Treponema pallidum subspecies pallidum is the causative agent of syphilis, a sexually transmitted infection (STI).

Epidemiology

• Incidence
  • 2-5/100,000
  • Varies by region
  • Incidence has increased in last 5-10 years
• Age
  • Peak age - teens to late twenties
• Transmission    
  • Sexual contact
  • Maternal vertical transmission

Organism

• Treponema pallidum subspecies pallidum is a member of the Spirochaetales family that causes syphilis and is distinct from endemic treponematoses of yaws (T. pallidum subspecies pertenue), pinta (T. pallidum subspecies carateum) and endemic syphilis (T. pallidum subspecies endemicum)
• The Spirochaetales family also includes:
  • Leptospira species
  • Borrelia species, including B. burgdorferi

Risk Factors for syphilis

• Early age at onset of sexual activity
• Infection with HIV
• Infection with gonorrhea
• Multiple sex partners
• Non-Caucasian
• Non-use of barrier methods of birth control
• Previous history of STI

Clinical Presentation

• Primary syphilis
  • Painless chancre at site of inoculation begins at about 3 weeks and may persist 4-6 weeks
• Secondary syphilis
  • Two types
    • Latent and early latent <1 year
    • Late latent greater than or equal to 1 year
  • Diffuse lymphadenopathy
  • Mucocutaneous lesions (condyloma lata)
  • Macular skin rash (frequently involves palms and soles)
  • Meningitis (rarely)
• Tertiary (late) syphilis
  • 15-40% of untreated patients develop disease
  • Cardiovascular - aortitis
  • Gummatous syphilis - granulomatous, nodular lesions in organs (commonly skin and bones)
  • Neurologic - general paresis, tabes dorsalis
• Congenital syphilis
  • Can occur during all stages of maternal syphilis
  • Typed according to age at diagnosis
    • Early (<2 years old, untreated)
      • Snuffles
      • Rash
      • Condyloma lata
      • Bone changes
      • Hepatosplenomegaly
      • Jaundice
      • Anemia
    • Late (>2 years, untreated)
      • 8th nerve deafness
      • Arthropathy (Clutton joints)
      • Neurosyphilis
      • Keratitis
    • Residual stigmata
      • Hutchinson’s teeth
      • Mulberry molars
      • Saddle nose
      • Saber shin
      • Rhagades scars
• Central nervous system manifestations (may occur at any stage)
  • Symptomatic forms
    • Meningeal syphilis (usually <1 year after infection)
      • Involves the brain or spinal cord
      • Symptoms include headache, stiff neck
    • Meningovascular syphilis (usually 5-10 years after infection)
      • Inflammation of pia and arachnoid, with focal arteritis
      • Stroke syndrome involving middle cerebral artery is common in young adults
    • Parenchymatous (late syphilis)
      • General PARESIS (acronym for Personality, Affect; Reflexes, Eye (argyll Robertson pupil), Sensorium, Intellect, Speech)
      • Tabes Dorsalis - demyelination of posterior columns, dorsal roots and dorsal root ganglia
        • Results in weakness, paresthesias, ataxia, dementia, personality changes, and decreased reflexes
        • Characterized by wide-based gait and bladder symptoms
      • Charcot joints - trophic joint degeneration
      • Optic atrophy (Argyll Robertson pupil) frequently associated with tabes dorsalis
  • May also be asymptomatic

Treatment

• All stages of neurosyphilis require treatment to prevent disease progression and sequelae
• Jarisch-Herxheimer reaction sometimes follows initial syphilis treatment
  • Fever/chills
  • Headache
  • Tachypnea
  • Tachycardia
  • Usually lasts <24 hours
  • Supportive care only
• Intrauterine treatment <16 weeks into pregnancy prevents fetal damage

Refer to Syphilis topic at www.arupconsult.com for a table of Comparisons of STI Screening Recommendations for Sexually Active Nonpregnant Women

Refer to Syphilis topic at www.arupconsult.com for a table of Comparisons of STI Screening Recommendations for Pregnant Women

Diagnosis

• Indications for testing - suspicion of syphilis because classic lesions are present, STI screening or concurrent STI
• Laboratory testing
  • Cannot be cultured in vitro
  • Darkfield exam if chancre (primary) or condylomata lata (secondary) present
  • Nontreponemal tests
    • Rapid plasma reagin (RPR) - if reactive, order titers
    • VDRL may be used first but has higher false-positive rate
    • Treponemal tests used for confirmation
      • Fluorescent treponemal antibody absorption (FTA-Abs)
      • Microhemagglutination tests for antibodies to Treponema pallidum (MHA-TP)
      • IgM antibody detection by ELISA
  • Patient with newly diagnosed HIV should have syphilis testing, and patient with newly diagnosed syphilis should have HIV testing
  • Nontreponemal tests measure IgM and IgG antibodies
    • Positive titers are used to follow response to therapy for infected patients
  • If patient has a negative test but continues to engage in risk behavior, retest in 3-12 months
• Diagnosis of neurosyphilis
  • In suspected cases, order VDRL on cerebrospinal fluid (CSF) and RPR from serum
  • If RPR is negative and a high index of suspicion for neurosyphilis remains, perform FTA-Abs from serum
    • Some patients have non-reactive non-treponemal tests in late neurosyphilis
  • Central nervous system (CNS) is usually the affected site in an HIV patient
• For further testing recommendations, see the Syphilis Testing Algorithm

Disease Monitoring

• Treatment followup
  • Nontreponemal tests best for monitoring treatment or testing for reinfection (RPR for serum, VDRL for spinal fluid)
  • In CNS disease - CSF titers with VDRL should decrease

Differential Diagnosis

• Herpes simplex (primary syphilis)
• Chancroid (primary syphilis)
• Lymphogranuloma venereum (primary syphilis)
• Behçet disease (primary syphilis)
• Contact dermatosis (secondary syphilis)
• Lichen planus
• Squamous cell carcinoma