Syphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum 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. The oldest and still most effective method is an intramuscular injection of benzathine 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.
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 the high incidence of unprotected sexual contact with prostitutes. 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. The ulcers suffered by British soldiers in Portugal were termed "The Black Lion".
The pre-Columbian theory holds that syphilis symptoms are described by Hippocrates in Classical Greece in its venereal/tertiary form. 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. This city's maritime history is thought to have been a key factor in the transmission of syphilis. Carbon dated skeletons of monks who lived in the friary showed bone lesions typical of venereal syphilis. Skeletons in pre-Columbus Pompeii and Metaponto in Italy demonstrating signs of congenital syphilis have also been found, although the interpretation of the evidence has been disputed.
The Columbian Exchange theory holds that syphilis was a New World disease brought back by Columbus and Martin Alonzo Pinzon. Supporters of the Columbian theory find syphilis lesions on pre-contact Native Americans and cite documentary evidence linking crewmen of Columbus's voyages to the Naples outbreak of 1494. A recent study of the genes of venereal syphilis and related bacteria has supported this theory, by locating an intermediate disease between yaws and syphilis in Guyana, South America.
Historian Alfred Crosby suggests both theories are correct in a combination theory. Crosby's argument is built on the similarities of the species of bacteria which cause yaws and syphilis. The bacterium that causes syphilis belongs to the same phylogenetic family as the bacteria which cause yaws and several other diseases. Despite a tradition of assigning yaws's homeland to sub-Saharan Africa, Crosby notes that there is no unequivocal evidence of any related disease being present in pre-Columbian Europe, Africa, or Asia, while there is indisputable evidence of syphilis' presence in the pre-Columbian Americas. Conceding this point, Crosby writes, "It is not impossible that the organisms causing treponematosis arrived from America in the 1490s...and evolved into both venereal and non-venereal syphilis and yaws."
However, Crosby considers it somewhat more likely that a highly contagious ancestral species of bacteria moved with early human ancestors across the land bridge of the Bering Straits many thousands of years ago without dying out in the original source population. He hypothesizes that "the differing ecological conditions produced different types of treponematosis and, in time, closely related but different diseases." Thus, a weak, non-syphilitic bacteria survived in the Old World to eventually give rise to yaws or bejel, while a New World version evolved into the milder pinta and the more aggressive syphilis.
Going further than Crosby in arguing for worldwide incidence of syphilis prior to Columbus, Douglas Owsley, the famed physical anthropologist at the Smithsonian Institution, has written that many medieval European cases of leprosy, colloquially called "lepra," were actually cases of syphilis. Although folklore claimed that syphilis was unknown in Europe until the return of the diseased sailors of the Columbian voyages, Owsley noted that a Chinese medical case recorded in 2637 B.C.E. seems to be describing a case of syphilis, and that a European writer who recorded an outbreak of "lepra" in 1303 C.E. is "clearly describing syphilis".
While working at the Rockefeller University (then called the Rockefeller Institute for Medical Research) in 1913, Hideyo Noguchi, a Japanese scientist, demonstrated the presence of the spirochete Treponema pallidum in the brain of a progressive paralysis patient, proving that Treponema pallidum was the cause of the disease. Prior to Noguchi's discovery, syphilis had been a burden to humanity in many lands, sometimes misdiagnosed and often misattributed to political enemies.
Some famous historical personages, including Franz Schubert, Charles VIII of France, Hernando Cortez of Spain, Adolf Hitler, Benito Mussolini, and Ivan the Terrible, have been alleged to have had syphilis. Guy de Maupassant and possibly Friedrich Nietzsche are thought to have been driven insane and ultimately killed by the disease. Al Capone contracted syphilis as a young man. By the time he was incarcerated at Alcatraz, it reached its third stage, neurosyphilis, leaving him confused and disoriented. Syphilis led to the death of artist Edouard Manet and artist Paul Gauguin is also said to have suffered from syphilis. Composers who succumbed to syphilis include Hugo Wolf, Frederick Delius, Scott Joplin, Gaetano Donizetti, and possibly Franz Schubert and Niccolò Paganini. 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. One suspected example is the insanity of noted composer Robert Schumann, although the precise cause of his death is still disputed by scholars.
The Russian author Leo Tolstoy suffered from syphilis during his youth, which was treated using arsenic treatment.
A recent article in the European Journal of Neurology (June 2004) hypothesized that the founder of communism in Russia, Vladimir Ilyich Lenin, died of neurosyphilis.
Karen Blixen, the author of Out of Africa, contracted syphilis from her husband while living in Africa. He had contracted the disease from an African woman with whom he had been unfaithful. After having undergone treatment in Denmark, she returned to Africa. Blixen was unable to have children.
The first well-recorded European outbreak of what is now known as syphilis occurred in 1494 when it broke out among French troops besieging Naples. The French may have caught it via Spanish mercenaries serving King Charles of France in that siege. From this centre, the disease swept across Europe. As Jared Diamond describes it, "when syphilis was first definitely recorded in Europe in 1495, its pustules often covered the body from the head to the knees, caused flesh to fall from people's faces, and led to death within a few months." In addition, the disease was more frequently fatal than it is today. Diamond concludes that "by 1546, the disease had evolved into the disease with the symptoms so well known to us today." The epidemiology of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease.
Primary syphilis is typically acquired via direct sexual contact with the infectious lesions of a person with syphilis. 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. Rarely, there may be multiple lesions present although typically 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 can not be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.
Tertiary syphilis usually occurs 1-10 years after the initial infection, though 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.
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 dilation and aortic regurgitation. This can be heard with a stethoscope as a heart murmur. 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, a bobbing of the head that de Musset first noted in Parisian prostitutes.
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.
There are four clinical types of neurosyphilis:
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 which ultimately results in death in as little as 2-3 years. Patients generally have progressive personality changes, memory loss, and poor judgment. More rarely, they can have psychosis, depression, or mania. Imaging of the brain usually shows atrophy.
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. Notably, 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. 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. 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.
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.
As the disease became better understood, more effective treatments were found. The first antibiotic to be used for treating disease was the arsenic-containing drug Salvarsan, developed in 1908 by Sahachiro Hata while working in the laboratory of Nobel prize winner Paul Ehrlich. This was later modified into 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 for tertiary syphilis because it produced 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. This discovery was championed by Julius Wagner-Jauregg, who won the 1927 Nobel Prize for Medicine for his work in this area. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant 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 and reliably cured.
Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be effectively treated with oral tetracycline or doxycycline although 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. 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.
HIV-infected patients with early syphilis may have a higher risk of neurological complications and a higher rate of treatment failure with currently recommended regimens. The magnitude of these risks, however, although not precisely defined, is probably small. Skin testing or desensitization is recommended in latent syphilis and neurosyphilis in other patients with HIV infection.
The study began in 1932 using a group of 600 black sharecroppers. Of these 600, 399 of the men had the disease and 201 were uninfected control patients. The PHS stated at first that treatment was supposed to be a part of the study, but they were unable to produce any useful data. It was then discovered that the PHS had decided to leave the men untreated and follow the course of the disease to these men's eventual deaths. They thought they were receiving experimental treatment for "bad blood" in exchange for free meals and a $50 death benefit. However, the study was designed to measure the progression of untreated syphilis and to determine whether syphilis caused cardiovascular damage more often than neurological damage, and to determine if the natural course of the disease was different in black men versus white men. By 1947 penicillin had become the standard treatment of syphilis. The men were never advised that they had syphilis, nor were they offered a treatment including Salvarsan or the other arsenical drugs that were in use at the beginning of the study.
The original study was meant to last six to nine months, but continued for 40 years, ending in 1972, long after forty wives and nineteen children had been infected, and many of the men had died of syphilis. Twenty-eight men died directly from syphilis, and one hundred from other complications, during the study. The study ended because of a story printed in the Washington Star. A class-action lawsuit was then filed against the federal government for the study. This lawsuit was settled out of court and the living subjects and their descendants were awarded a total of ten million dollars. After the settlement was awarded, the government passed the National Research Act, which required the government to review and approve all medical studies involving human subjects.
The artist Jan van der Straet, also known as Johannes Stradanus or simply Stradanus, painted a scene of a wealthy man receiving treatment of syphilis with the tropical wood guaiacum sometime around 1580. The title of the work is "Preparation and Use of Guayaco for Treating Syphilis." That the artist chose to include this image in a series of works celebrating the New World indicates how important a "cure" (however ineffective) for syphilis was to the European elite at that time. The richly colored and detailed work depicts four servants preparing the concoction while a physician looks on, hiding something behind his back while the hapless patient drinks.
The Norwegian, Edvard Munch painted "The sins of the father", a portrayal of a horrified woman with her baby, covered in a rash and with a deformed face lying on a cloth across her knees. This was to portray congenital syphilis, presumably common at the time.
There are references to syphilis in William Shakespeare's play Measure for Measure, particularly in a number of early passages spoken by the character Lucio. For example, Lucio says "[...] thy bones are hollow"; this is a reference to the brittleness of bones engendered by the use of mercury which was then widely used to treat syphilis.
In Shakespeare's play Othello, the clown at the beginning of Act III makes jest of Cassio, who is leading a musician troupe for Othello, by asking him if he had just arrived from Naples and playing with his nose. (Alluding to the reputation of Naples of being a likely place to contract syphilis, which eats away at the bridge of the nose.)
It has been suggested that the main character in Edgar Allan Poe's "The Tell-Tale Heart" may have been infected with neurosyphilis, due to his strange obsessions and apparent insanity.
Jonathan Swift's poetry mentions syphilis as a condition of prostitution which reaches the highest ranks of society. See, for example, "A Beautiful Young Nymph Going To Bed" and "The Progress of Beauty".
William Hogarth's works frequently show his subject's infection with syphilis. Two examples are A Harlot's Progress and Marriage à-la-mode. In both instances it is used to indicate the moral profligacy of the infected.
Some critics have argued that the character of Edward Rochester's first wife, Bertha, in Charlotte Brontë's novel Jane Eyre, suffers from the advanced stages of syphilitic infection, general paresis of the insane, and point to corroborative evidence within the text to substantiate this view.
The novel Candide by Voltaire describes Candide's mentor and teacher, Pangloss, as having contracted syphilis from a maidservant he slept with; the syphilis has ravaged and deformed his body. Pangloss explains to Candide that syphilis is 'necessary in the best of worlds' because the line of infection - which he explains - leads back to Christopher Columbus. If Columbus had not sailed to America and brought back syphilis, Pangloss states, the Europeans would not have been able to enjoy 'New World wonders' such as chocolate. (One of the purposes of the novel was to satirize Leibniz's philosophy as Pangloss's disingenuous rose-tinted viewpoint.) Pangloss eventually loses an eye and an ear to the syphilis before he is cured.
Henrik Ibsen's once-controversial play Ghosts has a young man who is suffering from a mysterious unnamed disease. Though it is never named, the events of the play make it plain that this is syphilis, an inheritance from his dissolute father. However, the young man's mother remains unaffected - this is because it is possible for a woman to carry syphillis and transmit it to her child in the womb without exhibiting any noticeable symptoms. Dr. Rank in Ibsen's play A Doll's House also has inherited syphilis.
Neal Stephenson's trilogy The Baroque Cycle has multiple characters and historical figures who have syphilis, most notably James II of England and Jack Shaftoe; the latter is cured of the disease by running a high fever.
In Christina Garcia's novel "Dreaming in Cuban," Felica contracts syphilis from her unfaithful husband. The syphilis and her family history lead Felica down a path towards insanity.
In Ken Follett's novel "A Dangerous Fortune," the wealthy Edward Pilaster contracts syphilis from his frequency of using brothels. When Edward's cohort Micky Miranda finds out, it looks as though his diabolical plans may have a snag.
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