Ocular Syphilis

Nicholas P Jones

The Royal Eye Hospital Manchester, UK Syphilis and uveitis

• Congenital N • Primary N

• Secondary (early, active) Y • (late, latent) N

• Late (symptomatic) (Y) Other secondary symptoms

• Headache – Global, persistent – Occasional meningism • Malaise, tiredness

• Lymphadenopathy • Condylomata lata Ocular syphilis - manifestations • Anterior uveitis/vitritis/panuveitis Ocular syphilis - manifestations • Retinitis/vasculitis Ocular syphilis - manifestations • Retinitis/vasculitis – with multifocal peri- retinal “satellite” lesions Ocular syphilis - manifestations

• Vitritis • Papillitis optic neuropathy Ocular syphilis - manifestations

• Placoid chorioretinitis • HIV+ ? Ocular syphilis – uncommon or rare manifestations

• Acute interstitial keratitis/sclerokeratitis • Neuroretinitis • Retinal vein occlusion • Exudative/serous retinal detachment • Necrotising retinitis When to suspect syphilis

• Any uveitis with: – skin rash, especially involving palms/soles or with mucosal ulcer – headache – history of sexually transmitted disease(s) including known HIV • Any retinitis or retinal vasculitis • Any unresponsive uveitis Posterior uveitis with skin lesions: Differential diagnosis

• Behçet’s disease

• Sarcoidosis Posterior uveitis with skin lesions: Differential diagnosis

• Syphilis

• Lupus Posterior uveitis with skin lesions: Differential diagnosis

• Varicella

• Others Uveitis with headache

• Behcet’s disease (idiopathic, encephalitis, aseptic meningitis)

• Syphilis (meningoencephalitis)

• APMPPE (meningism, cerebral vasculitis)

• Multiple sclerosis (focal demyelination)

• VKH (meningism [meningeal pigmented cells, pineal]) • Encephalitis (infective) – HSV, Lyme, Whipple’s, brucella – in the immunodeficient: cryptococcus, toxoplasma

• Systemic vasculitis (cerebral vasculitis) Syphilis - investigation

• Treponemal tests: – ELISAs including ICE, DBE – FTA-ABS – less common – TPHA, TPPA - less good • Non-treponemal tests: – Rapid Plasmin Reagent (RPR) – Venereal Disease Research Laboratory (VDRL) • quantitative (titre >1:4 shows current activity) • confirms active infection • monitors treatment progress

Syphilis - investigation

• Treponema pallidum cannot be cultured • T pallidum pertenue (yaws) and other endemic syphilis organisms are immunologically identical • Infection with T pallidum confers lifelong positive treponemal test, but NOT immunity: syphilis can be caught repeatedly Interpreting syphilis tests T pallidum PCR on intraocular fluid

• Sensitivity and specificity not ratified for intraocular use • TaqMan probe-enhanced real-time PCR enhances specificity • Vitreous may be significantly more productive than aqueous Refer to genitourinary medicine clinic because:

• Supervised treatment • Interpretation of repeated serology • Investigation/counselling for other sexually transmitted diseases including HIV/HepC – HIV accelerates neurosyphilis • Contact tracing and treatment Exclude active neurosyphilis?

• Headache nonspecific – (doesn’t indicate CNS infection) • Exclude focal neurological signs • CSF analysis if necessary: – WCC >20/microl, protein >45mg/dl – VDRL +ve (not RPR - v. insensitive) – Treponemal test +ve – FTA-ABS +ve, TPHA+ve = 87% sensitive, 94% specific • CT brain if necessary Syphilis - treatment

• Regime as for presumed neurosyphilis: – Procaine penicillin G 2.4MU/day I/M 17/7 – Probenecid 500mg QID oral 17/7 – Oral steroids to: • treat sight-threatening uveitis (40-60mg/day) • ameliorate Jarisch-Herxheimer reaction (20mg/day)

• Or: benzylpenicillin 18-24MU/day I/V 17/7 • Or: doxycycline 200mg BD 4/52 • Or: amoxycillin 2g TDS + probenecid 500QID 4/52

UK National Guideline 2002 for management of Late Syphilis (Assoc GUM) Response to treatment • May take weeks to settle, but often good VA • Retinal atrophy more extensive than areas of active retinitis: • Large visual field defects • Nyctalopia Post-treatment follow-up

• Monitor inflammation, symptoms, field • Monitor RPR; 4-fold rise = re-infection – treatment response much slower, uveitis risk low In conclusion:

• Syphilis is not uncommon: think of it! • Take a sexual/STD history • Serology is diagnostic - always include it if syphilis is possible • Always liaise with GUM physician • Treatment curative, but visual recovery may be delayed