Jeremy D. Wolfe

BASICS

DESCRIPTION

• Chronic, multiorgan, systemic bacterial infection caused by spirochete Treponema pallidum.

• Responsible for 1–2% of all uveitis cases.

• Ocular syphilis is considered a variant of neurosyphilis (see below).

• Congenital syphilis (systemic findings):

– Early (<2 years of age): Hepatosplenomegaly, long bone changes, mucocutaneous lesions of buttocks and thighs

– Late (>2 years of age): Frontal bossing, saddle-nose deformity, saber shins, Hutchinson teeth, deafness

• Acquired syphilis (systemic findings):

– Primary: Self-limited painless genital chancre

– Secondary: Maculopapular rash on palms and soles, generalized lymphadenopathy, fever, malaise

– Early latent (exposure within the last year): Seroreactivity without clinical manifestations

– Late latent or latent syphilis of unknown duration (exposure >1 year): Seroreactivity without clinical manifestations

– Tertiary: Gummas, neurosyphilis, cardiovascular abnormalities (aortitis)

EPIDEMIOLOGY

Incidence

• Congenital: 10.1/100,000 in 2008 (1)

– Increased 23% from 2005

• Primary & Secondary: 15.3/100,000 in 2008

– Increased 37% from 2005

• Regional: Highest rates (50%) in Southern US

• Age: Highest rates in 20–24 year olds

• 63% of cases in US among men who have sex with men

Prevalence

Due to the rarity of ocular syphilis and incomplete reporting to the CDC, true prevalence data (i.e., total cases) is not well known.

RISK FACTORS

• High-risk sexual behavior

• HIV coinfection

• Intravenous drug abuse

GENERAL PREVENTION

• Prenatal care to prevent congenital syphilis

• Safe sexual practices

PATHOPHYSIOLOGY

• Transmission of acquired syphilis may occur through direct contact with syphilis sore on external genitals, vagina, anus, rectum, or lips and mouth during vaginal, anal, or oral sex.

• Transmission of congenital syphilis occurs by transplacental contact.

• Ocular inflammatory response to infection caused by bacteria Treponema pallidum.

ETIOLOGY

Treponema pallidum, spirochete

COMMONLY ASSOCIATED CONDITIONS

• HIV

• Other sexually transmitted diseases

DIAGNOSIS

HISTORY

• Maternal syphilis

• HIV

• High risk sexual behavior

• Pain, redness, photophobia, blurred vision, floaters

PHYSICAL EXAM

• Syphilis may affect any or all ocular structures (2) [A]

• Congenital Syphilis:

– Early: Chorioretinitis, retinal vasculitis, “salt-and-pepper” retinal pigment mottling

– Late: Interstitial keratitis with corneal vascularization, ghost vessels

• Acquired Syphilis:

– Primary: Ocular manifestations rare

– Secondary: Anterior uveitis (granulomatous or non-granulomatous), iris nodules, scleritis, vitreitis, retinal vasculitis, retinal vascular occlusion, chorioretinitis (focal or multifocal), posterior placoid chorioretinitis, neuroretinitis, exudative retinal detachment, optic neuritis, cranial nerve palsies

– Latent: Asymptomatic with recurrences

– Tertiary: Argyll-Robertson pupil (pupil reacts to near target, not to light stimuli), cranial nerve palsies, other ocular findings similar to those with secondary syphilis.

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Initial lab tests

• Non-treponemal: Rapid Plasma Reagin (RPR) or Venereal Disease Research Laboratory (VDRL)

– Fourfold decrease in antibody titer used to monitor response to therapy

– False–positives (collagen-vascular disease) and false–negatives (prozone phenomenon)

• Treponemal-specific: Fluorescent treponemal antibody absorption (FTA-ABS) or microhemagglutination-T. pallidum (MHA-TP)

– Remain reactive from time of infection, thus should not be used to monitor therapeutic response.

• Lumbar puncture with cell count, protein, glucose, and CSF-VDRL to evaluate for neurosyphilis.

– CSF-VDRL is highly specific, but not sensitive

– 2006 CDC guidelines recommend lumbar puncture in all cases of ocular involvement, although practical indications for lumbar puncture are controversial (3)[A]

– Isolated syphilitic anterior uveitis without neurologic signs/symptoms may not require lumbar puncture

Follow-up & special considerations

• HIV serology due to high rates of coinfection

• False–positive and false–negative rates of syphilis serologic testing may be higher in HIV patients.

Imaging

Consider MRI for any suspected case of optic nerve involvement and/or neurosyphilis.

Diagnostic Procedures/Other

Lumbar Puncture with CSF-VDRL

Pathological Findings

Corkscrew morphology on darkfield microscopy (not commonly performed).

DIFFERENTIAL DIAGNOSIS

• Ocular syphilis carries a broad differential diagnosis due to its protean manifestations

– Sarcoidosis

– Tuberculosis

– Toxoplasmosis

– Vogt-Koyanagi-Harada syndrome

– HLA-B27 associated uveitis

– Pars planitis

– Acute retinal necrosis

– CMV retinitis

– Fungal endophthalmitis

– White dot syndromes (e.g., APMPPE)

– Lyme disease

– Behçet’s disease

– Diffuse unilateral subacute neuroretinitis

– Toxocariasis

– Presumed ocular histoplasmosis

TREATMENT

MEDICATION

First Line

• Congenital: Aqueous crystalline penicillin G 50,000 units/kg/d IV q12 hrs for first 7 days of life, and q8h thereafter for total of 10 days OR Procaine penicillin G 50,000 units/kg/d IM × 10 days (3)[A]

• Primary, secondary, or early latent syphilis: Benzathine penicillin G 2.4 MU IM in single dose (3)[A]

• Late latent or tertiary without evidence of neurosyphilis: Benzathine penicillin G 2.4 MU IM, weekly × 3 doses (3)[A]

• Neurosyphilis: Aqueous penicillin G 3-4 MU IV q4h × 10–14 days OR Procaine penicillin G 2.4 MU IM q day PLUS Probenecid 500 mg PO q.i.d × 10–14 days, followed by Benzathine penicillin G 2.4 MU IM, weekly × 3 doses (3)[A]

• Manage ocular inflammation with cycloplegics, and topical, periocular, and/or oral corticosteroids

• Note: Periocular (depot) steroids should not be employed until other infectious etiologies for inflammation are eliminated from differential diagnosis or identified and treated concurrently.

Second Line

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