1. Etiology and Overview
Causative Agent: Treponema pallidum, a spirochete transmitted primarily through sexual contact, or vertically (transplacental) from mother to fetus.
Epidemiological Note: Early detection and treatment are crucial to prevent progression through multiple stages and to avoid severe complications, especially in pregnancy.
2. Clinical Stages
Primary Syphilis
Incubation: Typically 3 weeks (range 3–90 days).
Presentation:
Chancre: A painless, firm, round ulcer with raised edges; commonly on the genitals, anus, or oral mucosa.
Lymphadenopathy: Non-tender, bilateral enlargement of regional lymph nodes.
Spontaneous Resolution: The chancre usually heals spontaneously within 2–8 weeks, even without treatment.
Diagnostic Considerations:
Early in the disease, non-treponemal tests (RPR, VDRL) may be negative; direct detection (darkfield microscopy) of lesion exudate can be more reliable in this stage.
Secondary Syphilis
Timeline: Occurs several weeks to a few months after the chancre appears.
Clinical Features:
Rash: Often involves the palms and soles (classically maculopapular).
Condyloma Lata: Moist, wart-like lesions in warm, intertriginous areas.
Systemic: Fever, malaise, generalized lymphadenopathy, and other constitutional symptoms.
Natural Course: Symptoms can spontaneously resolve but may recur in the first year.
Latent Syphilis
Definition: Asymptomatic phase, detectable only by serologic testing.
Subdivisions:
Early Latent (<1 year): Infectious, higher risk of relapse.
Late Latent (>1 year): Generally considered non-infectious, except for possible vertical transmission in pregnancy.
Tertiary Syphilis
Timeline: Develops years (3–10 or more) after the initial infection if untreated.
Key Manifestations:
Gummas: Granulomatous lesions affecting skin, bones, or internal organs.
Cardiovascular: Aortitis, aortic aneurysms.
Neurosyphilis: Can occur at any stage, but classically associated with tertiary syphilis. Manifestations include tabes dorsalis (degeneration of dorsal columns), general paresis, and Argyll Robertson pupils.
3. Syphilis in Pregnancy and Congenital Syphilis
Transplacental Transmission: Can occur after approximately 18 weeks of gestation.
Fetal/Neonatal Consequences:
Severe: Stillbirth, hydrops fetalis.
Postnatal: Hepatosplenomegaly, jaundice, anemia, thrombocytopenia.
Untreated Maternal Syphilis:
Increased risk of preterm birth, low birth weight, and neonatal infection.
Prevention: Universal prenatal screening and prompt treatment are critical.
4. Screening and Diagnosis
Initial Screening
Non-Treponemal Tests (RPR, VDRL): Useful for screening and for monitoring treatment response (titers should fall after successful therapy).
Treponemal Tests (TPPA, FTA-ABS, EIA/CIA): Used for confirmation. Once positive, these often remain positive for life.
Reverse Screening Algorithm
Step 1: Treponemal test (e.g., EIA/CIA, TPPA).
Step 2: If positive, confirm with a non-treponemal test (RPR or VDRL).
Step 3: If there is discordance (e.g., positive EIA but negative RPR), perform a second, different treponemal test (TPPA or FTA-ABS) to resolve.
CDC Guidelines for Pregnancy
Timing:
All pregnant women should be tested at the first prenatal visit.
Rescreen high-risk individuals at 28 weeks and again at delivery.
Neurosyphilis Workup
Indications: Neurological symptoms or high-risk latent syphilis.
CSF Analysis:
Positive VDRL in CSF is highly specific.
Elevated WBC count (>20 cells/mm³) and protein may also be seen.
5. Treatment
First-Line Treatment:
Benzathine Penicillin G is the gold standard for all stages of syphilis, including pregnancy.
Recommended Regimens:
Primary, Secondary, Early Latent (<1 year):
Benzathine penicillin G 2.4 million units IM, single dose.
Late Latent (>1 year) or Unknown Duration:
Benzathine penicillin G 2.4 million units IM once weekly for 3 weeks (total 3 doses).
Neurosyphilis:
Aqueous crystalline penicillin G 18–24 million units per day IV (divided every 4 hours) for 10–14 days.
Penicillin Allergy:
In pregnancy, penicillin desensitization is mandatory because alternative antibiotics (e.g., doxycycline, azithromycin) are not considered adequate for preventing congenital syphilis.
Jarisch-Herxheimer Reaction:
Definition: A systemic reaction (fever, chills, headache, myalgia) within 24 hours of starting antibiotics, caused by the rapid lysis of spirochetes.
Management:
Continue treatment; administer antipyretics (e.g., acetaminophen) to mitigate symptoms.
Pregnancy Considerations:
Closely monitor for uterine contractions and signs of preterm labor.
6. Follow-Up and Monitoring
Serologic Monitoring
Non-Treponemal Titers (RPR/VDRL):
Recheck at 6 and 12 months (and 24 months for some guidelines) in non-pregnant patients.
Expect a fourfold decrease in titer by 6 months (e.g., 1:16 to 1:4) as a marker of successful therapy.
Pregnancy-Specific Follow-Up
More frequent serologic tests (e.g., monthly or every 3 months) because of high stakes for the fetus.
Aim for a fourfold decrease in titers often within 3 months.
A fourfold increase in titer at any time suggests reinfection or treatment failure and warrants immediate re-evaluation.
Fetal Monitoring
Consider ultrasound evaluations for signs of congenital syphilis (e.g., hepatosplenomegaly, hydrops fetalis, placental thickening).
7. Key Takeaways from CDC and WHO Guidelines
Penicillin G remains the standard of care across all stages.
Serologic testing (RPR/VDRL) is essential for both diagnosis (with treponemal confirmation) and monitoring after treatment.
Pregnant women require closer follow-up and earlier serologic response is expected. Desensitization to penicillin is non-negotiable if there is an allergy.
Prompt detection and treatment are paramount to prevent long-term complications (e.g., neurologic or cardiovascular) and congenital syphilis.
Conclusion
Syphilis is a dynamic infection with clear-cut stages, each with its own diagnostic markers and clinical manifestations. The cornerstone of successful management is timely diagnosis, appropriate staging, and adequate penicillin-based treatment, particularly in pregnant women to prevent the devastating consequences of congenital syphilis. Regular serologic monitoring ensures therapeutic efficacy, identifies reinfections, and guides any need for retreatment.
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