SYPHILIS

Syphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum subspecies pallidum. The route of transmission of syphilis is almost always through 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 can generally be treated with antibiotics, including penicillin. If left untreated, syphilis can damage 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.[1][2]
Contents[hide]
1 Alternative names
2 Signs and symptoms
2.1 Primary syphilis
2.2 Secondary syphilis
2.3 Latent syphilis
2.4 Tertiary syphilis
2.5 Neurosyphilis
3 Diagnosis
3.1 Other Treponematoses
4 Prevention
5 Treatment
5.1 Late latent and infections of unknown duration
5.2 Treatment of neurosyphilis
5.3 Alternative regimens
5.4 Jarisch-Herxheimer reaction
5.5 Tuskegee syphilis study
6 Epidemiology
7 History
7.1 Origins
7.2 European outbreak
7.3 History of treatments
7.4 History of diagnosis
7.5 Notable syphilis-infected people in history
8 Society and culture
8.1 Art
8.2 Classic and antique literature
8.3 Modern literature
8.4 Film, television and stage
9 Gallery
10 See also
11 References
12 External links
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Alternative names
The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in his epic noted poem, written in Latin, titled 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").[3]
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 spread by foreign sailors and soldiers during their frequent, unprotected sexual contact with local prostitutes.
During the 16th century, it was called "great pox" in order 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"[4] (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. The ulcers suffered by British soldiers in Portugal were termed "The Black Lion".[5]
Signs and symptoms
Different manifestations occur depending on the stage of the disease:
Primary syphilis

PRIMARY CHANCRE OF SYPHILIS ON THE HAND

Primary chancre of syphilis at the site of infection on the penis
Primary syphilis is typically acquired via direct sexual contact with the infectious lesions of a person with syphilis.[6] Approximately 10–90 days after the initial exposure (average 21 days), a skin lesion appears at the point of contact, which is usually the genitalia, but can be anywhere on the body. This lesion, called a chancre, is a firm, painless skin ulceration localized at the point of initial exposure to the spirochete, often on the penis, vagina or rectum. In rare circumstances, there may be multiple lesions present, although it is typical that only one lesion is seen. The lesion may persist for 4 to 6 weeks and usually heals spontaneously. Local lymph node swelling can occur. During the initial incubation period, individuals are otherwise asymptomatic. As a result, many patients do not seek medical care immediately.
Syphilis cannot be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.[7]

Typical presentation of secondary syphilis rash on the palms of the hands and usually also seen on soles of feet
SECONDARY SYPHILIS
Secondary syphilis occurs approximately 1–6 months (commonly 6 to 8 weeks) after the primary infection. There are many different manifestations of secondary disease. There may be a symmetrical reddish-pink non-itchy rash on the trunk and extremities.[8] The rash can involve the palms of the hands and the soles of the feet. In moist areas of the body (usually vulva or scrotum), the rash becomes flat, broad, whitish, wart-like lesions known as condyloma latum.) Mucous patches may also appear on the genitals or in the mouth. All of these lesions are infectious and harbor active treponeme organisms. A patient with syphilis is most contagious when he or she has secondary syphilis. Other symptoms common at this stage include fever, sore throat, malaise, weight loss, headache, meningismus, and enlarged lymph nodes. Rare manifestations include an acute meningitis that occurs in about 2% of patients, hepatitis, renal disease, hypertrophic gastritis, patchy proctitis, ulcerative colitis, rectosigmoid mass, arthritis, periostitis, optic neuritis, interstitial keratitis, iritis, and uveitis.
LATENT SYPHILIS
Latent syphilis is defined as having serologic proof of infection without signs or symptoms of disease.[6] Latent syphilis is further described as either early or late. Early latent syphilis is defined as having syphilis for two years or less from the time of initial infection without signs or symptoms of disease. Late latent syphilis is infection for greater than two years but without clinical evidence of disease. The distinction is important for both therapy and risk for transmission. In the real-world, the timing of infection is often not known and should be presumed to be late for the purpose of therapy. Early latent syphilis may be treated with a single intramuscular injection of a long-acting penicillin. Late latent syphilis, however, requires three weekly injections. For infectiousness, however, late latent syphilis is not considered as contagious as early latent syphilis. Fifty percent of those infected with latent syphilis will progress into late stage syphilis, 25% will stay in the latent stage, and 25% will make a full recovery.
TERTIARY SYPHILIS
Tertiary syphilis usually occurs 1–10 years after the initial infection, however in some cases it can take up to 50 years. This stage is characterized by the formation of gummas, which are soft, tumor-like balls of inflammation known as granulomas. The granulomas are chronic and represent an inability of the immune system to completely clear the organism. They may appear almost anywhere in the body including in the skeleton. The gummas produce a chronic inflammatory state in the body with mass-effects upon the local anatomy. Other characteristics of untreated tertiary syphilis include neuropathic joint disease, which is a degeneration of joint surfaces resulting from loss of sensation and fine position sense (proprioception). The more severe manifestations include neurosyphilis and cardiovascular syphilis. In a study of untreated syphilis, 10% of patients developed cardiovascular syphilis, 16% had gumma formation, and 7% had neurosyphilis.[9]
Neurological complications at this stage can be diverse. In some patients, manifestations include generalized paresis of the insane, which results in personality changes, changes in emotional affect, hyperactive reflexes, and Argyll-Robertson pupil. This is a diagnostic sign in which the small and irregular pupils constrict in response to focusing the eyes, but not to light. Tabes dorsalis, also known as locomotor ataxia, a disorder of the spinal cord, often results in a characteristic shuffling gait. See below for more information about neurosyphilis.
Cardiovascular complications include syphilitic aortitis, aortic aneurysm, aneurysm of sinus of Valsalva, and aortic regurgitation. Syphilis infects the ascending aorta causing aortic dilation and aortic regurgitation. This can be heard with a stethoscope as a heart murmur. Contraction of the tunica intima leads to a tree bark appearance that is wrinkly. The aortic valve dilation and subsequent insufficiency leads to diastolic regurgitation and causes massive hypertrophy of the left ventricle. The heart grows so large (over 1000 grams) that the heart is termed cor bovinum (cow's heart). The course can be insidious, and heart failure may be the presenting sign after years of disease. The infection can also occur in the coronary arteries and cause narrowing of the vessels. Syphilitic aortitis can cause de Musset's sign,[10] a characteristic bobbing of the head in synchrony with the heartbeat. The clinical course of these cardiovascular effects causes mediastinal encroachment and secondary respiratory difficulties (dyspnea), difficulty swallowing (dyphagia), and persistent cough because of pressure on the recurrent laryngeal nerve triggering the cough reflex. Pain can stem from erosion of the ribs or vertebrae. Also, the cor bovinum can lead to coronary ostia obstruction and ischemia. The aneurysm developed during the disease course may also rupture leading to massive intrathoracic hemorrhage and likely death, although the most likely cause of death is the heart failure resulting from aortic regurgitation.
Neurosyphilis
Neurosyphilis refers to a site of infection involving the central nervous system (CNS). Neurosyphilis may occur at any stage of syphilis. Before the advent of antibiotics, it was typically seen in 25-35% of patients with syphilis.
Neurosyphilis is now most common in patients with HIV infection. Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV pandemic. The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, have not been well characterized. Furthermore, the alteration of host immunosuppression by antiretroviral therapy in recent years has further complicated such characterization.
Approximately 35% to 40% of persons with secondary syphilis have asymptomatic central nervous system (CNS) involvement, as demonstrated by any of these on cerebrospinal fluid (CSF) examination:
An abnormal leukocyte cell count, protein level, or glucose level
Demonstrated reactivity to Venereal Disease Research Laboratory (VDRL) antibody test
Commonly called Brain Syphilis, Neurosyphilis dementia is also a psychiatric diagnosis wherein a multitude of atypical anti-psychotic medications are used to help control the patient's irrational behaviors—with limited success. The term is used in traditional classifications of organic disorders of the brain.
There are four clinical types of neurosyphilis:
Asymptomatic neurosyphilis
Meningovascular syphilis
General paresis[11]
Tabes dorsalis
The late forms of neurosyphilis (tabes dorsalis and general paresis) are seen much less frequently since the advent of antibiotics. The most common manifestations today are asymptomatic or symptomatic meningitis. Acute syphilitic meningitis usually occurs within the first year of infection; 10% of cases are diagnosed at the time of the secondary rash. Patients present with headache, meningeal irritation, and cranial nerve abnormalities, especially the optic nerve, facial nerve, and the vestibulocochlear nerve. Rarely, it affects the spine instead of the brain, causing focal muscle weakness or sensory loss.
Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary syphilis infection. Meningovascular syphilis can be associated with prodromal symptoms lasting weeks to months before focal deficits are identifiable. Prodromal symptoms include unilateral numbness, paresthesias, upper or lower extremity weakness, headache, vertigo, insomnia, and psychiatric abnormalities such as personality changes. The focal deficits initially are intermittent or progress slowly over a few days. However, it can also present as an infectious arteritis and cause an ischemic stroke, an outcome more commonly seen in younger patients. Angiography may be able to demonstrate areas of narrowing in the blood vessels or total occlusion.
General paresis, otherwise known as general paresis of the insane, is a severe manifestation of neurosyphilis. It is a chronic dementia that ultimately results in death in as little as 2–3 years. In general, patients have progressive personality changes, memory loss, and poor judgment. In more rare instances, they can have psychosis, depression, or mania. Imaging of the brain usually shows atrophy.
Diagnosis
Poster for treatment of syphilis, showing a man and a woman bowing their heads in shame (ca. 1936).
It is only in the 20th century that effective tests and treatments for syphilis were developed. Microscopy of fluid from the primary or secondary lesion using darkfield illumination can diagnose treponemal disease with high accuracy. As there are other treponemes that may be confused with T. pallidum, care must be taken in evaluating with microscopy to correlate symptoms with the correct disease.

Star Wars themed parade float promoting syphilis testing at a 2005 parade in Seattle, Washington, United States.
Present-day syphilis screening tests, such as the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests are cheap and fast but not completely specific, as many other conditions can cause a positive result. These tests are routinely used to screen blood donors. It can be noted that the spirochete that causes syphilis does not survive the conditions used to store blood, and the number of transfusion transmitted cases of syphilis is minuscule; but the test is used to identify donors that might have contracted HIV from high risk sexual activity. The requirement to test for syphilis has been challenged due to the vast improvements in HIV testing. False positives on the rapid tests can be seen in viral infections (Epstein-Barr, hepatitis, varicella, measles), lymphoma, tuberculosis, malaria, Chagas Disease, endocarditis, connective tissue disease, pregnancy, intravenous drug abuse, or contamination.[6] As a result, these two screening tests should always be followed up by a more specific treponemal test. Tests based on monoclonal antibodies and immunofluorescence, including Treponema pallidum hemagglutination assay (TPHA) and Fluorescent Treponemal Antibody Absorption (FTA-ABS) are more specific and more expensive. Unfortunately, false positives can still occur in related treponomal infections such as yaws and pinta. Tests based on enzyme-linked immunosorbent assays are also used to confirm the results of simpler screening tests for syphilis.
Neurosyphilis is diagnosed by finding high numbers of leukocytes in the CSF or abnormally high protein concentration in the setting of syphilis infection.[6] In addition, CSF should be tested with the VDRL test although some advocate using the FTA-ABS test to improve sensitivity. There is anecdotal evidence that the incidence of neurosyphilis is higher in HIV patients, and some have recommended that all HIV-positive patients with syphilis should have a lumbar puncture to look for asymptomatic neurosyphilis.[12]
Other Treponematoses
Treponematoses are diseases caused by species of the spirochete Treponema. In addition to Syphilis, this group includes:
Yaws is a tropical disease characterized by an infection of the skin, bones and joints; it is caused by Treponema pallidum subspecies pertenue.
Pinta - caused by Treponema pallidum subspecies carateum.
Bejel - caused by Treponema pallidum subspecies endemicum.
Prevention
While abstinence from any sexual activity is very effective at helping prevent syphilis, it should be noted that T. pallidum readily crosses intact mucosa and cut skin, including areas not covered by a condom. Proper and consistent use of a latex condom may be effective against the spread of syphilis through sexual contact, although this cannot be guaranteed due to the ease with which non-genital body parts can be infected.[13]
Individuals sexually exposed to a person with primary, secondary, or early latent syphilis within 90 days preceding the diagnosis should be assumed to be infected and treated for syphilis, even if they are currently seronegative. If the exposure was more than 90 days before the diagnosis, presumptive treatment is recommended if serologic testing is not immediately available or if follow-up is uncertain. Patients with syphilis of unknown duration and nontreponemal serologic titers ≥1:32 may be considered as having early syphilis for purposes of partner notification and presumptive treatment of sex partners. Long-term sex partners of patients with late syphilis should be evaluated clinically and serologically and treated appropriately. All patients with syphilis should be tested for HIV. Patient education is important, as well.
Treatment
APPLICATION OF MERCURY.
The first-choice treatment for all manifestations of syphilis remains penicillin in the form of penicillin G.[14] The effect of penicillin on syphilis was widely known before randomized clinical trials were used; as a result, treatment with penicillin is largely based on case series, expert opinion, and years of clinical experience. Parenteral penicillin G is the only therapy with documented effect during pregnancy. For early syphilis, one dose of penicillin is sufficient.
Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be effectively treated with oral tetracycline or doxycycline; however, data to support this is limited. Ceftriaxone may be considered as an alternative therapy, although the optimal dose is not yet defined. However, cross-reactions in penicillin-allergic patients with cephalosporins such as ceftriaxone are possible. Azithromycin was suggested as an alternative. However, there have been reports of treatment failure due to resistance in some areas.[15] If compliance and follow-up cannot be ensured, the CDC recommends desensitization with penicillin followed by penicillin treatment. All pregnant women with syphilis should be desensitized and treated with penicillin. Follow-up includes clinical evaluation at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after treatment.
Azithromycin has been used to treat syphilis in the past because of easy once-only dosing. However, in one study in San Francisco, azithromycin-resistance rates in syphilis, which were 0% in 2000, were 56% by 2004.[16]
Late latent and infections of unknown duration
Late latent syphilis is defined as latency for greater than one year. If CSF examination yields no evidence of neurosyphilis, then penicillin G is recommended in weekly doses for 3 weeks. If allergic, then tetracycline or doxycycline may also be used for this stage, but for 28 days instead of the normal 14. As with before, the data to support use of tetracycline and ceftriaxone are limited.
Treatment of neurosyphilis
For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without positive CSF results, aqueous crystalline penicillin G is the treatment of choice. The recommended regimen is intravenous treatment every 4 hours or continuously for 10–14 days. If intravenous administration is not possible, then procaine penicillin is an alternative (administered daily with probenecid for two weeks). Procaine injections are painful, however, and patient compliance may be difficult to ensure. To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of benzathine penicillin G after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for neurosyphilis. No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. The only alternative that has been studied and shown to be effective is intramuscular ceftriaxone daily for 14 days.