Executive summary
- Syphilis is resurging sharply in the UK. Diagnoses have reached their highest levels since the 1940s, affecting men who have sex with men (MSM), heterosexual men and women, and causing congenital infections in neonates.
- Syphilis is a great mimic. Primary chancres are often painless and missed; secondary features are protean. Keep it in the differential for any unexplained rash, lymphadenopathy, or genital ulcer.
- Syphilis is a notifiable disease — report confirmed cases to the local HPT/UKHSA.
- Most cases should be managed in genitourinary medicine (GUM). Primary care's role is recognition, initial serology, and urgent referral. Treatment should be co-ordinated with a GUM clinician to ensure partner notification is completed.
Clinical stages
- Primary syphilis: Painless, indurated genital (or extragenital — oral, anal, finger) ulcer (chancre) appearing 9–90 days after exposure, typically with painless regional lymphadenopathy. Heals spontaneously in 3–6 weeks. Highly infectious.
- Secondary syphilis (4–10 weeks after primary): Systemic illness: generalised non-itchy maculopapular rash classically involving the palms and soles (very specific), condylomata lata (flat warty perianal/vulval lesions), mucous patches, patchy alopecia, flu-like illness, and generalised lymphadenopathy. Still infectious.
- Latent syphilis: Positive serology, no symptoms. Early latent: <2 years since infection. Late latent: ≥2 years or unknown duration. Early latent remains potentially infectious (relapses possible); late latent is not infectious but risks progression.
- Tertiary/late syphilis: Gummatous disease, cardiovascular syphilis (aortitis), or neurosyphilis (meningitis, tabes dorsalis, general paresis). Rare in the antibiotic era but important to consider in late presentations.
Serology interpretation
- Treponemal tests (TPPA/TPHA/EIA IgG): Specific antibody tests that remain positive for life after infection, even after successful treatment. A positive result confirms past or present treponemal infection — does not distinguish active from treated disease.
- Non-treponemal (RPR/VDRL): Non-specific cardiolipin tests that reflect disease activity. Titre falls with treatment and can be used to monitor treatment response. Biological false positives (pregnancy, autoimmune disease, viral illness) are possible.
- Standard screen: A combined treponemal EIA or TPPA plus RPR/VDRL. If treponemal positive but RPR negative, discuss with GUM — may represent previously treated or very early/late disease.
- Window period: Serological tests may be negative in very early primary syphilis (within 3–4 weeks of infection). If clinical suspicion is high (genital ulcer), refer urgently to GUM for dark-field microscopy or PCR of the ulcer.
Treatment (to be co-ordinated with GUM)
- Preferred first-line for all stages: Benzathine benzylpenicillin G (Bicillin L-A) 2.4 MU IM as a single dose for primary, secondary, and early latent syphilis. For late latent/unknown duration: 2.4 MU IM weekly for 3 weeks.
- Penicillin allergy: Doxycycline 100 mg twice daily for 14 days (early) or 28 days (late latent). Note: procaine penicillin is an alternative that GUM services may use.
- Neurosyphilis: Requires IV benzylpenicillin — hospital-managed.
- Pregnancy: Penicillin is the only reliably effective treatment to prevent congenital syphilis — desensitisation should be arranged if penicillin-allergic. Refer urgently to GUM and obstetrics.
- Jarisch–Herxheimer reaction: Fever, malaise, and worsening of lesions in the first 24 hours after penicillin. Warn patients; manage with paracetamol. Not an allergy.
Frequently asked questions
I found a positive syphilis serology — what do I do first?
Check whether there is a previous positive on record. If this is a new positive, refer urgently to GUM for full staging, treatment, and partner notification. Order an RPR/VDRL titre if not already done. The GUM team will determine treatment stage and arrange follow-up serology to confirm treatment response.
Should I routinely screen for syphilis in primary care?
Antenatal syphilis serology is routine and mandatory in the UK. Outside pregnancy, BHIVA/BASHH guidelines recommend at least annual syphilis testing for MSM who have new or multiple partners, and testing in anyone presenting with a genital ulcer, unexplained rash, or other STI. HIV-positive individuals should be screened at least annually.
Can syphilis cause a negative HIV test?
No, but the two infections facilitate each other. Active syphilis disrupts mucosal barriers and increases HIV transmission risk substantially. Always offer HIV testing alongside syphilis serology.
Transparency
This page is an educational, clinician-written summary of publicly available NICE guidance intended for trained healthcare professionals. It uses original wording (not copied text) and should be used alongside the full NICE source, local pathways, and clinical judgement. Doses provided are for general reference; always check the BNF/SPC.