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Ocular syphilis in HIV‐positive individuals

In their paper, ‘Syphilitic retinitis and uveitis in HIVpositive adults’, Hughes et al. present a detailed case series of 13 consecutive patients with syphilitic uveitis presenting over a 3-year period to two hospitals in Sydney, Australia. Six patients were HIV positive, and in this group retinitis occurred significantly more often than in the HIV-negative cohort (i.e. six of six HIV-positive vs. one of seven HIV-negative persons). Given the number of patients included, this case series is one of the more robust to appear in the recent literature on ocular syphilis. We look forward to the collection of more cases to confirm the reported association between HIV infection and syphilitic retinitis. If confirmed, this observation would have important diagnostic utility. After Treponema pallidum spirochetes disseminate to the eye, the effects may be manifold, are often devastating, and rarely, if ever, are stereotyped. To recognize the manifestations of ocular syphilis, one needs to consider all the tissues of the eye. Thus, patients may present with episcleritis, scleritis, dacryoadenitis, anterior uveitis, intermediate uveitis, papillitis, retinal vasculitis, neuroretinitis and chorioretinitis. In the past, ocular syphilis has been described as manifesting most commonly as an isolated anterior uveitis. However, in the recent literature, including the series by Hughes et al., posterior segment inflammation predominates. This may be a real association, indicative perhaps that a more aggressive subspecies of T. pallidum is relatively more prevalent today, or it may be a spurious conclusion resulting from the inherent selection bias of reported cases. Alternatively the finding may reflect increasing rates of co-infection with HIV and syphilis, an association that others have proposed portends posteriorly located, aggressive and refractory eye disease. In view of this, it is interesting to note the recently published case series by Anshu et al. Of 22 consecutive patients with syphilitic uveitis, the authors found non-granulomatous anterior uveitis in 62% and posterior uveitis in only 14% of individuals; none of the 22 patients tested positively for HIV. There appears to be an emerging clinical picture in patients with ocular syphilis who present with retinitis. Authors have described patches of creamy, diffuse retinitis with overlying punctate, superficial retinal precipitates. Wickremasinghe et al. considered this presentation to be so characteristic, it led to a diagnosis of ocular syphilis that might otherwise have been missed, by encouraging the authors to retest a patient who initially presented with negative luetic serology. They suggested that some subspecies of T. pallidum contributing to the current epidemic may have an increased propensity to produce this previously unrecognized clinical picture. In the case series reported by Hughes et al., two of the seven patients presenting with retinitis had this clinical picture, and both were HIV positive. While certainly not a sensitive clinical finding, this form of retinitis may prove to be highly specific for ocular syphilis. However, given the myriad of presentations and the lack of truly pathognomonic features of this disease, the majority of patients seen with ocular syphilis will not have a clinical finding with high positive predictive value. Penicillin remains the mainstay of treatment for syphilis, including ocular syphilis, although formal guidelines do not exist. There is a frequent association between syphilitic uveitis and neurosyphilis, as such the US Centers for Disease Control and Protection (CDC) recommends that practitioners manage patients with either of these manifestations identically, including the use of initial and follow-up examinations of the cerebrospinal fluid. The suggested treatment for neurosyphilis, and hence syphilitic uveitis, is intravenous aqueous crystalline penicillin G at a dose of 3 to 4 million units every 4 h for 10 to 14 days; alternatively, a 10to 14-day course of procaine penicillin, 2.4 million units intramuscularly once daily, with probenecid, 500 mg orally 4 times daily, may be given. Even with these regimens, the relapse or reinfection rate for ocular syphilis may be as high as 14%. Given the potential impact of HIV status on both diagnosis and treatment of the infection, with higher likelihood of falsenegative luetic serology and treatment relapse if an individual is HIV positive, most authors agree that HIV testing should be performed on all patients who present with ocular syphilis. HIV positivity, and not the treatment regimen used (i.e. intravenous vs. intramuscular), appears to be the primary risk factor for treatment failure. After reaching a nadir in 2000 (since reporting began in 1941), the incidence of primary and secondary syphilis in the USA has risen annually, primarily among men and, in particular, men who have sex with men. In 2008, the CDC surveillance report described the largest number of new cases to date (i.e. 13 500 persons), which represented an 18% increase from the previous year. The reasons for this surge, though not entirely clear, may relate to a reframed public perception of HIV from death sentence to treatable chronic disease, which has paved the way for high risk sexual behaviours. The alarming increase in incidence, which is reflected in reports from around the globe, including the paper by Hughes et al., has important implications for practicing ophthalmologists. Of 100 cases of confirmed or probable neurosyphilis diagnosed in Los