Syphilis

Syphilis
Specialty	Infectious diseases, dermatology

Syphilis is a sexually transmitted infection (STI) caused by a spirochaete bacterium, Treponema pallidum. Syphilis has many alternate names, including "syph", "the Pox" (or "great pox", to distinguish it from smallpox), "lues" (hence luiphobia, or fear of syphilis), and the "French disease."

The route of transmission of 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, oral treatment 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.

Another treatment is to administer several tablets of azithromycin (which has a long duration of action) orally under observation. This latter course may soon be obsolete, as strains of syphilis resistant to azithromycin have developed, and accounted for 56% of San Francisco infections in 2004.[1] 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.

History

There are two thoughts on the origin of syphilis: the Columbian and pre-Columbian theories. There are ongoing debates in anthropological and historical fields about the validity of either theory.

The pre-Columbian 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 Columbian theory.

The Columbian Exchange 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's crew to the outbreak. Supporters of the Columbian theory find syphilis lesions on pre-contact Native Americans. Again, all the anthropological evidence is heatedly discussed on both sides of the Columbian/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 its 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 smallpox (variola), but has no relation to the smallpox virus. However the name is misleading, as smallpox 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 the Italians also called it the "Spanish disease", the French called it the la maladie anglaise ("the English disease") and "Italian disease" or "Neapolitan disease", the Russians called it the "Polish disease", and the Arabs called it the "Disease of the Christians". The term "lues" was also used.

A number of famous historical personages, including Charles VIII and Ivan the Terrible, have been alleged to have had syphilis. Guy de Maupassant and Friedrich Nietzsche are both 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, making him confused and disoriented. The painter Paul Gauguin is also said to have suffered from syphilis.

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.

See also: List of notable people identified as probably syphilitic

Etymology

"Syphilis" is (somewhat inaccurate) Greek for "he who likes pigs". It was the name of a character in a poem written in Latin by Girolamo Fracastoro in 1530, named Syphilis sive morbus gallicus (Latin for "Syphilis or the French disease"). In the story, Syphilis was a swineherd who had the disease, but people misunderstood the book title and thus the name came to mean the disease.

Stages of syphilis

Different manifestations occur at each stage of the disease:-

Primary syphilis

Chancres on penis due to primary syphilitic infection

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

Secondary syphilis manifested on labia

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( a degeneration of joint surfaces resulting from loss of proprioception) , 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 be 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. Fetus in the utero is most liable to be infected with syphilis after the fifth month. 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. Affected children are highly infectious until about 2 years of age.

Neurosyphilis

Neurosyphilis refers to a site of infection involving the neurologic system. As such, neurosyphilis may occur at any stage of syphilis. Neurosyphilis in patients with HIV infection is well described. Reports of neurosyphilis in HIV-infected persons are similar to cases reported before the HIV epidemic. The precise extent and significance of neurologic involvement in HIV-infected patients with syphilis, reflected by either laboratory or clinical criteria, remain incompletely characterized. Furthermore, the alteration of host immunosuppression by ART in recent years has further complicated such characterization.

Approximately 35% to 40% of persons with secondary syphilis have asymptomatic CNS involvement, as demonstrated by any of the following on CSF examination: an abnormal cell count, protein level, or glucose level; or demonstrated reactivity to Venereal Disease Research Laboratory (VDRL) antibody test. Acute syphilitic meningitis usually occurs within the first 2 years of infection; 10% of cases are diagnosed at the time of the secondary rash. Patients present with headache, meningeal irritation, and cranial nerve abnormalities, typically involving cranial nerves at the base of the brain. Meningovascular syphilis occurs a few months to 10 years (average, 7 years) after the primary infection. Unlike the sudden onset of thrombotic or embolic stroke syndromes, meningovascular syphilis is associated with prodromal symptoms lasting weeks to months before focal deficits of a vascular syndrome are identifiable. Prodromal symptoms include unilateral numbness, paresthesias, 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.

Testing

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 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 test. Both of these early tests have been superseded.

Present-day syphilis tests, such as the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests, while useful, are still not completely specific, as many other conditions can cause a positive result. 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 related treponomal infections such as yaws and pinta. However, a simple microscopy of chancre fluid using dark ground illumination provide a quick and effective test.

In one of the best-documented episodes of unethical human medical experimentation in the twentieth century, the Tuskegee syphilis study continued to study the lifetime course of syphilis in a group of African Americans long after effective treatments for syphilis were available. In the July 17, 1998 issue of the journal Science, a group of biologists reported complete sequencing of the genome of T. pallidum.

Treatment

History

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 his 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.

Current Treatment

The first choice treatment for Primary, secondary, and early latent infection remains penicillin, in the form of Benzathine penicillin G, 2.4 MU IM in a single dose. Individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be effectively treated with oral tetracyclines (100 mg orally twice a day for 14 days). Ceftriaxone may be considered as an alternative therapy, although the optimal dose is not yet defined and close clinical and serologic follow-up is essential. If ceftriaxone is used for the treatment of early syphilis, some experts recommend 1 g daily, given intramuscularly or intravenously, for 8 to 10 days. (47,159,160)

For late latent and infections of unknown duration- If the CSF examination yields no evidence of neurosyphilis, then a total of 7.2 million units of benzathine penicillin G is recommended (administered as 3 doses of 2.4 million units by intramuscular injection weekly for 3 successive weeks). If allergic, then tetracyclines may be used for this stage also, but for 28 days instead of the normal 14.

For patients diagnosed with neurosyphilis (including ocular or auditory syphilis with or without positive LP results), aqueous crystalline penicillin G is the treatment of choice (administered as 18-24 million units intravenously per day; ie, 3-4 million units every 4 hours or continuous infusion for 10-14 days). If intravenous administration is impossible, then aqueous procaine penicillin G is an alternative (administered as 2.4 million units intramuscularly daily plus probenecid 500 mg by mouth 4 times daily for 14 days). 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 (total 7.2 million units intramuscularly) 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, but in special circumstances the only alternative that has been studied is ceftriaxone 2 g intramuscularly for 14 days.

Alternative regimens (eg, tetracyclines) are not well studied in HIV infection and a careful follow-up is recommended. Tetra-cyclines are contraindicated in pregnancy. Skin testing or desensitization to facilitate therapy with penicillin is recommended in pregnant patients and for treatment of latent syphilis and neurosyphilis in other patients with HIV infection. 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.

Oral Azithromycin given as a single dose of 2 g has been used successfully to treat syphilis in a pilot study of 328 patients in Tanzania (Riedner 2005), but resistance to azithromycin (eg, as high as 56% in San Francisco in 2004)[2] has made it an unacceptable alternative.

HIV-infected patients with early syphilis may have a higher risk of neurologic 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.

Before administering any treatment, clinicians should warn all patients about the possibility of a Jarisch-Herxheimer reaction, which occurs most often in secondary syphilis and with penicillin therapy, and may be more common in HIV-infected patients.[3] This reaction is characterized by fever, fatigue, and transient worsening of any mucocutaneous symptoms, and usually subsides within 24 hours. These symptoms can be alleviated with acetaminophen and should not be mistaken for drug allergy. In addition, clinicians should inform HIV-infected patients that currently recommended regimens may be less effective for them than for patients without HIV infection and that close serologic follow-up is therefore essential.

Syphilis in art and literature

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.

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".

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.

Henrik Ibsen's controversial (at the time) 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. Dr Rank in Ibsen's play A Doll's House also has inherited syphilis.

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.

The artist Kees van Dongen produced a series of illustrations for the anarchist publication L'Assiette au Beurre showing the descent of a young prostitute from poverty to her death from syphilis as a criticism of the social order at the end of the 19th century.

Also, in Charles Dickens' novel Tale of Two Cities, references are made that allude to the main character, Sydney Carton, having syphilis.

Mention must be made of the anonymous American medical students' description of syphilis in a series of early 20th-century American limericks, using medical terminology to ghastly comic effect. It was first published in Journal of the American Medical Association January 1942: [4]

Thomas Disch in his novel Camp Concentration describe a fictional strain of syphilis that enhances intelligence but is lethal.

See also

• Other treponematous diseases:-
  • Yaws is a tropical disease characterized by an infection of the skin, bones and joints; it is caused by a spirochete bacterium, Treponema pallidum, sp. pertenue, also called Treponema pertenue
  • Pinta - caused by Treponema carateum
  • Bejel - caused by Treponema endemicum

External links

• UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV
• Sexually Transmitted Diseases/Infections Resource Center from the Association of Reproductive Health Professionals
• "A New Gold Standard For Syphilis?" Poster Presentation for European Academy of Dermatology and Venereology 2004 Spring Symposium
• Kipkeepers, Pox and Gleet Vendors: A Rapid History of Syphilis
• POX: Genius, Madness, and the Mysteries of Syphilis
• Secrets of the Dead (PBS): The Syphilis Enigma
• Syphilis and AIDS: Lessons from history
• "Syphilis fact sheet" from the Center for Disease Control
• The chapter on syphilis from a book on Dermatology and Venerology — contains some good pictures
• The treatment of dementia paralytica by malaria inoculation (A Nobel Prize lecture, December 13, 1927)
• Homosexual men boost increase in syphilis rate
• National Institute of Allergy and Infectious Diseases Factsheet
• Los Angeles MSM Face New Wave of Syphilis