Syphilis¶
Chapter 187 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Syphilis is a chronic systemic infection caused by Treponema pallidum subspecies, transmitted primarily through sexual contact.
- The disease progresses through primary, secondary, latent, and tertiary stages, with congenital syphilis being a critical complication in untreated maternal infections.
- Penicillin remains the gold standard for treatment, with alternative regimens for penicillin-allergic patients, including doxycycline and ceftriaxone.
- Serologic testing (lipoidal and treponemal assays) is essential for diagnosis, with confirmation required to differentiate true positives from false positives.
- Neurosyphilis requires lumbar puncture and CSF analysis, with specific treatment protocols for different stages and populations (e.g., HIV-infected patients).
1. DEFINITION & OVERVIEW¶
Syphilis is a chronic systemic infection caused by Treponema pallidum subspecies, typically transmitted sexually. It is characterized by episodic active disease interspersed with asymptomatic latency. The infection can progress to severe complications, including cardiovascular, neurological, and congenital manifestations.
1.1 Pathogenesis¶
T. pallidum enters through mucous membranes or skin abrasions, disseminates via lymphatics and bloodstream, and evades immune responses through antigenic variation. The organism has limited metabolic capabilities, relying on host-derived nutrients.
1.2 Clinical Stages¶
Primary (chancre), secondary (rash, lymphadenopathy), latent (asymptomatic), and tertiary (gummas, cardiovascular, neurosyphilis). Congenital syphilis occurs via transplacental transmission.
2. EPIDEMIOLOGY¶
Syphilis incidence has surged globally, with 8 million new infections annually. In the U.S., cases increased 6.6-fold since 2000, with 59,061 reported P&S cases in 2022. MSM and African American populations are disproportionately affected. HIV co-infection and substance use are significant risk factors.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
T. pallidum subspecies (pallidum, pertenue, endemicum, carateum) are spirochetes with a trilaminar cytoplasmic membrane and endoflagella. Immune evasion via antigenic variation of TprK surface proteins contributes to persistent infection.
3.1 Transmission¶
Sexual contact (chancre, mucous patches), non-sexual skin contact, vertical transmission, blood transfusion, and organ donation. Oral and genital mucosa may serve as transmission routes.
3.2 Immune Evasion¶
Antigenic variation of TprK surface proteins allows immune evasion. T. pallidum relies on host-derived nutrients and has limited metabolic capabilities.
4. CLINICAL FEATURES¶
Primary (painless chancre), secondary (macular rash, lymphadenopathy), latent (asymptomatic), tertiary (gummas, cardiovascular, neurosyphilis), and congenital syphilis (neonatal manifestations). Atypical presentations include mucous patches and condylomata lata.
4.1 Primary Syphilis¶
Painless chancre at infection site (penis, vagina, rectum). Spontaneous healing within 4–6 weeks. Regional lymphadenopathy.
4.2 Secondary Syphilis¶
Generalized rash, mucous patches, lymphadenopathy. Constitutional symptoms (fever, weight loss). May resolve spontaneously.
5. DIFFERENTIAL DIAGNOSIS¶
Herpes simplex, chancroid, traumatic injury, donovanosis, HIV-related ulcers, and other STIs. Atypical presentations may mimic other infections or autoimmune conditions.
6. INVESTIGATIONS & DIAGNOSIS¶
Serologic tests (VDRL, RPR, FTA-ABS, TPPA) for diagnosis. CSF analysis for neurosyphilis. PCR for confirmation in equivocal cases. Lipoidal tests may yield false positives in autoimmune conditions or drug users.
6.1 Serologic Testing¶
Lipoidal tests (VDRL, RPR) detect IgG/IgM against cardiolipin. Treponemal tests (FTA-ABS, TPPA) are more sensitive for early detection. False positives may occur in HIV or autoimmune diseases.
6.2 CSF Analysis¶
Mononuclear pleocytosis, elevated protein, and CSF VDRL reactivity indicate neurosyphilis. CSF FTA-ABS is more sensitive than CSF VDRL.
7. MANAGEMENT & TREATMENT¶
Penicillin G benzathine is the first-line treatment. Alternatives for penicillin-allergic patients include doxycycline, tetracycline, or ceftriaxone. Neurosyphilis requires aqueous penicillin. Congenital syphilis requires maternal and neonatal treatment.
Table 187-1: Recommendations for the Treatment of Syphilis¶
| STAGE OF SYPHILIS | PATIENTS WITHOUT PENICILLIN ALLERGY | PATIENTS WITH CONFIRMED PENICILLIN ALLERGY |
|---|---|---|
| Primary, secondary, or early latent | Penicillin G benzathine (2.4 mU IM) for 3 weeks | Doxycycline (100 mg PO bid) or tetracycline HCl (500 mg PO qid) for 2 weeks |
| Neurosyphilis, ocular syphilis, or otic syphilis | Aqueous crystalline penicillin G (18–24 mU/d IV) for 10–14 days | Desensitize and treat with penicillin |
| Congenital syphilis | Penicillin G benzathine (7.2 million units total) | Doxycycline (100 mg PO bid) for 10–14 days |
7.1 Treatment Regimens¶
Penicillin G benzathine (2.4 million units IM) for early syphilis. Aqueous penicillin for neurosyphilis. Doxycycline (100 mg PO bid) for 2 weeks for allergic patients.
7.2 Pregnancy Management¶
Penicillin is the only recommended treatment. Desensitization for penicillin-allergic patients. Neonatal screening for congenital syphilis.
7.3 Jarisch-Herxheimer Reaction¶
Fever, chills, and myalgia may occur after treatment initiation. Managed with supportive care; steroids are not required.
8. PROGNOSIS & COMPLICATIONS¶
Untreated syphilis leads to severe complications (cardiovascular, neurosyphilis, congenital syphilis). HIV co-infection increases risk of neurosyphilis and treatment failure. Early treatment prevents progression.
8.1 Congenital Syphilis¶
Neonatal manifestations include rhinitis, mucocutaneous lesions, bone changes, and CNS involvement. Untreated cases may result in stillbirth, prematurity, or death.
8.2 Neurosyphilis¶
Late-stage complications include tabes dorsalis, general paresis, and meningovascular syphilis. Requires CSF examination and specific treatment.
9. SPECIAL CONSIDERATIONS¶
Management in pregnancy, HIV co-infection, and pediatric populations. Penicillin remains the only recommended treatment for syphilis in pregnancy. HIV-infected patients require close monitoring for neurosyphilis.
9.1 HIV Co-Infection¶
Higher risk of neurosyphilis and treatment failure. RPR titers ≥ 1:32 and CD4+ counts ≤ 350/ µ L indicate higher risk. Desensitization for penicillin-allergic HIV patients.
9.2 Congenital Syphilis¶
Neonatal screening, maternal treatment, and long-term follow-up. Infants with reactive serology require CSF examination and treatment.
10. KEY POINTS & CLINICAL PEARLS¶
Penicillin is the gold standard for syphilis. Serologic testing must be confirmed with treponemal assays. Neurosyphilis requires CSF examination. Congenital syphilis mandates maternal and neonatal treatment. HIV-infected patients require close monitoring for neurosyphilis.