Primary Syphilis

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].

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].

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.