Syphilis

Overview

Syphilis is a systemic infection caused by the spirochaete *Treponema pallidum*, progressing through distinct stages if untreated. Notifiable disease with rising UK incidence, particularly in MSM.

Presentation

•Primary - single, painless, indurated ulcer (chancre) at inoculation site + non-tender regional lymphadenopathy; heals spontaneously in 3-6 weeks

•Secondary - generalised symmetrical non-itchy maculopapular rash classically involving palms and soles; generalised lymphadenopathy, condylomata lata, mucous patches, 'moth-eaten' alopecia, malaise, fever

•Latent - asymptomatic; positive serology only. Early latent <2 years (infectious); late latent >2 years

•Tertiary - occurs in ~1/3 untreated patients; gummatous disease, cardiovascular syphilis, or neurosyphilis

•Cardiovascular syphilis - endarteritis of vasa vasorum → aortitis of ascending aorta → proximal aortic aneurysm, aortic regurgitation, coronary ostial stenosis; 'tree-bark' aortic calcification on imaging

•Neurosyphilis - meningitis (early), meningovascular (stroke-like), tabes dorsalis (lightning pains, ataxia, loss of proprioception, Charcot joints), general paresis (dementia, seizures); Argyll Robertson pupil is pathognomonic

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Argyll Robertson pupil - small, irregular pupils that accommodate but do not react to light ('accommodates but does not react'). Pathognomonic of neurosyphilis.

•Congenital syphilis - early (<2 years): rhinitis ('snuffles'), maculopapular rash, hepatosplenomegaly, osteitis. Late (>2 years): Hutchinson's triad - interstitial keratitis, sensorineural deafness, Hutchinson's teeth (notched peg-shaped incisors); saddle-nose deformity, sabre tibia

Investigations

•Dark-field microscopy of chancre exudate - direct visualisation of spirochaetes; highly specific; first-line for primary lesions

•Non-treponemal tests (VDRL/RPR) - screening and monitoring treatment response (titres fall with successful treatment); false positives in pregnancy, SLE, viral infections, antiphospholipid syndrome

•Treponemal tests (TPHA/TPPA/FTA-ABS/EIA) - confirm positive NTT; remain positive for life even after treatment, so cannot monitor response

•Lumbar puncture - required if neurosyphilis suspected; CSF white cells, protein, and VDRL

•Echocardiogram/CT aorta - if cardiovascular syphilis suspected

•HIV serology and full STI screen - all patients

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In primary syphilis, serology may be negative (window period). If clinical suspicion is high, repeat serology at 6 weeks. Do not delay treatment if the clinical picture is convincing.

Management

•First-line (primary, secondary, early latent): benzathine penicillin G 2.4 million units IM single dose

•First-line (late latent >2 years or unknown, non-neurological tertiary): benzathine penicillin G 2.4 million units IM weekly for 3 doses

•First-line (neurosyphilis): IV benzylpenicillin for 10-14 days (benzathine penicillin does not reliably penetrate CSF)

•Second-line (penicillin allergy, early syphilis): doxycycline 100 mg orally twice daily for 14 days - NOT suitable in pregnancy

•Second-line (penicillin allergy, late latent): doxycycline 100 mg orally twice daily for 28 days

•Second-line (penicillin allergy, neurosyphilis): ceftriaxone; desensitisation to penicillin preferred in pregnancy

Follow-up

•Monitor treatment response with non-treponemal tests (RPR/VDRL) - fourfold or greater fall in titre at 3-6 months confirms adequate treatment

•Treponemal tests remain positive for life - cannot be used to monitor response

•Contact tracing mandatory; syphilis is a notifiable disease under the Health Protection (Notification) Regulations 2010

Jarisch-Herxheimer Reaction

•Occurs in up to 70% treated for early syphilis, within 2-8 hours of first antibiotic dose

•Caused by massive treponemal antigen release triggering cytokine storm

•Features: fever, rigors, flushing, headache, myalgia, transient worsening of rash - self-limiting within 24 hours

•Management: reassurance, paracetamol, adequate hydration - do NOT stop treatment

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Jarisch-Herxheimer reaction is NOT an allergic reaction. Warn patients before treatment. Particularly important in pregnancy (can precipitate preterm labour/fetal distress) and neurosyphilis (may transiently worsen neurological features).