Syphilitic Uveitis

Article initiated by: Arjun B. Sood, MD

All authors and Ghazala D. O'Keefe, MD, Arjun B. Sood, MD, Koushik Tripathy, MD (AIIMS), FRCS (Glasgow), Alan Palestine, MD, Amanda
contributors: Mohanan Earatt MBBS MS(Ophth) MRCS(Glasgow) MRCSEd FICO, Jennifer I Lim MD, Homaira Ayesha Hossain, MD

Assigned editor: Homaira Ayesha Hossain, MD

Review: Assigned status Update Pending

by Ghazala D. O'Keefe, MD on September 18, 2022.

Contents
1 Disease Entity
1.1 Brief History
1.2 Timeline of Syphilis in the United States
1.3 Risk Factors and At-Risk Populations
2 Diagnosis
2.1 History
2.2 Physical examination
2.3 Ocular Symptoms
2.4 Clinical Diagnosis and Ocular Findings
2.5 Testing for Suspected Syphilis
2.5.1 Serologic Tests
2.5.2 Nontreponemal Tests (NTT)
2.5.3 Treponemal Tests (TT)
2.6 CDC recommendations for Syphilis Testing and Management
2.6.1 Reverse Sequence Testing
2.6.2 Other Tests
3 Management and other considerations
3.1 Medical therapy
3.2 Medical follow up
3.3 Prognosis
4 References

Disease Entity
Syphilis is an infectious disease caused by Treponema Pallidum and is most commonly spread through sexual transmission. Syphilitic uveitis is the most
common ocular manifestation and is a potentially blinding disease.

Brief History
Syphilis was first reported in Europe in the 15th century. There was rapid spread throughout Europe that was associated with the French invasion of Italy in
1494. The origin of syphilis has been well debated for over 500 years. Due to the temporal relation with Christopher Columbus’s voyage in 1492, many
theorized the disease was brought to Europe by Columbus and his crew – the “Columbian Hypothesis.” Others theorized the disease was already present in the
Old World before the 1490’s and the emergence of the disease in the 15th century was attributed to increased virulence and medical recognition – the “Pre-
Columbian Hypothesis.” It is a debate that still continues today but an extensive review published by Harper et al. in 2011 supports the Columbian Hypothesis.

Timeline of Syphilis in the United States

1905, Treponema pallidum was first described by Schaudin and Hoffin as the causative bacteria of syphilis. They demonstrated spirochetes in Giema
stained smears from syphilitic lesions.
1943: first reported cure with penicillin
1947: incidence of primary and secondary syphilis was 66.4 cases/100,000
1956: rates decline to 3.9 cases/100,000
1999: introduction of the National Plan to Eliminate Syphilis from the United States announced by the United States Surgeon General
2000: lowest ever recorded rate of 2.1 cases/100,000 (approximately 5,979 cases in year 2000)
2000-2012: steady increase with incidence exceeding 55,000 new cases a year

Risk Factors and At-Risk Populations

Men who have sex with men (MSM)
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 HIV co-infection
Unprotected sex

Diagnosis
Syphilis is known as the Great Imitator as systemic manifestations vary. Ocular manifestations can affect any part of the eye, with syphilitic uveitis being the
most common.

History
Any patient with intraocular inflammation (uveitis) should have a thorough history and review of systems. Information or risk factors that may suggest syphilis
include a history of unprotected sex, recent STDs or HIV infection, MSM and substance abuse.

Physical examination

Systemic features of Syphilis

Syphilis can affect many parts of the body. Most common physical exam findings include:

Skin Rash
Palms and Sole maculopapular rash
Genital and Perianal chancres
Lymph Node Swelling
Oral Cavity gummas

Ocular Symptoms
Due to the varying degrees of presentation patients may complain of blurry vision, floaters, light sensitivity, double vision, eye pain, and foreign body sensation

Clinical Diagnosis and Ocular Findings

Anatomic Location Ocular Findings
Conjunctiva Mucous Patches, Papillary Conjunctivitis, Graulomatous Conjunctivitis
Sclera Episcleritis and Scleritis
Cornea Stromal Keratitis, marginal corneal infiltrates, Keratic precipitates
Lens Congenital Cataract, Uveitic cataract
Iritis, iridocyclitis, iris nodules, multifocal choroiditis, Posterior Placoid chorioretintis (typical), round viteous floaters just in front of the
Uveal Tract
retina
Retina/RPE retinal vasculitis, RPE mottling, necrotizing retinitis, serous retinal detachment, CME, retinochoroiditis, tractional retinal detachment
Optic Nerve optic atrophy, papilledema, inflammatory disc edema
Pupils Argyll Robertson Pupil
Cranial Nerve and
Extraocular motility deficit
Brainstem
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Images of posterior placoid chorioretinitis are available at https://imagebank.asrs.org/discover-new/files/1/25?q=Posterior%20Placoid%20Chorioretinitis

Testing for Suspected Syphilis

Serologic Tests
Serologic testing is the mainstay for diagnosis of ocular syphilis

Nontreponemal Tests (NTT)

Measures antibodies against lipoidal antigens released by damaged host cells and possibly spirochetes
Examples: RPR (rapid plasma reagin), VDRL (venereal disease research laboratory)
Most useful test to track active disease and treatment efficacy

Treponemal Tests (TT)

Measures antibodies against Treponema pallidum proteins
Examples: EIA (enzyme immunoassay), FTA-ABS (Fluorescent treponemal antibody absorption), TPPA (T pallidum particle agglutination), TPHA
(Treponema pallidum hemagglutination), CIA (chemiluminescence immunoassay)
Stays positive for life

CDC recommendations for Syphilis Testing and Management

:
 Laboratory diagnosis of syphilis

Reverse Sequence Testing

The CDC recommended testing algorithm for syphilis is shown. The algorithm starts with a highly sensitive but non specific immunoassay for treponemal
antibodies. If the test is negative, syphilis is ruled out. If the test is positive then a non-treponemal test is performed. A positive non-treponemal test (RPR) is
diagnostic of syphilis. A negative RPR following a positive EIA is a discordant test result. The negative RPR must be confirmed by a different treponemal test,
the TPPA, which is both sensitive and specific.

Other Tests
Other tests like Polymerase Chain Reaction and Immunoblot are being investigated for application in the diagnosis of ocular syphilis.

Molecular diagnostics involving the assessment of levels of cytokines and biomarkers for diagnostic purposes are being studied.[1]

Management and other considerations

Treatment is the same as neurosyphilis: 10-14 day course of systemic antibiotics.
All patients testing positive for syphilis should be tested for HIV due to the high rate of co-infection.
All patients should undergo lumbar puncture and CSF analysis.
Treatment should not be delayed while waiting for lumbar puncture.
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Medical therapy
IV Penicillin G 24 million units daily 10-14 day course OR IM Procaine Penicillin 2.4 million units daily and Probenicid 2 grams daily
Alternative therapeutic regimens including Ceftriaxone or Doxycycline have been attempted in patients who cannot be given Penicillin, albeit with varying
success rates.
Adjunctive Therapy:
Topical Steroids
Oral Steroids: useful to decrease inflammatory reaction (Jarisch–Herxheimer reaction) but there is no agreement on if and when to initiate. Those who
utilize systemic steroids suggest starting with 40mg daily 2-3 days after initiation of systemic antibiotics. Oral steroid should not be started without
proper antimicrobial cover which may worsen the disease (https://link.springer.com/article/10.1186/s12348-018-0164-5).

Medical follow up
Repeat lumbar puncture indicated at 6 months post-treatment if initial CSF VDRL is positive.
Persistent ocular inflammation despite full treatment course of antibiotics and oral corticosteroids may indicate treatment failure though this is rare.
Consultation with infectious disease specialist is recommended to determine need for re-hospitalization and repeat systemic antibiotics.
Titers are expected to decrease 4 fold after successful treatment.

Prognosis
The CDC has reported several cases of blindness related to syphilitic uveitis; however, prompt diagnosis and management with antibiotics leads to good visual
acuity outcomes.
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 References
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