding fourfold titer decline (e.g., from 1:32 to 1:8 or lower).
From a neurology standpoint, if this patient has any neurological symptoms -- cognitive changes, cranial neuropathy, myelopathy, uveitis, hearing loss, or autonomic features -- neurosyphilis must be considered and CSF evaluation is warranted (CSF VDRL, cell count, protein).
Neurosyphilis: When to Suspect It
Indications for LP in a syphilis-positive patient:
Any neurological or psychiatric symptoms
Ocular or otologic symptoms (uveitis, hearing loss, vertigo)
RPR titer of 1:32 or higher (some guidelines use this threshold; 1:8 is borderline)
HIV co-infection
Treatment failure (fourfold rise in titer or failure to decline appropriately)
CSF Criteria for Neurosyphilis
Definite neurosyphilis requires:
CSF VDRL reactive (highly specific, but insensitive - only 30-70% sensitive)
Probable neurosyphilis:
CSF pleocytosis (>5 WBC/mm³) and/or elevated protein, in the appropriate clinical context, even with a non-reactive CSF VDRL.
CSF FTA-ABS is sensitive but not specific; a negative CSF FTA-ABS effectively excludes neurosyphilis. A positive result alone is insufficient for diagnosis.
Staging of Syphilis
Stage ||| Timing ||| Key Features
Primary ||| 10-90 days post-exposure ||| Painless chancre
Secondary ||| 4-10 weeks after chancre ||| Rash (palms/soles), condyloma lata, systemic symptoms
Early latent ||| Within 1 year of infection ||| Asymptomatic, RPR reactive
Late latent ||| >1 year or unknown duration ||| Asymptomatic, RPR reactive
Tertiary ||| Years later ||| Gummas, cardiovascular syphilis, neurosyphilis
Neurosyphilis can occur at any stage, not just tertiary.
Treatment
Primary, secondary, early latent: Benzathine penicillin G 2.4 million units IM single dose
Late latent or unknown duration: Benzathine penicillin G 2.4 million units IM weekly x 3 doses.
Neurosyphilis: Aqueous crystalline penicillin G 18-24 million units/day IV x 10-14 days (preferred)
Neurosyphilis alternative:
Procaine penicillin G 2.4 million units IM daily + probenecid 500 mg PO QID x 10-14 days
Penicillin allergy in neurosyphilis: desensitization is recommended; doxycycline and ceftriaxone are options but evidence is weaker.
Post-Treatment Follow-up
Repeat RPR at 6 and 12 months (and 24 months for late latent or neurosyphilis)
Treatment success: fourfold decline in titer (e.g., 1:8 to 1:2)
Treatment failure or reinfection: fourfold rise in titer
For neurosyphilis: repeat LP at 6 months to confirm CSF normalization