Continuing medical education
Sexually acquired syphilis: Historical aspects, microbiology, epidemiology, and clinical manifestations

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Syphilis is caused by infection with the spirochetal bacterium Treponema pallidum subsp. pallidum. It was first recognized in the late 15th century. Since 2000, the incidence of sexually acquired syphilis has increased substantially in the developed world, with men who have sex with men and persons living with HIV infection disproportionately affected. Clinical manifestations of syphilis are protean and often include mucocutaneous manifestations. The first article in this continuing medical education series reviews historical aspects, microbiology, epidemiology, and clinical manifestations of sexually acquired syphilis.

Introduction

Key points

  1. Syphilis is caused by the spirochete Treponema pallidum subsp. pallidum

  2. The incidence of syphilis is increasing worldwide

  3. Stages of syphilis infection include primary, secondary, early nonprimary nonsecondary, and unknown duration or late syphilis

Syphilis is an infection caused by the spirochete Treponema pallidum subsp. pallidum. First described in the late 15th century, syphilis has been a frequent—and often controversial—topic in medicine, public health, and social commentary. Because its protean clinical manifestations can mimic other diseases, syphilis has been called “the great imitator.” “He who knows syphilis,” Sir William Osler famously said, “knows medicine.”

Since 2000, the incidence of syphilis has increased in the United States.1 Because syphilis has prominent mucocutaneous manifestations, dermatologists can play important roles in both diagnosis and management. The first article in this continuing medical education series covers historical aspects, microbiology, epidemiology, and clinical manifestations of acquired syphilis in adults. The second article in this series addresses testing and management of syphilis. Multiple organizations have released guidelines for syphilis management. In this continuing medical education series we cite guidelines from the U.S. Centers for Disease Control and Prevention (CDC). Although congenital syphilis is an increasingly important issue, it is not covered here.

The origins of syphilis remain controversial. It was first reported in the Old World in the 1490s, when Italian physicians described a new disease affecting invading French soldiers. The “Columbian hypothesis” holds that syphilis was a New World disease brought to the Old World in 1493 by Columbus's returning seamen. Competing hypotheses include the “pre-Columbian hypothesis,” which postulates that syphilis existed in both the Old and New Worlds before Columbus's voyage, and the “evolutionary/Unitarian hypothesis,” which theorizes that treponemal diseases were distributed worldwide, with different treponemes affecting different populations.2, 3

Syphilis spread quickly across Europe. It was initially a virulent disease, called “the Great Pox,” characterized by large, painful, foul-smelling sores and significant mortality.3 Within about 50 years, however, it began presenting more mildly. That evolution may have been the result of natural selection for less virulent strains because more virulent strains caused disease that was debilitating to the infected and obvious to potential sexual partners.4

The name syphilis comes from a poem written by Girolamo Fracastoro in 1530 in which a shepherd named Syphilus angers the god Apollo, who curses the population with a disease bearing the shepherd's name.5, 6 Syphilis is also called lues, from the Latin word for plague.7

Pre–penicillin era treatments included purgative agents, heat, and pyrogens. Mercury was used widely in topical salves, oral compounds, injections, and fumigation. Treatment could last for years, giving rise to the saying, “A night with Venus, and a lifetime with mercury.”8

Nobel Prizes in Physiology or Medicine were twice awarded for syphilis treatments. Dr Paul Ehrlich received one in 1908 for discovering arsphenamine, an arsenical compound called “the magic bullet.”5 The second went to Dr Julius Wagner-Jauregg in 1927 for developing malariotherapy to treat neurosyphilis. Malariotherapy rested on the belief that fevers induced by inoculating patients with Plasmodium vivax killed heat-sensitive T pallidum bacteria. Notably, about 15% of patients undergoing malariotherapy died.9

Penicillin was reported as an effective treatment for syphilis in 1943 and remains the recommended therapy, with no known resistant cases.10

T pallidum subsp. pallidum is a slow-growing, motile spirochete bacterium with a long spiral shape. Humans are its only natural host and it cannot be cultured in vitro. It is closely related (>99% DNA homology) to other pathogenic treponemes, including Treponema pallidum subsp. pertenue, which causes yaws; Treponema carateum, which causes pinta; and Treponema pallidum subsp. endemicum, which causes endemic syphilis or bejel.11

Sexual acquisition of syphilis occurs when an infectious lesion (chancre, mucous patch, or condyloma lata) contacts the skin or mucous membrane of an uninfected person, often (but not exclusively) during oral, vaginal, or anal sex. The risk of transmission after sexual exposure is estimated at approximately 33%.12 Bloodborne and in utero transmission can also occur.

Public health practitioners typically focus on the epidemiology of primary and secondary syphilis because those stages of syphilis are infectious and represent a barometer of infectivity in a population. Here we present case counts (with incidence in parentheses, expressed as cases per 100,000 population per year) for primary and secondary syphilis in the United States.

In 1941, when syphilis surveillance began, there were 68,231 cases (51.7).13 The highest case count and incidence occurred in 1946, which saw 94,957 cases (70.9).13 The widespread use of penicillin and improved prevention and control efforts led to a decline; in 1956, 6392 cases (3.9) occurred.13 Cases and incidence waxed and waned during the 1960s and 1970s. During an epidemic in the 1980s and 1990s, cases and incidence rose to a high of 50,578 (20.3) in 1990.13 Starting in 1995, cases and incidence rates fell yearly, leading CDC to launch a national plan to eliminate syphilis.14

However, after reaching a nadir in 2000, with 5979 cases (2.1), syphilis has increased every year since.15, 16 The 30,644 cases (9.5) in 2017, the last year for which national data were available, represented more than a quadrupling since 2000 and an 10% increase from 2016.1

In 2017, 88% of cases overall occurred in men, and 58% of cases overall occurred in men who have sex with men (MSM), including 52% who had sex with men only, and 6% who had sex with men and women.1 Risk factors for syphilis infection among MSM include methamphetamine use, acquiring sexual partners from the Internet, and previous syphilis infection.17, 18, 19 The ongoing syphilis epidemic among MSM underscores the importance of eliciting a sexual history, including gender(s) of sex partner(s), from patients in whom syphilis is suspected.20 Eliciting gender identity should also be considered because some studies show that transgender women are at higher risk.21, 22

Among women, syphilis cases and incidence during 2000 to 2012 fluctuated, with a high of 2445 (1.7) in 2000 and a low of 1217 (0.8) in 2003. Syphilis among women has increased yearly since 2003, more than doubling from 1458 cases (0.9) in 2012 to 3722 cases (2.3) in 2017. That rise has been accompanied by a near-tripling in congenital syphilis cases, from 334 in 2012 to 918 in 2017.1, 23

Syphilis has increased in all age groups. In 2017, syphilis cases and incidence were highest in the 25- to 29-year-old age group, with 6838 cases (29.9). In adolescents 10 to 14 years of age and 15 to 19 years of age there were 20 cases (0.1) and 1421 cases (6.7), respectively, in 2017, compared with 15 cases (0.1) and 1298 cases (6.1), respectively, in 2016. In persons >65 years of age, cases increased to 349 (0.7) in 2017 from 279 (0.6) in 2016.1

Disproportionately higher rates of primary and secondary syphilis have occurred among African American men and women and among Hispanic men.20

Rates of HIV infection are higher among persons with syphilis than the general population. In 2017, HIV coinfection was present in 46% of MSM, 8.8% of men who have sex with women, and 4.5% of women diagnosed with primary or secondary syphilis.1 By comparison, the estimated overall HIV prevalence in the United States among persons ≥13 years of age was 0.4% in 2015.24 All persons diagnosed with syphilis who are not known to be coinfected with HIV should be tested for HIV.22

Outbreaks of ocular syphilis in the United States have increasingly occurred since 2014, prompting the CDC to issue a clinical advisory in 2015 that was still in effect as of August 2018.25, 26 The epidemiology of persons affected with ocular syphilis has mirrored that of syphilis overall.25

As in the United States, syphilis incidence among MSM has increased throughout the developed world.27, 28 As for the global burden of disease, among persons 15 to 49 years of age in 2012, an estimated 18 million were infected with syphilis, with the highest prevalence in Africa; in addition, 5.6 million new infections occurred, translating to an incidence of 150 in 100,000 persons.29

Section snippets

Clinical manifestations

Key points

  1. The clinical manifestations of syphilis are highly variable

  2. Syphilis staging nomenclature continues to evolve

  3. Neurosyphilis, otic syphilis, and ocular syphilis can occur during any stage

Most information on the natural history of syphilis comes from either the preantibiotic era30, 31 or the infamous Tuskegee study, in which penicillin was intentionally withheld from poor African American participants from 1932 until 1972.32

The infection proceeds through stages that have distinct clinical

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    Date of release: January 2020

    Expiration date: January 2023

    Funding sources: None.

    Conflicts of interest: None disclosed.

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