Syphilitic Uveitis

Ocular syphilis is intraocular inflammation caused by Treponema pallidum. It can occur at any stage and can mimic any form of uveitis, which is why it is called the great imitator.

• Incidence has risen worldwide, particularly in men who have sex with men and in HIV-infected patients; about 5 to 10 percent of patients with secondary syphilis have ocular involvement.
• Patterns: anterior (granulomatous or non-granulomatous with roseolae of the iris), intermediate, posterior (acute syphilitic posterior placoid chorioretinopathy with yellow placoid lesions at the macula, necrotising retinitis, retinal vasculitis, multifocal chorioretinitis), panuveitis, optic neuritis and perineuritis, and interstitial keratitis (congenital and late).
• Bilateral in about 50 to 60 percent. Any ocular involvement is treated as neurosyphilis.
• HIV co-infection is common (about 50 percent in some series).

• Blurred vision, floaters, redness, photophobia, scotomas, photopsia; sometimes preceded by rash on palms and soles, mucosal lesions, condylomata lata, lymphadenopathy, fever.
• Anterior chamber cells and flare, keratic precipitates, iris nodules and roseolae, vitritis, optic disc oedema, vasculitis, placoid lesions at the macula (ground glass retina with fluorescein hyperfluorescence), pinpoint retinal lesions, exudative detachment.
• Late: Argyll Robertson pupils (small, irregular pupils that accommodate but do not react to light), tabes dorsalis, general paresis, optic atrophy, chorioretinitis with pigment (salt and pepper).
• History of genital ulcer or previous untreated syphilis, sexual risk exposures.

• Serology: treponemal test (treponemal enzyme immunoassay, Treponema pallidum particle agglutination or haemagglutination, fluorescent treponemal antibody absorption) and non-treponemal test with titre (rapid plasma reagin, VDRL); a positive treponemal test with compatible findings is diagnostic. Non-treponemal tests can be negative in about 10 percent of late disease, so treponemal tests are required.
• HIV testing, plus tests for gonorrhoea, chlamydia and hepatitis B and C.
• Lumbar puncture for cerebrospinal fluid cell count, protein, VDRL and treponemal tests (neurosyphilis is present in a proportion of ocular cases; treat as neurosyphilis regardless).
• Optical coherence tomography and fluorescein angiography; MRI brain if neurological signs.
• Examination of contacts.

• Treat as neurosyphilis (regardless of cerebrospinal fluid result):
  • Aqueous benzylpenicillin 18 to 24 million units per day, given as 3 to 4 million units intravenously every 4 hours (or continuous infusion), for 10 to 14 days.
  • Alternative: procaine penicillin 2.4 million units intramuscularly daily plus probenecid 500 mg orally four times daily, both for 10 to 14 days.
  • Penicillin allergy: desensitisation is preferred; alternative ceftriaxone 2 g intravenously or intramuscularly daily for 10 to 14 days, or doxycycline 200 mg orally twice daily for 28 days (less proven).
  • Some clinicians add benzathine penicillin 2.4 million units intramuscularly weekly for 3 weeks after the intravenous course.
• Corticosteroids after antibiotic cover: oral prednisolone 0.5 to 1 mg/kg daily (typically 40 to 60 mg) started once penicillin cover is under way (or 24 hours before the first dose to limit the Jarisch-Herxheimer reaction), tapered over 2 to 4 weeks, with topical prednisolone acetate 1 percent and atropine 1 percent for anterior inflammation. Warn about the Jarisch-Herxheimer reaction (fever, worsening inflammation in first 24 hours).
• Follow non-treponemal titres at 3, 6, 12 and 24 months (a fourfold fall within 6 to 12 months indicates a response); repeat cerebrospinal fluid examination at 6 months if abnormal initially.
• HIV: start or optimise antiretroviral therapy; partner notification, treatment of partners, and sexually transmitted infection counselling.
• Visual prognosis is good with early treatment, but late optic atrophy and retinal damage are permanent.