syphilis syphilis syphilis (/ˈsɪfəlɪs/) is a sexually transmitted infection caused by the bacterium treponema pallidum subspecies pallidum. the signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary). the primary stage classically presents with a single chancre (a firm, painless, non-itchy skin ulceration usually between 1 cm and 2 cm in diameter) though there may be multiple sores. in secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet. there may also be sores in the mouth or vagina. in latent syphilis, which can last for years, there are few or no symptoms. in tertiary syphilis, there are gummas (soft, non-cancerous growths), neurological problems, or heart symptoms. syphilis has been known as "the great imitator" as it may cause symptoms similar to many other diseases. syphiliselectron micrograph of treponema pallidumspecialtyinfectious diseasesymptomsfirm, painless, non-itchy skin ulcercausestreponema pallidum usually spread by sexdiagnostic methodblood tests, dark field microscopy of infected fluiddifferential diagnosismany other diseasespreventioncondoms, long-term monogamous relationshipstreatmentantibioticsfrequency45.4 million / 0.6% (2015, global)deaths107,000 (2015, global) syphilis is most commonly spread through sexual activity. it may also be transmitted from mother to baby during pregnancy or at birth, resulting in congenital syphilis. other diseases caused by treponema bacteria include yaws (t. pallidum subspecies pertenue), pinta (t. carateum), and nonvenereal endemic syphilis (t. pallidum subspecies endemicum). these three diseases are not typically sexually transmitted. diagnosis is usually made by using blood tests; the bacteria can also be detected using dark field microscopy. the centers for disease control and prevention (u.s.) recommend all pregnant women be tested. the risk of sexual transmission of syphilis can be reduced by using a latex or polyurethane condom. syphilis can be effectively treated with antibiotics. the preferred antibiotic for most cases is benzathine benzylpenicillin injected into a muscle. in those who have a severe penicillin allergy, doxycycline or tetracycline may be used. in those with neurosyphilis, intravenous benzylpenicillin or ceftriaxone is recommended. during treatment people may develop fever, headache, and muscle pains, a reaction known as jarisch–herxheimer. in 2015, about 45.4 million people had syphilis infections, of which six million were new cases. during 2015, it caused about 107,000 deaths, down from 202,000 in 1990. after decreasing dramatically with the availability of penicillin in the 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (hiv). this is believed to be partly due to increased sexual activity, prostitution, and decreasing use of condoms. signs and symptoms syphilis can present in one of four different stages: primary, secondary, latent, and tertiary, and may also occur congenitally. it was referred to as "the great imitator" by sir william osler due to its varied presentations. primary primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person. approximately 2–6 weeks after contact (with a range of 10–90 days) a skin lesion, called a chancre, appears at the site and this contains infectious spirochetes. this is classically (40% of the time) a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders approximately 0.3–3.0 cm in size. the lesion may take on almost any form. in the classic form, it evolves from a macule to a papule and finally to an erosion or ulcer. occasionally, multiple lesions may be present (~40%), with multiple lesions being more common when coinfected with hiv. lesions may be painful or tender (30%), and they may occur in places other than the genitals (2–7%). the most common location in women is the cervix (44%), the penis in heterosexual men (99%), and anally and rectally in men who have sex with men (34%). lymph node enlargement frequently (80%) occurs around the area of infection, occurring seven to 10 days after chancre formation. the lesion may persist for three to six weeks if left untreated. secondary typical presentation of secondary syphilis with a rash on the palms of the hands reddish papules and nodules over much of the body due to secondary syphilis secondary syphilis occurs approximately four to ten weeks after the primary infection. while secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucous membranes, and lymph nodes. there may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles. the rash may become maculopapular or pustular. it may form flat, broad, whitish, wart-like lesions on mucous membranes, known as condyloma latum. all of these lesions harbor bacteria and are infectious. other symptoms may include fever, sore throat, malaise, weight loss, hair loss, and headache. rare manifestations include liver inflammation, kidney disease, joint inflammation, periostitis, inflammation of the optic nerve, uveitis, and interstitial keratitis. the acute symptoms usually resolve after three to six weeks; about 25% of people may present with a recurrence of secondary symptoms. many people who present with secondary syphilis (40–85% of women, 20–65% of men) do not report previously having had the classical chancre of primary syphilis. latent latent syphilis is defined as having serologic proof of infection without symptoms of disease. it develops after secondary syphilis and is divided into early latent and late latent stages. early latent syphilis is defined by the world health organization as less than 2 years after original infection. early latent syphilis is infectious as up to 25% of people can develop a recurrent secondary infection (during which spirochetes are actively replicating and are infectious). two years after the original infection the person will enter late latent syphilis and is not as infectious as the early phase. the latent phase of syphilis can last many years after which, without treatment, approximately 15-40% of people can develop tertiary syphilis. tertiary model of a head of a person with tertiary (gummatous) syphilis, musée de l'homme, paris tertiary syphilis may occur approximately 3 to 15 years after the initial infection, and may be divided into three different forms: gummatous syphilis (15%), late neurosyphilis (6.5%), and cardiovascular syphilis (10%). without treatment, a third of infected people develop tertiary disease. people with tertiary syphilis are not infectious. gummatous syphilis or late benign syphilis usually occurs 1 to 46 years after the initial infection, with an average of 15 years. this stage is characterized by the formation of chronic gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size. they typically affect the skin, bone, and liver, but can occur anywhere. cardiovascular syphilis usually occurs 10–30 years after the initial infection. the most common complication is syphilitic aortitis, which may result in aortic aneurysm formation. neurosyphilis refers to an infection involving the central nervous system. involvement of the central nervous system in syphilis (either asymptomatic or symptomatic) can occur at any stage of the infection. it may occur early, being either asymptomatic or in the form of syphilitic meningitis; or late as meningovascular syphilis, manifesting as general paresis or tabes dorsalis. meningovascular syphilis involves inflammation of the small and medium arteries of the central nervous system. it can present between 1–10 years after the initial infection. meningovascular syphilis is characterized by stroke, cranial nerve palsies and spinal cord inflammation. late symptomatic neurosyphilis can develop decades after the original infection and includes 2 types; general paresis and tabes dorsalis. general paresis presents with dementia, personality changes, delusions, seizures, psychosis and depression. tabes dorsalis is characterized by gait instability, sharp pains in the trunk and limbs, impaired positional sensation of the limbs as well as having a positive romberg's sign. both tabes dorsalis and general paresis may present with argyll robertson pupil which are pupils that constrict when the person focuses on near objects (accommodation reflex) but do not constrict when exposed to bright light (pupillary reflex). congenital main article: congenital syphilis congenital syphilis is that which is transmitted during pregnancy or during birth. two-thirds of syphilitic infants are born without symptoms. common symptoms that develop over the first couple of years of life include enlargement of the liver and spleen (70%), rash (70%), fever (40%), neurosyphilis (20%), and lung inflammation (20%). if untreated, late congenital syphilis may occur in 40%, including saddle nose deformation, higouménakis' sign, saber shin, or clutton's joints among others. infection during pregnancy is also associated with miscarriage. the three main dental defects in congenital syphilis are hutchinson's incisors (screwdriver-shaped incisors), moon's molars or bud molars, and fournier's molars or mulberry molars (molars with abnormal occlusal anatomy resembling a mulberry). cause bacteriology histopathology of treponema pallidum spirochetes using a modified steiner silver stain main article: treponema pallidum treponema pallidum subspecies pallidum is a spiral-shaped, gram-negative, highly mobile bacterium. three other human diseases are caused by related treponema pallidum subspecies, including yaws (subspecies pertenue), pinta (subspecies carateum) and bejel (subspecies endemicum). unlike subspecies pallidum, they do not cause neurological disease. humans are the only known natural reservoir for subspecies pallidum. it is unable to survive more than a few days without a host. this is due to its small genome (1.14mbp) failing to encode the metabolic pathways necessary to make most of its macronutrients. it has a slow doubling time of greater than 30 hours. the bacterium is known for its ability to evade the immune system and its invasiveness. transmission syphilis is transmitted primarily by sexual contact or during pregnancy from a mother to her baby; the spirochete is able to pass through intact mucous membranes or compromised skin. it is thus transmissible by kissing near a lesion, as well as oral, vaginal, and anal sex. approximately 30% to 60% of those exposed to primary or secondary syphilis will get the disease. its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50% chance of being infected. most new cases in the united states (60%) occur in men who have sex with men; and in this population 20% of syphilis cases were due to oral sex alone. syphilis can be transmitted by blood products, but the risk is low due to screening of donated blood in many countries. the risk of transmission from sharing needles appears to be limited. it is not generally possible to contract syphilis through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing. this is mainly because the bacteria die very quickly outside of the body, making transmission by objects extremely difficult. diagnosis this poster acknowledges the social stigma of syphilis, while urging those who possibly have the disease to be tested (circa 1936). micrograph of secondary syphilis skin lesions. (a/b) h&e stain of ss lesions. (c/d) ihc staining reveals abundant spirochetes embedded within a mixed cellular inflammatory infiltrate (shown in the red box) in the papillary dermis. the blue arrow points to a tissue histiocyte and the read arrows to two dermal lymphocytes. syphilis is difficult to diagnose clinically during early infection. confirmation is either via blood tests or direct visual inspection using dark field microscopy. blood tests are more commonly used, as they are easier to perform. diagnostic tests are unable to distinguish between the stages of the disease. blood tests blood tests are divided into nontreponemal and treponemal tests. nontreponemal tests are used initially, and include venereal disease research laboratory (vdrl) and rapid plasma reagin (rpr) tests. false positives on the nontreponemal tests can occur with some viral infections, such as varicella (chickenpox) and measles. false positives can also occur with lymphoma, tuberculosis, malaria, endocarditis, connective tissue disease, and pregnancy. because of the possibility of false positives with nontreponemal tests, confirmation is required with a treponemal test, such as treponemal pallidum particle agglutination (tpha) or fluorescent treponemal antibody absorption test (fta-abs). treponemal antibody tests usually become positive two to five weeks after the initial infection. neurosyphilis is diagnosed by finding high numbers of leukocytes (predominately lymphocytes) and high protein levels in the cerebrospinal fluid in the setting of a known syphilis infection. direct testing dark field microscopy of serous fluid from a chancre may be used to make an immediate diagnosis. hospitals do not always have equipment or experienced staff members, and testing must be done within 10 minutes of acquiring the sample. two other tests can be carried out on a sample from the chancre: direct fluorescent antibody (dfa) and polymerase chain reaction (pcr) tests. dfa