syphilis

Definition

Syphilis is an infectious systemic disease that may be either congenital or acquired through sexual contact or contaminated needles.

Description

Syphilis has both acute and chronic forms that produce a wide variety of symptoms affecting most of the body's organ systems. The range of symptoms makes it easy to confuse syphilis with less serious diseases and ignore its early signs. Acquired syphilis has four stages (primary, secondary, latent, and tertiary) and can be spread by sexual contact during the first three of these four stages.

Syphilis, which is also called lues (from a Latin word meaning plague), has been a major public health problem since the sixteenth century. The disease was treated with mercury or other ineffective remedies until World War I, when effective treatments based on arsenic or bismuth were introduced. These were succeeded by antibiotics after World War II. At that time, the number of cases in the general population decreased, partly because of aggressive public health measures. This temporary decrease, combined with the greater amount of attention given to AIDS in recent years, leads some people to think that syphilis is no longer a serious problem. In actual fact, the number of cases of syphilis in the United States has risen since 1980. This increase affects both sexes, all races, all parts of the nation, and all age groups, including adults over 60. The number of women of childbearing age with syphilis is the highest that has been recorded since the 1940s. About 25, 000 cases of infectious syphilis in adults are reported annually in the United States. It is estimated, however, that 400, 000 people in the United States need treatment for syphilis every year, and that the annual worldwide total is 50 million persons.

The increased incidence of syphilis in recent years is associated with drug abuse as well as changes in sexual behavior. The connections between drug abuse and syphilis include needle sharing and exchanging sex for drugs. In addition, people using drugs are more likely to engage in risky sexual practices. With respect to changing patterns of conduct, a sharp increase in the number of people having sex with multiple partners makes it more difficult for public health doctors to trace the contacts of infected persons. High-risk groups for syphilis include:

• sexually active teenagers
• people infected with another sexually transmitted disease (STD), including AIDS
• sexually abused children
• women of childbearing age
• prostitutes of either sex and their customers
• prisoners
• persons who abuse drugs or alcohol

The chances of contracting syphilis from an infected person in the early stages of the disease during unprotected sex are between 30–50%.

— Rebecca J. Frey

A chronic infectious disease caused by a spirochete (Treponema pallidum), either transmitted by direct contact, usually in sexual intercourse, or passed from mother to child in utero, and progressing through three stages characterized respectively by local formation of chancres, ulcerous skin eruptions, and systemic infection leading to general paresis.

[New Latin, from “Syphilis, sive Morbus Gallicus,” “Syphilis, or the French Disease,” title of a poem by Girolamo Fracastoro (1478?–1553), from Syphilus, the poem's protagonist.]

WORD HISTORY   In 1530 Girolamo Fracastoro, a physician, astronomer, and poet of Verona, published a poem entitled “Syphilis, sive Morbus Gallicus,” translated as “Syphilis, or the French Disease.” In Fracastoro's poem the name of this dreaded venereal disease is an altered form of the name of the hero Syphilus, a shepherd who is supposed to have been the first victim of the disease. Where the name Syphilus itself came from is not known for certain, but it has been suggested that Fracastoro borrowed it from Ovid's Metamorphoses. In Ovid's work Sipylus (spelled Siphylus in some manuscripts) is the oldest son of Niobe, who lived not far from Mount Sipylon in Asia Minor. Fracastoro's poem about Syphilus was modeled on the story of Niobe. Fracastoro went on to use the term syphilis again in his medical treatise De Contagione, published in 1546. The word that Fracastoro used in Latin was eventually borrowed into English, being first recorded in 1718.

A sexually transmitted infection of humans caused by Treponema pallidum ssp. pallidum, a corkscrew-shaped motile bacterium (spirochete). Due to its narrow width, T. pallidum cannot be seen by light microscopy but can be observed with staining procedures (silver stain or immunofluorescence) and with dark-field, phase-contrast, or electron microscopy. The organism is very sensitive to environmental conditions and to physical and chemical agents. The complete genome sequence of the T. pallidum Nichols strain has been determined. The nucleotide sequence of the small, circular treponemal chromosome indicates that T. pallidum lacks the genetic information for many of the metabolic activities found in other bacteria. Thus, this spirochete is dependent upon the host for most of its nutritional requirements. See also Bacterial genetics; Electron microscope; Immunofluorescence.

Syphilis is usually transmitted through direct sexual contact with active lesions and can also be transmitted by contact with infected blood and tissues. If untreated, syphilis progresses through various stages (primary, secondary, latent, and tertiary). Infection begins as an ulcer (chancre) and may eventually involve the cardiovascular and central nervous systems, bones, and joints. Congenital syphilis results from maternal transmission of T. pallidum across the placenta to the fetus. See also Sexually transmitted diseases.

Treponema pallidum is an obligate parasite of humans and does not have a reservoir in animals or the environment. Syphilis has a worldwide distribution. Its incidence varies widely according to geographical location, socioeconomic status, and age group. Although syphilis is controlled in most developed countries, it remains a public health problem in many developing countries. Studies have shown that syphilis is a risk factor for infection with the human immunodeficiency virus (HIV) since syphilitic lesions may act as portals of entry for the virus. There is little natural immunity to syphilis infection or reinfection.

Parenteral penicillin G is the preferred antibiotic for treatment of all stages of syphilis. Alternative antibiotics for syphilis treatment include erythromycin and tetracycline. There is currently no vaccine to prevent syphilis. However, it is anticipated that information obtained from the T. pallidum genome sequence will lead to further improvements in diagnostic tests for syphilis and to the eventual development of a vaccine that would prevent infection. See also Antibiotic; Public health.

A contagious venereal disease caused by Treponema pallidum and usually transmitted by direct contact. Oral lesions include primary chancre, secondary mucous patches and split papule, and tertiary gumma.

Definition

Syphilis is an infectious systemic disease that may be either congenital or acquired through sexual contact or contaminated needles.

Description

Syphilis has both acute and chronic forms that produce a wide variety of symptoms affecting most of the body's organ systems. The range of symptoms makes it easy to confuse syphilis with less serious diseases and ignore its early signs. Acquired syphilis has four stages (primary, secondary, latent, and tertiary) and can be spread by sexual contact during the first three of these four stages.

Syphilis, which is also called lues (from a Latin word meaning "plague"), has been a major public health problem since the sixteenth century. The disease was treated with mercury or other ineffective remedies until World War I, when effective treatments based on arsenic or bismuth were introduced. These were succeeded by antibiotics after World War II. At that time, the number of cases in the general population decreased, partly because of aggressive public health measures. This temporary decrease, combined with the greater amount of attention given to AIDS in recent years, leads some people to think that syphilis is no longer a serious problem. In fact, the number of cases of syphilis in the United States rose between 1980 and 2001. This increase affected both sexes, all races, all parts of the nation, and all age groups, including adults over 60. The number of women of childbearing age with syphilis is the highest that has been recorded since the 1940s. About 25,000 cases of infectious syphilis in adults are reported annually in the United States. It is estimated, however, that 400,000 people in the United States need treatment for syphilis every year, and that the annual worldwide total is 50 million persons.

In 1999, the Centers for Disease Control and Prevention (CDC) joined several other federal agencies in announcing the "National Plan to Eliminate Syphilis in the United States." Eliminating the disease was defined as the absence of transmission of the disease; that is, no transmission after 90 days following the report of an imported index case. The national goals for eliminating syphilis include bringing the annual number of reported cases in the United States below 1000, and increasing the number of syphilis-free counties to 90% by 2005. In November 2002, the CDC released figures for 2000–2001, which indicate that the number of reported cases of primary and secondary syphilis rose slightly. This rise, however, occurred only among men who have sex with other men. The CDC also stated that the number of new cases of syphilis has actually declined among women as well as among non-Hispanic blacks.

The increased incidence of syphilis since the 1970s is associated with drug abuse as well as changes in sexual behavior. The connections between drug abuse and syphilis include needle sharing and exchanging sex for drugs. In addition, people using drugs are more likely to engage in risky sexual practices. As of 2002, the risk of contracting syphilis is particularly high among those who abuse crack cocaine.

With respect to changing patterns of conduct, a sharp increase in the number of people having sex with multiple partners makes it more difficult for public health doctors to trace the contacts of infected persons. Women are not necessarily protected by having sex only with other women; in the past few years, several cases have been reported of female-to-female transmission of syphilis through oral-genital contact. In addition, the incidence of syphilis among men who have sex with other men continues to rise. Several studies in Latin America as well as in the United States reported in late 2002 that unprotected sexual intercourse is on the increase among gay and bisexual men.

Changing patterns of sexual behavior have led to a striking increase in the number of cases of syphilis in eastern Europe since the collapse of the Soviet Union; Slovenia reported an 18-fold increase in reported cases of syphilis just between 1993 and 1994. Over half of the new cases were linked to a source of infection in another European country.

In general, high-risk groups for syphilis in the United States and Canada include:

• sexually active teenagers
• people infected with another sexually transmitted disease (STD), including AIDS, herpes, and gonorrhea
• sexually abused children
• women of childbearing age
• prostitutes of either sex and their customers
• prisoners
• persons who abuse drugs or alcohol

The chances of contracting syphilis from an infected person in the early stages of the disease during unprotected sex range from 30–50%.

Causes & Symptoms

Syphilis is caused by a spirochete, Treponema pallidum. A spirochete is a thin spiral- or coil-shaped bacterium that enters the body through the mucous membranes or breaks in the skin. In 90% of cases, the spiro-chete is transmitted by sexual contact. Transmission by blood transfusion is possible but rare, not only because blood products are screened for the disease, but also because the spirochetes die within 24 hours in stored blood. Other methods of transmission are highly unlikely because T. pallidum is easily killed by heat and drying.

Primary Syphilis

Primary syphilis is the stage of the organism's entry into the body. The first signs of infection are not always noticed. After an incubation period ranging from 10–90 days, the patient develops a chancre, which is a small blister-like sore about 0.5 in (13 mm) in size. Most chancres are on the genitals, but may also develop in or on the mouth or on the breasts. Rectal chancres are common in male homosexuals. Chancres in women are sometimes overlooked if they develop in the vagina or on the cervix. The chancres are not painful and disappear in three to six weeks even without treatment. They resemble the ulcers of lymphogranuloma venereum, herpes simplex virus, or skin tumors.

About 70% of patients with primary syphilis also develop swollen lymph nodes near the chancre. The nodes may have a firm or rubbery feel when the doctor touches them but are not usually painful.

Secondary Syphilis

Syphilis enters its secondary stage ranging from six to eight weeks to six months after the infection begins. Chancres may still be present but are usually healing. Secondary syphilis is a systemic infection marked by the eruption of skin rashes and ulcers in the mucous membranes. The skin rash may mimic a number of other skin disorders such as drug reactions, rubella ringworm, mononucleosis, and pityriasis rosea. Characteristics that point to syphilis include:

• a coppery color
• absence of pain or itching
• occurrence on the palms of hands and soles of feet

The skin eruption may resolve in a few weeks or last as long as a year. The patient may also develop condylomata lata, which are weepy pinkish or gray areas of flattened skin in the moist areas of the body. The skin rashes, mouth and genital ulcers, and condylomata lata are all highly infectious.

About 50% of patients with secondary syphilis develop swollen lymph nodes in the armpits, groin, and neck areas; about 10% develop inflammations of the eyes, kidney, liver, spleen, bones, joints, or the meninges (membranes covering the brain and spinal cord). They may also have a flulike general illness with a low fever, chills, loss of appetite, headaches, runny nose, sore throat, and aching joints.

Latent Syphilis

Latent syphilis is a phase of the disease characterized by relative absence of external symptoms. The term latent does not mean that the disease is not progressing or that the patient cannot infect others. For example, pregnant women can transmit syphilis to their unborn children during the latency period.

The latent phase is sometimes divided into early latency (less than two years after infection) and late latency. During early latency, patients are at risk for spontaneous relapses marked by recurrence of the ulcers and skin rashes of secondary syphilis. In late latency, these recurrences are much less likely. Late latency may either resolve spontaneously or continue for the rest of the patient's life.

Tertiary Syphilis

Untreated syphilis progresses to a third or tertiary stage in about 35–40% of patients (only those who go untreated). Patients with tertiary syphilis cannot infect others with the disease. It is thought that the symptoms of this stage are a delayed immune hypersensitivity reaction to the spirochetes. Some patients develop so-called benign late syphilis, which begins between three and 10 years after infection and is characterized by the development of gummas. Gummas are rubbery tumor-like growths that are most likely to involve the skin or long bones but may also develop in the eyes, mucous membranes, throat, liver, or stomach lining. Gummas are increasingly uncommon since the introduction of antibiotics for treating syphilis. Benign late syphilis is usually rapid in onset and responds well to treatment.

CARDIOVASCULAR SYPHILIS. Cardiovascular syphilis occurs in 10–15% of patients who have progressed to tertiary syphilis. It develops between 10 and 25 years after infection and often occurs together with neurosyphilis. Cardiovascular syphilis usually begins as an inflammation of the arteries leading from the heart and heart attacks, scarring of the aortic valves, congestive heart failure, or the formation of an aortic aneurysm.

NEUROSYPHILIS. About 8% of patients with untreated syphilis will develop symptoms in the central nervous system that include both physical and psychiatric symptoms. Neurosyphilis can appear at any time from five to 35 years after the onset of primary syphilis. It affects men more frequently than women and Caucasians more frequently than African Americans.

Neurosyphilis is classified into four types:

• Asymptomatic. In this form of neurosyphilis, the patient's spinal fluid gives abnormal test results but there are no symptoms affecting the central nervous system.
• Meningovascular. This type of neurosyphilis is marked by changes in the blood vessels of the brain or inflammation of the meninges (the tissue layers covering the brain and spinal cord). The patient develops headaches, irritability, and visual problems. If the spinal cord is involved, the patient may experience weakness of the shoulder and upper arm muscles.
• Tabes dorsalis. Tabes dorsalis is a progressive degeneration of the spinal cord and nerve roots. Patients lose their sense of perception of body position and orientation in space (proprioception), resulting in difficulties walking and loss of muscle reflexes. They may also have shooting pains in the legs and periodic episodes of pain in the abdomen, throat, bladder, or rectum. Tabes dorsalis is sometimes called locomotor ataxia.
• General paresis. General paresis refers to the effects of neurosyphilis on the cortex of the brain. The patient has a slow but progressive loss of memory, decreased ability to concentrate, and less interest in self-care. Personality changes may include irresponsible behavior, depression, delusions of grandeur, or complete psychosis. General paresis is sometimes called dementia paralytica, and is most common in patients over 40.

Special Populations

NEWBORNS. Congenital syphilis has increased at a rate of 400–500% over the past decade, on the basis of criteria introduced by the Centers for Disease Control (CDC) in 1990. In 1994, more than 2,200 cases of congenital syphilis were reported in the United States. The prognosis for early congenital syphilis is poor: about 54% of infected fetuses die before or shortly after birth. Those who survive may look normal at birth but show signs of infection between three and eight weeks later.

Infants with early congenital syphilis have systemic symptoms that resemble those of adults with secondary syphilis. There is a 40–60% chance that the child's central nervous system will be infected. These infants may have symptoms ranging from jaundice, enlargement of the spleen and liver, and anemia to skin rashes, condylomata lata, certain congenital bone abnormalities, inflammation of the lungs, "snuffles" (a persistent runny nose), and swollen lymph nodes.

CHILDREN. Children who develop symptoms after the age of two years are said to have late congenital syphilis. The characteristic symptoms include facial deformities (saddle nose), Hutchinson's teeth (abnormal upper incisors), saber shins, dislocated joints, deafness, mental retardation, paralysis, and seizure disorders.

PREGNANT WOMEN. Syphilis can be transmitted from the mother to the fetus through the placenta at any time during pregnancy, or through the child's contact with syphilitic ulcers during the birth process. The chances of infection are related to the stage of the mother's disease. Almost all infants of mothers with untreated primary or secondary syphilis will be infected, whereas the infection rate drops to 40% if the mother is in the early latent stage and 6–14% if she has late latent syphilis.

Pregnancy does not affect the progression of syphilis in the mother; however, pregnant women should not be treated with tetracyclines.

HIV PATIENTS. Syphilis has been closely associated with HIV infection since the late 1980s. Syphilis sometimes mimics the symptoms of AIDS. Conversely, AIDS appears to increase the severity of syphilis in patients suffering from both diseases, and to speed up the development or appearance of neurosyphilis. Patients with HIV are also more likely to develop lues maligna, a skin disease that sometimes occurs in secondary syphilis. Lues maligna is characterized by areas of ulcerated and dying tissue. In addition, HIV patients have a higher rate of treatment failure with penicillin than patients without HIV.

ADULT MALES. A recent study indicates that infection with syphilis increases a man's risk of developing prostate cancer in later life. It is thought that infection may represent one mechanism among several through which prostate cancer may develop.

Diagnosis

Patient History and Physical Diagnosis

The diagnosis of syphilis is often delayed because of the variety of early symptoms, the varying length of the incubation period, and the possibility of not noticing the initial chancre. Patients do not always connect their symptoms with recent sexual contact. They may go to a dermatologist when they develop the skin rash of secondary syphilis rather than to their primary care doctor. Women may be diagnosed in the course of a gynecological checkup. Because of the long-term risks of untreated syphilis, certain groups of people are now routinely screened for the disease:

• pregnant women
• sexual contacts or partners of patients diagnosed with syphilis
• children born to mothers with syphilis
• patients with HIV infection
• persons applying for marriage licenses

When the doctor takes the patient's history, he or she will ask about recent sexual contacts in order to determine whether the patient falls into a high-risk group. Other symptoms, such as skin rashes or swollen lymph nodes, will be noted with respect to the dates of the patient's sexual contacts. Definite diagnosis, however, depends on the results of laboratory blood tests.

Blood Tests

There are several types of blood tests for syphilis presently used in the United States. Some are used in follow-up monitoring of patients as well as diagnosis.

NONTREPONEMAL ANTIGEN TESTS. Nontreponemal antigen tests are used as screeners. They measure the presence of reagin, which is an antibody formed in reaction to syphilis. In the Venereal Disease Research Laboratory (VDRL) test, a sample of the patient's blood is mixed with cardiolipin and cholesterol. If the mixture forms clumps or masses of matter, the test is considered reactive or positive. The serum sample can be diluted several times to determine the concentration of reagin in the patient's blood.

The rapid plasma reagin (RPR) test works on the same principle as the VDRL. It is available as a kit. The patient's serum is mixed with cardiolipin on a plastic-coated card that can be examined with the naked eye.

Nontreponemal antigen tests require a doctor's interpretation and sometimes further testing. They can yield both false-negative and false-positive results. False-positive results (test shows a positive result when the patient does not have the disease) can be caused by other infectious diseases, including mononucleosis, malaria, leprosy, rheumatoid arthritis, and lupus. HIV patients have a particularly high rate (4%, compared to 0.8% of HIV-negative patients) of false-positive results on reagin tests. False negative results (patient does have the disease, but test comes back negative) can occur when patients are tested too soon after exposure to syphilis; it takes about 14–21 days after infection for the blood to become reactive.

TREPONEMAL ANTIBODY TESTS. Treponemal anti-body tests are used to rule out false-positive results on reagin tests. They measure the presence of antibodies that are specific for T. pallidum. The most commonly used tests are the microhemagglutination-T. pallidum (MHA-TP) and the fluorescent treponemal antibody absorption (FTA-ABS) tests. In the FTA-ABS, the patient's blood serum is mixed with a preparation that prevents interference from antibodies to other treponemal infections. The test serum is added to a slide containing T. pallidum. In a positive reaction, syphilitic antibodies in the blood coat the spirochetes on the slide. The slide is then stained with fluorescein, which causes the coated spirochetes to fluoresce when the slide is viewed under ultraviolet (UV) light. In the MHA-TP test, red blood cells from sheep are coated with T. pallidum antigen. The cells will clump if the patient's blood contains anti-bodies for syphilis.

A newer treponemal antibody test developed in Belgium, the INNO-LIA, uses recombinant and peptide antigens derived from T. pallidum proteins. Preliminary testing in Europe indicates that the INNO-LIA is the most accurate of the available treponemal antibody tests for syphilis.

Treponemal antibody tests are more expensive and more difficult to perform than nontreponemal tests. They are therefore used to confirm the diagnosis of syphilis rather than to screen large groups of people. These tests are, however, very specific and very sensitive; false-positive results are relatively unusual.

INVESTIGATIONAL BLOOD TESTS. As of 1998, ELISA, Western blot, and PCR testing are being studied as additional diagnostic tests, particularly for congenital syphilis and neurosyphilis.

Other Laboratory Tests

MICROSCOPE STUDIES. The diagnosis of syphilis can also be confirmed by identifying spirochetes in samples of tissue or lymphatic fluid. Fresh samples can be made into slides and studied under darkfield illumination. A newer method involves preparing slides from dried fluid smears and staining them with fluorescein for viewing under UV light. This method is replacing dark-field examination because the slides can be mailed to professional laboratories.

SPINAL FLUID TESTS. Testing of cerebrospinal fluid (CSF) is an important part of patient monitoring as well as a diagnostic test. The VDRL and FTA-ABS tests can be performed on CSF as well as on blood. An abnormally high white cell count and elevated protein levels in the CSF, together with positive VDRL results, suggest a possible diagnosis of neurosyphilis. CSF testing is not used for routine screening. It is used most frequently for infants with congenital syphilis, HIV-positive patients, and patients of any age who are not responding to penicillin treatment.

Treatment

It is difficult to obtain information about alternative treatments for syphilis. The disease has a high profile as a public health issue and few alternative practitioners want to risk accusations of minimizing its dangers. One respected resource for alternative therapies states bluntly, "Syphilis should not be treated only with natural therapies." Most naturopathic practitioners agree that antibiotics are essential for the treatment of syphilis. Others would add that recovery from the disease can be assisted by dietary changes, sleep, exercise, and stress reduction, and immune support measures.

Homeopathy

Homeopathic practitioners are forbidden by law in the United States to claim that homeopathic treatment can cure syphilis. Given the high rate of syphilis in HIV-positive patients, however, some alternative practitioners who are treating AIDS patients with homeopathic remedies maintain that they are beneficial for syphilis as well. The remedies suggested most frequently are Medorrhinum, Syphilinum, Mercurius vivus, and Aurum. The use of Mercurius vivus as a homeopathic remedy reflects the past use of mercury to treat syphilis prior to the discovery of penicillin. Syphilinum represents a class of homeopathic remedy called nosodes. A nosode is a homeopathic medicine made from diseased material, such as bacteria, viruses, or pus. Its effect is based on the homeopathic law of similars, in which a substance that causes a specific set of symptoms in a healthy person is determined curative when given to a sick person with the same symptoms. Syphilinum is a nosode made from a dilution of killed Treponema pallidum. The historical link between homeopathy and syphilis is Hahnemann's theory of miasms, which he defined as fundamental predispositions toward disease that were transmitted from one generation to the next. He thought that the syphilitic miasm was the second oldest cause of constitutional weakness in humans.

Other

Traditional Chinese medicine (TCM) and other alternative methods emphasize the mental aspects of conditions and diseases such as syphilis. Mind-body medicine, guided imagery and affirmations are often used to help support a person through such a disease. New thought holds that humans can control physical as well as mental or spiritual events through the power of thinking itself. Some alternative therapies reflect new thought beliefs by maintaining that humans make themselves ill through harmful thought patterns, and that they can heal themselves by affirming positive beliefs. The affirmation suggested for healing syphilis is "I decide to be me." Most alternative practitioners would recommend this or similar new thought affirmations only as adjuncts to conventional medical treatment for syphilis.

One interesting recent historical development is that outdated or discredited treatments for syphilis have resurfaced as alternative treatments for AIDS or cancer. One study of alternative treatments for HIV infection notes that hyperthermia, which involves treating a disease by giving the patient a fever, originated as a treatment for syphilis. Syphilis patients were given malaria in the belief that the resultant fever would kill the spiro-chetes that cause syphilis.

Another example is the so-called Hoxsey treatment for cancer, which was started in the 1920s by an Illinois practitioner named Harry Hoxsey. The treatment is no longer legally available in the United States but is offered through a clinic in Tijuana, Mexico. The treatment consists of several chemical mixtures applied externally and a formula of nine herbs taken internally. The Hoxsey herbal formula is almost identical to a remedy that was listed in the 1926 and 1936 editions of the United States National Formulary called "Compound Fluidextract of Trifolium." It was recommended as a treatment for secondary and tertiary syphilis. One of the external Hoxsey compounds contains both arsenic and antimony, which were used to treat syphilis before the use of antibiotics. The internal formula includes Phytolacca americana, or pokeweed, which was used by Native Americans to treat syphilitic chancres; and Stillingia sylvatica, or queens-root, which has also been used to treat syphilis. There is no demonstrated data to support the therapy's effectiveness for syphilis.

It should be noted that many alternative medicine therapies that claim to help such infectious diseases as syphilis have little data supporting their effectiveness.

Allopathic Treatment

Medications

Syphilis is treated with antibiotics given either intramuscularly (benzathine penicillin G or ceftriaxone) or orally (doxycycline, minocycline, tetracycline, or azithromycin). Neurosyphilis is treated with a combination of aqueous crystalline penicillin G, benzathine penicillin G, or doxycycline. It is important to keep the levels of penicillin in the patient's tissues at sufficiently high levels over a period of days or weeks because the spiro-chetes have a relatively long reproduction time. Penicillin is more effective in treating the early stages of syphilis than the later stages.

In the fall of 2000, the CDC convened a group of medical advisors to discuss backup medications for treating syphilis. Although none of the newer drugs will displace penicillin as the primary drug, the doctors recommended azithromycin and ceftriaxone as medications that should have a larger role in the treatment of syphilis than they presently do.

Doctors do not usually prescribe separate medications for the skin rashes or ulcers of secondary syphilis. The patient is advised to keep them clean and dry, and to avoid exposing others to fluid or discharges from condylomata lata.

Pregnant women should be treated as early in pregnancy as possible. Infected fetuses can be cured if the mother is treated during the second and third trimesters of pregnancy. Infants with proven or suspected congenital syphilis are treated with either aqueous crystalline penicillin G or aqueous procaine penicillin G. Children who acquire syphilis after birth are treated with benzathine penicillin G.

Jarisch-Herxheimer Reaction

The Jarisch-Herxheimer reaction, first described in 1895, is a reaction to penicillin treatment that may occur during the late primary, secondary, or early latent stages. The patient develops chills, fever, headache, and muscle pains within two to six hours after the penicillin is injected. The chancre or rash gets temporarily worse. The Jarisch-Herxheimer reaction, which lasts about a day, is thought to be an allergic reaction to toxins released when the penicillin kills massive numbers of spirochetes.

Expected Results

The expected results of alternative therapies used as adjuncts to conventional antibiotic treatment, for stress reduction or similar purposes, would include improvements in the patient's emotional and spiritual quality of life. The effectiveness of homeopathic treatment for syphilis has not been evaluated in clinical trials, although there are anecdotal reports of successful treatment of syphilis by homeopathic methods.

Analysis of the Hoxsey formulae, however, indicate that they should not be used to treat syphilis or other venereal diseases. Two ingredients in the internal formula have toxic effects: queensroot contains an irritant that can cause inflammation or swelling of the skin and mucous membranes, while pokeweed can cause potentially fatal respiratory paralysis. In addition, the arsenic and antimony in the external formula could potentially cause heavy metal toxicity.

Prevention

Immunity

Patients with syphilis do not acquire lasting immunity against the disease. As of 2002, no effective vaccine for syphilis has been developed even though the genome of T. pallidum was completely sequenced in 1998. The sequencing may, however, speed up the process of developing an effective vaccine. Prevention depends on a combination of personal and public health measures.

Lifestyle Choices

The only reliable methods for preventing transmission of syphilis are sexual abstinence or monogamous relationships between uninfected partners. Condoms offer some protection but protect only the covered parts of the body.

Public Health Measures

CONTACT TRACING. United States law requires reporting of syphilis cases to public health agencies. Sexual contacts of patients diagnosed with syphilis are traced and tested for the disease. Tracing includes all contacts for the past three months in cases of primary syphilis and for the past year in cases of secondary disease. Neither the patients nor their contacts should have sex with anyone until they have been tested and treated.

Because of the rising incidence of syphilis abroad, a growing number of public health physicians are recommending routine screening of immigrants, refugees, and international adoptees for syphilis as of late 2002.

All patients who test positive for syphilis should be tested for HIV infection at the time of diagnosis.

PRENATAL TESTING OF PREGNANT WOMEN. Pregnant women should be tested for syphilis at the time of their first visit for prenatal care, and again shortly before delivery. Proper treatment of secondary syphilis in the mother reduces the risk of congenital syphilis in the infant from 90% to less than 2%.

As of late 2002, many obstetricians and gynecologists are recommending routine screening of nonpregnant as well as pregnant women for syphilis. At present, only about half of obstetricians and gynecologists in the United States screen nonpregnant women for chlamydia and gonorrhea, while fewer than a third screen them for syphilis.

EDUCATION AND INFORMATION. Patients diagnosed with syphilis should be given information about the disease and counseling regarding sexual behavior and the importance of completing antibiotic treatment. It is also important to inform the general public about the transmission and early symptoms of syphilis, and provide adequate health facilities for testing and treatment.

Resources

Books

Burton Goldberg Group. Alternative Medicine: The Definitive Guide. Fife, WA: Future Medicine Publishing, Inc., 1995.

Fiumara, Nicholas J. "Syphilis." In Conn's Current Therapy, edited by Robert E. Rakel. Philadelphia: W.B. Saunders Company, 1998.

Jacobs, Richard A. "Infectious Diseases: Spirochetal." In Current Medical Diagnosis & Treatment 1998, edited by Lawrence M. Tierney Jr. et al. Stamford, CT: Appleton & Lange, 1998.

Ramin, Susan M., et al. "Sexually Transmitted Diseases and Pelvic Infections." In Current Obstetric & Gynecologic Diagnosis & Treatment, edited by Alan H. DeCherney and Martin L. Pernoll. Norwalk, CT: Appleton & Lange, 1994.

Sigel, Eric J. "Sexually Transmitted Diseases." In Current Pediatric Diagnosis & Treatment, edited by William W. Hay Jr., et al. Stamford, CT: Appleton & Lange, 1997.

"Syphilis." Section 13, Chapter 164 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Wolf, Judith E. "Syphilis." In Current Diagnosis 9, edited by Rex B. Conn, et al. Philadelphia: W.B. Saunders Company, 1997.

Periodicals

Augenbraun, M. H. "Treatment of Syphilis 2001: Nonpregnant Adults." Clinical Infectious Diseases 35 (October 15, 2002) (Suppl. 2): S187–S190.

Campos-Outcalt, D., and S. Hurwitz." Female-to-Female Transmission of Syphilis: A Case Report." Sexually Transmitted Diseases 29 (February 2002): 119–120.

Centers for Disease Control. "Primary and Secondary Syphilis—United States, 2000-2001." Morbidity and Mortality Weekly Report 51 (November 1, 2002): 971–973.

Dennis, L. K., and D. V. Dawson. "Meta-Analysis of Measures of Sexual Activity and Prostate Cancer." Epidemiology 13 (January 2002): 72–79.

Gibbs, R. S. "The Origins of Stillbirth: Infectious Diseases." Seminars in Perinatology 26 (February 2002): 75–78.

Grgic-Vitek, M., I Klavs, M. Potocnik, and M. Rogl-Butina. "Syphilis Epidemic in Slovenia Influenced by Syphilis Epidemic in the Russian Federation and Other Newly Independent States." International Journal of STD and AIDS 13 (December 2002) (Suppl. 2): 2–4.

Hagedorn, H. J., A. Kraminer-Hagedorn, K. de Bosschere, et al. "Evaluation of INNO-LIA Syphilis Assay as a Confirmatory Test for Syphilis." Journal of Clinical Microbiology 40 (March 2002): 973–978.

Hogben, M., J. S. Lawrence, D. Kasprzyk, et al. "Sexually Transmitted Disease Screening by United States Obstetricians and Gynecologists." Obstetrics and Gynecology 100 (October 2002): 801–807.

Kolivras, A., J. de Maubeuge, M. Song, et al. "A Case of Early Congenital Syphilis." Dermatology 204 (2002): 338–340.

Pao, D., B. T. Goh, and J. S. Bingham. "Management Issues in Syphilis." Drugs 62 (2002): 1447–1461.

Ross, M. W., L. Y. Hwang, C. Zack, et al. "Sexual Risk Behaviours and STIs in Drug Abuse Treatment Populations Whose Drug of Choice is Crack Cocaine." International Journal of STD and AIDS 13 (November 2002): 769–774.

Stauffer, W. M., D. Kamat, and P. F. Walker. "Screening of International Immigrants, Refugees, and Adoptees." Primary Care 29 (December 2002): 879–905.

Sutmoller, F., T. L. Penna, C. T. de Souza, et al. "Human Immunodeficiency Virus Incidence and Risk Behavior in the 'Projeto Rio': Results of the First 5 Years of the Rio de Janeiro Open Cohort of Homosexual and Bisexual Men, 1994–98." International Journal of Infectious Diseases 6 (December 2002): 259–265.

Whittington, W. L., T. Collis, C. Dithmer-Schreck, et al. "Sexually Transmitted Diseases and Human Immunodeficiency Virus-Discordant Partnerships Among Men Who Have Sex With Men." Clinical Infectious Diseases 35 (October 15, 2002): 1010–1017.

Organizations

Centers for Disease Control and Prevention. 1600 Clifton Road NE, Atlanta, GA, 30333. (404) 639-3534.

[Article by: Rebecca J. Frey, PhD]

Syphilis is a sexually transmitted disease (STD) caused by Treponema pallidum, a spirochete that can be transmitted during vaginal, anal, or oral sex. An estimated 70,000 syphilis cases occur in the United States annually.

Without treatment, syphilis in adults progresses through four stages: primary, secondary, latent, and tertiary. Persons with syphilis are most infectious during the primary and secondary stages. Primary syphilis is marked by an infectious sore (chancre) that resolves on its own. Without treatment, syphilis bacteria spread through the bloodstream and lead to the secondary stage, which is characterized by a skin rash and systemic symptoms. These symptoms can come and go over one to two years, during which an infected person can infect others. If untreated, the infection progresses to a latent stage. Symptoms disappear, and the disease is no longer infectious, but the bacteria remain in the body and can damage vital organs. In about a third of untreated persons, the results of the internal damage show up years later in the tertiary stage. Symptoms include paralysis, blindness, dementia, impotence, joint damage, heart problems, tumors, and deep sores. The damage can be serious enough to cause death. An untreated pregnant woman in an infectious stage of syphilis can pass the infection to her developing fetus.

Syphilis bacteria can be detected by laboratory examination of material from infectious sores. A safe, accurate, and inexpensive blood screening test is also available. Syphilis is treatable with penicillin. Persons who engage in sexual behaviors that place them at risk of STDs should use latex or polyurethane condoms every time they have sex and limit the number of sex partners. Pregnant women should be screened for syphilis. Infected persons should notify all sex partners so they can receive treatment.

(SEE ALSO: Sexually Transmitted Diseases)

Bibliography

Centers for Disease Control and Prevention (1998). "1998 Guidelines for Treatment of Sexually Transmitted Diseases." Morbidity and Mortality Weekly Report 47(RR-1):28–41.

Sparling, P. F. (1999). "Natural History of Syphilis." In Sexually Transmitted Diseases, 3rd edition. eds. K. Holmes, P. Mardh, P. Sparling et al. New York: McGraw-Hill.

— ALLISON L. GREENSPAN; JOEL R. GREENSPAN

For more information on syphilis, visit Britannica.com.

A sexually transmitted disease caused by a microorganism. In its initial stages (called primary syphilis), it is manifested by a skin ulcer called a chancre. If the disease is not treated by penicillin or other antibiotics, the infection becomes chronic. In so-called tertiary syphilis, virtually any tissue in the body can be damaged, including the cardiovascular and nervous systems. The disease, if left untreated, can cause blindness, mental illness, and death.

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Syphilis
Classification and external resources
Image of spiral-shaped organisms responsible for causing syphilis
ICD-10	A50.-A53.
ICD-9	090-097
MedlinePlus	001327
eMedicine	med/2224  emerg/563 derm/413
MeSH	D013587

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. One of the oldest and still the most effective method is an intramuscular injection of benzathine penicillin.^{[citation needed]} 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 1 Alternative names 2 Origins 3 History 3.1 European outbreak 3.2 Notable syphilis-infected people in history 4 Syphilis infection 4.1 Primary syphilis 4.2 Secondary syphilis 4.3 Latent syphilis 4.4 Tertiary syphilis 4.5 Neurosyphilis 5 Diagnostic tests 5.1 Early 20th century 5.2 Modern diagnostic tests 5.3 Other Treponematoses 6 Treatment 6.1 Prevention 6.2 History of treatments 6.3 Current treatment 6.3.1 Late latent and infections of unknown duration 6.3.2 Treatment of neurosyphilis 6.3.3 Alternative regimens 6.4 Jarisch-Herxheimer reaction 6.5 Tuskegee syphilis study 7 Syphilis in art and literature 7.1 Art 7.2 Classic and antique literature 7.3 Modern literature 7.4 Film, television and stage 8 Gallery 9 See also 10 References 11 External links

Alternative names

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").^[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" (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".^[4]

Origins

Three theories on the origin of syphilis have been subject to debate in anthropological and historical fields.

The "pre-Columbian theory" holds that syphilis was present in Europe before the discovery of the Americas. Some scholars believe its symptoms were 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, meaning the continual arrival of sailors from distant places, is thought to have been a key factor in the transmission of syphilis.^[5] 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,^[6][7] although the interpretation of this evidence has been disputed.^[8]

The "Columbian Exchange theory" holds that syphilis was a New World disease brought back by Columbus and Martin Alonso Pinzon.^{[citation needed]} Supporters of the Columbian theory find syphilis lesions in pre-contact Indigenous peoples of the Americas and cite documentary evidence linking crewmen of Columbus's voyages to the Naples syphilis outbreak of 1494.^[9] 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.^[10][11]

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 the tradition of assigning the homeland of yaws to sub-Saharan Africa, Crosby notes that there is no unequivocal evidence of any related disease having been present in pre-Columbian Europe, Africa, or Asia. There is indisputable evidence of syphilis having existed in the pre-Columbian Americas. 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."^[12]

However, Crosby considers it more likely that a highly contagious ancestral species of the 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."^[12] Thus, a weak, non-syphilitic bacterium survived in the Old World to eventually give rise to yaws or bejel. A New World version evolved into the milder pinta and the more aggressive syphilis.

Also arguing for worldwide incidence of syphilis prior to Columbus' voyage, Douglas Owsley, famed physical anthropologist at the Smithsonian Institution, suggests in an article with John Lobdell 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,

... syphilis probably cannot be "blamed"—as it often is—on any geographical area or specific race. The evidence suggests that the disease existed in both hemispheres from prehistoric times. It is only coincidental with the Columbus expeditions that the syphilis previously thought of as "lepra" flared into virulence at the end of the fifteenth century.^[13]

Lobdell and Owsley noted that a European writer who recorded an outbreak of "lepra" in 1303 was "clearly describing syphilis."^[13]

History

Portrait of Gerard de Lairesse by Rembrandt van Rijn, ca. 1665–67, oil on canvas. De Lairesse, himself a painter and art theorist, suffered from congenital syphilis that severely deformed his face and eventually blinded him.^[14]

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.^[15] Prior to Noguchi's discovery, syphilis had been a burden to humanity in many lands. Without its cause being understood, it was sometimes misdiagnosed and often misattributed to damage by political enemies.

Some famous historical personages, including Charles VIII of France, Hernando Cortez of Spain, Adolf Hitler, Benito Mussolini, and Ivan the Terrible, were 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 was also said to have suffered from syphilis. Composers who succumbed to syphilis included Hugo Wolf, Frederick Delius, Scott Joplin, Gaetano Donizetti, and possibly Franz Schubert and Niccolò Paganini.

Mental illness 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 of syphilis was the insanity of noted composer Robert Schumann, although the precise cause of his death has been disputed by scholars.

The Russian author Leo Tolstoy suffered from syphilis during his youth, which was treated using contemporary arsenic treatment.^[16] 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.^[17]

From 1932–1972, the U.S. Public Health Service conducted what became known as the Tuskegee Study of Untreated Syphilis in the Negro Male (also known as the Tuskegee Syphilis Study or the Tuskegee Experiment). It was a clinical study, conducted in Tuskegee, Alabama. Nearly 400 poor, mostly illiterate, African-American men with syphilis were deliberately and systematically denied effective treatment so that researchers could observe the natural progression of the disease when left untreated. The controversy over the unethical behavior of the researchers conducting this study eventually led to major changes in how patients are protected in clinical studies.

European outbreak

A medical illustration attributed to Albrecht Dürer (1496) depicting a person with syphilis. Here, the disease is believed to have astrological causes.

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.^[18] The French may have caught it via Spanish mercenaries serving King Charles of France in that siege.^[13] From this centre, the disease swept across Europe. As Jared Diamond describes it, "[W]hen 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,"[B]y 1546, the disease had evolved into the disease with the symptoms so well known to us today."^[19] The epidemiology of this first syphilis epidemic shows that the disease was either new or a mutated form of an earlier disease.

Researchers concluded that syphilis was carried from the New World to Europe after Columbus' voyages. The findings suggested Europeans could have carried the nonvenereal tropical bacteria home, where the organisms may have mutated into a more deadly form in the different conditions and low immunity of the population of Europe.^[20] Syphilis was a major killer in Europe during the Renaissance.^[21]

Notable syphilis-infected people in history

Keys: S—suspected case; †—died of syphilis

• Endre Ady (1877-1919), Hungarian poet †
• Maurice Barrymore (1849–1905) actor †
• John Batman (1801–1839), founder of Melbourne †
• Charles Baudelaire (1821–1867), poet †
• Karen Blixen (1885–1962), writer
• Manuel Maria Barbosa du Bocage (1765–1805), poet †
• Napoleon Bonaparte (1769–1821), emperor of France S
• António Botto (1897–1959), poet
• Camilo Castelo Branco (1825–1890), writer
• Beau Brummell (1778–1840), fashion arbiter
• Al Capone (1899–1947), gangster †
• Henry Stuart, Lord Darnley (1545–1567), second husband of Mary Queen of Scots
• Frederick Delius (1862–1934), composer †
• Gaetano Donizetti (1797–1848), composer
• Bedřich Smetana (1824–1884), composer †
• Paul Gauguin (1848–1903), painter †
• Heinrich Heine (1797–1856), poet †
• Henry VIII (1491–1547), king of England S
• Adolf Hitler (1889–1945), Nazi leader S
• Ivan the Terrible (1530–1584), Czar of Russia
• Scott Joplin (1867/8–1917), composer †
• John Keats (1795–1821), poet S
• William Lobb (1809–1864), plant collector S
• Édouard Manet (1832–1883), painter †
• Guy de Maupassant (1850–1893), writer †
• Friedrich Nietzsche (1844–1900), philosopher S
• Jack Pickford (1896–1933), actor †
• Martin Alonso Pinzon (1441–1493) captain of the Pinta †
• Leo Tolstoy (1828–1910), writer S
• Vincent Van Gogh (1853–1890), painter S
• Oscar Wilde (1854–1900), writer S
• Eugen Sandow (1867–1925), bodybuilder S^[22]
• Franz Schubert (1797–1828), composer †
• Henri de Toulouse-Lautrec (1864–1901), painter †
• John Wilmot, 2nd Earl of Rochester (1647–1680), writer †
• Hugo Wolf (1860–1903), composer †
• Mikhail Vrubel (1856–1910), painter
• Kostas Karyotakis (1896–1928), Greek poet
• Lord Randolph Churchill (1849–1895), British politician, father of Winston Churchill
• Harry Nelson Pillsbury (1872–1906), chess master †

Syphilis infection

Different manifestations occur depending on the stage of the disease:

Primary syphilis

Primary chancre of syphilis at the site of infection on the hand

Primary syphilis is typically acquired via direct sexual contact with the infectious lesions of a person with syphilis.^[23] 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.^[24]

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.^[25] The rash can involve the palms of the hands and the soles of the feet. In moist areas of the body, the rash becomes flat, broad, whitish lesions known as condylomata lata. 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.^[23] 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. 50% 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

Model of the head of a patient with tertiary syphilis

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.^[26]

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,^[27] a bobbing of the head that de Musset first noted in Parisian prostitutes. 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

There are four clinical types of neurosyphilis:

• Asymptomatic neurosyphilis
• Meningovascular syphilis
• General paresis^[28]
• 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 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.

Diagnostic tests

Early 20th century

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 Wassermann test. Both of these early tests have been superseded by newer analytical methods.

Modern diagnostic tests

It was 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. 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.^[23] 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.^[23] 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.^[29]

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.

Treatment

Depression-era U.S. poster advocating early syphilis treatment

Application of mercury.

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.^[30]

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.

History of treatments

There were originally no effective treatments for syphilis. The Spanish priest Francisco Delicado wrote El modo de adoperare el legno de India (Rome, 1525) about the use of Guaiacum in the treatment of syphilis. He himself suffered from syphilis. Another common remedy was mercury: the use of which gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury".^[31] It was administered multiple ways including by mouth,^{[citation needed]} by rubbing it on the skin^{[citation needed]} and by injection.^[32] One of the more curious 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 grueling process for the patient and the least effective for delivering mercury to the body. The use of mercury was the earliest known suggested treatment for syphilis, dating back to The Canon of Medicine (1025) by the Persian physician, Ibn Sina (Avicenna).^[33]

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 (a form of pyrotherapy). 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.^[34]

Current treatment

The first-choice treatment for all manifestations of syphilis remains penicillin in the form of penicillin G.^[35] 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 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.^[36] 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.^[37]

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. Neurosyphilis dementia is also a psychiatric diagnosis where as a multitude of atypical anti-psychotic medications are used to help control the patient's irrational behaviors with limited success. Also used in traditional classification of Organic Disorders in the brain. Also commonly called Brain Syphilis.

Alternative regimens

Alternative regimens such as tetracyclines are not well studied in HIV infection and a careful follow-up is recommended. Tetra-cyclines are contraindicated in pregnancy.

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.

Jarisch-Herxheimer reaction

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.^[38] 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 (paracetamol) 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.

Tuskegee syphilis study

Main article: Tuskegee Study of Untreated Syphilis in the Negro Male

One of the best-documented US cases of unethical human medical experimentation in the twentieth century was the Tuskegee syphilis study. The study took place in Tuskegee, Alabama, and was supported by the U.S. Public Health Service (PHS) in partnership with the Tuskegee Institute.^[39]

The study began in 1932, when syphilis was a widespread problem, especially in poor communities, and when there was not effective treatment or cure. Study researchers recruited a group of 600 black male sharecroppers in the rural area of Tuskegee, Alabama. Of these 600, 399 of the men had the disease in the latent, asymptomatic stage. Two hundred-one men were uninfected control patients. The PHS intended to study the progress of the disease and the effects of current treatments at different stages. Available treatments had such severe side effects that doctors questioned whether treatment provided the best outcome for the patient, or whether a man might do as well with no treatment. Patients were misled about the diagnosis of their disease, and about aspects of treatment, such as a painful lumbar puncture for evaluation. During the crisis of the Great Depression, in a segregated state with underfunded services for blacks, patients were recruited in exchange for physical exams, free health care of minor illnesses, free meals and transportation the day of exams, and a $50 death benefit. The study was designed to measure the progression of untreated syphilis. It also was to determine whether syphilis caused cardiovascular damage more often than neurological damage, as untreated disease led to effects in numerous body systems. Researchers hoped to determine whether the natural course of the disease was different in black men versus white men; historically, researchers had by then accumulated more information on the disease in white men.

By 1947 penicillin had been validated as an effective cure for syphilis and was becoming widely used by doctors and public health centers to treat the disease. PHS study directors continued the study, denying patients treatment by penicillin, and actively discouraging them from having penicillin administered by other sources. 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 study patients in phases, with treatment after six to nine months. It continued to follow the original members and their families for 40 years. The study ended in 1972, long after 40 wives and 19 children had been infected, and many men had died of syphilis. During the study, 28 men died directly from syphilis, and 100 from other complications. The study ended because a PHS scientist leaked information about it to the Washington Star.

Survivors and patients' families filed a class-action lawsuit 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.

Syphilis in art and literature

This section may need to be rewritten entirely to comply with Wikipedia's quality standards, as List of trivia rather than an overview. You can help. The discussion page may contain suggestions. (May 2007)

Art

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.

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.^[40] 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.^[41]

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, common at the time.

Classic and antique literature

Delicado featured the effects of syphilis in his Portrait of Lozana: The Lusty Andalusian Woman (1528).

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.^{[citation needed]}

Francisco de Quevedo puns in his Buscón^[42] about a nose entre Roma y Francia meaning both "between Rome and France" and "between dull and eaten by the French illness".

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".

Moll dies of syphillis, Hogarth's A Harlot's Progress.

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 in Pangloss's disingenuous rose-tinted viewpoint. Pangloss eventually loses an eye and an ear to the syphilis before he is cured.

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

In Sarah Grand's late Victorian novel 'The Heavenly Twins', one of the main female characters, Edith Beale, contracts syphilis from her husband and then passes it on to her child. Edith's once beautiful face is marred by the disease, while she descends into madness and eventual death. Sarah Grand uses this character to show the importance of sex education for women, so that they may protect themselves from marrying men who have been diseased by their own sexual exploits.

In Eça de Queiroz's novel written in 1870, 'The Mystery of the Sintra Road', some of the characters have syphilis, and it plays an important role in the plot of a recent movie adaptation.^[43]

In William Blake's 1794 poem, London, he alludes to syphilis as "the youthful harlot's curse," writing that it "[b]lasts the new-born infant's tear, / And blights with plagues the marriage-hearse."

Henrik Ibsen's once-controversial play Ghosts has a young man who is suffering from a mysterious 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.

Modern literature

• Isak Dinesen's memoir Out of Africa noted her being infected with syphilis by her husband Bror von Blixen-Finecke.
• Unnamed American medical students described syphilis in a series of early 20th-century American limericks, using medical terminology in the Journal of the American Medical Association January 1942.^[44]
• Thomas Disch in his novel Camp Concentration describe a fictional strain of syphilis that enhances intelligence but is lethal.
• In Thomas Mann's novel Doktor Faustus, the Faust character, Adrian Leverkühn, acquires his genius for musical composition from the neurological effects of syphilis.
• In Dick Francis' novel, Bonecrack the character Enso Rivera is suffering from megalomania caused by syphilis.
• Neal Stephenson's trilogy The Baroque Cycle has multiple characters and historical figures who have syphilis.
• In Leonard Cohen's second novel Beautiful Losers, the character F. is described as having the terminal stages of syphilis.
• In Christina Garcia's novel Dreaming in Cuban, Felicia contracts syphilis from her unfaithful husband.
• In Ken Follett's novel "A Dangerous Fortune," the wealthy Edward Pilaster contracts syphilis from using prostitutes.

Film, television and stage

Because it was for so long incurable, syphilis has been used as a plot device in many dramatic films, television shows, and plays. Few, such as the Warner Brothers film Dr. Ehrlich's Magic Bullet (1940), focus on the history of the disease. Most involve characters suffering late-stage syphilis, both because neurological damage provides an excuse for strange behaviors and because the disease came to symbolize evils that might be hidden, or problems with family inheritance (which could also apply to personality or genetic defects.) In recent years, syphilis has been mentioned on Grey's Anatomy, House M.D., Law & Order: SVU, Buffy the Vampire Slayer, Angel, and other television shows. A few particularly notable portrayals include:

• Miss Evers' Boys (1992) is a stage play written by Dr. David Feldshuh, based on the decades-long Tuskegee syphillis experiment. The play was subsequently adapted into a 1997 HBO TV movie. It was nominated for eleven Emmy Awards and won in four categories, including Outstanding Made for Television Movie.
• In Japanese director Akira Kurosawa's film The Quiet Duel (1949), Toshirô Mifune plays a doctor who contracts syphilis after cutting his finger with a scalpel while operating on an infected soldier.
• In Spanish film Alatriste, the main character finds the love of his life, actress María de Castro, dying in a hospital for syphilitics. It is implied that she caught the disease from an affair with Philip IV of Spain.
• In the Masterpiece Theatre version of Bram Stoker's Dracula, Arthur Holmwood, whose father dies of syphilitic insanity, enlists the services of Count Dracula in hopes of curing his congenital syphilis.
• In The Libertine, a 2004 film with Johnny Depp, the main character John Wilmot, second Earl of Rochester, is portrayed as having died of syphilis.

Gallery

Electron micrograph of Treponema pallidum	Syphilis lesions on a patient's back	Syphilis lesions on a patient's chest	Chancres on the penile shaft due to a primary syphilitic infection
Secondary syphilis manifested perineal condylomata lata lesions, which presented as gray, raised papules that sometimes appear on the vulva or near the anus, or in any other warm intertriginous region.	Gumma of the nose due to long standing tertiary syphilis

See also

• Tuberculosis (TB)
• Diphtheria
• Side-chain theory
• Paul Ehrlich
• Felix Milgrom
• Hideyo Noguchi Africa Prize – May 2008
• Treponema pallidum
• Globalization and disease
• Pandemic
• Tuskegee Study of Untreated Syphilis in the Negro Male
• General paresis of the insane

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External links

Wikimedia Commons has media related to: Syphilis

• "Sex, Sin, and Science: A History of Syphilis in America " by John Parascandola
• "Syphilis fact sheet" from the Center for Disease Control
• UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV
• "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
• Secrets of the Dead (PBS): The Syphilis Enigma
• Syphilis and AIDS: Lessons from history
• The treatment of dementia paralytica by malaria inoculation (A Nobel Prize lecture, December 13, 1927)
• New study blames Columbus for syphilis spread Reuters January 15, 2008
• Origins of Syphilis NYTimes April 29, 2008

v • d • e Diseases of the skin and appendages by morphology Growths Epidermal wart · callus · seborrheic keratosis · acrochordon · molluscum contagiosum · actinic keratosis · squamous cell carcinoma · basal cell carcinoma · merkel cell carcinoma · nevus sebaceous · trichoepithelioma Pigmented Freckles · lentigo · melasma · nevus · melanoma Dermal and subcutaneous epidermal inclusion cyst · hemangioma · dermatofibroma · keloid · lipoma · neurofibroma · xanthoma · Kaposi's sarcoma · infantile digital fibromatosis · granular cell tumor · leiomyoma · lymphangioma circumscriptum · myxoid cyst Rashes With epidermal involvement Eczematous contact dermatitis · atopic dermatitis · seborrheic dermatitis · stasis dermatitis · lichen simplex chronicus · Darier's disease · glucagonoma syndrome · langerhans cell histiocytosis · lichen sclerosus · pemphigus foliaceus · Wiskott-Aldrich syndrome · Zinc deficiency Scaling psoriasis · tinea (corporis · cruris · pedis · manuum · faciei) · pityriasis rosea · secondary syphillis · mycosis fungoides · systemic lupus erythematosus · pityriasis rubra pilaris · parapsoriasis · ichthyosis Blistering herpes simplex · herpes zoster · varicella · bullous impetigo · acute contact dermatitis · pemphigus vulgaris · bullous pemphigoid · dermatitis herpetiformis · porphyria cutanea tarda · epidermolysis bullosa simplex Papular scabies · insect bite reactions · lichen planus · miliaria · keratosis pilaris · lichen spinulosus · transient acantholytic dermatosis · lichen nitidus · pityriasis lichenoides et varioliformis acuta Pustular acne vulgaris · acne rosacea · folliculitis · impetigo · candidiasis · gonococcemia · dermatophyte · coccidioidomycosis · subcorneal pustular dermatosis Hypopigmented tinea versicolor · vitiligo · pityriasis alba · postinflammatory hyperpigmentation · tuberous sclerosis · idiopathic guttate hypomelanosis · leprosy · hypopigmented mycosis fungoides Without epidermal involvement Red Blanchable Erythema Generalized drug eruptions · viral exanthems · toxic erythema · systemic lupus erythematosus Localized cellulitis · abscess · boil · erythema nodosum · carcinoid syndrome · fixed drug eruption Specialized urticaria · erythema (multiforme · migrans · gyratum repens · annulare centrifugum · ab igne) Nonblanchable Purpura Macular thrombocytopenic purpura · actinic purpura Papular disseminated intravascular coagulation · vasculitis Indurated scleroderma/morphea · granuloma annulare · lichen sclerosis et atrophicus · necrobiosis lipoidica Miscellaneous disorders Ulcers Hair telogen effluvium · androgenic alopecia · trichotillomania · alopecia areata · systemic lupus erythematosus · tinea capitis · loose anagen syndrome · lichen planopilaris · folliculitis decalvans · acne keloidalis nuchae Nail onychomycosis · psoriasis · paronychia · ingrown nail Mucous membrane aphthous stomatitis · oral candidiasis · lichen planus · leukoplakia · pemphigus vulgaris · mucous membrane pemphigoid · cicatricial pemphigoid · herpesvirus · coxsackievirus · syphilis · systemic histoplasmosis · squamous cell carcinoma

v • d • e Sexually transmitted diseases and infections (STD/STI) (primarily A50-A64, 090-099) Bacterial Chancroid (Haemophilus ducreyi) · Chlamydia/Lymphogranuloma venereum (Chlamydia trachomatis) · Donovanosis or Granuloma Inguinale (Klebsiella granulomatis) · Gonorrhea (Neisseria gonorrhoeae) · Syphilis (Treponema pallidum) · Ureaplasma infection (Ureaplasma urealyticum) Protozoal Trichomoniasis (Trichomonas vaginalis) Parasitic Crab louse/crabs · Scabies Viral AIDS (HIV-1/HIV-2) · Cervical cancer & Genital warts (condyloma) (Human papillomavirus (HPV)) · Hepatitis B (Hepatitis B virus) · Herpes simplex (HSV1/HSV2) · Molluscum contagiosum (MCV) General inflammation female: Cervicitis · Pelvic inflammatory disease (PID) male: Epididymitis · Prostatitis either: Proctitis · Urethritis/Non-gonococcal urethritis (NGU) Other Ectopic pregnancy · Premature birth · Infertility · Reactive arthritis

v • d • e Infectious diseases · Bacterial diseases: non-proteobacterial G- (primarily A00-A79, 001-041,080-109) Spirochaete Spirochaetaceae Treponema Treponema pallidum (Syphilis/Bejel, Yaws) · Treponema carateum (Pinta) · Treponema denticola Borrelia Borrelia recurrentis (Relapsing fever) · Borrelia burgdorferi (Lyme disease, Erythema chronicum migrans, Neuroborreliosis) Leptospiraceae Leptospira Leptospira interrogans (Leptospirosis) Spirillaceae Spirillum Spirillum minus (Rat-bite fever/Sodoku) Chlamydiae Chlamydophila Chlamydophila psittaci (Psittacosis) · Chlamydophila pneumoniae Chlamydia Chlamydia trachomatis (Chlamydia, Lymphogranuloma venereum, Trachoma) Bacteroidetes Bacteroides fragilis · Capnocytophaga canimorsus · Porphyromonas gingivalis · Prevotella intermedia · Bacteroides forsythus Fusobacteria Fusobacterium necrophorum (Lemierre's syndrome) · Fusobacterium nucleatum · Fusobacterium polymorphum

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Common misspelling(s) of syphilis

• syphyllis

Dansk (Danish)
n. - syfilis

Nederlands (Dutch)
syfilis, geslachtsziekte

Français (French)
n. - syphilis

Deutsch (German)
n. - Syphilis

Ελληνική (Greek)
n. - (παθολ.) σύφιλη

Italiano (Italian)
sifilide

Português (Portuguese)
n. - sífilis (f)

Русский (Russian)
сифилис

Español (Spanish)
n. - sífilis

Svenska (Swedish)
n. - syfilis

中文（简体）(Chinese (Simplified))
梅毒

中文（繁體）(Chinese (Traditional))
n. - 梅毒

한국어 (Korean)
n. - 매독

日本語 (Japanese)
n. - 梅毒

العربيه (Arabic)
‏(الاسم) مرض السفيس‏

עברית (Hebrew)
n. - ‮עגבת, סיפיליס‬

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