Caused by Treponema pallidum, a spirochete, transmitted through contact with infectious lesions or bodily fluids.

It is predominantly transmitted through sex, from mother to child during pregnancy and rarely via blood transfusions or organ transplants.

Incidence is increasing, especially among men.

In 2019 the incidence of all stages of syphilis was 39.7 per 100,000 per year and 38,990 patients were diagnosed with primary or secondary syphilis.

Transmission occurs most frequently during sexual contact, including oral sex.

More than half of men with incident syphilis are reported to have had sex with men, and 42% of those men are infected with HIV.

There is a strong association between incident syphilis and increased risk of HIV infection.

Men who have sex with me are disproportionately affected, accounting for the majority (57%) of all primary and secondary syphilis cases.

In the US there is a second recent epidemic affecting heterosexual men and women.

Primary and secondary syphilis among women more than doubled between 2014 and 2018.

Men account for greater than 80% of cases.

The first recognized sexually transmitted disease.

The number of syphilis cases rose by a factor of six among women who use methamphetamine, heroin, or other injected drugs or sex with a person who injected drugs.

Transmission occurs through minor skin or mucosal lesions with the site of inoculation usually congenital, but may be extra genital.

Risk of developing syphilis from unprotected sex from an individual with infectious syphilis is approximately 30-50%.

Very rarely can be transmitted through nonsexual contact including blood transfusions or via the placenta.

The time of inoculation with T pallidum to the presentation of primary syphilis with a chancre is inversely proportional the inoculation dose and is usually 10-90 days.

Primary syphilis is characterized by one or more indurated chancres at the side of an inoculation, which usually is painless, and occurs within three weeks after exposure.

After the primary lesion resolves, a macular rash often appears in the second phase.

The rash frequently, but not always, involves the palms and soles, and may desquamate.

Other clinical manifestations of secondary syphilis include lymphadenopathy, alopecia, condyloma, and oral mucosal patches.

T. pallidum disseminates after infection, within days, with early invasion of distant tissues, including the CNS, and transplacental infection of the fetus in a pregnant woman.

T pallium cannot be cultured.

The usual time from inoculation to the appearance of secondary syphilis is 60-180 days.

Can present in any of three critical stages, and each stage has a classic manifestation.

Primary syphilis is marked by a painless chancre, secondary syphilis associated with macularpapular, rash, and neurologic or cardiovascular involvement is typical of the tertiary syphilis.

Chancre is a painless sore or ulcer that occurs in primary disease, that can appear anywhere on the body but usually appears on the genitals, rectal area or mouth.

The primary stage made manifest is a solitary chancre, indurated, ulcerated with a clean base.

Primary stage lesion typically appears at the site of contact with the sex partner’s infectious lesion.

Chancres may appear from day 10 to 3 months after infection begins and occurs at the site that infection enters the body.

Chancre typically present within 2 weeks of sexual exposure.

The chancre usually disappears within 6 weeks, with or without treatment.

Primary syphilis chancre lesions typically appear 1-3 weeks after exposure.

Regional lymphadenopathy develops approximately 9 to 90 days after exposure.

Primary ulcers may be multiple, shallow, and painful.

Secondary syphilis usually appears 2-10 weeks after the resolution of the primary chancre lesion, but considerable overlap exists between the stages.

Secondary syphilis which occurs in 75% of patients with untreated primary.

Secondary syphilis is defined by bacterial dissemination after the primary lesion and its most consistent feature is a macular rash.

Syphilis has non specific manifestations include: fever, malaise, headache, and weight loss.

Secondary syphilis manifestations include a mild, non-pruritic rash, especially on the palms and soles, fever, lymphadenopathy, mucosal lesions, and occasionally hepatitis.

The classic maculopapular r rash involves the  palms and soles and occurs in 48 to 70% of patients.

Secondary syphilis may cause alopecia, abdominal pain, and joint swelling.

Primary syphilitic chancre typically appears in genitalia, however 5 to 10% are extragenital involving mainly the oral and anal mucosa.

Primary and secondary syphilis or the sexually transmissible stages of infection.

The chancre may be associated with regional lymphadenopathy.

Common sites of extragenital lesions including the chin, ear, neck, fingers, chest, arms, and tonsils.

Anal chancre lesions usually develop after anal intercourse in homosexual men.

Treponema Pallidum can penetrate mucosal surfaces but not intact skin.

Minor skin trauma doing sexual contact facilitates the entry of T pallidum into a host.

Extra genital chancre lesions are often misdiagnosed and unlike genitalia lesions on the fingers, tongue, and Anus are often painful.

Identification of T pallidum can be made by a tissue examination of chancre tissue with a dark field microscope.

Not uncommon for the painless, and vaginally hidden chancre that can disappear in 3-6 weeks in women to be missed and such patients may present with secondary syphilis.

Primary and secondary stages are most infectious stages.

Most affected persons aged 25-29 years and men are significantly more likely than women to be affected.

Malority of cases in the US in men having sex with men aged 35-44 years.

Since 2000, when the incidence was at an all time low, there has been 7 successive years of increasing rates of infection with 41,000 cases reported in 2007.

Rates among whites 0.5 cases per 100,000 persons in 2000 increased to 1.6 cases per 100,000 persons in 2004.

Rate of 5.3 cases per hundred thousand people was recorded in 2013.

The majority of new cases occur among men who have sex with men.

In recent years rates have increased across racial and ethnic groups, disproportionately affecting black individuals primarily in the western and southern regions of the United States.

Rate in blacks 31 cases per 100,000 persons.

Increases in rates due to increase in high risk behavior among men.

Highest rates in south of the U.S.

Approximately 55,000 cases annually..

Disproportionately affects black Americans with primary and secondary syphilis 42 times more common among black than white women.

Significantly higher rates among men who have sex with men and in men who are HIV positive.

In HIV-infected men it is associated with a slight transient decrease in the CD4 cell count and an increase in viral load, implying that syphilis may increase the risk of HIV transmission, even in patients receiving antiretroviral therapy and with the viral load less than 500 copies/mL(Jarzebowski W et al).

70% of patients with syphilis diagnosed in 2004 occurred among men who have sex with men, and many are HIV positive.

Up to 70% of gay men and men who have sex with men and who have syphilis may be infected with HIV.

In 2006 64% of patients with primary or secondary syphilis occurs in men who have sex with men.

In cities in the U.S. 20-73% of men who have sex with men with syphilis are HIV infected.

12.5% of women with syphilis are HIV positive.

Natural history divided into early infectious syphilis and late syphilis.

The number of cases of congenital syphilis are increasing.

The two stages separated by a symptom-free latent phase during the first part of which infectious lesions may recur.

Infectious syphilis includes primary lesions with chancre and regional lymphadenopathy, secondary lesions involving skin and mucous membranes, occasionally bone, CNS or liver, relapsing lesions during early latency, and congenital lesions.

Early infectious syphilis associated with abundance of spirochete lesions, and minimal tissue reaction.

Late syphilis has lesions in skin, bones, viscera, cardiovascular, CNS and ocular involvement.

Late syphilis not contagious and few spirochetes demonstrated, with tissue reaction severe and suggestive of hypersensitivity.

Secondary syphilis usually produces a maculopapular or papulosquamous rash on the extremities.

Rash of secondary syphilis may occur anywhere on the body and may appear while the chancre is healing or is resolved.

Secondary syphilis may occur on the palms and soles appearing as rough red or brown spots.

The rash of secondary syphilis usually not associated with itching.

Secondary syphilis rash may be associated with fever, enlarge lymph nodes, sore throat, headache, fever, myalgias, anorexia and fatigue.

Lues maligna refers to a severe form of secondary syphilis with pustular and vesicular lesions accompanied by the systemic symptoms.

Neurologic involvement occurs during all stages of syphilis.

Routine CSF examination for persons with early syphilis is not recommended.

CSS examination is necessary in a patient with neurologic signs of symptoms and in neurologically asymptomatic patients with tertiary syphilis.

Tertiary syphilis occurs in approximately 1/3 of the latent syphilis cases and can affect multiple organ systems.

Syphilis remains latent in approximately 70% of untreated persons, but progresses to tertiary syphilis in the remaining 30%.

Certain treponemal tapes have increased propensity to invade the CNS.

CNS invasion by treponemes is accompanied by abnormal CSF findings in up to 50% of the persons after early infection even in the absence of clinical features.

CSF abnormalities typically resolved after recommended therapy.

With secondary syphilis involvement may include CNS disease, gastrointestinal system, renal, musculoskeletal or eye systems..

Cardiovascular disorders occur 15-30 years after infection and may lead to aortic aneurysms, aortic insufficiency, coronary artery stenosis, and myocarditis.

Most cases come to medical attention when the patients are in the second stage of disease.

Differential diagnoses include drug eruptions, erythema multiforme, guttate psoriasis, lichen planus, pityriasis rosea, Rocky Mountain spotted fever and scarlet fever.

If left untreated primary disease progresses to secondary syphilis, which can then progress to latent an tertiary disease.

Host immunity controls bacterial replication inducing latency, which is defined by infection without signs or symptoms of syphilis.

Early latent infection is required within the previous 12 months, and late latent is one acquire more than 12 months previously.

Up to 25% of untreated patients with latent syphilis may develop symptoms of secondary syphilis, typically within the first year.

Untreated patients approximately 70% will maintain lifelong latency and the remainder will develop tertiary disease consisting of cardiac syphilis effecting 10% of untreated patients 20 to 30 years after infection and gummatous syphilis affecting 15% of untreated patients years after.


Tertiary, or late stage, disease associated with heart and brain lesions.

Tertiary syphilis may lead to strokes, loss of vision, hearing dementia and death.

Tertiary disease can cause areas of necrosis, gummas, in affected organs and tissues.

Increases the susceptibility of infected persons to HIV acquisition and the likelihood that dually infected persons transmit HIV to their sex partners.

Nontreponemal tests for syphilis include the rapid plasma regain test, the automated reagin test and the VDRL test which measure antibodies against cardiolipin-lecithin-cholesterol antigen.

Nontreponemal tests are sensitive for the diagnosis of syphilis except during early primary infection and are relatively nonspecific.

False positive tests for syphilis occur in inflammatory and infectious conditions.

Serological tests are non-reactive and up to 30% of patients with primary syphilis, and testing should be repeated in two weeks if the initial test is non-reactive.

Nontreponemal test titers often decline rapidly after treatment but may decline more slowly in the absence of treatment. 

Treponemal test remain reactive irrespective of the treatment history, but up to 24% of patients treated in the early stage of syphilis have seroreversion years after therapy.

Positive nontreponemal assays must be confirmed by a treponemal test.

The treponemal tests generally mean reactive lifelong following infection irrespective of treatment history.

Use of condoms during all sexual activity can reduce the risk of infection.

Meningomyelitis associated with positive plasma reagin test, CSF pleocytosis and ataxia.

Syphilitic meningitis typically occurs approximately 12 months after primary infection.

Syphilitic meningitis associated with headache meningeal signs and cranial nerve palsies.

Pachymeningitis can occur in the brain and in the spinal cord and with vascular involvement can lead to ischemic strokes.

CSF reactive non-treponemal test is highly predictive of neurosyphilis although it is less than 80% sensitive.

No single test confirms neurosyphilis, which telies on the interpretation of the CSF-VDRL test, white blood cell count and proteins.

Among 40% of patients with optic syphilis and 90% of patients with otic syphilis, CSF examination may be normal

A CSF treponemal test can be sensitive, but lacks specificity owing  to passive transfer of serum IgG antibodies across the blood-CSF barrier or to traces of blood in the CSF.

No standard test for the diagnosis of neurosyphilis exist, therefore a combination of laboratory test and clinical signs and symptoms are used.

Neurosyphilis can occur at any stage of infection, within six weeks of infection between 25 and 60% of patients have evidence of CNS dissemination, although only 5% develop symptoms.

Early neurosyphilis usually presents is meningitis and  neurosyphilis  can result in generalized paresis or tabes dorsalis.

General paresis occurs in 2 to 5% of patients who remained untreated after 20 to 30 years NTBs the cells develops in 2 to 9% of patients who are untreated after 3 to 50 years.

Hepatitis is a rare complication of primary and secondary disease.

Syphilitic aortitis results from an inflammatory response to Treponema pallidum infection prior to antibiotic treatment, and it accounted for more than 10% of cardiovascular deaths in the US.

Antibiotics and rapid screening tests have made syphilitic aortitis a rare clinical entity.

In syphilitic aortitis chronic inflammation of the ascending aorta results in replacement of the lumen with fibrin.

Latent syphilis refers to infected patients without any signs or symptoms at any stage of the disease.

Early latent syphilis, an asymptomatic process that can occur between primary and secondary stages and can also occur after resolution of the secondary stage lesions.

Up to 24% of patients with early latent syphilis the course is interrupted by relapse with recurrent infectious secondary lesions.

The high proportion of early latent syphilis cases suggest the primary and secondary syphilis lesions frequently go unnoticed or or misidentified.

Congenital disease can be transmitted to the fetus and cause serious complications.

The majority of cases are diagnosed by serologic testing.

Detection can be demonstrated on dark field microscopic examination of primary, moist secondary, or neonatal lesions using PCR or histology to identify T pallidum.

typically the diagnosis is established with a Treponema test, for antibodies produced specifically against T pallidum such  as the T pallidum particle agglutination assay.

The treponemal test is not useful for monitoring response to therapy, relapse, or infection.




The standard screening begins with nontreponema test, a rapid plasmin reagin (RPR) or venereal disease research laboratory (VDRL), with reactivity confirmed who the use of a highly sensitive and specific  test for T. pallidum

Penicillin treatment of choice for all stages.

Parenteral penicillin is first line therapy for all stages of syphilis.

Resistance to penicillin has not been observed in T. pallidum

2.4 million units of long-acting penicillin G benzathine given intramuscularly sustains treponemicidal drug levels in the blood for 7 to 10 days and is effective in the treatment of uncomplicated early syphilis.

Late latent syphilis is treated with a total of three doses of Penicillin G benzathine given at weekly intervals.

Neurosyphilis, ocular or otic syphilis are treaty with intravenous aqueous penicillin G because the inability to achieve measurable levels of penicillin G benzathine in the CSF.

Tetracycline is effective in treating early syphilis and its efficacy is similar to that of penicillin G benzathine.

Ceftriaxone has the same efficacy is penicillin in all stages of syphilis.

Azithromycin  is effective in the treatment of early syphilis, however resistance has been detected and the drug is no longer used for the treatment of syphilis.

All pregnant women should be tested/screened for syphilis early in pregnancy and at28 weeks of gestation and at delivery.






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