Durray Nayab Ali
Abstract
Reports of syphilis in England have increased over the last 10 years. This bacterial infection is transmitted through direct contact with active primary and secondary lesions. Ocular syphilis can result from dissemination of the organism to different organs. Symptoms vary and include vision loss, photopsia, scotoma and eye pain. Syphilis results in ocular inflammation and typically presents with uveitis affecting both posterior and/or anterior segments. Serological testing is the mainstay of diagnosis but all patient should also be tested for HIV co-infection. Early administration of antibiotics improves prognosis.
Aetiology and Epidemiology
Syphilis is a bacterial infection caused by the spirochete, Treponema Pallidum: a phylum of bacteria which has characteristically long helically coiled cells and an associated flagellum (1). Infection is a result of the bacteria penetrating intact mucous membranes or injured skin and is acquired directly, usually by sexual contact, with active primary or secondary lesions (2,3). First recognised in Italy in the 15th century, the disease swept across Europe during the 18th and 19th century, and eventually declined during the mid-20th century due to the development and use of antibiotics (1,3). Over the last 10 years we have seen an increase in syphilis in England with three times as many reported syphilis cases (4). With increasing cases of the disease, you may expect an increase in patients with ocular syphilis, with one study identifying 40% of patients with syphilis presenting primarily with ocular disease (5).
The global prevalence of syphilis among adults aged 15-49 years was 18 million cases in 2012 with an estimated incidence of 5.6 million new syphilis cases in men and women (6). In the UK, the prevalence of syphilis has increased over the last several years to a peak in 2019, which demonstrated the highest number of syphilis cases since the 1940’s and an increase in 10% from 2018 (4). Recent data displays that the rate decreased during the COVID-19 pandemic, however by the end of 2021 returned to pre-pandemic levels (7). In 2022, infectious syphilis diagnoses increased by 15.2% compared to 2021 to 8,692 diagnoses (8). 71% of all infectious syphilis cases reported in England 2021 were in gay, bisexual and other men who have sex with men as well as being disproportionately higher among those of Black Caribbean background (7).
Stages of Disease
Primary syphilis is characterised by local dermatological manifestations and a lack of associated clinical neurological signs or symptoms (2). The primary stage typically presents on average 3 weeks after exposure as a painless ulcer (chancre) at the site of inoculation (3,9). Moderate lymphadenopathy is associated with primary syphilis and the chancre become indurated and eventually ulcerated (3). It is self-limiting at this stage and early treatment can prevent progression of the disease to neurosyphilis (2).
Secondary syphilis typically develops within the first three months of infection with a disseminated mucocutaneous rash involving the palms of the hands, soles of feet and/or trunk as the most common manifestation (1,3). During this acute disseminated phase where the organism deposits in a variety of tissues the disease is highly infectious (2,3). Non-specific symptoms may also be present and can include malaise, sore throat, muscle aches and weight loss (3,9).
Manifestations of secondary syphilis typically resolve spontaneously within 3 months of appearance (3). The latent stage, which refers to when the disease does not present with symptoms, can be divided into early (<2 years duration) and late (>2 years duration) (9). In late latent stage serological testing will be positive but sexual transmission is unlikely. Latent syphilis ends when antibiotic therapy is administered or the disease progresses into tertiary syphilis (3).
When latent syphilis becomes symptomatic it is referred to as tertiary syphilis and can present with gumma (a localised tissue and bone destruction), symptomatic late neurosyphilis and cardiovascular syphilis (3,9). A small percentage of individuals with secondary syphilis will develop neurosyphilis which includes ocular manifestations and meningitis (3,9).
Ocular Syphilis
Ocular syphilis can manifest at any stage of the disease (1). However, there is evidence to show that it presents at an increasing rate in secondary syphilis or latent syphilis (10–12). Cases of reported neurological and ocular manifestations appear to be higher among those who have co-existing HIV infection (11). Time till presentation with symptoms varies but typically occurs at around 4-10 weeks (1,13). Ocular signs and symptoms are wide-ranging and include vision loss, photopsia, floaters, red eye, relative afferent pupillary defects and scotomas (10,14). Ocular manifestation of the disease can be both bilateral and unilateral, with one study identifying that in those with unilateral disease, the left eye was predominantly affected (13).
Syphilis results in ocular inflammation which appears to typically affect the posterior segment or both posterior and anterior segments (13). In one study non-granulomatous iridocyclitis and posterior uveitis present most commonly in ocular syphilis, followed by panuveitis and intermediate uveitis (15). Anterior segment involvement is variable in ocular syphilis with some patients demonstrating non-specific granulomatous anterior uveitis or iris nodules (10). Syphilic anterior uveitis is usually associated with a raised intra-ocular pressure (1). Common posterior segment findings have been reported including vitritis, chorioretinitis and retinitis (13,15). Posterior uveitis is a common finding in HIV negative patients (12). Acute posterior placoid chorioretinopathy is characteristically seen in secondary and latent syphilis and presents as one or more yellowish placoid like retinochoroidal lesions located in the macula (1). Symptoms are usually mild and fully recover with early treatment (10). Less common findings of ocular syphilis also include non-necrotizing anterior scleritis, non-necrotizing sclero-keratitis and optic neuritis (15). Syphilic phlebitis has also been reported(14).
Syphilis is regarded as the great imitator and thus should also be considered in patients presenting with episcleritis, scleritis, optic neuritis, keratitis and iridocyclitis with or without iris nodules (1,16). Neurosyphilis can produce Argyll Robertson pupils and optic atrophy, whilst the most common finding in tertiary syphilis is bilateral diffuse periostitis (1).
Diagnosis and Management
Serological testing is the current predominantly used investigation of choice for the diagnosis of syphilis (17). This consists of treponemal and non-treponemal testing to detect antibodies to T. Pallidium (1,17). Non treponemal tests detect total IgM and IgG antibodies against lipoidal antigens that are released from damaged host cells and bacteria usually a few weeks after infection (9). Treponemal tests mainly detect IgG antibodies and have increased sensitivity and specificity for T. Pallidium, remaining positive throughout life (1,9). There are two main syphilis testing algorithms that exist with a ‘traditional’ and ‘reverse’ algorithm (1,9). The traditional algorithm for laboratory testing of syphilis begins with a non-treponemal test followed by a treponemal test for confirmation of the reactive non treponemal serology (17,18). Reverse-syphilis screening algorithm uses a treponemal-specific immunoassay for initial screening of disease and reactive samples are then tested with non-treponemal assays for confirmation of the disease (1,9). CSF analysis is also required to rule out neurosyphilis in cases of ocular syphilis (1). Most notably, it is essential to also test patients for HIV, as studies have found up to a third of patients are HIV positive (13).
Penicillin is typically the first choice of treatment with benzathine penicillin G being the mainstay of treatment, although doxycycline and ceftriaxone have also been identified to be effective treatments for early syphilis when penicillin is contraindicated (19). Oral steroids may also be used to reduce ocular inflammation; however, this should not delay initiation of antibiotics as disease progression may occur and lead to vision loss (20). Other treatments to be considered include topical mediation such as NSAIDs, steroids and mydriatics to relieve acute ocular symptoms (1). Non-treponemal tests are used to monitor disease response to treatment in the following months due to its correlation with disease activity (19).
The prognosis for early treatment of syphilis is positive with studies demonstrating patients presenting with reduced visual acuity typically returned to their baseline after treatment (13). Left untreated, 25% patients will experience one or more relapses (1).
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