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Ocular Syphilis in Context

Hook, Edward W. III MD

doi: 10.1097/OLQ.0000000000000499
The Real World of STD Prevention

From the *University of Alabama at Birmingham, Birmingham, AL

Conflict of interest: None declared.

Correspondence: Edward W. Hook, III, M.D., The University of Alabama at Birmingham, 703 19th Street South, ZRB 242, Birmingham, AL 35294-0007. E-mail:

Received for publication June 7, 2016, and accepted June 8, 2016.

Syphilis is back (again)! In the past decade, United States syphilis rates have more than doubled as the epidemiology of the infection has shifted from the largely heterosexual disease which characterized the epidemic of the 1990s to an infection which is now most common among men who have sex with men, particularly those with human immunodeficiency virus (HIV) coinfection.1 A national strategy to intervene upon increasing syphilis rates which addresses characteristics of the current epidemic is being formulated, led by the Centers for Disease Control and Prevention (CDC) with the input from scientists and public health experts across the nation. At the same time, with the resurgence of syphilis it has once again become apparent that infections are often not detected by health care providers at the earliest opportunities, delaying diagnosis and permitting continued transmission. Once again, there is a need to reacquaint clinicians with risk factors and clinical presentations of this highly variable disease. Hopefully, the CDC will embrace this urgent need.

The resurgence of syphilis has also raised new questions about this ancient disease. Concomitant with increasing syphilis rates, astute clinicians in Washington State noted an upswing in ocular syphilis and sounded the alert.2 The clinical advisory which followed from the CDC3 has since led to increased reporting and vigilance in looking for ocular involvement in persons with syphilis, resulting in hundreds of ocular syphilis diagnoses over the past 2 years from across the nation.

As cases have accrued, so have questions: is this something new? Does ocular syphilis reflect the impact of HIV on the natural history of syphilis? Does the sudden upswing in reported ocular syphilis cases represent the emergence of a new, more aggressive, oculotropic strain of Treponema pallidum? The answer to the first question comes to us from review of materials written in the preantibiotic era—ocular syphilis is not a new phenomenon, having been well described in texts published before the availability of penicillin when syphilis was far more common than it is today.4–6 In the pre-penicillin era, syphilitic iritis was noted to occur insidiously, to occur in persons with both early and late syphilis, and to occasionally be a manifestation of therapeutic relapse following insufficient therapy with arsenical agents.5 Because late manifestations of syphilis are less common at this time than in the pre-penicillin era, most iritis now appear to occur in persons with early syphilis.7 However, the other characteristics of current cases resemble those reported many years ago. This issue of Sexually Transmitted Diseases, updates these earlier observations and begins to answer emerging questions about the presentations and risks for modern ocular syphilis. The manuscript by Marx and coworkers7 describing cases seen at several centers across the United States provides a case series which helps to describe how ocular syphilis presents and provides valuable lessons for clinicians. This series of 6 patients with ocular syphilis demonstrates that: ocular syphilis is now most often seen in persons with early syphilis, acquired within a year or 2 preceding diagnosis; that ocular syphilis tends to not occur abruptly but to progress over a period of weeks or months; that health care providers may not consider syphilis in persons presenting with ocular complaints; that the problem occurs both in persons with and without HIV; and that while ocular syphilis is certainly a manifestation of central nervous system involvement by the disease, many patients with the illness have normal lumbar puncture results. These observations resemble findings from a 1941 article by Moore and colleagues who reported ocular findings in 4.5% of the patients4 and are reinforced by a recent article in Sexually Transmitted Diseases by Dr. Julia Dombrowski and colleagues8 which indicate that when sought, sometimes subtle ocular involvement was demonstrable in 4.8% of patients with early syphilis and that when auditory abnormalities are also sought, visual or hearing changes could be detected in 7.9% of patients. As in the pre-penicillin era, ocular or auditory symptoms were detected somewhat more often among persons with late syphilis; however, because early syphilis patients were evaluated more often than persons with late disease, far more patients with ocular syphilis were seen among persons with early (most often secondary) syphilis. These data indicate a pressing need to work to heighten syphilis awareness among clinicians who may not work in the sexual health field. How to do this in a changing clinical landscape in which dedicated services for sexually transmitted infections (STIs) are diminishing is a daunting problem. The CDC's National Network of STD Prevention Training Centers may play a role in efforts to increase awareness of the current epidemic syphilis.

A second article in this issue of Sexually Transmitted Diseases addresses the important question of whether or not a new or specific strain of T. pallidum is responsible for the increased of numbers of ocular syphilis cases detected. Using sophisticated molecular typing methods to evaluate specimens collected across the nation, Oliver and colleagues9 provide data which suggest that no single type of T. pallidum is uniquely present in persons with ocular syphilis. Although this observation by no means rules out the possibility that other genetic factors might predispose certain strains of T. pallidum to cause ocular disease, this study demonstrates that multiple strains are causing ocular syphilis and further reinforces the impression set forth by Dombrowski and colleagues8 that ocular syphilis may be less of a new phenomenon than a process which is being detected more often as syphilis rates increase in the United States and demonstrating the need for a campaign to heighten awareness of syphilis and its myriad manifestations.

Syphilis remains a challenging problem and a reminder of the all too common misperception on the part of both clinicians and the general public that STIs are someone else's problems. The current resurgence of syphilis in the United States and Western Europe also serves to remind us of the many questions regarding the disease. When broadly and steadfastly applied, currently available tools and strategies for syphilis control have succeeded in lowering syphilis rates. The current epidemic has brought attention to this recurring problem and will likely lead to investment of the time and resources needed to address the current epidemic. Sustaining these strategies, as well as using new tools to detect and control syphilis is a more daunting task. A starting point for such efforts is to work to broaden screening and to reacquaint clinicians how this disease, as well as other STIs may potentially impact their patients and to work to broadly incorporate the concept of sexual health for clinicians. Such efforts should be a high priority for public health practitioners and for policy makers.

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1. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2014. Atlanta. Department of Health and Human Services; 2015.
2. Centers for Disease Control and Prevention. Notes from the field: MMWR Morbid Mortal Wkly Rep 2015; 64: 1150–1152.
3. Centers for Disease Control and Prevention. Clinical Advisory: Ocular syphilis in the United States, 2016;
4. Moore JE, Gieske M. Syphilitic iritis. Am J Opthal 1931; 14:110–116.
5. Moore JE. The Modern Treatment of Syphilis, 2nd Edition. Baltimore MD, Charles C Thomas 1941:317–343.
6. Stokes JH, Beerman H, Ingraham NR. Modern Clinical Syphilology. 3rd ed. Philadelphia PA: WB Saunders and Co, 1945 1932—Ocular syphilis noted in 2.8% (91/3244) early syphilis patients (Stokes et al, Modern Clinical Syphilology, 1945.
7. Marx GE, Dhanireddy S, Marrazzo JM, et al. Variations in clinical presentation of ocular syphilis: Case series reported from a growing epidemic in the United States. Sex Transm Dis 2016 In press.
8. Dombrowski JC, Pedersen RA, Marra CM, et al. Prevalence estimates of complicated syphilis. Sex Transm Dis 2015; 42:702–704.
9. Oliver S, Sahi SK, Tantalo LC, et al. Molecular typing of Treponema pallidum in ocular syphilis. Sex Transm Dis 2016 In Press.
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