Grand Rounds

Prat Itharat MDDecember 1, 2006

Vanderbilt Eye Institute

History 49 year old Caucasian male “red eye” for 3 days Questions?

History Redness in left eye for 3 days Gradual onset of redness OS Associated with photophobia, tearing Blurry vision OS Global headache, 4/10 No flashes, floaters No nausea, vomiting

History POH: no lasers/surgeries/trauma PMH: chronic sinusitis, GERD,

seasonal allergies PSH: negative FH: no glaucoma SH: 1ppd cig; +etoh; no ivda

History Allg: nkda Meds: ranitidine, loratadine,

mometasone, citalopram ROS: fevers, chills, sore throat,

cough; no back pain

Ocular examination

VAsc OD: 20/60

OS: 20/400 PH 20/200 Pupils: no rapd Ta: OD 26 OS 20 Motility: full ou CVF: full ou Ext: wnl ou

Ocular examination

SLEl/l: wnl ouconj: quiet od; 2+injection oscornea: clear oua/c: d+q od; 2+cells osiris: intact oulens: 1+nsc ouant vit: quiet od; +1 cells os

Ocular examination

Differential Diagnosis

Differential Diagnosis

Toxoplasmosis Syphilis Tuberculosis Fungal – cryptococcal, pneumocystis

carinii Sarcoidosis Lymphoma Bacterial endophthalmitis Acute retinal necrosis Metastases Lyme, cat-scratch

Our patient

Empirically started on sulfadiazine, pyrimethamine and folinic acid for toxoplasmosis

CXR, ACE, RPR, HIV, CBC, PPD Returned twice within the week

without improvement Blood cultures obtained

Our patient

CXR - old granulomatous disease; no active lesion

ACE - wnl PPD – negative RPR - positive FTA-ABS – reactive TPPA – reactive HIV – negative Cultures - negative

Our patient

Further questioning-syphilis 1970s – “I don’t know how”-red rash below waist -”blister” on arch of foot-since 7/1/06, has not been feeling well, treated by outside facility without improvement

Our patient

Poor follow-up CDC notified Received 2.5M units PCN IM weekly

x3 VA improved; constitutional

symptoms improved; no pain, photophobia

Scheduled to follow up at VA clinic

Syphilis

Spirochete bacterium Treponema pallidum

0.18 microns in width; 5-15 microns long

Sexual transmission most common Transplacental transmission

Syphilis: epidemiology

Syphilis: epidemiology

Syphilis: stages

Primary: -after 10-90 days incubation (3 weeks avg)-painless chancre at site of inoculation-lymphadenopathy-resolve spontaneously in 4 weeks

Syphilis: stages

Secondary: -6 weeks to 6 months after chancre-develop in 25% untreated patients-hematogenous spread-maculopapular rash (70%)

Syphilis: stages

Secondary: -lymphadenopathy, HA, malaise, joint pain, mouth ulcers, hair loss-resolve spontaneously but 25% recurrent-10% ocular findings

Syphilis: stages

Latent phase Tertiary stage (40% untreated)

-vasculitis-local granulomatous reaction = gumma-cardiac: aortitis/aortic insufficiency/aneurysm-neuro: tabes dorsalis, general paresis, meningitis, stroke

*CNS findings may present early

Syphilis: ocular

Young et al. Ocular Manifestations and treatment of syphilis. Seminars in Ophthalmology 20(2005): 161-167.

Syphilis: Ocular

Congenital-pigmentary retinopathy -interstitial keratitis-cataracts

Syphilis: Ocular

Uveitis most common presentation May occur as soon as 6 weeks or in

latent phase Granulomatous or non-

granulomatous Unilateral or bilateral Prior to 1940, second most common

cause of uveitis Only 2.45% of cases (Tamesis and

Foster); others 1-2% of uveitis Iris atrophy, nodules, roseola

Syphilis: Ocular

Chorioretinitis: posterior pole/mid-periphery

Lesions usually ½ to 1 DD but can be confluent

Variable amount of vitritis May be associated with vasculitis,

papillitis, serous RD, BRVO, necrotizing retinitis

May just involve RPE (syphilitic posterior placoid chorioretinitis)

Syphilis: Ocular

Syphilis: Ocular

Syphilis: Ocular

Syphilis: Ocular

Argyll Robertson pupil Miotic, irregular Light-near dissociation Interruption of fibers from pretectum

to EW nuclei Also seen ms, dm, chronic

alcoholism, encephalitis

Syphilis: workup

Definitive: darkfield microscopy or direct fluorescent antibody of tissue/exudate

Non-treponemal tests: RPR/VDRL Treponemal tests FTA-ABS/TP-PA PCR HIV: may cause false negative CSF: in HIV+

Syphilis: workup

Syphilis: treatment

Primary, secondary, early latent: benzathine penicillin G 2.4M units IMx1

Late latent, uncertain duration, tertiary syphilis: penicillin G 2.4M units IMx3 (weekly)

Alternatives: doxycycline 100mg BID for 2/4 weeks or tetracycline 500mg QID for 2/4 weeks

Neurosyphilis: aqueous penicillin G 3-4M units IV Q4H for 10-14 days

Syphilis: treatment

Jarisch-Herxheimer reaction: hypersensitivity reaction to antigens

Fever, myalgia, headache, malaise May be associated with worsening

ocular findings May been avoided with steroids

Syphilis: treatment

VDRL/RPR does not respond in all treated

97% of primary stage 77% of secondary stage VDRL usually positive for life FTA-ABS positive for life

Bibliography Knox, David. Retinal syphilis and tuberculosis. Chapter 100.

Retina (1994): Mosby 1633-1641. Uptodate Clinical Medicine Exposto et al. Evaluation of the Treponema pallidum Particle

Agglutination Technique (Tppa) in the diagnosis for neurosyphilis. J Clin Lab Analysis 20 (2006):233-238.

Szilard Kiss, Francisco Max Damico, and Lucy H Young. Ocular Manifestations and Treatment of Syphilis. Seminars in Ophthal 20(2005): 161-167.

Lehoang, et al. Syphilic Uveitis in patients infected with human immunodeficiency virus. Graefe Arch Clin Exp Ophthal 243(2005): 863-869.

Rao et al. Syphilis: Reemergence of an Old Adversary. Ophthal 113:11(2006): 2074-2079.

Margo, CE and Hamed LM. Ocular Syphilis. Survey of Ophthal 37:3(1992): 203-220.

Good luck, applicants!