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ICD-10 A50-A53
ICD-9 090-097
OMIM [1]
DiseasesDB [2]
MedlinePlus [3]
eMedicine /
MeSH {{{MeshNumber}}}

Syphilis (historically called lues) is a sexually transmitted disease (STD) that is caused by a spirochaete bacterium, Treponema pallidum. Syphilis has many alternate names, such as: Miss Siff, the Pox (or greatpox, to distinguish it from smallpox), and has been given many national attributions, e.g. the "French disease" or the "English disease".

The route of transmission for syphilis is almost invariably by sexual contact; however, there are examples of direct contact infections (see yaws) and of congenital syphilis (transmission from mother to child in utero).

The signs and symptoms of syphilis are myriad; before the advent of serological testing, diagnosis was more difficult and the disease was dubbed the "Great Imitator" because it was so often confused with other diseases.

Syphilis can be treated with penicillin or other antibiotics. Statistically, treatment with a course of pills is dramatically less effective than other treatments, because patients tend not to complete the course. The oldest, and still most effective, method is to inject benzathine penicillin into each buttock (procaine is added to make the pain bearable); the dose must be given half in each buttock because the amount given would be too painful if given in a single injection. An alternative treatment is to administer several tablets of azithromycin orally (which has a long duration of action) under observation. This latter course, however, may be falling on hard times, as strains of syphilis resistant to azithromycin have developed and may account for 10% of cases in some areas in 2004. Other treatments are less effective as the patient is required to take pills several times a day.

If not treated, syphilis can cause serious effects such as damage to the nervous system, heart, or brain. Untreated syphilis can be fatal.


There are two thoughts on the origin of Syphilis: the Colombian and pre-Colombian theses. There are ongoing debates in anthropological and historical fields about the validity of either theory.

The pre-Colombian theory holds that syphilis symptoms are described by Hippocrates in Classical Greece in its venereal/tertiary form. Some passages in the Bible could refer to syphilis, especially Exodus 20:5 where the sins of the father are visited unto the third and fourth generation. There are other suspected syphilis findings for pre-contact Europe, including at a 13-14th century Augustinian friary in the northeastern English port of Kingston upon Hull. The anthropological evidence is contested by those who follow the Colombian theory.

The Colombian theory holds that syphilis was a New World disease brought back by Columbus. The first well-recorded outbreak of what we know as syphilis occurred in Naples in 1494. There is some documentary evidence to link Columbus' crew to the outbreak. Supporters of the Colombian theory find syphilis lesions on pre-contact Native Americans. Again, all the anthropological evidence is heatedly discussed on both sides of the Colombian/pre-Columbian debate. (Baker, et al.)

Alfred Crosby has argued that neither side has the full story. Syphilis is a form of Yaws, which has existed in the Old World since time immemorial. Crosby argues that syphilis is a specific form of Yaws that had evolved in the New World and was brought back to the old, "the differing ecological conditions produced different types of treponematosis and, in time, closely related but different diseases". (ref:225 Crosby)

The epidemiology of the first syphilis epidemic indicates that the disease was either new or a mutated form of an earlier disease. The disease swept across Europe from the early epicenter at Naples. The early form was much more virulent than the disease of today, the incubation period was shorter, only a few months, and the symptoms were more severe. In addition, the disease was more frequently fatal than it is today. By 1546, the disease had evolved into the form we know now.

Syphilis had many different names. Great pox was used during the 16th century to distinguish it from smallpox. Great pox produced a similar rash in its early stages to small pox, but other than that it has no relation to the Variola virus. However the name is misleading, as small pox was a far more deadly disease. Because of the outbreak in the French army, it was first called morbus gallicus, or the French disease. In that time it is noteworthy that the Italians also called it the "Spanish disease", the French called it the la maladie anglaise - the English disease and "Italian" or "Neapolitan disease", the Russians called it the "Polish disease", and the Arabs called it the "Disease of the Christians". The name "syphilis" was first applied by Girolamo Fracastoro in 1530 from the name of a shepherd in a poem by Leonardo da Vinci.

The insanity caused by late-stage syphilis was once one of the more common forms of dementia; this was known as the general paresis of the insane.

Stages of syphilis

Different manifestations occur at each stage of the disease.

Primary syphilis

File:Penis syphilis.png

Primary syphilis is manifested after an incubation period of 10-90 days (the average is 21 days) with a primary sore. During the initial incubation period, individuals are asymptomatic. The sore, called a chancre, is a firm, painless skin ulceration localized at the point of initial exposure to the bacterium, often on the penis, vagina or rectum. Local lymph node swelling can occur. The primary lesion may persist for 4 to 6 weeks and then heal spontaneously.

Secondary syphilis

File:Vaginal syphilis (disturbing image).jpg

Secondary syphilis is characterized by a skin rash that appears 1-6 months (commonly 6 to 8 weeks) after the primary infection. This is a symmetrical reddish-pink non-itchy rash on the trunk and extremities, which unlike most other kinds of rash involves the palms of the hands and the soles of the feet; in moist areas of the body the rash becomes flat broad whitish lesions called condylomata lata. Mucous patches may also appear on the genitals or in the mouth. 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, iritis, and uveitis.

Tertiary syphilis

Tertiary syphilis occurs from as early as one year after the initial infection but can take up to ten years to manifest - though cases have been reported where this stage has occurred fifty years after initial infection. This stage is characterised by gummas, soft, tumor-like growths, readily seen in the skin and mucous membranes, but which can occur almost anywhere in the body, often in the skeleton. Other characteristics of untreated syphilis include Charcot's joints (joint deformity), and Clutton's joints (bilateral knee effusions). The more severe manifestations include neurosyphilis and cardiovascular syphilis.

Neurological complications at this stage include generalized paresis of the insane which results in personality changes, changes in emotional affect, hyperactive reflexes, and Argyll-Robertson pupils, 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.

Cardiovascular complications include aortic aortitis, aortic aneurysm, aneurysm of sinus of Valsalva, and aortic regurgitation, and are a frequent cause of death. Syphilitic aortitis can cause de Musset's sign (a bobbing of the head that de Musset first noted in Parisian prostitutes).

Latent syphilis

Latent syphilis is defined as having serologic proof of infection without signs or symptoms of disease. Latent syphilis is further described as either early or late. Early latent syphilis is defined as having syphilis for one year or less from time of initial infection without signs or symptoms of disease. Late latent syphilis, then, is infection for greater than one year but having no clinical evidence of disease. The distinction is important for two reasons, therapy and risk for transmission.

In practice, the time of initial infection is often not known and in this case should then presumed to be late for the purpose of therapy. Early latent syphilis may be treated with a single IM injection of a long-acting penicillin. Late latent syphilis, however, requires three such injections, each a week apart. For infectiousness, however, late latent syphilis is not considered contagious while early latent is. Thus, if the duration of infection is not known, one should presume the patient is early and contagious.

Congenital syphilis

Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with secondary or tertiary syphilis. According to the CDC, 40% of births to syphilitic mothers are stillborn, 40-70% of the survivors will be infected, and 12% of these will subsequently die prematurely. Manifestations of congenital syphilis include abnormal x-rays; Hutchinson's teeth (centrally notched, widely-spaced peg-shaped upper central incisors); mulberry molars (sixth year molars with multiple poorly developed cusps); frontal bossing; saddle nose; poorly developed maxillae; enlarged liver; enlarged spleen; petechiae; other skin rash; anemia; lymph node enlargement; jaundice; pseudoparalysis; and snuffles, the name given to rhinitis in this situation. Rhagades, linear scars at the angles of the mouth and nose result from bacterial infection of skin lesions. Death from congenital syphilis is usually through pulmonary hemorrhage.


It was only in the 20th century that effective tests and treatments for syphilis were developed.

In 1906, the first effective test for syphilis, the Wassermann test, was developed. Although it had some false positive results, it was a major advance in the prevention of syphilis. By allowing testing before the acute symptoms of the disease had developed, this test allowed the prevention of the transmission of syphilis to others, even though it did not provide a cure for those infected.

In the 1930s the Hinton test, developed by William Augustus Hinton, and based on flocculation, was shown to have fewer false positive reactions than the Wasserman. These have been superseded by current-day tests.

Current-day syphilis tests, such as the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) test, while useful, are not accurate as many other conditions can cause a positive result

Newer tests based on monoclonal antibodies and immunofluorescence, including Treponema pallidum haemagglutination assay (TPHA) and Fluorescent Treponemal Antibody Absorption (FTA-ABS) are more specific, but are still unable to rule out non-syphillis Treponomal infections such as Yaws and Pinta.

However, it must not be forgotten that microscopy of chancre fluid using dark ground illumination can be extremely quick and effective.

In one of the best-documented episodes of human medical experimentation in the twentieth century, the Tuskegee syphilis study continued to study the lifetime course of syphilis in a group of black Americans long after effective treatments for syphilis were available.

In the July 17, 1998 issue of the journal Science, a group of biologists reported the sequencing of the genome of T. pallidum.


There were originally no effective treatments for syphilis. The most common in use were guaiacum and mercury: the use of mercury gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury". Though no proper studies were done to prove it, mercury may have been an effective means to treat syphilis. It was administered multiple ways including by mouth and by rubbing it on the skin. One of the more fascinating methods was fumigation, in which the patient was placed in a closed box with their head sticking out. Mercury was placed in the box and a fire was started under the box which caused the mercury to vaporize. It was a gruelling process for the patient and the least effective for delivering mercury to the body.

As the disease became better understood, more effective treatments were found, beginning with the use of the arsenic-containing drug Salvarsan from 1910, and later, Neosalvarsan.

Unfortunately, these drugs were not 100% effective, especially in late disease. It had been observed that some who develop high fevers could be cured of syphilis. Thus, for a brief time malaria was used as treatment because it produces prolonged and high fevers. This was considered an acceptable risk because the malaria could later be treated with quinine which was available at that time. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvunct therapy.

These treatments were finally rendered obsolete by the discovery of penicillin, and its widespread manufacture after World War II allowed syphilis to be effectively cured for the first time.

To this day, the first choice treatment for syphilis remains penicillin, in the form of benzathine penicillin G or aqueous procaine penicillin G injections. Individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be effectively treated with oral tetracyclines.

Oral Azithromycin given as a single dose of 2g has been used successfully to treat syphilis in a pilot study of 328 patients in Tanzania (Riedner 2005), but resistance to azithromycin has been reported in the US and elsewhere, which makes it doubtful that this treatment will become widespread in the US.

See also

External links

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