Syphilis

Detailed Overview

Transmission occurs primarily via direct contact with an infectious lesion (chancre) during sexual intercourse, or vertically from mother to fetus (congenital syphilis). The primary stage features a painless ulcer. If untreated, spirochetes disseminate hematogenously, leading to the secondary stage marked by a diffuse maculopapular rash involving the palms and soles. After years of latency, about 30% of untreated individuals progress to tertiary syphilis, suffering severe end-organ damage including neurosyphilis (tabes dorsalis, general paresis) and cardiovascular syphilis (aortic root aneurysms).

Epidemiology & Demographics

Rates have been surging globally. In the US, primary and secondary syphilis rates increased by over 70% in the last decade. It disproportionately affects Men who have Sex with Men (MSM), accounting for over half of all cases. Congenital syphilis rates are also rising alarmingly.

Etiological Mechanism

The sole causative agent is Treponema pallidum, a thin, tightly coiled, motile spirochete that cannot be cultured in vitro and is highly fragile outside the human host.

Primary Causes

Sexual contact with an infected partner

Transplacental maternal-fetal transmission

Blood transfusion (rare)

• Unprotected Sexual Intercourse: Inconsistent condom use and having multiple or anonymous sexual partners.
• HIV Infection: Strong synergistic epidemiological relationship; syphilis facilitates HIV transmission via genital ulcers, and HIV alters the clinical course of syphilis.
• Substance Use: Methamphetamine and IV drug use are strongly linked to high-risk sexual behaviors facilitating transmission.

T. pallidum penetrates intact mucous membranes or microscopic dermal abrasions. It replicates locally and induces an intense endarteritis (inflammation of small arteries) with a perivascular infiltrate of plasma cells and macrophages, leading to local tissue ischemia and the formation of the primary painless chancre. Within hours, spirochetes disseminate via lymphatics and blood. In secondary syphilis, immune complex deposition and massive bacteremia cause generalized mucocutaneous lesions. Tertiary syphilis is driven by a delayed-type hypersensitivity reaction to persistent low-burden spirochetes, forming destructive granulomas (gummas) in tissues and causing obliterative endarteritis of the vasa vasorum, leading to aortic aneurysms.

Characteristic Clinical Presentation

• Painless Genital Ulcer: Primary stage: A firm, round, painless chancre at the site of inoculation, healing spontaneously in 3-6 weeks.
• Palmar/Plantar Rash: Secondary stage: Diffuse, non-itchy maculopapular rash uniquely involving the palms of the hands and soles of the feet.
• Condylomata Lata: Secondary stage: Highly infectious, raised, painless, grey-white wart-like lesions in moist areas (perineum).

Physical Examination Signs

• Argyll Robertson Pupil
• Tabes Dorsalis

• Aortic Aneurysm/Dissection: Destruction of the ascending aorta leading to massive aneurysm and potentially fatal rupture.
• General Paresis: A severe, progressive dementia with personality changes and delusions caused by direct brain parenchymal infection.

Diagnostic Criteria & Guidelines

Diagnosis requires a two-step serological algorithm. Traditional sequence: Non-treponemal screening test (RPR or VDRL) followed by a confirmatory Treponemal specific test (FTA-ABS or TP-PA). Reverse sequence starts with a Treponemal EIA.

Differential Diagnosis

• Herpes Simplex Virus (Chancres are painful in HSV)
• Pityriasis Rosea (Rash mimic)
• Chancroid

Laboratory Tests & Biomarkers

• Rapid Plasma Reagin (RPR): Quantitative titer (e.g., 1:32). High titers indicate active disease; a 4-fold decrease indicates successful treatment.
• Treponemal Test (FTA-ABS): Positive. Remains positive for life, regardless of treatment (serological scar).
• CSF VDRL: If neurosyphilis is suspected, lumbar puncture showing positive CSF VDRL, elevated protein, and pleocytosis is diagnostic.

Imaging Modalities & Findings

• CT/MRI Brain:
• CT Angiography of Chest:

• Primary Syphilis
  Characterized solely by the painless chancre and regional non-tender lymphadenopathy.
• Secondary Syphilis
  Systemic dissemination: rash, alopecia, condylomata lata, fever, and generalized lymphadenopathy.
• Latent Syphilis (Early vs Late)
  Asymptomatic period. Early latent is <1 year duration; Late latent is >1 year duration.
• Tertiary Syphilis
  Gummatous lesions, cardiovascular syphilis (aortitis), and late neurosyphilis.

Second-Line & Adjunctive Therapy

For Penicillin-allergic non-pregnant patients: Doxycycline 100 mg PO BID for 14 days (or 28 days for late latent). For Neurosyphilis: Aqueous Crystalline Penicillin G 18-24 million units IV daily for 10-14 days. NOTE: Pregnant women with penicillin allergy MUST be admitted, desensitized to penicillin, and treated with Penicillin G.

Surgical & Procedural Management

Aortic root replacement surgery for severe cardiovascular syphilis.

Recommended Lifestyle Changes

• Abstain from sexual contact until chancre/rash is completely healed and 7 days after treatment is completed.
• Partner notification and empiric treatment of all sexual contacts within the last 90 days.

Patient Counseling & Advice

Warn patients about the Jarisch-Herxheimer reaction: a self-limiting acute febrile illness occurring 2-24 hours after treatment, caused by massive release of treponemal lipoproteins from dying bacteria. It is NOT a penicillin allergy.

Follow-Up & Monitoring Schedule

Clinical and serologic (RPR titers) follow-up at 6, 12, and 24 months. A 4-fold drop in RPR titer (e.g., 1:32 to 1:8) confirms cure. Failure to decline indicates treatment failure or reinfection.

Preventive Strategies

Consistent and correct condom use. Regular screening for high-risk populations (MSM, HIV+). Mandated screening for all pregnant women at the first prenatal visit to prevent congenital syphilis.

Excellent with appropriate penicillin therapy, achieving near 100% cure rates in early stages. Tertiary organ damage (aneurysms, dementia) is irreversible even if the infection is cured.