Color slit lamp photograph of large “granulomatous” keratic precipitates in a patient with syphilitic uveitis (Reproduced with permission from Wender J, Eliott D, Jumper JM, Cunningham ET Jr. How to recognize ocular syphilis. Rev Ophthalmol, 2008, November, 124–130)
Color slit lamp photograph of iris roseola in a patient with syphilitic uveitis. Two patent iridotomies are visible at 2 and 10 o’clock (Reproduced with permission from Wender J, Eliott D, Jumper JM, Cunningham ET Jr. How to recognize ocular syphilis. Rev Ophthalmol, 2008, November, 124–130)
Cataracts have been described uncommonly in association with both congenital and acquired syphilis.
18.104.22.168 Posterior Segment
Posterior segment complications appear to be particularly common in patients with syphilis . Although the clinical presentation can be varied and a wide assortment of findings has been reported, there are posterior findings that, while not necessarily pathognomonic, are highly suggestive of syphilitic infection.
Isolated vitritis can occur in patients with syphilis; however, vitreous inflammation tends to occur more often in association with other posterior segment findings, most commonly retinitis [19, 20]. One report highlighted three cases of primary vitritis as the initial manifestation of syphilitic uveitis . All the patients in the report were HIV positive.
While isolated optic disc edema has been reported as a presenting sign of syphilis [22, 23], optic disc swelling typically occurs in the setting of active uveitis (Fig. 4.3) [19, 20, 24].
Color fundus photograph of syphilitic papillitis in an HIV-positive patient (Reproduced with permission from Wender J, Eliott D, Jumper JM, Cunningham ET Jr. How to recognize ocular syphilis. Rev Ophthalmol, 2008, November, 124–130)
Numerous descriptions and variations of retinitis have been reported in cases of syphilitic uveitis including wedge-shaped retinitis, ground-glass retinitis, and necrotizing retinitis [2, 11, 20, 25, 26]. Active syphilitic retinitis often contains both vasculitis and superficial precipitates or accumulations (Fig. 4.4), which together are quite suggestive of syphilis . Similarly, acute syphilitic posterior placoid chorioretinitis (ASPPC), first described by Gass in 1990 , is a classic finding of syphilis (Fig. 4.5). In ASPPC, the lesions are typically yellow-white, placoid, circular, or oval and involve the macular or extramacular area. An active leading edge was often observed. Fluorescein angiography shows a hypofluorescent central lesion in the early-phase frames with progressive hyperfluorescence in the later frames, often observed with leopard spotting [2, 20, 27]. Spectral domain optical coherence tomography imaging shows characteristic outer retinal abnormalities, including disruption of the ellipsoid band, nodular thickening of the retinal pigment epithelium (RPE), loss of the outer segment/RPE junction, and in some cases loss of the external limiting membrane. Subretinal fluid was also observed, although was transient. Usually these findings reversed following appropriate treatment; however in some cases, the damage to the outer retinal anatomy was permanent and poor vision persisted [20, 28].
Color fundus photograph of characteristic “ground-glass” retinitis associated with a serous retinal detachment, focal inflammatory accumulations, and retinal vasculitis in an HIV-positive patient with syphilitic uveitis (Reproduced with permission from Wender J, Eliott D, Jumper JM, Cunningham ET Jr. How to recognize ocular syphilis. Rev Ophthalmol, 2008, November, 124–130)
Color fundus photograph (a) and serial fluorescein angiographic images (b, c) of acute syphilitic posterior placoid chorioretinopathy (ASPPC) showing a characteristic macular lesion and progressive hyperfluorescence (Reproduced with permission from Wender J, Eliott D, Jumper JM, Cunningham ET Jr. How to recognize ocular syphilis. Rev Ophthalmol, 2008, November, 124–130)
Localized exudative retinal detachments are relatively common in posterior syphilitic uveitis and have been widely reported [29–31]. Rhegmatogenous retinal detachments, in comparison, are much less common [32, 33]. Rhegmatogenous detachments typically occur early in the course of treatment, as the infection resolves, but prior to the resolution of inflammation, and are thought to be due to contraction of the vitreous (Fig. 4.6) .
B-scan ultrasonography showing a total rhegmatogenous retinal detachment in a patient with syphilitic panuveitis
Diagnosis of the “great imitator” requires a high level of clinical suspicion. The definitive method for diagnosis is direct visualization of T. pallidum using dark-field microscopy; however due to the technological difficulties of this test, it is rarely performed . Serologic testing can be divided into two groups. First, the nontreponemal tests such as the venereal disease research laboratory (VDRL) and the rapid plasma reagin (RPR) tests detect antibodies to cardiolipin (lecithin) cholesterol antigen. The titers of the nontreponemal tests are often used as an indicator of both disease activity and of appropriate and complete treatment. In contrast, direct treponemal tests such as enzyme immunoassays (EIAs) and chemiluminescent immunoassays (CIAs) detect antibodies directed against treponemal antigens and so are used as more sensitive and specific indicators of past or current infection. These direct treponemal assays will remain reactive for years, despite adequate therapy .
Most practitioners today use both treponemal and nontreponemal tests to confirm syphilis infection in patients with syphilitic uveitis. The nontreponemal tests are inexpensive and often used for screening; however, they are not specific for syphilis, can produce false-positive results, and can be falsely negative in early stages of infection. If there is discordance between the treponemal and nontreponemal serologies, a confirmatory Treponemal pallidum particle agglutination (TP-PA) test can be used for syphilis diagnosis. In patients with confirmed syphilis infection, HIV testing is also warranted.
4.6 Differential Diagnosis
The differential diagnosis is quite broad for syphilitic uveitis, given its varied ocular manifestations. Nonulcerative stromal keratitis is often associated with congenital or acquired syphilis, but the differential includes tuberculosis, leprosy, sarcoidosis, lymphoma, Lyme disease, herpes simplex virus and herpes zoster virus, Epstein-Barr virus, mumps, human T-lymphotropic virus type 1, leishmaniasis, onchocerciasis, trypanosomiasis, Cogan’s syndrome, or trauma such as contact lens overwear. In cases of syphilitic panuveitis, the differential diagnosis includes endogenous endophthalmitis, sarcoidosis, toxoplasmosis, tuberculosis, Lyme disease, Behçet’s disease, and viral retinitis such as cytomegalovirus or acute retinal necrosis. The differential diagnosis for posterior placoid chorioretinopathy due to syphilis is similar to the differential for panuveitis, tuberculosis, Lyme disease, toxoplasmosis, and sarcoidosis, but also should include fungal infections, lymphoma, persistent placoid maculopathy, and metastasis.
Patients with a new diagnosis of syphilis must first be reported in most countries and regions, patients with a new diagnosis of syphilis should be reported to the local health authorities. Penicillin G is the drug of choice for all stages of syphilis, although the specifics of the regimen are debated. In immunocompetent patients with early syphilis, defined as primary, secondary, or latent of less than 1 year’s duration, a single intramuscular injection of 2.4 million units of benzathine penicillin G is considered adequate. Recommended treatment for patients with active chorioretinal disease is aqueous crystalline penicillin G (18–24 million units IV daily) or procaine penicillin (2.4 million units IM daily) with oral probenecid (500 mg four times daily) for 10–14 days. Response to treatment is verified by a fourfold decrease in titer by the same nontreponemal test. If there is confirmed neurosyphilis with positive cerebrospinal fluid, patients should be monitored at 6-month intervals with CSF studies until the cell count normalizes. In patients with concurrent HIV infection, the treatment regimen should be for 3 weeks rather than 10–14 days, and serologic testing should be performed at 6-month intervals for 2 years to monitor for treatment failure [11, 25].