Ocular syphilis in patients with nonreactive RPR and positive treponemal serologies: a retrospective observational cohort study.

BACKGROUND: Screening for syphilis increasingly relies on positive treponemal rather than nontreponemal tests (rapid plasma reagin [RPR]). We compared ocular syphilis in patients with nonreactive versus positive RPR. METHODS: We conducted a retrospective observational cohort study of ocular syphilis treated at two New England hospitals 1996-2021 based on ophthalmologist-diagnosed eye findings and positive treponemal serology, regardless of RPR. We excluded patients with alternative diagnoses. We categorized RPR into nonreactive RPR, low-titer RPR (<1:8), and high-titer RPR (≥1:8) and compared early and long-term response to therapy. RESULTS: Our sample included 115 patients with ocular syphilis (median follow-up 2.5 years): 25 (22%) nonreactive RPR, 21 (18%) low-titer RPR, 69 (60%) high-titer RPR. Compared with nonreactive and low-titer RPR, people with high-titer RPR were younger (mean 47 years, p<0.001), more likely male (93%, p<0.001) and more likely to be living with HIV (49%, p<0.001). People with nonreactive and low-titer RPR were less likely than high-titer RPR to have posterior/panuveitis (32% and 29% versus 75%, p<0.001) or abnormal CSF (26% and 35% versus 75%, p<0.001), and more likely to present with chronic eye findings (20% and 29% versus 1%, p<0.001). In long-term follow up, eye findings improved and did not recur in most patients (62% nonreactive, 68% low-titer, 96% high-titer RPR); improved but recurred in 29%, 11%, and 4%, respectively; and were stable in 10%, 21%, and 0%, respectively. CONCLUSION: Patients with ocular syphilis and nonreactive RPR are similar to patients with low-titer RPR, and antibiotic therapy is beneficial in most.

Relapsed Mpox Keratitis, St. Louis, Missouri, USA.

We describe a case of a 46-year-old man in Missouri, USA, with newly diagnosed advanced HIV and PCR-confirmed mpox keratitis. The keratitis initially resolved after intravenous tecovirimat and penicillin for suspected ocular syphilis coinfection. Despite a confirmatory negative PCR, he developed relapsed, ipsilateral PCR-positive keratitis and severe ocular mpox requiring corneal transplant.

Could ceftriaxone be a viable alternative to penicillin for the treatment of ocular syphilis?

This study was conducted to compare the effectiveness of ceftriaxone with that of aqueous crystalline penicillin G in treating ocular syphilis. We conducted a retrospective study from 2010 to 2021. Syphilis patients were administered either ceftriaxone (2 g intravenously daily for 14 days) or aqueous crystalline penicillin G [4 million units (MU) intravenously every 4 h for 14 days] as therapeutic interventions. Subsequently, we utilized these two groups to assess the serological results, cerebrospinal fluid analysis, and visual acuity at time intervals spanning 3 to 6 months post-treatment. A total of 205 patients were included, with 34 assigned to the ceftriaxone group and 171 to the penicillin group. The median age of patients was 56 years, with an interquartile range of 49-62 years, and 137 of them (66.8%) were male. Between 3 and 6 months after treatment, 13 patients (38.2%) in the ceftriaxone group and 82 patients (48.0%) in the penicillin group demonstrated effective treatment based on the clinical and laboratory parameters. The crude odds ratio (OR) was 0.672 (95% confidence interval [CI]: 0.316-1.428, P = 0.301), indicating no significant difference in effectiveness between the two groups. Thirty patients (17.5%) in the penicillin group and six patients (17.6%) in the ceftriaxone group did not experience successful outcomes. Notably, no serious adverse effects were reported in both the groups. There was no significant difference in the effectiveness of ceftriaxone and aqueous crystalline penicillin G in treating ocular syphilis. The administration of ceftriaxone without requiring hospitalization presents a convenient and safe alternative treatment option for ocular syphilis.

Ocular syphilis masquerading as refractory retinal diseases.

PURPOSE: To report two cases of syphilis masquerading as chronic refractory macular diseases. CASE DESCRIPTIONS: Two patients had been diagnosed with neovascular age-related macular degeneration (neovascular AMD) and diabetic macular edema (DME), respectively. The disease worsened despite repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) and also surgical treatment (in suspected case of DME). Systemic evaluations were positive for syphilis. Intravenous penicillin was started, and the macular diseases improved. The lesions were well controlled afterward. CONCLUSIONS: The current two cases demonstrated that ocular syphilis can masquerade as refractory chronic retinal diseases such as DME and neovascular AMD. Laboratory evaluations for syphilis may be needed, not only for uveitis but also for refractory retinal diseases. Indocyanine green angiography may be helpful to reveal occult syphilis.

Neurosyphilis in a young man having HIV infection, blurring of vision and skin rash.

We report a 22-year-old homosexual man, a known case of HIV-1 infection but non-compliant to medications, who presented with a 5-month history of progressive painless non-pruritic coin-shaped skin lesions and recent gradual bilateral blurring of vision. His history divulged a primary syphilitic event 1 year prior to the present clinical manifestations. Investigation led to the diagnosis of neurosyphilis with ocular involvement with concurrent signs of secondary syphilis. Treatment with aqueous crystalline penicillin G, ophthalmic steroid and tropicamide drops, and topical emollients resulted in significant clinical improvement of ocular symptoms and skin lesions. The diagnosis of neurosyphilis requires a high degree of clinical suspicion and should be included in the differential diagnosis of unexplained ocular symptoms, particularly in men who have sex with men and HIV-infected patients. This is necessary for the early diagnosis, appropriate management, and good outcome of these patients.

Presentation of Ocular Syphilis with Bilateral Optic Neuropathy.

A 60-year-old otherwise healthy male presented with a 1 year history of bilateral progressive visual loss. His best-corrected visual acuity was counting fingers at 2 m with his right eye and counting fingers at 0.5 m with his left eye. Visual field testing revealed bilateral near-total loss of visual fields. Slit-lamp examination was unremarkable, apart from bilateral grade two nuclear sclerotic cataracts. Both optic discs were pale-looking with some retinal pigment epithelial alterations at the left papillomacular region. Enhanced depth imaging optical coherence tomography depicted punctate hyperreflective dots at the inner choroidal level corresponding to the retinal pigment epithelial changes in the left eye. Fundus autofluorescence imaging revealed patchy hyper-autofluorescent and hypo-autofluorescent areas, and there was mild staining in the early and late phases of the fluorescein angiogram at the papillomacular region in the left eye. A diagnosis of bilateral optic neuropathy was made. A full systemic work-up was carried out, and serological tests pointed out the presence of syphilis with normal cranial magnetic resonance imaging. He was treated accordingly. Our case clearly demonstrates the importance of a high clinical suspicion for syphilis in cases of optic neuropathy.

The Mydriatic Red Eye as the Initial Presentation of Syphilis.

BACKGROUND: Syphilis is a sexually transmitted infection that has been increasing in prevalence since the early 2000s. Ocular involvement occurs in a minority of patients and must be in the differential diagnosis for patients who present with red eye and uveitis. CASE REPORT: A 29-year-old woman presented to the emergency department with a painful, mydriatic red eye. Review of systems revealed a rash as well as a recent genital lesion and, on further questioning, she admitted to a history of intravenous drug use and high-risk sexual activity. Ophthalmology was consulted and the patient was diagnosed with bilateral uveitis. Serologic testing was positive for syphilis, and she was admitted and treated with intravenous penicillin, with resolution of her uveitis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Red eye is a common ocular symptom in patients presenting to the emergency department. The differential diagnosis of the red eye is broad and can range from benign etiologies, such as conjunctivitis, to life- and sight-threatening conditions, such as endogenous endophthalmitis. Systemic diseases such as syphilis may present with primarily ocular symptoms, and ocular syphilis must be identified and managed appropriately to prevent devastating sequelae.

Prevalence of Self-reported Neurologic and Ocular Symptoms in Early Syphilis Cases.

BACKGROUND: Neurosyphilis, a complication of syphilis, can occur at any stage of infection. Measuring the prevalence of neurosyphilis is challenging, and there are limited data on the prevalence of neurologic or ocular symptoms among patients with syphilis. We sought to describe the prevalence of neurologic and/or ocular symptoms among early syphilis (ES) cases and the clinical management of symptomatic cases enrolled in the STD Surveillance Network (SSuN) Neuro/Ocular Syphilis Surveillance project. METHODS: Persons diagnosed with ES were selected for interviews based on current health department protocols in 5 participating SSuN jurisdictions from November 2016 through October 2017. All interviewed ES cases were screened for self-reported neurologic and/or ocular symptoms. Additional clinical information on diagnostic testing and treatment for cases concerning for neurosyphilis/ocular syphilis was obtained from providers. RESULTS: Among 9123 patients with ES who were interviewed, 151 (1.7%; 95% confidence interval [CI], 1.4%-1.9%) reported ≥ 1 neurologic or ocular symptom. Of the 53 (35%) who underwent lumbar puncture, 22 (42%) had documented abnormal cerebrospinal fluid, of which 21 (95%) were treated for neurosyphilis/ocular syphilis. Among the remaining 98 symptomatic patients with no documented lumbar puncture (65%), 12 (12%) were treated for and/or clinically diagnosed with neurosyphilis/ocular syphilis. CONCLUSIONS: We observed a low prevalence of self-reported neurologic and/or ocular symptoms in interviewed ES cases. Approximately one-third of ES cases who self-reported symptoms underwent further recommended diagnostic evaluation. Understanding barriers to appropriate clinical evaluation is important to ensuring appropriate management of patients with possible neurologic and/or ocular manifestations of syphilis.

Secondary syphilis with ocular involvement in a HIV-infected patient - case report.

We describe the case of a HIV-infected patient, in whom a secondary syphilis with skin lesions and ocular involvement developed. On admission papular skin rash and partial visual loss with left eye were observed. Serological tests for syphilis were positive in very high titers. Ophthalmological examination revealed ocular abnormalities indicating ocular syphilis. Cerebrospinal fluid (CSF) tests showed elevated concentration of immunoglobulin G (IgG) with normal white blood count and albumin concentration, serological treponemal tests for syphilis were positive. Intravenous therapy with Penicillinum Crystallisatum (Benzylpenicillinum kalicum) was administered, according to the neurosyphilis treatment schedule, achieving resolution of the skin lesions and partial vision improvement, a month after the end of the treatment a complete recovery of the vision was noted. Serological tests` for syphilis titers decreased fourfold. Described case confirms reasonability of examination for syphilis in patients with sudden vision disturbances, especially those HIV-infected. It also indicates that early appropriate treatment of the ocular syphilis prevents permanent loss of vision.

Masqueraders of multiple evanescent white dot syndrome (MEWDS).

PURPOSE: To describe disorders that can masquerade as multiple evanescent white dot syndrome (MEWDS). DESIGN: Retrospective, multicenter case series. PARTICIPANTS: Patients who presented with clinical findings compatible with a diagnosis of MEWDS but were ultimately diagnosed with an alternative inflammatory, infectious, or neoplastic disorder. METHODS: Clinical records and multimodal imaging findings including fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were analyzed. MAIN OUTCOME MEASURES: Inclusion criteria to be defined as a masquerade syndrome for MEWDS included the presence of disseminated grayish-white outer retinal spots that were hyperautofluorescent on FAF and associated with ellipsoid zone (EZ) disruption on OCT. RESULTS: Twenty-two eyes of 13 patients were identified. All patients presented with the classic findings of MEWDS listed above. A MEWDS-like presentation was bilateral in nine of 13 patients (69%). Final diagnosis was determined on the basis of additional investigations including serologies and biopsy. These diagnoses included syphilis (three patients), lymphoma (three patients), idiopathic multifocal choroiditis (two patients), idiopathic retinal phlebitis (one patient), idiopathic acute zonal occult outer retinopathy (one patient), sarcoidosis (one patient), tuberculosis (one patient), and cancer-associated retinopathy (one patient). The outer retinal lesions and imaging findings resolved with treatment for the associated systemic disorders. CONCLUSIONS: Widespread grayish-white outer retinal spots associated with hyperautofluorescence on FAF and disruption of the EZ on OCT are not pathognomonic for MEWDS. A high index of suspicion must be maintained for masqueraders of MEWDS, which can include serious inflammatory, infectious, and neoplastic disorders.

Time to development of ocular syphilis after syphilis infection.

To provide an estimate of the incubation period of ocular syphilis based on serology using both clinical data and stored serum samples, we retrospectively reviewed patients with HIV-1 infection who presented with ocular syphilis between August 1997 and July 2015 in a tertiary hospital in Japan. The incubation period of ocular syphilis was defined as the time from syphilis infection to the development of ocular symptoms due to ocular syphilis. During the study period, 20 patients were diagnosed with ocular syphilis and 8 patients were enrolled in the present study. All patients were Japanese men who have sex with men with a median age of 46 years (IQR 41.5-53.5). The median CD4 count was 668.5/µL (IQR 567.8-734.3) and 5 of the 8 patients had HIV-1 viral load of less than 50 copies/mL. All study patients presented to our clinic because of the development of ocular symptoms, and they did not have any other symptoms compatible with primary, secondary, or tertiary syphilis. The median time between syphilis infection and development of ocular symptoms was 11 months (IQR 4-19, range 2.5-45). Seven out of eight (87.5%) cases developed ocular syphilis within 2 years of syphilis infection. Ocular syphilis should be suspected even in patients with early syphilis who present with ocular symptoms. Moreover, routine serologic screening for syphilis among patients with HIV-1 infection is critical for prevention of irreversible visual loss in ocular syphilis cases.

Clinical manifestations and cerebrospinal fluid status in ocular syphilis in HIV-Negative patients.

BACKGROUND: Syphilis with ocular involvement has reemerged as a critical health problem. The aim of the present study was to explore the clinical manifestations and cerebrospinal fluid (CSF) status in ocular syphilis in human immunodeficiency virus (HIV)-negative patients. METHODS: The clinical records of patients with ocular syphilis presenting to the Shanghai Xuhui Central Hospital in the period from January 2011 to December 2012 were retrospectively reviewed. RESULTS: The median age of 25 HIV-negative patients with ocular syphilis was 53 years, 18 patients (72.0 %) were males and 7 (28.0 %) were females. None of them self-identified themselves as men who had sex with men (MSM). The ocular lesions included: uveitis (13 cases), optic neuropathy (6 cases), retinal vasculitis (5 cases), retinal detachment (3 cases), and neuroretinitis (4 cases). Serum toluidine red unheated serum test (TRUST) titer ranged from 1 to 512, with a median of 64. Overall, 18 (72.0 %) of the 25 patients had abnormal CSF results, 15 (60.0 %) CSF samples had elevated white blood cell counts, 13 (52.0 %) had elevated protein levels, and 9 (36.0 %) had reactive CSF Venereal Disease Research Laboratory (VDRL) test, respectively. Mann-Whitney U tests showed higher serum TRUST titer (>32) correlated with the abnormal CSF results. CONCLUSIONS: The demographic characteristics of patients with ocular syphilis in this study were different from previous reports. The study showed a high CSF abnormal rate in HIV-negative patients. The recommendation for CSF examination from all patients with ocular syphilis, including HIV-negative cases, is strongly supported by the present data.

Ocular syphilis in patients with Human Immunodeficiency Virus infection.

As Acquired Immunodeficiency Disease (AIDS) turns thirty-years old, much progress has been made. 56,000 new cases of the Human Immunodeficiency Virus (HIV) infection are expected in Americans this year. At least half or more will be in African Americans. Reports of the association between syphilis and HIV infection are well documented. We present a case of bilateral optic neuritis and panuveitis as the initial presentation in a previously undiagnosed patient with human immunodeficiency virus (HIV) and syphilis.

Insights into ocular syphilis in Nepal.

PURPOSE: This study aims to elucidate the demographic characteristics, clinical features, diagnostic approaches, and medical management of patients with ocular syphilis, known as 'the great masquerader,' at a tertiary eye care center in Nepal. METHODS: We conducted a retrospective review involving 15 eyes from ten patients with ocular syphilis treated at a uveitis referral center between 2020 and 2022. Lumbar puncture was performed if neurosyphilis was suspected. Treatment success was defined as the absence of ocular inflammation in both eyes and a decrease in Veneral disease research laboratory (VDRL) titres after completing therapy. RESULTS: A total of 15 eyes of 10 patients were diagnosed with syphilitic uveitis based on positive treponemal and non-treponemal serological tests. The mean age of the patient was 39.9 years (range 22-54 years) with an equal distribution between males and females. HIV coinfection was not found in any of the patients. Syphilitic uveitis was the primary presentation in nine patients (90%), while one patient presented with recurrent nodular scleritis. Ocular involvement was bilateral in 50% (5 patients). The mean duration between the initial symptom and the first presentation was 8.7 weeks (range: 4 days to 24 weeks). The most common ocular findings was panuveitis (6 eyes). Eight patients with early syphilis received weekly intramuscular injections of benzathine penicillin G for 3 weeks whereas 2 patients with neurosyphilis were treated with intravenous ceftriaxone 1 gm twice a day for 14 days. Signs and symptoms of majority of patients improved with systemic therapy for syphilis. CONCLUSIONS: Syphilitic uveitis should be included in the differential diagnosis of any form of ocular inflammation.

Acute vision changes as the presenting symptom of ocular syphilis - A case series of two.

Introduction: Syphilis, a bacterial infection caused by Treponema pallidum, can affect a wide variety of organ systems of its host. We aim to present the cases of two patients who presented to an urban, tertiary care, academic Emergency Department with ocular symptoms who underwent imaging, laboratory, and specialist evaluation and were ultimately diagnosed with ocular syphilis. Case Report: The first patient is a 46-year-old female who presented to the Emergency Department with painless complete vision loss in a unilateral eye. Her exam was significant for bilateral papilledema, and further workup revealed a retinal detachment in the affected eye. Rapid plasma reagin (RPR) titers resulted positive with 1:128 and a reactive fluorescent treponemal antibody (FTA). Further workup including lumbar puncture and magnetic resonance imaging were unable to be obtained due to patient refusal and multiple discharges against medical advice. The second patient is a 38-year-old female with a history of intravenous drug use who presented for bilateral circumferential peripheral vision loss with central sparing. The examination showed bilateral papilledema. Lumbar puncture was performed with normal intracranial pressure. RPR titers resulted positive with 1:128. MRI and ophthalmology evaluation did not reveal any other etiology or explanation for papilledema. Conclusion: This case series highlights the importance of considering syphilis as a possible cause of ocular symptoms in high risk patient populations and the need for prompt and appropriate treatment given the increasing prevalence of syphilis worldwide.

Ocular Syphilis and Syphilitic Meningitis as the Initial Symptoms of Neurosyphilis in an HIV-Negative Patient: A Case Report.

Syphilis is an infectious disease caused by the spirochete bacteria Treponema pallidum and is most commonly transmitted via contact of mucous membranes with infectious lesions during sexual intercourse. It is called the "great mimicker" due to its ability to infect a wide variety of organs and, as a result, produce a multitude of symptoms. Neurosyphilis, an infection of the central nervous system, can occur at any stage of infection. Cases of early neurosyphilis may not present with any prior history of syphilis infection or classical symptoms of primary or secondary infection. Homosexual men are disproportionately affected by the increasing rate of transmission.In this case, a 43-year-old man was diagnosed with neurosyphilis, initially presenting with bilateral papilledema concerning for idiopathic intracranial hypertension. A detailed social history revealed that the individual was sexually active with a male partner. Despite nonreactive results from the rapid plasma reagin and CSF Venereal Disease Research Laboratory tests, further serum workup yielded positive results for treponemal antibodies. Evidence of facial nerve involvement was also found on MRI. These findings were consistent with a diagnosis of ocular syphilis with syphilitic meningitis involving cranial nerve VII. This case demonstrates the importance of clinical suspicion for syphilis when indicated by social history, even when screening tests are negative, due to the potential for false negatives and highly variable clinical presentation.

Co-infectious Uveitis With Syphilis and Lyme Disease: A Case Report.

Uveitis is the inflammation of the uveal tract (i.e., iris, ciliary body, and choroid). Uveitis is categorized into the following three types based on the anatomical location of inflammation: anterior, intermediate, and posterior uveitis. Severe cases may lead to panuveitis, where all three layers may become inflamed potentially resulting in permanent vision loss. Uveitis can arise from different underlying disorders, including infectious causes or autoimmune disorders. Syphilis and Lyme disease are uncommon causes of uveitis. Eye involvement can occur at any stage in Lyme disease, characterized by diverse manifestations such as conjunctivitis, episcleritis, keratitis, uveitis, neuroretinitis, and retinal vasculitis. Patients may present with symptoms of blurred vision, eye pain or discomfort, visual floaters, headache, or intolerance to light. Patients can risk vision loss if not diagnosed and treated promptly.

Anterior Non-Necrotizing Scleritis with Active Uveitis in Cases of Ocular Syphilis.

PURPOSE: To study clinical characteristics and management outcomes of cases of ocular syphilis co-presenting with scleritis and active uveitis. METHODS: A retrospective analysis of cases diagnosed with ocular syphilis between January 2020 and December 2023 was conducted at a tertiary eye care centre. Clinical records, investigations, and outcomes were reviewed to identify cases with scleritis with active uveitis. Demographic data, clinical features, treatment modalities, and resolution patterns were analyzed. RESULTS: Among the 135 eyes of 95 cases of ocular syphilis studied, scleritis with uveitis was observed in 3.70% of eyes (five eyes). All cases with scleritis and uveitis were unilateral and male, with ages ranging from 32 to 61 years. Concurrent features included placoid chorioretinitis, retinal vasculitis, and anterior uveitis. Misdiagnosis with subsequent oral steroid therapy precipitated scleritis as an exacerbation in two cases. Three cases, which were previously undiagnosed, were found to be HIV-positive. Scleritis manifested as anterior, non-necrotizing inflammation, often accompanied by chemosis, and responded rapidly to antibiotic and non-steroidal anti-inflammatory therapy. Scleritis resolution preceded that of chorioretinitis and retinal vasculitis. CONCLUSIONS: Non-necrotizing anterior scleritis with chemosis can be a rare presentation of active syphilitic uveitis. Large placoid chorioretinitis lesions, preceding inadvertent oral steroid and/or undiagnosed HIV status were the possible risk factors for the development of concurrent scleritis.

Clinical characteristics and outcomes of people living with HIV and ocular syphilis during the COVID-19 health emergency.

BACKGROUND: The global shift in healthcare during the COVID-19 pandemic led to challenges in the care of people living with HIV. METHODS: We conducted a retrospective study that aimed to delineate sociodemographic, clinical characteristics and outcomes, of people living with HIV diagnosed with ocular syphilis. RESULTS: Fifty-three people living with HIV were identified with ocular syphilis. Thirty-eight (71.6%) presented ocular symptoms. Twenty-three (43.3%) underwent lumbar puncture, 5 (9.4%) were positive for neurosyphilis. Forty-seven (88.6%) received treatment, 32 (68%) received standard treatment with aqueous crystalline penicillin G, and 15 (31.9%) were treated with alternative regimens due to the impossibility of hospitalization. Six (11.3%) individuals were lost to follow-up and/or did not receive treatment. Eighteen (56.2%) out of 32 individuals in the aqueous crystalline penicillin G group experienced serological response, 5 (15.6%) experienced treatment failure, and 9 (28.1%) were lost to follow-up. In the alternative therapy group, 12 out of 15 individuals (80%) experienced serological response. One (6.7%) experienced treatment failure, and 2 (13.3%) were lost to follow-up. CONCLUSIONS: During the COVID-19 health emergency in Mexico, alternative treatments for ocular syphilis demonstrated favorable clinical outcomes amid challenges in accessing hospitalization.