eMedicine Specialties > Infectious Diseases > Sexually Transmitted Diseases

Syphilis

Author: Peter F Liu, MD, Staff Physician, Department of Emergency Medicine, Virginia Hospital Center Arlington
Coauthor(s): Brian Euerle, MD, FACEP, Associate Professor, Department of Emergency Medicine, Director of Emergency Ultrasound Program, University of Maryland School of Medicine; Pranatharthi Haran Chandrasekar, MD, Director of Infectious Disease Fellowship, Professor, Department of Internal Medicine, Harper Hospital, Wayne State University School of Medicine
Contributor Information and Disclosures

Updated: May 21, 2009

Introduction

Background

Syphilis is a venereal disease caused by infection with the spirochete Treponema pallidum. It can also be acquired via exposure to infected blood. T pallidum is able to cross the placenta in pregnant women and result in fetal infection.

Untreated syphilis progresses through 4 stages: primary, secondary, latent, and tertiary. Known as a great imitator, syphilis can be a diagnostic challenge because of its wide-ranging clinical presentations.

Pathophysiology

Three genera of spirochetes cause human infection: (1) Treponema, which causes syphilis, yaws, and pinta; (2) Borrelia, which causes Lyme disease and relapsing fever; and (3) Leptospira, which causes leptospirosis.

T pallidum is transmitted via penetration of the spirochetes through mucosal membranes and abrasions on epithelial surfaces. Incubation time from exposure to development of primary lesions, which occur at the primary site of inoculation, averages 3 weeks but can range from 10-90 days. Pathologically, the primary lesion of syphilis is a focal endarteritis and periarteritis. Studies in rabbits show that spirochetes can be found in the lymphatic system as early as 30 minutes after primary inoculation, suggesting that syphilis is a systemic disease from the outset.

The primary lesion of syphilis is the chancre. Histologically, it is characterized by mononuclear leukocytic infiltration, macrophages, and lymphocytes. The inflammatory reaction causes an obliterative endarteritis. In this stage, the spirochete can be isolated from the surface of the ulceration or the overlying exudate of the chancre. Whether treated or not, healing occurs within 3-12 weeks, with considerable residual fibrosis.

Secondary syphilis lesions are quite variable in their manifestations. Widespread mucocutaneous lesions are observed over the entire body. Most often, the lesions are macular, discrete, reddish brown, and 5 mm or smaller in diameter; however, they can be pustular, annular, or scaling. All such lesions contain treponemes. Of these, wet mucous patches are the most contagious. Histologically, the inflammatory reaction is similar to but less intense than that of the primary chancre.

Currently, late syphilitic disease is rare. It mainly affects the cardiovascular system (80-85%) and the CNS (5-10%). The pathognomonic lesion of tertiary syphilis is the gumma, which is characterized by a center of necrotic tissue with a rubbery texture. Gummas principally form in the liver, bones, and testes. Histological examination shows palisaded macrophages and fibroblasts, as well as plasma cells surrounding the margins. Treponemes are rarely visualized or recovered from these lesions.

Frequency

United States

During most of the 20th century, the incidence of syphilis declined. The incidence dramatically decreased during the 1940s, following the advent of penicillin therapy; however, during the mid 1980s, the trend reversed. Increases in the use of intravenous drugs and crack cocaine, the exchange of sex for drugs, indiscriminate or anonymous sex, and the number of people with multiple sexual partners contributed to the turnaround. From 1986-1990, the rate of syphilis nearly doubled, reaching a peak of 53.8 cases per 100,000 population in 1990.

After 1990, the incidence decreased; in 2000, the number of syphilis cases reported was at an all-time low. Increased awareness, aggressive screening, and emphasis on primary prevention contributed to the decrease.

Recently, the number of syphilis cases in the United States has slightly increased. The Centers for Disease Control and Prevention (CDC) reported that, from 2003-2004, the rate of primary and secondary syphilis increased 8%, from 2.5 to 2.7 cases per 100,000 population.¹ Preliminary 2007 syphilis data showed that the US rate of primary and secondary syphilis increased 12% between 2006 and 2007, from 3.3 to 3.7 cases per 100,000 population.

Mortality/Morbidity

• The morbidity of syphilis ranges from the relatively minor symptoms of the primary stages of infection to the more significant constitutional systemic symptoms of secondary syphilis and the significant neurological and cardiovascular consequences of tertiary disease.
• Twenty percent of untreated patients with tertiary syphilis die of the disease.
• Since latent syphilis can persist for years or decades, the manifestations of tertiary syphilis often occur much later in life, causing significant morbidity.

Race

Non-Hispanic blacks are at higher risk for syphilis than non-Hispanic whites. In 1997, the reported incidence of syphilis among non-Hispanic blacks was 22 cases per 100,000 population. This was 44 times higher than the rate in non-Hispanic whites.² This ratio had declined to 8:1 by 2002, after implementation of a national plan to eliminate syphilis in the United States.

Since 2002, the incidence of syphilis has steadily increased among all races. From 2005 to 2006, the incidence of primary and secondary syphilis increased in all racial and ethnic groups, with a 5.6% increase in non-Hispanic whites (from 1.8 to 1.9 per 100,000 population), 16.5% in African Americans (from 9.7 to 11.3 per 100,000 population), 12.5% among Hispanics (from 3.2 to 3.6 per 100,000 population), 18.2% among Asian/Pacific Islanders (from 1.1 to 1.3 per 100,000 population), and 37.5% among American Indian/Alaska Natives (from 2.4 to 3.3 per 100,000 population). The data can be found on the CDC Web site.

Sex

Male-to-female ratios of primary and secondary syphilis increased from 1.6:1 in 1965 to nearly 3:1 in 1985. Since then, the ratio decreased, reaching a nadir in 1994-95.

Since 2002, the incidence of primary and secondary syphilis has risen 54% among men (from 3.7 per 100,000 in 2002 to 5.7 per 100,000 in 2006). Among women, the rates of primary and secondary syphilis remain lower. After a decade of declines, the overall prevalence of syphilis among females increased 11.1% between 2005 and 2006 (from 0.9 to 1 per 100,000). Based on 2006 data, males with primary and secondary syphilis outnumber females 6 to 1.

Studies of patients diagnosed with sexually transmitted diseases (STDs) demonstrate that men are screened for syphilis in emergency departments and health clinics more often than women. Although surveillance data based on risk behavior are not available, a separate CDC analysis suggests that approximately 64% of all adult primary and secondary syphilis cases in 2004 were among men who have sex with men, up from an estimated 5% in 1999.

Sex-based trends in syphilis can be found on the CDC Web site.³

Age

Syphilis is most common during the years of peak sexual activity. Most new cases occur in men and women aged 15-40 years. The age-based frequency of syphilis peaks at 25-29 years.

An age-based breakdown of syphilis can be found on the CDC Web site.

The incidence of congenital syphilis has increased 3.7% from 2005-2006 after 14 years of decline in the United States (from 8.2 to 8.5 cases per 100,000 live births). Between 1996 and 2005, the yearly incidence of congenital syphilis decreased by an average of 14.1% (see the CDC Web site for more information).

Clinical

History

The presentation of syphilis varies, and a high index of suspicion is needed for prompt diagnosis. Rigorous attention to the time course of symptoms is required for proper staging.

Obtain a thorough sexual and social history, including the number of sexual partners, condom use, history of STDs in the patient and their partners, intravenous drug use, and exposure to blood products. In children and infants, seek a maternal history, history of exposure to individuals with syphilis or blood products, and a history of sexual abuse. (For more information on pediatric syphilis, see the article Syphilis in eMedicine’s Pediatrics: General Medicine volume.)

• Primary syphilis
  • Primary syphilis manifests mainly on the glans penis in males and on the vulva or cervix in females. Regional nontender lymphadenopathy follows invasion.
    
    

    

    Syphilis. These photographs depict the characteristic chancre observed in primary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

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    Syphilis. These photographs depict the characteristic chancre observed in primary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

    
    
    

    

    Syphilis. This photograph depicts primary syphilis "kissing" lesions. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

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    Syphilis. This photograph depicts primary syphilis "kissing" lesions. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

  • Ten percent of syphilitic lesions are found on the anus, fingers, oropharynx, tongue, nipples, fingers, or other extragenital sites.
  • Lesions (chancres) are usually solitary, raised, firm papules that can be several centimeters in diameter. The chancre erodes to create an ulcerative crater within the papule, with slightly elevated edges around the central ulcer.
• Secondary syphilis
  • Secondary syphilis manifests in various ways. It usually includes a localized or diffuse mucocutaneous rash and generalized nontender lymphadenopathy.
    
    

    

    Syphilis. These photographs show the disseminated rash observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

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    Syphilis. These photographs show the disseminated rash observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

  • Constitutional symptoms of secondary syphilis include malaise, sore throat, headache, fever, anorexia, and meningismus (rarely).
  • Other less-common manifestations include GI involvement, hepatitis, nephropathy, proctitis, arthritis, and optic neuritis.
• Latent syphilis
  • Syphilis primarily spreads during the first year after infection.
  • Affected patients may recall symptoms of primary and secondary syphilis.
  • They are asymptomatic during the latent phase, and the disease is detected only by serologic tests.
  • Latency may last from a few years to as many as 25 years before the destructive lesions of tertiary syphilis manifest.
  • Latent syphilis is divided into early latent and late latent. The distinction is important because treatment for each is different.
    • The early latent period is the first year after the resolution of primary or secondary syphilis. Asymptomatic patients who have a newly active serologic test after having a serologically negative test result within 1 year are also considered to be in the early latent period.
    • Late latency syphilis is not infectious; however, women in this stage can spread the disease in utero.
• Tertiary syphilis
  • Late syphilis is slowly progressive and may affect any organ.
  • The disease is generally not thought to be infectious at this stage.
• Congenital syphilis
  • Early congenital syphilis occurs within the first 2 years of life.
  • Late congenital syphilis emerges in children older than 2 years.

Physical

• Primary syphilis
  • Classic chancres are not painful and are associated with regional lymphadenopathy. They can become painful if suprainfected with bacteria.
  • The patient is typically afebrile.
  • Symmetric rash is typical; however, the presence of overlying superinfection, scratching, or scaling may make the presentation atypical.
• Secondary syphilis
  • The rash may be macular, papular, pustular, or mixed.
  • Early syphilitic lesions are typically round, discrete, reddish brown macules and are usually distributed on the trunk and extremities. These measure approximately 5 mm in diameter. The rash is nonpruritic, and the macules are symmetric.
  • Red papular lesions may appear on the palms, soles, face, and scalp and may become necrotic. The lesions can cross the lifelines of the palms and soles. Alopecia may also occur.
    
    

    

    Syphilis. Palmar lesions observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

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    Syphilis. Palmar lesions observed in secondary syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

  • Reddish brown papular lesions on the penis or anogenital area can coalesce into large elevated plaques (condylomata lata) up to 2-3 cm in diameter. These can be confused with condylomata acuminata or venereal warts.
    
    

    

    These photographs illustrate examples of condylomata lata. The lesions resemble genital warts (condylomata acuminata). Fluids exuding from these lesions are highly infectious. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

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    These photographs illustrate examples of condylomata lata. The lesions resemble genital warts (condylomata acuminata). Fluids exuding from these lesions are highly infectious. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

  • Superficial painless mucous patches may develop on the tongue, oral mucosa, lips, penis, and vulva. These erosions harbor treponemes and can transmit disease.
  • Thirty percent of patients experience recurring symptoms after the primary or secondary stage of syphilis. Lesions are less numerous but are still infectious.
• Tertiary syphilis
  • Tertiary syphilis (gummatous syphilis) manifests cutaneously or may involve visceral organs.
  • Cutaneous gummas may be single or multiple. They are generally asymmetric and grouped together. The lesions may mimic other granulomatous ulcerative lesions and may be histologically indistinguishable from them. Visceral lesions often cause local destruction of the affected organ.
  • The liver and skeleton are commonly affected in tertiary syphilis.
  • Fever, jaundice, anemia, and nighttime skeletal pain are characteristic.
  • Cardiovascular syphilis usually involves the aorta. Invading treponemes cause scarring of the tunica media. Over many years, the inflammatory scarring weakens the aortic wall, leading to aneurysm formation, which causes incompetence of the aortic valve and narrowing of the coronary ostia.
  • Neurosyphilis manifests as an insidious but progressive loss of mental and physical functions and is accompanied by mood alterations. It is caused by invasion of T pallidum into the CNS. Neurosyphilis chiefly manifests as the 3 following entities:
    • Meningovascular syphilis is characterized by obliterative endarteritis and perivascular inflammation in the brain.
    • Paretic syphilis is the result of widespread parenchymal invasion that causes individual cell death and brain atrophy.
    • Tabes dorsalis is the result of damage to the sensory nerves in dorsal roots, producing ataxia and loss of pain sensation, proprioception, and deep tendon reflexes in joints.
• Congenital syphilis
  • Clinical evidence of early congenital syphilis is similar to that of secondary syphilis in adults. The rash has a higher probability of being atypical and can be vesicular or bullous instead of the characteristic reddish brown macular rash.
  • Additional symptoms of early congenital syphilis include the following:
    • Hemorrhagic rhinitis
    • Periostitis
    • Pseudoparalysis, often due to pain secondary to osteochondritis
    • Mucous patches
    • Perioral fissures
    • Hepatosplenomegaly
    • Generalized lymphadenopathy
    • Hydrops
    • Glomerulonephritis
    • Thrombocytopenia
    • Neurologic involvement
    • Ocular involvement
      
      

      

      Syphilis. This photograph illustrates chorioretinitis of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

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      Syphilis. This photograph illustrates chorioretinitis of congenital syphilis. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

  • Late congenital syphilis mainly manifests as neurologic symptoms. Cardiovascular abnormalities are rare. Symptoms include the following:
    • Prominent frontal bones, depression of nasal bridge, abnormal maxilla development, anterior tibial bowing
    • Clutton joints (arthritis of both knees)
    • Interstitial keratitis
    • Hutchinson incisors
      
      

      

      Syphilis. This photograph shows an example of Hutchinson teeth in congenital syphilis. Note notching. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

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      Syphilis. This photograph shows an example of Hutchinson teeth in congenital syphilis. Note notching. Used with permission from Wisdom A. Color Atlas of Sexually Transmitted Diseases. Year Book Medical Publishers Inc; 1989.

    • Mulberry molars
    • Deafness
    • Paroxysmal cold hemoglobinuria
    • Gummatous involvement

Causes

Syphilis is caused by infection with the spirochete T pallidum, a thin helical cell approximately 0.15 µm X 6-50 µm. T pallidum is a labile organism that cannot survive drying or exposure to disinfectants; thus, fomite transmission (eg, from toilet seats) is virtually impossible. T pallidum is solely a human pathogen and does not naturally occur in other species. T pallidum has, however, been cloned in Escherichia coli and has been used experimentally in rabbits. Transmission of T pallidum occurs via penetration of the spirochetes through mucosal membranes and abrasions on epithelial surfaces. It is primarily spread through sexual contact but can be spread by exposure to blood products and transferred in utero.

• Risk factors of syphilis include the following:
  • Unprotected sex, promiscuous sex, and intravenous drug use are the major risk factors.
  • Health care workers are at occupational risk.
  • See Frequency, Race, Sex, and Age.

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