Four of the 10 patients had an undiagnosed maculopapular rash that was consistent with secondary syphilis at the time of presentation. Among the 4 patients with a maculopapular rash, 1 also had a headache, and 3 were HIV-positive. Four of the 10 patients had a history of untreated chancre that was consistent with primary syphilitic infection. No patient presented with clinical signs of tertiary syphilis. At presentation, all patients had a positive MHA-TP (range, 1:4–1:20,480) and a positive VDRL (range, 1:16–1:1280).
Nine of 10 patients had a lumbar puncture before treatment; the single patient who did not have a lumbar puncture was HIV-negative. All nine patients who had lumbar punctures had elevated cerebrospinal fluid protein, and eight of the nine patients (88.9%) had pleocytosis. The CSF of two patients had a positive VDRL test.
Three patients (30%) were treated with intravenous penicillin G, 24 million units per day for at least 14 days; six patients (60%) were treated with intravenous ceftriaxone sodium 1 g/d for 14 days; and one HIV-negative patient (10%) was treated with 2.4 million units of intramuscular benzathine-benzyl penicillin, 1 dose per week for 3 weeks. All patients were reexamined at 1 month after initiation of treatment, and in all patients, ocular inflammation resolved (Fig. 1B). Median visual acuity after treatment was 20/25 (range, 20/20–20/63). Posttreatment CSF analysis was not performed. Follow-up longer than 1 month after treatment was available in four patients (mean, 20 weeks; range, 15 weeks to 24 months), and no recurrence of infection was noted.
Between 2001 and 2004, the French Department of Disease Control encountered a dramatic increase in the number of new cases of syphilis from 37 cases in 2000, to 207 cases in 2001, and to 401 cases in 2002.1 The percentage of syphilitic uveitis among all uveitis patients in our eye clinic was lower than in other studies,2–4 but dramatically increased between 2001 and 2003, in parallel with the increase reported by the French Departments for Disease Control. Age and gender at diagnosis of syphilis in our study was similar to the data collected in French health departments since 2000.1
The increase in the number of new cases of ocular syphilis in France correlates with the HIV epidemic in male homosexuals,5 and a similar situation is evident in Western Europe.1 After declining in the 1990s,4,6 syphilis in the United States of America is increasing again,7 especially among male homosexuals,8 many of whom are coinfected with HIV.9 The risk factors for syphilis and HIV infection in this population are multiple sexual partners and unprotected sexual practices. In our series, 80% of the patients were coinfected with HIV; while this is higher than in other reports,10 in HIV-positive patients, the diagnosis of syphilis can be mistaken for AIDS.
Ocular involvement in syphilis is rare. Gass et al. reported that uveitis was present in 4.6% of patients examined with secondary syphilis.11 Syphilis is often overlooked as a cause of uveitis because it manifests with a wide variety of ocular signs that mimic other diseases, and for this reason has long been known as “the great impersonator.”12 Delays in diagnosis and treatment can lead to irreversible visual loss, due to optic nerve and retinal atrophy.2,12,13 Typically, uveitis occurs during the secondary stage of syphilis14 and includes acute iritis, posterior uveitis, panuveitis, diffuse chorioretinitis, and perivasculitis.13 In secondary syphilis, serologic tests are usually uniformly positive, and less than 30% of patients have pleocytosis in the cerebrospinal fluid.15,16
The incidence of syphilis-related ocular complications appears to be increased by coinfection with HIV.2 For this reason HIV-positive patients in our series had a lumbar puncture. Eight patients with secondary syphilis in our series had ocular and cutaneous manifestations with a markedly abnormal cerebrospinal fluid analysis, and seven of these eight patients were HIV-positive. The central nervous system was infected by Treponema pallidum in two patients, as indicated by a positive cerebrospinal fluid VDRL test, suggesting that HIV-positive patients with ocular syphilis may be at increased risk of developing neurosyphilis. Indeed, an acceleration of the normal course of syphilis has been described when patients are simultaneously infected with HIV.17,18 Our results did not suggest a correlation between ocular syphilis and the stage of HIV infection. Although there is no explanation for the latter observation, our results agree with other studies.19,20
In our series, CD4+ lymphocyte counts varied considerably, similar to other reports,19 and a CD4 cell count <200 cells/mm3 was not necessary to develop syphilitic infection.
It is uncertain whether concurrent infection with HIV-1 alters the course and effectiveness of standard therapy for syphilis20 like that of other infectious disease such as tuberculosis.21 In our series, ocular syphilis in HIV-positive patients was treated with standard antibiotic regimens for neurosyphilis.21,22 The influence of ocular involvement and poorer response to neurosyphilis treatment are difficult to substantiate.21
In our series, ocular syphilis in HIV coinfected patients received the neurosyphilis treatment, corresponding to the treatment accepted in the literature.21,22 One HIV-negative patient received intramuscular benzathine penicillin, a standard treatment for secondary syphilis.23 The failure rate after recommended penicillin regimens for early syphilis is estimated to be 0.8% in HIV-negative patients and is probably higher in HIV-positive patients.20
In our series, intraocular inflammation resolved and best corrected visual acuity recovered in all patients by 1 month after treatment, indicating successful short-term response to treatment. Because our follow-up was limited, we cannot make conclusions about the long-term effect of treatment, although relapses did not occur in the four patients who had longer follow-up.
Syphilis is the most common bacterial eye infection to cause intraocular inflammation in HIV-positive patients. This report reemphasizes that all patients with newly diagnosed intraocular inflammation should be tested for syphilis.24,25 Moreover, the fact that ocular syphilis was associated with HIV infection in 80% of the patients highlights the need for HIV screening in patients with ocular syphilis.
In summary, our data showed an unexpectedly high incidence of ocular syphilis in a tertiary eye care referral center, in Paris, France, between 2001 and 2004. A diagnosis of ocular syphilis should be considered in any patient presenting with visual symptoms who also has a rash and/or headache, irrespective of the patient's CD4 cell count. HIV-positive patients with ocular syphilis should receive the standard treatment for neurosyphilis, whereas HIV-negative patients with ocular syphilis can be treated with the standard regimen for secondary syphilis.
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