Want to receive publications straight to your inbox?

CATIE
  • Doctors at two Montreal hospitals reviewed patient records for cases of ocular syphilis
  • Syphilis affected the eye in 3% of patients who were diagnosed with the infection
  • Ocular syphilis signals that infection has affected the brain, requiring tailored care

Over the past 20 years there has been a large increase in cases of syphilis in Canada and other high-income countries. Some sexually active gay, bisexual and other men who have sex with men (MSM) have been hit hard by the resurgence of syphilis. The germs that cause syphilis—treponemes—enter the body during sex and within days can spread to the brain, cardiovascular system, liver, kidneys and other vital organs. Although this sexually transmitted infection (STI) can cause complex multi-stage disease, regular syphilis screening followed by prompt treatment can resolve this infection.

In 2015 the U.S. Centers for Disease Control and Prevention (CDC) alerted healthcare providers about an apparent increase in syphilis that affected the eyes (ocular syphilis). In some cases, people with ocular syphilis suffered severe loss of vision and even blindness. Since that time, additional reports from the U.S., British Columbia and Alberta as well as anecdotal reports from doctors in other parts of Canada (and other countries) have confirmed an increase in ocular syphilis.

In Montreal

A team of ophthalmologists at two hospitals in Montreal collaborated and reviewed health-related information about ocular syphilis at their clinics. They found ocular syphilis was relatively uncommon, affecting 3% of people with syphilis. Nearly 80% of people with ocular syphilis were male, and at least one-third were HIV-positive. In general, cases responded well to antibiotic treatment.

In their review, the doctors found that there was room for improvement in the care of people with ocular syphilis. The doctors made recommendations and underscored the importance of following guidelines for the treatment of syphilis.

Study details

Doctors reviewed medical records collected from the following two hospitals:

  • Hôpital Maisonneuve-Rosemont
  • Centre Hospitalier de l’University de Montréal (CHUM)

They confirmed syphilis diagnoses with Laboratoire de santé publique du Québec.

A total of 4,680 people had a positive syphilis test. Out of those people, 115 visited the ophthalmology departments of the two hospitals and were diagnosed with ocular syphilis.

The average profile of participants at the time they were diagnosed with ocular syphilis was as follows:

  • age – 55 years
  • 79% men, 21% women
  • HIV status – 25% had been previously diagnosed; 7% were newly diagnosed; 34% were negative at their last test; 34% did not know their status
  • CD4+ cell count among HIV-positive people – 360 cells/mm3
  • stage of syphilis — the majority of participants were distributed in the following stages of syphilis: secondary syphilis – 30%; late latent – 26%; tertiary – 26%
  • lumbar puncture (spinal tap) – the brain is surrounded by a clear liquid called the cerebrospinal fluid (CSF). A lumbar puncture is done to take a small amount of CSF for analysis. In the present study it was done in 55% of cases.
  • at least 52% of cases were MSM (demographic data were incomplete)

Results

Among the 115 participants with ocular syphilis, nearly half had problems affecting both eyes at the time they sought care. Common diagnoses were interstitial keratitis and uveitis. Symptoms associated with these conditions would likely have been one or more of the following:

  • eye pain
  • eye redness
  • reduced vision
  • increased sensitivity to light
  • excessive release of tears

In nearly 20% of cases the nerve that sends images from the eye to the brain (the optic nerve) was injured and inflamed.

Lumbar puncture

Doctors performed lumbar puncture on 63 people with ocular syphilis. In 71% of these cases, analyses of CSF samples found abnormalities such as antibodies associated with syphilis and higher-than-normal levels of two measures: white blood cells and protein.

Treatment

Most participants (70%) were treated with intravenous penicillin or a combination of intravenous penicillin followed by intramuscular penicillin. Other participants were treated with alternatives: oral antibiotics (such as azithromycin or doxycycline) or intravenous antibiotics (such as ceftriaxone). On average, most people had resolution of visual problems after treatment.

However, doctors noted that 18% of cases were not treated. About half of the untreated people stopped further contact with the ophthalmology clinics. In addition, four other people refused an offer of treatment and seven others had recently been treated for syphilis with intramuscular penicillin.

Focus on HIV

There were 37 cases whose HIV status was known prior to syphilis diagnosis; all were men. These men were mostly MSM and were, on average, younger (43 vs. 53 years) compared to HIV-negative people with ocular syphilis.

According to the doctors, “Overall, HIV-infected patients had a higher rate of abnormal CSF analysis results”—usually elevated levels of white blood cells and protein.

Bear in mind

Cases of syphilis have been increasing in Canada and other high-income countries over the past 20 years. Since the total number of cases of syphilis is increasing, the number of cases of ocular syphilis will likely increase as well. Fortunately, research suggests that a strain of syphilis that preferentially infects the eyes has not developed.

The Montreal doctors stated that it is possible that the actual number of cases of ocular syphilis is higher than they reported. For instance, some cases could have been managed by ophthalmologists at other centres in the region.

The doctors stated: “Despite the apparent association between [HIV and syphilis] it is worrisome to notice that over one-third of our patients did not have HIV testing…a positive syphilis test should prompt clinicians to perform HIV screening.”

The doctors underscored that leading STI guidelines from the CDC, the Public Health Agency of Canada and Europe advise clinicians to request a lumbar puncture in patients with ocular syphilis.

They recommended that intravenous aqueous penicillin G be used in people with ocular syphilis. This recommendation was given because, in their view (and those of leading infectious disease specialists), the presence of ocular syphilis is a signal that treponemes have entered the brain.

The Montreal doctors encouraged clinicians to monitor patients with ocular syphilis at six and 12 months after completion of antibiotic therapy. They found that only 37% of patients with ocular syphilis were assessed six months after the completion of therapy. The figure for 12 months after completion of therapy was even lower (25%).

Finally, the doctors noted that syphilis can cause a wide range of health problems and, as such, “testing for syphilis should be part of the work-up of any ocular inflammation.”

Resources

Canadian guidelines on STIs – Management and treatment of syphilis

Syphilis – British Columbia Centre for Disease Control

La prise en charge et le traitement de la syphilis chez les adultes infectés par le virus de l'immunodéficience humaine (VIH) – Guide pour les professionnels de la santé du Québec – Version résumée –  Ministère de la Santé et des Services sociaux du Québec

Syphilis – Public Health Agency of Canada

Syphilis - BMJ

SyphilisCATIE Factsheet

British Columbia — Increasing cases of syphilis affecting the eye CATIE News

Syphilis cases on the rise among HIV-positive people in CalgaryCATIE news

American doctors focus on cases of ocular syphilisCATIE News

More cases of ocular syphilis reported in the United StatesCATIE News

—Sean R. Hosein

REFERENCES:

  1. Vadboncoeur J, Labbé AC, Fortin C, et al. Ocular syphilis: case series (2000-2015) from 2 tertiary care centres in Montreal, Canada. Canadian Journal of Ophthalmology. 2020; in press.
  2. Eslami M, Noureddin G, Pakzad-Vaezi K, et al. Resurgence of ocular syphilis in British Columbia between 2013-2016: a retrospective chart review. Canadian Journal of Ophthalmology. 2020; in press.
  3. Lukehart SA, Hook EW 3rd, Baker-Zander SA, et al. Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment. Annals of Internal Medicine. 1988 Dec 1;109(11):855-62.
  4. Singh AE. Ocular and neurosyphilis: epidemiology and approach to management. Current Opinion in Infectious Diseases. 2020 Feb;33(1):66-72.
  5. Bazewicz M, Lhoir S, Makhoul D, et al. Neurosyphilis cerebrospinal fluid findings in patients with ocular syphilis. Ocular Immunology and Inflammation. 2019 Oct 24:1-7.
  6. Hamze H, Ryan V, Cumming E, et al. HIV seropositivity and early syphilis stage associated with ocular syphilis diagnosis: A case-control study in British Columbia, Canada, 2010-2018. Clinical Infectious Diseases. 2020; in press.
  7. Landry T, Smyczek P, Cooper R, et al. Retrospective review of tertiary and neurosyphilis cases in Alberta, 1973-2017. BMJ Open. 2019 Jun 22;9(6):e025995.
  8. Menard A, Meddeb L, Conrath J, et al. Ocular syphilis, an old adversary is back in the old world too! AIDS. 2018 Oct 23;32(16):2433-2434.
  9. Cope AB, Mobley VL, Oliver SE, et al. Ocular syphilis and human immunodeficiency virus coinfection among syphilis patients in North Carolina, 2014-2016. Sexually Transmitted Diseases. 2019 Feb;46(2):80-85.
  10. Beale MA, Marks M, Sahi SK, et al. Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages. Nature Communications. 2019 Jul 22;10(1):3255.
  11. Oliver S, Sahi SK, Tantalo LC, et al. Molecular typing of Treponema pallidum in ocular syphilis. Sexually Transmitted Infections. 2016 Aug;43(8):524-7.
  12. Marra CM, Tantalo LC, Sahi SK, et al. Reduced Treponema pallidum-specific opsonic antibody activity in HIV-infected patients with syphilis. Journal of Infectious Diseases. 2016 Apr 15;213(8):1348-54.