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].

• 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]

• 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]

  Non-tender regional lymphadenopathy is often observed 1-2 weeks after the appearance of the typical skin lesion. In most patients, chancres resolve spontaneously after approximately 3-6 weeks, but lymphadenopathy may be present much longer. [symptoma.com]

  Constitutional symptoms – Fever/malaise/sore throat Lymphadenopathy – Firm, rubbery. Often symmetric and wide spread (approximately 50%). [clinicaladvisor.com]

• Inflammation

  Later manifestations of congenital syphilis include bone and teeth deformities, such as “saddle nose” (due to destruction of the nasal septum), “saber shins” (due to inflammation and bowing of the tibia), “Clutton’s joints” (due to inflammation of the [emedicine.medscape.com]

  The result of the inability of the immune system to clear the infection The gummas induce a state of chronic inflammation Quaternary syphilis Late stage syphilis. [almostadoctor.co.uk]

  Histologically, the mucocutaneous lesions of secondary syphilis show the same plasma cell infiltrate and obliterative endarteritis as the primary chancre, although the inflammation is often less intense. [humpath.com]

• 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]

  sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection. [15] [52] [53] Left untreated, it has a mortality rate of 8% to 58%, with a greater death rate among males. [2] The symptoms of syphilis have become [en.wikipedia.org]

  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]

• Sepsis

  This type of rash is also typical of erythema multiforme, Rocky Mountain spotted fever, hand-foot-and-mouth disease, tinea manum, meningococcal sepsis, and scarlet fever. [consultant360.com]

• Nausea

  Symptoms and signs of this reaction include: Chills Fever General ill feeling ( malaise ) Headache Muscle and joint pain Nausea Rash These symptoms usually disappear within 24 hours. [medlineplus.gov]

  Symptoms of Jarisch-Herxheimer include: chills rash fever of up to 104 degrees Fahrenheit tachycardia ( rapid heart rate ) hyperventilation headache muscle aches joint pain nausea The Jarisch-Herxheimer reaction is common and potentially serious. [healthline.com]

  This can cause symptoms, such as high fever, profuse sweating, night sweats, nausea, and vomiting. [poz.com]

  Patients with syphilitic meningitis present with typical symptoms of meningitis, including headache, nausea and vomiting, and photophobia, but are typically afebrile. Patients may exhibit cranial nerve abnormalities. [emedicine.medscape.com]

• Vomiting

  This can cause symptoms, such as high fever, profuse sweating, night sweats, nausea, and vomiting. [poz.com]

  Patients with syphilitic meningitis present with typical symptoms of meningitis, including headache, nausea and vomiting, and photophobia, but are typically afebrile. Patients may exhibit cranial nerve abnormalities. [emedicine.medscape.com]

  Abdominal symptoms: right upper quadrant pain, jaundice, nausea, vomiting. Detailed skin, lymphatic and genital exam. Serologic testing is the mainstay for diagnosis of syphilis. [clinicaladvisor.com]

  Visceral crises (episodic pain) are a variant of tabes dorsalis; paroxysms of pain occur in various organs, most commonly in the stomach (causing vomiting) but also in the rectum, bladder, and larynx. [msdmanuals.com]

  The Jarisch-Herxheimer reaction is a self-limited reaction associated with initiation of anti-treponemal therapy and is characterized by fever, malaise, nausea, vomiting, and less frequently, chills and exacerbation of a secondary syphilis rash. [std.uw.edu]

• Perianal Ulcer

  Diseases Characterized by Genital, Anal, or Perianal Ulcers. Available online at http://www.cdc.gov/std/treatment/2010/genital-ulcers.htm. Accessed January 2013. [labtestsonline.org]

• 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]

• 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]

  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]

• Papule

  Because the chancre began as a papule, the borders of the ulcer are raised, smooth, and sharply defined. The chancre of chancroid is soft and painful. [dartmouth.edu]

  Signs Solitary Chancre (hallmark of Primary Syphilis) Painless Papule ulcerates Indurated lesion with smooth base and firm border Chancre distribution Forms a Genital Ulcer in nearly all cases (may form on Cervix or perianally) May be difficult to visualize [fpnotebook.com]

  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]

  The rash and any papules present are highly infectious. [almostadoctor.co.uk]

  Human papillomavirus Lymphogranuloma venereum: primary stage Painless papule, shallow erosion, or ulcer; may be multiple or single Chlamydia trachomatis TABLE 1 Selected Differential Diagnosis of Genital Lesions Disorder or disease Characteristics of [aafp.org]

• Skin Ulcer

  Primary symptoms include: Appearance of a single, firm, usually painless, non-itchy skin ulceration called a “chancre.” The chancre typically appears three to 90 days after exposure to the bacterium. Appearance of multiple chancres. [soc.ucsb.edu]

  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. [2] The lesion may take on almost any form. [en.wikipedia.org]

  Unusual skin ulceration in an HIV-positive patient who had cutaneous syphilis and neurosyphilis. Br J Dermatol 1997; 136:946-8. 20. [hivinsite.ucsf.edu]

• 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]

• Personality Change

  Heart disease (cardiovascular problems), seizures, mental illness, personality changes, impotence, bladder dysfunction, and eye problems such as degeneration of the optic nerve of the eye (optic atrophy) and the development of Argyll Robertson pupils [rarediseases.org]

  changes and impotence due to nerve or brain damage Diagnosis If your doctor suspects that you have syphilis, he or she will look for any of the typical symptoms of the disease, especially for a chancre in the genital area. [drugs.com]

  Impairment of memory and speech, personality changes, irritability, and psychotic symptoms develop and may advance to progressive dementia. [emedicine.medscape.com]

  […] and cognitive changes, visual changes, hearing loss, neuropathy, and loss of bowel and bladder functions. [aafp.org]

• Irritability

  Impairment of memory and speech, personality changes, irritability, and psychotic symptoms develop and may advance to progressive dementia. [emedicine.medscape.com]

  Irritability, difficulty concentrating, deterioration of memory, defective judgment, headaches, insomnia, fatigue, and lethargy are common; seizures, aphasia, and transient hemiparesis are possible. Hygiene and grooming deteriorate. [msdmanuals.com]

  Patients present with headache, meningeal irritation, and cranial nerve abnormalities, typically involving cranial nerves at the base of the brain (especially II, VI, VII, and VIII). [hivinsite.ucsf.edu]

• Syphilitic Chancre

  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]

  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]

  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]

  Primary Syphilis—Oral Chancre This woman with primary syphilis developed an oral chancre at the right corner of her mouth. Syphilitic chancres are typically round, firm, and painless. [std.uw.edu]

• Chancroid

  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]

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].

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]

TREATMENT The choice of treatment in cases of syphilis depends on clinically staging the infection into early and late syphilis as defined above. Benzathine penicillin is the preferred treatment. [mshc.org.au]

[…] 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]

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]

[…] 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]

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]

Can Syphilis Be Prevented? The only way to prevent syphilis and other STDs is not to have sex (oral, vaginal, or anal). If someone decides to have sex, using a latex condom every time can prevent most STDs. [kidshealth.org]

External resources CDC National Prevention Information Network (NPIN) National Center for HIV, STD and TB Prevention P.O. [drugs.com]

Centers for Disease Control and Prevention. Syphilis Fact Sheet. Available online at http://www.cdc.gov/std/Syphilis/STDFact-Syphilis.htm. Accessed June 2009. Centers for Disease Control and Prevention. STD surveillance, 2007. [labtestsonline.org]

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.