Syphilis is a chronic systemic sexually transmitted disease (STD) caused by Treponema pallidum. This pathogen can invade various tissues and organs throughout the body, leading to diverse clinical manifestations. If left untreated, syphilis progresses through distinct stages over time.
Related Factors for Disease Onset
Treponema pallidum, also known as the pale spirochete, is difficult to grow in artificial culture media. It degrades cellular polysaccharides via mucopolysaccharidase, resulting in ulcerative lesions or tissue necrosis. Antibodies against Treponema pallidum provide no protective immunity and may persist in the bloodstream for long periods, potentially even lifelong.
Modes of Transmission
The primary mode of transmission is sexual contact. Rarely, infection may occur through breastfeeding, contact with contaminated clothing, or medical instrumentation. Untreated individuals are highly infectious for 1–2 years after contracting syphilis, with transmissibility declining over time. Patients with syphilis for over four years are generally no longer infectious.
After the fourth month of pregnancy, Treponema pallidum can cross the placenta and infect the fetus through the umbilical vein, resulting in congenital syphilis. Even if a pregnant woman’s syphilis has persisted beyond four years, the pathogen can still infect the fetus via the placenta, leading to congenital syphilis. Neonates may also acquire the infection during delivery through obstetric transmission, although this does not fall under congenital syphilis.
Effects on Mother and Infant
Transmission of Treponema pallidum to the fetus via the placenta may lead to miscarriage, preterm birth, stillbirth, low birth weight, or congenital syphilis. Approximately 30% of stillbirths can be attributed to congenital syphilis. Survivors often experience severe symptoms. Early manifestations include vesiculobullous lesions, rashes, rhinitis with nasal congestion, hepatosplenomegaly, and lymphadenopathy. Late manifestations, typically occurring after two years of age, include Hutchinson teeth, saddle nose, interstitial keratitis, periostitis, and neurosensory deafness. Both mortality and disability rates are markedly elevated.
Clinical Manifestations
Early syphilis is characterized by chancre, syphilitic lymphadenitis, and systemic cutaneous and mucosal lesions such as syphilitic rash, condylomata lata, syphilitic alopecia, and mucosal erythroplakia, edema, and erosions in the oral cavity, pharynx, or genital tract. Late syphilis may involve permanent damage to the skin and mucous membranes and may invade the cardiovascular or nervous systems, posing life-threatening risks.
Diagnosis and Differential Diagnosis
Syphilis is classified into acquired (post-natal) syphilis and congenital syphilis, depending on the mode of transmission. Based on disease progression, syphilis is divided into early syphilis and late syphilis. Early syphilis includes primary syphilis, secondary syphilis, and early latent syphilis, while late syphilis includes tertiary syphilis, cardiovascular syphilis, neurosyphilis, and late latent syphilis.
Primary syphilis primarily manifests as chancre and syphilitic lymphadenitis, typically without systemic symptoms. Lesions may resolve spontaneously within weeks. Approximately 25% of untreated or inadequately treated cases progress to secondary syphilis, which is characterized by cutaneous, mucosal, and systemic involvement.
Untreated or improperly treated early syphilis may evolve into tertiary syphilis after 3–4 years (with a range of 2 to 20 years). About 40% of cases progress to this stage, which predominantly features nodular syphilids and gummas. Additionally, various critical tissues and organs may be affected.
Individuals with a history of syphilitic infection, no overt clinical symptoms, and a positive syphilis serological result but normal cerebrospinal fluid examination are considered to have latent syphilis. Latent syphilis is classified into early latent syphilis (disease duration of ≤2 years) and late latent syphilis (disease duration >2 years or when the duration is unknown).
Diagnosis is based not only on medical history and clinical manifestations but also laboratory findings:
Pathogen Examination
Secretions from lesions can be examined using dark-field microscopy or direct fluorescent antibody testing to detect Treponema pallidum, confirming the diagnosis.
Serological Testing
Non-Treponemal Antigen Tests
Semi-quantitative antibody titer tests, such as the Rapid Plasma Reagin (RPR) test and Venereal Disease Research Laboratory (VDRL) test, are highly sensitive but less specific. These tests reflect disease activity and treatment response but require confirmation by treponemal tests.
Treponemal Antigen Tests
Qualitative tests, including the Treponema pallidum particle agglutination (TPPA) test, Treponema pallidum hemagglutination (TPHA) test, and fluorescent treponemal antibody-absorption (FTA-ABS) test, detect specific IgG antibodies. These antibodies remain positive for life and thus are not suitable for monitoring treatment response or distinguishing between relapse and reinfection.
Cerebrospinal Fluid Examination
Cerebrospinal fluid testing, including VDRL, leukocyte count, and protein quantification, is essential for diagnosing neurosyphilis.
Diagnostic or highly suggestive criteria for congenital syphilis include:
- Clinical manifestations consistent with congenital syphilis.
- Detection of Treponema pallidum in affected tissues, placenta, amniotic fluid, or umbilical cord blood.
- Positive anti-Treponema pallidum IgM antibodies in body fluids.
- A fourfold or greater increase in antibody titers in umbilical or neonatal blood compared to maternal blood when using non-treponemal tests.
Differential Diagnosis
Primary syphilis should be distinguished from chancroid, genital herpes, pyoderma-like chancroid, and genital tumors.
Secondary syphilis should be differentiated from psoriasis, pityriasis rosea, lichen planus, and cutaneous lymphoma.
Tertiary syphilis should be distinguished from cutaneous tuberculosis, leprosy, and skin tumors.
Treatment
The treatment principle involves early, adequate, and standardized use of antimicrobial agents to prevent complications as much as possible.
Early Syphilis
Benzathine penicillin G 2.4 million units is administered intramuscularly in divided doses into both buttocks once a week for two consecutive doses. An alternative is procaine penicillin G 0.8 million units given intramuscularly once a day for 15 consecutive days. For those unable to use penicillin, ceftriaxone 0.5–1 g can be administered by intramuscular or intravenous injection once daily for 10 days. Doxycycline 0.1 g orally twice daily for 15 days is also an option for patients with penicillin allergy.
Late Syphilis
Benzathine penicillin G 2.4 million units is administered intramuscularly in divided doses into both buttocks once weekly for three consecutive doses. Another option is procaine penicillin G 0.8 million units by intramuscular injection once daily for 20 consecutive days for one course of treatment, with a second course of treatment being considered after a two-week hiatus. For patients allergic to penicillin, doxycycline 0.1 g orally twice daily for 30 days is an alternative.
Syphilis During Pregnancy
The recommended dose of benzathine penicillin G is the same as for late syphilis. Alternatively, procaine penicillin G 0.8 million units can be given by intramuscular injection once daily for 15 consecutive days. For pregnant women allergic to penicillin, there is currently no optimal alternative treatment. Ceftriaxone 1 g administered intramuscularly once daily for 10 days may be cautiously considered. Erythromycin can be used only if resistance is ruled out. Tetracycline and doxycycline are contraindicated during pregnancy.
Management During Delivery
Pregnancy complicated by syphilis is not an indication for cesarean delivery. Pregnant women treated with erythromycin during pregnancy should undergo retreatment after delivery with doxycycline (0.1 g, twice daily for 15 days), during which breastfeeding should be suspended. As erythromycin and azithromycin do not cross the placenta, neonates born to such mothers should immediately begin treatment for syphilis. Penicillin treatment should include monitoring for and prevention of the Jarisch-Herxheimer reaction, which may present as fever, uterine contractions, reduced fetal movements, or late decelerations on fetal heart monitoring. Breastfeeding is safe for women who have received standard treatment with good outcomes and for whom fetal infection has been excluded prior to delivery.
Congenital Syphilis
The first-line treatment is aqueous penicillin at a dose of 50,000 units/kg administered intravenously. For neonates aged 0–7 days, the frequency is every 12 hours, and for those older than 7 days, every 8 hours, for a total of 10–14 days. Alternatively, procaine penicillin at 50,000 units/kg by intramuscular injection once daily for 10–14 days may be used.
Follow-Up
Treatment efficacy is evaluated based on antibody titer changes using non-treponemal antigen tests. For early syphilis, a reduction in titer by 2 dilutions within 3 months and by 4 dilutions within 6 months is expected. Most cases of primary syphilis seroconvert within one year, while secondary syphilis often seroconverts within two years. Approximately 50% of late syphilis cases remain seropositive even two years after treatment. Sustained low-level titers persisting for over three years in late syphilis cases are diagnostic of serologic fixation. Follow-up after delivery is the same as for non-pregnant syphilis patients. Neonates born to mothers with syphilis during pregnancy require close clinical monitoring.