Syphilis
Exam Tips
- Think syphilis in any painless indurated genital ulcer, palmoplantar rash, or unexplained multisystem picture, especially with STI risk factors.
- Neurosyphilis can occur at any stage; ocular or auditory symptoms are red flags requiring urgent specialist treatment.
- For monitoring, non-treponemal titres (RPR/VDRL) are used for response; treponemal tests often remain positive for life.
- In pregnancy, penicillin is mandatory (after desensitization if allergic) because alternatives are not reliable for preventing congenital syphilis.
- Image-based OSCE prep: review classic appearances of chancre, condylomata lata, snail-track oral lesions, and palmoplantar secondary rash in UK sexual health teaching atlases/guideline figures.
Definition
Syphilis is a chronic, systemic sexually transmitted infection caused by the spirochaete Treponema pallidum, with acquired and congenital forms. Untreated disease evolves through primary, secondary, latent, and sometimes tertiary stages, and can later cause irreversible neurological, ocular, and cardiovascular damage despite apparent early symptom resolution.
Pathophysiology
T. pallidum enters through mucosal surfaces or abraded skin during sexual contact (or transplacentally in pregnancy), replicates locally, then disseminates via lymphatics and bloodstream. Early disease reflects active replication and bacteraemia (chancre, rash, mucosal lesions, lymphadenopathy), while latent disease is serologically positive without symptoms. Persistent infection can trigger delayed end-organ inflammation years later, including obliterative endarteritis and granulomatous gumma formation, with neurosyphilis possible at any stage.
Risk Factors
- Unprotected vaginal, anal, or oral sex
- Men who have sex with men (especially with multiple/anonymous partners)
- Previous or current STI, including HIV coinfection
- Transactional sex
- Illicit drug use (including injecting drug use and needle sharing)
- Social deprivation, homelessness, migrant/refugee vulnerability
- Pregnancy (risk of vertical transmission to fetus)
Clinical Features
Symptoms
- Painless genital, anal, or oral ulcer (primary chancre), though may be painful or multiple
- Non-itchy generalized rash, often including palms and soles
- Constitutional symptoms: fever, malaise, headache, myalgia
- Patchy hair loss in secondary syphilis
- Visual or auditory symptoms (blurred vision, hearing change/tinnitus) suggesting ocular/otosyphilis
- Late disease symptoms: sensory ataxia, lightning pains, cognitive decline, chest pain/dyspnoea from aortic disease
Signs
- Indurated ulcer with clean base and well-defined edge, with regional lymphadenopathy
- Maculopapular/papular/macular rash including palmoplantar involvement
- Condylomata lata in moist anogenital/perineal areas
- Oral mucous patches ('snail-track' lesions)
- Generalized non-tender lymphadenopathy
- Neurological signs in late disease (Argyll Robertson pupil, tabetic gait, focal deficits)
Investigations
Management
Lifestyle Modifications
- Urgent referral to GUM/sexual health services for staging, treatment, partner notification, and public health management
- Avoid sexual contact (or use strict barrier protection) until treatment completed and infectious risk judged resolved by specialist follow-up
- Screen and treat recent sexual partners according to exposure window
- Offer HIV prevention/risk-reduction counselling and condom advice
- In pregnancy, coordinate same-day obstetric and sexual health input
Pharmacological Treatment
Penicillin antibiotics (first-line)
- Benzathine benzylpenicillin 2.4 million units IM single dose (early syphilis: primary, secondary, early latent)
- Benzathine benzylpenicillin 2.4 million units IM weekly for 3 doses (late latent or unknown duration)
Administer in specialist care with baseline and follow-up non-treponemal titres. Warn about Jarisch-Herxheimer reaction (acute fever/headache/myalgia within 24 hours), especially important in pregnancy due to fetal distress risk.
Alternatives when penicillin cannot be used (non-pregnant adults, specialist advice)
- Doxycycline 100 mg orally twice daily for 14 days (early syphilis)
- Doxycycline 100 mg orally twice daily for 28 days (late latent/unknown duration)
Avoid doxycycline in pregnancy and breastfeeding where contraindicated; ensure adherence and close serological follow-up because evidence base is weaker than for penicillin.
Neurosyphilis/ocular syphilis regimens
- Benzylpenicillin 1.8-2.4 g IV every 4 hours for 10-14 days
- Alternative regimen: Procaine benzylpenicillin 1.8-2.4 million units IM once daily plus probenecid 500 mg orally four times daily for 10-14 days
Treat as neurosyphilis urgently in hospital; do not delay for eye symptoms because permanent visual loss can occur.
Pregnancy-specific management
- Benzathine benzylpenicillin as stage-appropriate first-line treatment in pregnancy
Penicillin is the only proven regimen to prevent congenital syphilis; if true penicillin allergy, arrange desensitization and treat with penicillin in specialist care.
Complications
- Neurosyphilis (meningitis, stroke from arteritis, cranial neuropathies, general paresis, tabes dorsalis)
- Ocular/otosyphilis with potential permanent visual or hearing loss
- Cardiovascular syphilis (aortitis, ascending aortic aneurysm, aortic regurgitation, heart failure)
- Gummatous syphilis affecting skin, bone, or other organs
- Adverse pregnancy outcomes (miscarriage, stillbirth, preterm birth, congenital infection)
- Increased HIV transmission/acquisition risk
- Psychological and social harms (stigma, relationship disruption)
Prognosis
Outcomes are excellent with timely antibiotic treatment in early disease, with serological response expected on follow-up. Without treatment, about one-quarter develop secondary features within weeks and around one-third may progress to late sequelae over decades. In established late disease, treatment prevents further progression but existing neurological or cardiovascular injury may not fully reverse.
Sources & References
🏥BMJ Best Practice(1)
💊BNF Drug References(1)
- Ceftriaxone[management.pharmacological]
✅NICE Guidelines(1)
- Syphilis[overview]
📖Textbook References(7)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1591)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1590)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1590)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 481, 482)[context]
- [Oxford Medical Handbooks] Ian Wilkinson, Tim Raine, Kate Wiles, Anna Goodhart, Catriona Ha - Oxford Handbook of Clinical Medicine (2017, Oxford University Press) - libgen.li.pdf(pp. 481)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 862)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 862)[context]