Syphilis overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. The signs and symptoms of syphilis are numerous; before the advent of serological testing, precise diagnosis was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Syphilis (unless antibiotic-resistant) can be easily treated with antibiotics including penicillin. The oldest and still most effective method is an intramuscular injection of benzathine penicillin. If not treated, syphilis can cause serious effects such as damage to the heart, aorta, brain, eyes, and bones. In some cases these effects can be fatal. In 1998, the complete genetic sequence of T. pallidum was published which may aid understanding of the pathogenesis of syphilis.

Historical Perspective

The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in his epic noted poem, written in Latin, entitled Syphilis sive morbus gallicus (Latin for "Syphilis or The French Disease") in 1530. The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's Metamorphoses). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him. From this character Fracastoro derived a new name for the disease, which he also used in his medical text De Contagionibus ("On Contagious Diseases"). Until that time, as Fracastoro notes, syphilis had been called the "French disease" in Italy and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turks called it the "Christian disease" or "Frank disease" (frengi) and the Tahitians called it the "British disease". These 'national' names are due to the disease often being present among invading armies or sea crews, due to their high amount of unprotected sexual contacts with prostitutes. It's interesting to notice how the invaders named it after the invaded country and vice versa. It was also called "Great pox" in the 16th century to distinguish it from smallpox. In its early stages, the Great pox produced a rash similar to smallpox (also known as variola). However, the name is misleading, as smallpox was a far more deadly disease. The terms "Lues" (or Lues venerea, Latin for "venereal plague") and "Cupid's disease" have also been used to refer to syphilis. In Scotland, Syphilis was referred to as the Grandgore. It was also called The Black Lion.

Classification

Syphilis can be congenital or acquired and is classified as primary, secondary, latent and tertiary.

Pathophysiology

Syphilis is caused by a spirochete, treponema pallidum. It has an incubation period of 3 - 12 weeks. Spirochete penetrates intact mucous membrane or microscopic dermal abrasions and rapidly enters systemic circulation with the central nervous system being invaded during the early phase of infection. The meninges and blood vessels are initially involved with the brain parenchyma and spinal cord being involved in the later stages of the disease. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity to the spirochete.

Causes

Syphilis is caused by a spirochete, treponema pallidum. The spirochete rapidly penetrates via intact mucosal membranes or microscopic dermal abrasions. It is spread through intimate sexual contact, blood transfusion or vertical transmission from infected mother to fetus.

Differentiating Syphilis from other Diseases

Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Hence, patients with tertiary syphilis should also be tested for other sexually transmitted diseases such as chlamydia, gonorrhea, trichomoniasis, bacterial vaginosis and HIV infection.

Epidemiology and Demographics

The rate of primary and secondary syphilis reported in the United States decreased during the 1990s; in 2000, the rate was the lowest since reporting began in 1941. The low rate of infectious syphilis and the concentration of the majority of syphilis cases in a small number of geographic areas in the United States led to the development of the CDCs National Plan to Eliminate Syphilis, which was announced by Surgeon General David Satcher in October 1999 and revised in May 2006.2

Although the rate of primary and secondary syphilis in the United States declined 89.7% between 1990 and 2000, the rate of primary and secondary syphilis increased annually between 2001 and 2007. Overall increases in rates between 2001 and 2007 were observed primarily among men (from 3.0 cases per 100,000 population to 6.6 cases per 100,000 population). After persistent declines from 1992 to 2003, the rate of primary and secondary syphilis among women increased from 0.8 cases per 100,000 population in 2004 to 0.9 cases per 100,000 population in 2005 to 1.0 case per 100,000 population in 2006, to 1.1 case per 100,000 population in 2007.

Syphilis remains an important problem in the South and in urban areas in other regions of the country. Increases in cases among MSM have occurred and have been characterized by high rates of HIV co-infection and high-risk sexual behavior.3-7 The estimated proportion of primary and secondary syphilis cases attributable to MSM increased from 4% in 2000 to 62% in 2004. In 2005, CDC requested that all state health departments report sex of sex partners for persons with syphilis. In 2007, 65% of those primary and secondary syphilis cases in 44 states and Washington D.C. with available information were among MSM. Of reported male cases with primary and secondary syphilis, sex of partner information in 2007 was available for 79%.

Syphilis, a genital ulcerative disease, causes significant complications if untreated and facilitates the transmission of HIV. Untreated early syphilis in pregnant women results in perinatal death in up to 40% of cases and, if acquired during the four years preceding pregnancy, may lead to infection of the fetus in 80% of cases.

Risk Factors

Risk factors of syphilis include unprotected sex, IV drug abuse and occupational risk for health care professionals.

Clinical Presentation

• On the basis of clinical findings, the disease has been divided into a series of overlapping stages, which are used to help guide treatment and follow-up.
• Persons who have syphilis might seek treatment for signs or symptoms of primary infection (i.e., ulcer or chancre at the infection site), secondary infection (i.e., manifestations that include, but are not limited to, skin rash, mucocutaneous lesions, and lymphadenopathy), neurologic infection (i.e., cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities, which might occur through the natural history of untreated infection), or tertiary infection (i.e., cardiac or gummatous lesions).
• Latent infections (i.e., those lacking clinical manifestations) are detected by serologic testing. Latent syphilis acquired within the preceding year is referred to as early latent syphilis; all other cases of latent syphilis are either late latent syphilis or latent syphilis of unknown duration.

Diagnosis

• Darkfield examinations and tests to detect T. pallidum in lesion exudate or tissue are the definitive methods for diagnosing early syphilis.[2]

• Although no T. pallidum detection tests are commercially available, some laboratories provide locally developed PCR tests for the detection of T. pallidum.

• A presumptive diagnosis of syphilis is possible with the use of two types of serologic tests:

• nontreponemal tests (e.g., venereal disease research laboratory (VDRL) and rapid plasma reagent test) and
• treponemal tests (e.g., fluorescent treponemal antibody absorbed (FTA-ABS) tests, the T. pallidum passive particle agglutination (TP-PA) assay, various enzyme immunoassays, and chemiluminescence immunoassays).

• The use of only one type of serologic test is insufficient for diagnosis, because each type of test has limitations, including the possibility of false-positive test results in persons without syphilis.

• False-positive nontreponemal test results can be associated with various medical conditions unrelated to syphilis, including autoimmune conditions, older age, and injection-drug use; [3] therefore, persons with a reactive nontreponemal test should receive a treponemal test to confirm the diagnosis of syphilis.

Treatment

• Penicillin G, administered parenterally, is the preferred drug for treating all stages of syphilis.

• The preparation used (i.e., benzathine, aqueous procaine, or aqueous crystalline), the dosage, and the length of treatment depend on the stage and clinical manifestations of the disease.

• Selection of the appropriate penicillin preparation is important, because T. pallidum can reside in sequestered sites (e.g., the CNS and aqueous humor) that are poorly accessed by some forms of penicillin.

• Combinations of benzathine penicillin, procaine penicillin, and oral penicillin preparations are not considered appropriate for the treatment of syphilis.

• During pregnancy, parenteral penicillin G is the only therapy with documented efficacy for syphilis. Pregnant women with syphilis in any stage who report penicillin allergy should be desensitized and treated with penicillin

• The Jarisch-Herxheimer reaction is an acute febrile reaction

• Frequently accompanied by headache, myalgia, fever, and other symptoms that usually occur within the first 24 hours after the initiation of any therapy for syphilis.

• Patients should be informed about this possible adverse reaction.

• The Jarisch-Herxheimer reaction occurs most frequently among patients who have early syphilis, presumably because bacterial burdens are higher during these stages.

• Antipyretics can be used to manage symptoms, but they have not been proven to prevent this reaction.

• The Jarisch-Herxheimer reaction might induce early labor or cause fetal distress in pregnant women, but this should not prevent or delay therapy.

References

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