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General Medicine

Syphilis

A multi-stage sexually transmitted bacterial infection causing painless sores, followed by systemic rashes, and potentially ending in severe brain and heart damage if left untreated.

Source: WHO / CDC / NIH Evidence Guidelines
Updated: Aug 19, 2026
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Red Flag Warning & Emergency Situations

Emergency Management: Neurosyphilis presenting with acute stroke-like symptoms (Meningovascular Syphilis). Requires urgent Lumbar Puncture and initiation of IV Penicillin G.

Core Definition:

Syphilis is a complex, chronic systemic sexually transmitted infection caused by the spirochete bacterium Treponema pallidum. Often dubbed 'The Great Imitator', it presents in distinct sequential clinical stages (primary, secondary, latent, and tertiary), separated by periods of asymptomatic latency, and can invade nearly every organ system, most notably the central nervous system and cardiovascular system.

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)

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.

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.

First-Line Treatment:

For Primary, Secondary, and Early Latent: Benzathine Penicillin G 2.4 million units IM in a single dose. For Late Latent or Unknown Duration: Benzathine Penicillin G 2.4 million units IM weekly for 3 weeks (total 7.2 million units).

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.

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.

Authoritative Sources & Evidence References
World Health Organization (WHO) & CDC Guidelines: Information compiled from current international clinical practice guidelines.

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