Anterior uveitis Granulomatous type IOP rise Transillumination defect Viral anterior uveitis?
Posterior scleritis Good general health No rheumatoid disease Probably idiopathic ?
52 year-old white male • VA loss RE • fascicular VFD • swollen disc and disc hemorrhage • AION ?
Retinitis fociImmunocompetent mangranular aspect hazy vitreousviral retinitis ?
100 µV/div Nightblindness Severe VF constriction OU Almost flat ERG OU Hereditary retinal dystrophy ?
The great imitator Philippe Kestelyn, MD, PhD, MPH Department of Ophthalmology Ghent University Hospital Belgium
’’The great imitator’’ Lecture for the British Medical Society in 1879 Jonathan Hutchinson
Pubmed search • The great imitator strikes back • The return of the great imitator • The new great imitator (Lyme disease)
SyphilisEpidemiology • 12 million new cases of syphilis worldwide each year • uncommon in Europe • serious problem in developing countries • serious sequelae / risk of congenital infection
Syphilis • sexually transmitted disease caused by Treponema pallidum • penetrates intact mucous membranes and abraded skin • incubation from 10 to 90 days • spread through the lymphatics to the bloodstream • hematogenous dissemination • 3 stages: primary, secondary and tertiary syphilis • 70% of patients remain in latent stage after secondary stage • 30% go on to develop tertiary syphilis
Congenital Syphilis • transplacental transmission of T. pallidium first 3 months • preventable! • intrauterine death or serious congenital abnormalities • generalized rash, jaundice, rhinitis • osteochondritis and X-ray abnormalities of bones in > 90% • chorioretinitis often present • DD rubella, CMV, toxoplasmosis • diagnosis: FTA-ABS (IgM)
Late congenital syphilis silent infection at birth • after 2 years : • interstitial keratitis in 20 % • Hutchinson’s triad: • interstitial keratitis • notched thin upper incisors with abnormal spacing • deafness
Ocular involvement in the different stages of syphilis • Primary syphilis: conjunctival chancre (rare) • Secondary syphilis: anterior and posterior involvement with pronounced inflammation • iritis (roseolae) • acute syphilitic posterior placoid chrioretinitis • inner retinal punctate lesions • retinal necrosis • Tertiary stage: chronic anterior and posterior uveitis (chronic and mild vitritis, vasculitis, pigment epitheliopathy)
Anterior segment involvement in syphilis • starts as unilateral iritis • contralateral eye involved in 50% of patients • from mild nongranulomatous to severe granulomatous • often notion of skin rash (secondary stage) • resistant to corticosteroid treatment
Luetic anterior uveitis • 65-year-old male • bilateral anterior uveitis • resistant to topical steroid treatment • history of “allergic” skin reaction
Posterior segment complications of syphilis • posterior scleritis • vitritis • vasculitis • venous and arterial occlusive disease • chorioretinitis , • retinal necrosis • acute syphilitic posterior placoid chorioretinitis • punctate inner retinopathy • retinal detachment with choroidal effusion • pseudoretinitis pigmentosa • macular edema, neuroretinitis • papillitis, optic perineuritis
Luetic papillitis • 52 year-old white male • VA loss RE • fascicular VFD • nocturnal sweats • skin rash 2 months ago • VDRL +, RPR + • LP : protein, VDRL + pleocytosis,
Luetic retinitis (HIV-) A 32-year- old white male patient complains of hazy vision in the left eye; no general health problems, but syphilis serology strongly positive…
Before and after treatment Full recovery of visual acuity after penicillin G therapy
Syphilis in patients with HIV infection • recognition of concurrent infection mandatory • accelerated course of syphilis • greater likelyhood of posterior uveitis, bilateral disease and neurosyphilis • treatment failures more common • serologic tests less reliable • “neurosyphilis treatment” for all patients ?
HIV and ocular syphilis • Bilateral disease • Accelerated course and extensive tissue destruction (retinalk necrosis) • False negative serology (indirect test)
Bilateral Luetic Uveitis: post Rx PPLE PPRE
Bilateral Luetic Uveitis Inf perif LE PPRE
Bilateral Luetic Uveitis: post Rx FFA Inf perif LE FFA PPRE
RE LE 200 µV/div 100 µV/div 50 µV/div Normal Control Full-Field Flash ERG Scotopic Maximal Photopic 30Hz Flicker RE LE 100 µV/div 20 µV/div
Bilateral luetic uveitisLaboratory results • HIV positive; 624 CD4 cells /microliter • Toxoplasmosis IgG - IgM - • Epstein-Barr IgG 260 IU/ml IgM - • CMV IgG > 2000 IgM 2.0 (PCR negative) • HSV IgG 1700 IgM - • VZV IgG 1600 IgM – • RPR negative
“Prozone” phenomenon = disequilibrium between antibody and antigen levels present in less than 1% of patients with secondary syphilis false negative test
Another presentation of syphilitic posterior uveitis… Middle aged man with mild visual impairment and bilateral inflammation
Acute syphilitic placoid pigment epitheliopathy • first described by Gass • considered to be pathognomonic for syphilis • “leopard spots” on FA in the cicatricial phase
A 3rd rather typical presentation of posterior syphilitic involvement... Middle aged man with mild visual impairment and bilateral inflammation
Syphilitic punctate inner retinitis in immunocompetent gay men. Wickremasinghe et al. Ophthalmology 116:1195-1200, 2009.
Non-specific tests for syphilis = cardiolipin from beef heart detects anti-lipid IgG and IgM formed in patients in response to: • lipoidal material released from cells damaged by the infection • lipids in the surface of T. pallidum • VDRL (venereal disease research lab) • RPR (rapid plasma reagin test) • decline after effective AB therapy (indicator) • false positive results
Specific tests • = detection of antibodies to specific treponemal antigens • FTA-ABS (fluorescent treponemal antibody absorption) • TPHA (T. pallidum hemagglutination assay) • become positive earlier and stay positive throughout life • cannot be used as indicators of therapeutic response
Treatment of ocular syphilis • same treatment regimen as for neurosyphilis • 18 to 24 million units of penicilllin G IV/day for 2 weeks • doxycycline 100 mg orally BID for 30 days • tetracycline 500 mg QID orally for 30 days • corticosteroids may be added once effective antibiotherapy has been started
Endemic treponematoses • Genus treponema: 4 human pathogens • T. pallidum, subspecies pallidum = venereal sypilis • T. pallidum, subspecies endemicum = endemic syphilis or bejel • T. pallidum, subspecies pertenue = yaws • Treponema carateum = pinta
Endemic treponematoses Common features • Primary and secondary lesions • After latency some patients develop laate-stage disease • Cutaneous manifestations prominent • Penicillin = drug of choice • No serologic tests at present can differentiate endemic trepanomatoses from each other or from venereal syphilis
Endemic treponematoses Important differences • Target population • Young children versus neonates and adults • Mode of transmission • Hand-to-hand or fomites versus sexual or transplacental • Tertiary and systemic involvement • Rare versus common • Optic atrophy and uveitis described in endemic syphilis (Tabara)
Take home… • The great imitator is still there • Syphilis serolgy is mandatory in all patients presenting with unexplained intraocular inflammation • It is an inexpensive and reliable tool to unmask the great imitator • If not recognized in time, syphilitic retinitis may destroy the retina in a short time period (HIV patients) • Excellent prognosis with early and adequate treatment