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Primary Syphilis

Primary syphilis is the first clinical stage of the sexually transmitted infection caused by Treponema pallidum, a spirochetal bacterial pathogen. A painless ulcer or chancre developing at the site of treponemal inoculation of the skin after intercourse, most commonly appearing on the penis, is the hallmark of primary syphilis. The diagnosis is made by clinical assessment and thorough laboratory studies that confirm the infection.


Syphilis, one of the most common sexually-transmitted infections (STD) worldwide, is caused by a spirochete, Treponema pallidum, and the clinical course of syphilis is divided into four stages - primary, secondary, latent, and tertiary [1] [2] [3] [4]. Primary syphilis is the initial manifestation, characterized by the appearance of a painless papule eventually turning into an indurated ulcer on the skin or mucous membranes (known as the syphilitic chancre) [1] [5] [6] [7]. The chancre is seen at the initial site of bacterial inoculation, and the diameter of the lesion ranges from a few millimeters up to a few centimeters without exudate, although secondary infection can produce a purulent discharge from the lesion [4] [6]. Earlier syphilis occurred primarily in heterosexual men and women, however, now the incidence has increased amongst men having sex with men (MSM), with the glans penis being the most common site of the syphilitic chancre, usually after an incubation period of 10-90 days [3] [4] [6]. However, the lesion may appear at any site on the external genitalia, the anus, and perianal areas or in the oral cavity, and sometimes more than one chancre develops, especially in immunosuppressed individuals (such as those suffering from human immunodeficiency virus infection) [2] [4] [6]. Non-tender regional lymphadenopathy is often observed 1-2 weeks after the appearance of the typical skin lesion [1] [3] [4] [6]. In most patients, chancres resolve spontaneously after approximately 3-6 weeks, but lymphadenopathy may be present much longer [4].

  • This most recent wave of infections, spread through gang networks and prostitution rings, has made their jobs not only difficult but also dangerous.[nytimes.com]
  • ‘He never married, and it is possible that as a young man he contracted syphilis during a single sexual encounter with a prostitute.’[en.oxforddictionaries.com]
  • Aka Prostitiues pupils – like prostitutes, they accommodate, but they don’t react![almostadoctor.co.uk]
  • View Article PubMed PubMed Central Google Scholar Ebenstein A, Jennings E: 'Bare Branches', Prostitution, and HIV in China: A Demographic Analysis. Gender Policy and HIV in China: Catalyzing Policy Change.[bmcpublichealth.biomedcentral.com]
  • This includes persons whose have multiple sexual partners, use illegal drugs, use alcohol, have unprotected sex, and are prostitutes.[microbewiki.kenyon.edu]
Unsafe Sexual Practices
  • These are available for purchase online. not sharing sex toys avoiding alcohol and drugs that could potentially lead to unsafe sexual practices Having syphilis once does not mean a person is protected from it.[medicalnewstoday.com]
  • Safer-sex messages should include reducing the number of sexual partners; knowing the health status and HIV infection status of partners; avoiding unsafe sexual practices, not just for HIV, but for all STDs; and using barrier protection methods such as[hivinsite.ucsf.edu]
  • The oral aspects of early syphilis and the need for dentists to be aware of changing epidemiological trends in relevant infectious diseases are highlighted.[ncbi.nlm.nih.gov]
Inguinal Lymphadenopathy
  • We report a case of primary syphilis presenting as erosive and crusted balanoposthitis with an underlying chancre, penile edema, and bilateral inguinal lymphadenopathy in a heterosexual man.[ncbi.nlm.nih.gov]
  • Physical exam is significant for a diffuse, erythematous maculopapular rash, patchy alopecia on his scalp, wart-like white lesions on the base of his penis, and bilateral inguinal lymphadenopathy. VDRL and FTA-ABS were positive.[medbullets.com]
  • Inguinal lymphadenopathy arises in men with ulcers on the genitals and cervical lymphadenopathy in patients with ulcers in the mouth.[dermnetnz.org]
Perianal Ulcer
  • Diseases Characterized by Genital, Anal, or Perianal Ulcers. Available online at . Accessed January 2013. Syphilis Testing Algorithms Using Treponemal Tests for Initial Screening --- Four Laboratories, New York City, 2005--2006.[labtestsonline.org]
Rectal Pain
  • Rectal pain, which we attributed to secondary infection, was the chief complaint in three patients. Two patients also complained of tender lymphadenopathy.[ncbi.nlm.nih.gov]
Tongue Ulcer
  • Lips and tongue ulcers are the most frequently reported lesions and tonsillar ulcers are much more rare. We report the case of a 24-year-old woman with a syphilitic ulcer localized in her left tonsil.[ncbi.nlm.nih.gov]
Tonsillar Ulcer
  • Lips and tongue ulcers are the most frequently reported lesions and tonsillar ulcers are much more rare. We report the case of a 24-year-old woman with a syphilitic ulcer localized in her left tonsil.[ncbi.nlm.nih.gov]
Tongue Ulcer
  • Lips and tongue ulcers are the most frequently reported lesions and tonsillar ulcers are much more rare. We report the case of a 24-year-old woman with a syphilitic ulcer localized in her left tonsil.[ncbi.nlm.nih.gov]
Mucocutaneous Rash
  • Secondary syphilis Secondary syphilis may present in many different ways but usually includes a localized or diffuse mucocutaneous rash and generalized nontender lymphadenopathy.[emedicine.medscape.com]
Insect Bite
  • Routine laboratory investigations requested by the family doctor were normal; the patient was an office worker and anamnesis was negative for local traumas and/or insect bites.[journals.lww.com]
  • Other differential diagnoses to be considered include other forms of non-scarring patchy alopecia such as trichotillomania, traction alopecia, alopecia neoplastica and tinea capitis, which can all be ruled out by biopsy [ 7, 9, 12 ].[omicsonline.org]
  • The differential diagnosis includes ulcerative genital lesions such as chancroid, herpes progenitalis, aphthae (Behçet’s syndrome), and traumatic ulcers such as occur with biting.[dartmouth.edu]
  • Lesions that can be confused with the chancre of primary syphilis include herpes simplex virus infection, chancroid, fixed drug eruption, lymphogranuloma venereum, granuloma inguinale (donovanosis), traumatic ulcer, furuncle (boil), and aphthous ulcer[aafp.org]
  • […] typically heal spontaneously in 3 to 6 weeks, but also as quickly as 1 week or as slowly as 12 weeks Chancres increase the risk of acquiring HIV and other sexually transmitted diseases Anorectal chancres may resemble herpes simplex virus infection, chancroid[pathologyoutlines.com]
  • […] hands and soles, pink to red macules Pityriasis – herald patch, macular, usually itchy Viral exanthems – most often with associated viral syndrome history Disseminated herpes simplex – usually vesicular, more painful Tinea versicolor Erythema multiforme Chancroid[clinicaladvisor.com]
Syphilitic Chancre
  • Primary syphilis is the initial manifestation, characterized by the appearance of a painless papule eventually turning into an indurated ulcer on the skin or mucous membranes (known as the syphilitic chancre).[symptoma.com]
  • Six patients were seen with primary syphilitic chancres on their fingers between 1965 and 1980. Of these, two had bipolar chancres on their fingers and genitals resulting from sexual foreplay.[ncbi.nlm.nih.gov]
  • Concepts Sign or Symptom ( T184 ) MSH D002601 ICD10 A51.0 SnomedCT 266127002, 58433006 English Chancre, Chancres, Syphilitic chancre, Syphilitic chancre NOS, Chancre [Disease/Finding], primary syphilis, chancre syphilitic, chancres, chancre, syphilis[fpnotebook.com]
  • Extragenital syphilitic chancres. J Am Acad Dermatol 1986; 14:1094–1095. 4. Alessi E, Ghislanzoni M, Scioccati L, et al. PCR: A useful adjunct to the diagnosis of syphilis. Technical note preliminary results.[journals.lww.com]
  • Syphilitic chancres are typically round, firm, and painless. Photograph credit: Centers for Disease Control and Prevention Public Health Image Library (Robert E. Sumpter, 1967). Figure 15.[std.uw.edu]


A detailed patient history and a proper physical examination can reveal sufficient data to make a presumptive diagnosis of syphilis in its primary stage. During the interview with the patient, physicians should assess sexual history, unprotected sex, multiple partners, etc.. and inspection and observation of typical skin lesions during physical examination could raise clinical suspicion. To confirm syphilis as the underlying cause, several diagnostic tests are available:

  • Antibody testing - On the basis of their ability to detect T. pallidum antigens and respective antibodies in a direct or indirect fashion, two types of tests are described in the literature: Treponemal and non-treponemal. Detection of antibodies through a fluorescent treponemal antibody absorption assay (FTA-ABS), T. pallidum particle agglutination assay (TPPA), and T. pallidum hemagglutination assay (TPHA) are treponemal tests that yield reactive or non-reactive results in blood [2] [5] [6] [7]. On the other hand, Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR) and toluidine red unheated serum test (TRUST) are widely used three non-treponemal tests that measure the response of antibodies to cardiolipin [5] [7].
  • Microscopy and other direct methods - Because serology testing does not provide a 100% positivity rate, especially in primary stages of the disease, spirochetal bacteria can be visualized with dark field microscopy, a specialized technique that necessitates the use of immunofluorescent stains, as T. pallidum is too thin to be visible on standard microscopy [3] [4][6] [7]. In addition, detection of bacterial genetic material through polymerase chain reaction (PCR) testing is another definite diagnostic method, but its cost and scarce availability are the main limitations [2] [5] [6].
Lymphocytic Infiltrate
  • The second biopsy showed abundant neutrophils near the follicular ostium and a perifollicular and perivascular lymphocytic infiltrate compatible with acute bacterial folliculitis.[omicsonline.org]
Rectal Biopsy Abnormal
  • Spectrum of rectal biopsy abnormalities in homosexual men with intestinal symptoms. Gastroenterology 1986;91:651-9]. The number of reported cases of primary syphilis is increasing especially among this group of people [Goh BT. Syphilis in adults.[ncbi.nlm.nih.gov]


  • BACKGROUND: Benzathine penicillin G is the treatment of choice for infectious syphilis, but tetracycline and doxycycline are believed to be effective second-line treatments.[ncbi.nlm.nih.gov]


  • […] favorable prognosis for patients diagnosed with either primary or secondary syphilis 20% of untreated patients with tertiary syphilis die of the disease prognosis for tertiary syphilis depends on the extent of scarring and tissue damage with adequate[medbullets.com]
  • Prognosis With proper antibiotic treatment, early syphilis infection can be cured without causing permanent damage. Although later stages of syphilis also respond to antibiotics, treatment will not repair any organ damage caused by the disease.[drugs.com]
  • Prognosis Syphilis can naturally either resolve itself (and remain in an indefinite latent stage) or it can progress to the tertiary stage of infection, often resulting in death if left untreated.[soc.ucsb.edu]
  • Secondary syphilis has a good prognosis with treatment. The key elements of counseling surrounds partner notification and testing, as well as counseling around safe sexual activity and substance abuse.[clinicaladvisor.com]


  • Etiology Treponema bacteria (particularly during stages I/II) are highly contagious! Sexual contact with a partner who suffers from active syphilis will lead to infection in 30% of cases![amboss.com]
  • […] traumatic ulcer, furuncle (boil), and aphthous ulcer. 12 A selected differential diagnosis is provided in Table 1. 12, 13 View/Print Table TABLE 1 Selected Differential Diagnosis of Genital Lesions Disorder or disease Characteristics of genital lesion Etiology[aafp.org]
  • Sanchez J, Volquez C, Totten PA, Campos PE, Ryan C, et al. (2002) The etiology and management of genital ulcers in the Dominican Republic and Peru. Sex Transm Dis 29: 559–567. View Article Google Scholar 57.[journals.plos.org]
  • In the HIV/syphilis coinfected patient, elevated CSF leukocytes of greater than 10 to 20 white blood cells/µL should prompt serious consideration of a diagnosis of neurosyphilis if no other etiology is identified.[hivinsite.ucsf.edu]
  • […] dollars spent on sexually transmitted diseases and HIV infection in the United States (approximately 12.6 billion dollars is associated with the care of persons with HIV infection). [ 8 ] Microbiology and Pathogenesis Organism and Classification The etiologic[std.uw.edu]


  • The oral aspects of early syphilis and the need for dentists to be aware of changing epidemiological trends in relevant infectious diseases are highlighted.[ncbi.nlm.nih.gov]
  • […] a spirochete, Treponema pallidum transmitted through sexual contact–especially since toilet seats have been definitively excluded Sobering factoid Risk of contracting syphilis from an infected sex partner after one episode of unprotected sex is 30% Epidemiology[medical-dictionary.thefreedictionary.com]
  • China Journal of Epidemiology. 2001, 22: 191- View Article Google Scholar Zeng X, Hong F, Luo B, Li P, Cai Y: Syphilis epidemiology in Shenzhen 1984-2001.[bmcpublichealth.biomedcentral.com]
Sex distribution
Age distribution


  • References: [3] [4] Pathophysiology Clinical features Primary syphilis Primary lesion ( chancre ) Typically starts out as a solitary, raised papule (usually on the genitals) Evolves into painle ss, firm ulcer with indurated borde rs and smooth base Resolves[amboss.com]
  • Precise understanding of the pathophysiology of syphilis is compromised by the inability to grow the spirochete in culture, and therefore it has been studied in animal models and in some controversial human studies, for example, the Tuskegee study in[clinicaladvisor.com]


  • Oral administration of cephalexin for five days did not prevent the infection buy may have prolonged the incubation period.[ncbi.nlm.nih.gov]
  • The total for 2015, including those with later-stage disease, was nearly 75,000, according to the Centers for Disease Control and Prevention. Image Left, Ms.[nytimes.com]
  • Modern Preventive Medicine. 2003, 30- Google Scholar Gong X, Ye S, Zhang J, Zhang G, Shao G: Sexually transmitted disease epidemiology in China 1991-2001.[bmcpublichealth.biomedcentral.com]
  • Syphilis can be prevented by abstaining from casual sexual activity and using condoms correctly during any sexual contact.[skinsight.com]



  1. Bjekić M, Marković M, Sipetić S. Clinical manifestations of primary syphilis in homosexual men. Braz J Infect Dis. 2012;16(4):387-389.
  2. Henao-Martínez AF, Johnson SC. Diagnostic tests for syphilis: New tests and new algorithms. Neurol Clin Pract. 2014;4(2):114-122.
  3. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
  4. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.
  5. Morshed MG, Singh AE. Recent Trends in the Serologic Diagnosis of Syphilis. Papasian CJ, ed. Clin Vaccine Immunol. 2015;22(2):137-147.
  6. Ficarra G, Carlos R. Syphilis: The Renaissance of an Old Disease with Oral Implications. Head and Neck Pathology. 2009;3(3):195-206.
  7. Mattei PL, Beachkofsky TM, Gilson RT, Wisco OJ. Syphilis: a reemerging infection. Am Fam Physician. 2012;86(5):433-440.

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Last updated: 2019-07-11 21:41