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 foci
Immunocompetent
man
granular aspect
hazy vitreous
viral 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)
Syphilis
Epidemiology
• 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
Luetic anterior uveitis
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
Posterior scleritis in a TP seropositive patient
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
PPRE
PPLE
Bilateral Luetic Uveitis
PPRE
Inf perif LE
Bilateral Luetic Uveitis: post Rx
FFA PPRE
FFA Inf perif LE
Full-Field Flash ERG
Scotopic
Maximal
Photopic
30Hz Flicker
RE
LE
100
µV/div
20
µV/div
100
µV/div
50
µV/div
RE
LE
200
µV/div
Normal Control
Bilateral luetic uveitis
Laboratory 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
Leopard-spot like lesions on FA in the cicatricial phase
 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 laatestage 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
Thank you !