The literature on ocular syphilis among HIV-infected individuals is limited. In this systematic analysis, we report the clinical and laboratory findings associated with 101 cases of ocular syphilis among HIV-infected individuals. Although this was a systematic review, there was a large amount of heterogeneity in the quality of data and follow-up.
The age, sex, CD4 profile and HIV-1 RNA measurements are consistent with data from US studies of neurosyphilis.27,38
Rash consistent with secondary syphilis was described in a majority of patients, which is similar to a study of neurosyphilis among patients with HIV38
and earlier pre-HIV era studies.39,40
In addition, the high RPR/VDRL titres in the majority of patients suggest that most patients were in the earlier stages of infection. Since the onset of symptoms was not clear in most cases, a more precise discrimination of syphilis stage was not possible. These findings are also consistent with the pre-HIV literature that found a relationship between higher non-treponemal test results and neurosyphilis.41
While a wide range of serum RPR titres have been observed in neurosyphilis studies,27,38
we were able to uncover three cases of ocular syphilis with negative serum RPR/VDRL titres. Although further information about prozone phenomena or the presence of non-syphilis treponeme might explain these cases, there were limited available data on prozone phenomena from the primary manuscripts and follow-up inquiries. Negative non-treponemal tests in the setting of ocular syphilis have been reported among HIV uninfected individuals related to prozone phenomena21
and to other causes,42,43
suggesting that this may not be unique to HIV-infected individuals. These three cases suggest that ocular syphilis may occur in the setting of a negative serum non-treponemal test, emphasising the need for treponemal diagnostic testing and, possibly, lumbar puncture in patients suspected of having ocular syphilis.
This study found a trend towards higher CSF WBC counts in patients with lower CD4 counts (p=0.055). At the same time, seven patients with ocular syphilis and HIV infection had normal CSF white blood cell count, total protein and CSF VDRL titres; all these patients were from the HAART era. This correlated with the finding that those with suppressed viraemia were less likely to have a reactive CSF VDRL test. Syphilis literature from the 1980s suggested that most patients with ocular syphilis had an elevated CSF white blood cell count and total protein,43
consistent with our results. There are conflicting data about the CSF VDRL test among patients who have ocular syphilis. While one study from the pre-HIV era found that none of 50 individuals with ocular syphilis had a reactive CSF VDRL test,43
a greater number of reactive CSF VDRL positive cases were found in an HIV-era study32
and our pooled data.
Several previous case series of ocular syphilis among HIVinfected patients have noted a tendency towards posterior uveitis19,20,31,37
but our analysis supported only the association between posterior uveitis and low CD4 counts. It is unclear why posterior uveitis appears more commonly in HIV-infected patients with low CD4 cell counts. Most patients with uveitis secondary to syphilis have good visual prognosis. Patients with posterior uveitis with central chorioretinal lesions and optic neuritis have poorer prognosis than patients with anterior uveitis and other categories of inflammation.
Persistent symptoms are common among HIV-infected patients with neurosyphilis. A prospective study of 41 HIV-infected patients with neurosyphilis found that patients’ main complaint persisted at 1 year in 38% of cases,27
and another study found that 30% of treated cases had persistent symptoms. 38
However, the patients with ocular syphilis in our analysis had good response to treatment based on repeat examination. Although data are available for only 35 patients, 97% of the cases showed definitive improvement or normal visual acuity on follow-up.
While visual improvement was rapid in most patients after treatment, a small number of patients had persistent visual acuity problems. There were limited data on follow-up and also on the use of steroids which may help prevent visual acuity problems. The importance of completing an adequate course of intravenous antibiotics for all patients with neurosyphilis cannot be overstated.44
The US CDC recommends 10–14 days of intravenous penicillin, although these guidelines are based on limited data.45
A full course of intravenous penicillin may be especially important in patients who may have a compromised immune system.3
Several studies noted early administration of steroids in patients with uveitis in order to prevent an ocular Jarisch–Herxheimer reaction46,47
and prevent further inflammation related to uveitis.48
This study has several limitations worthy of consideration. There was substantial heterogeneity in the quality of the data and follow-up in the analysed literature. Publication bias probably revealed a greater number of severe cases, although based on laboratory abnormalities and clinical course, this group of patients with ocular syphilis and HIV probably has less severe disease than other cohorts with neurosyphilis.27,38
Since RPR and VDRL tests were done at different laboratories, comparison of values must be interpreted with caution. Not all patients underwent lumbar puncture and were followed up for repeat visual acuity examination, but patients who had persistent visual problems would probably be followed up. In addition, the CSF WBC cut-off point of 5 WBC/mm3
was chosen because most studies reported that value. Among HIV-infected people, this cut-off point may have lower specificity when diagnosing neurosyphilis.41
Despite the advent of HAART, ocular syphilis remains an important clinical concern among patients with HIV infection. It can occur in patients with negative serum RPR or VDRL test and clinicians must obtain serum treponemal tests when the suspicion of ocular syphilis is high. Lumbar puncture is recommended for the evaluation of all patients with ocular syphilis as a substantial proportion will have evidence of neurosyphilis. Although the visual recovery of patients who completed 10–21 days of intravenous antibiotic therapy was good, behavioural counselling and close follow-up are advised. More research is needed to better understand ocular syphilis among HIV-infected patients.