Infectious Disease Book

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SyphilisAka: Treponema pallidum, Tabes dorsalis, Primary Syphilis, Secondary Syphilis, Tertiary Syphilis, Latent Syphilis, Neurosyphilis, Syphilitic paresis, Dementia paralytica

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  1. Epidemiology
    1. Resurgence of Syphilis with HIV in 1980s
  2. Etiology
    1. Caused by Spirochete Treponema pallidum
  3. Risk factors: Cohorts with highest Prevalence in U.S.
    1. Homosexual men
    2. Males
    3. Southern and urban centers
    4. African americans
  4. Stages: Primary Syphilis
    1. Findings
      1. Regional Lymphadenopathy
      2. Chancre
        1. Painless Papule ulcerates
        2. Indurated lesion with smooth base and firm border
    2. Timing
      1. Chancre at 10 to 90 days after exposure
      2. Chancre heals within 3 to 6 weeks
    3. Diagnostic Test Sensitivity in Primary Syphilis
      1. Dark-field Exam of chancre: 80%
      2. Non-Treponemal tests (e.g. RPR): 78-86%
      3. Treponemal tests (e.g. FTA-ABS): 76-84%
  5. Stages: Secondary Syphilis
    1. Timing
      1. Begins 2 to 8 weeks following onset of chancre
    2. Nonspecific symptoms
      1. Malaise
      2. Fatigue
      3. Headache
      4. Fever
      5. Sore Throat
    3. Signs
      1. Generalized Lymphadenopathy
      2. Papulosquamous Dermatosis
        1. Characteristics
          1. Pale, red discrete round lesions
          2. Scaling over surface
        2. Size: "Nickels and Dimes"
          1. Papules <1cm (Dimes): Usually 5-10 mm
          2. Plaques >1cm (Nickels)
        3. Distribution: Symmetric palms, soles and trunk
      3. Condyloma lata
        1. Papules coalesce
        2. Become large, flat highly contagious lesions
          1. Involves moist areas
          2. Involves genitalia
      4. Highly infectious lesions can occur on mucus membrane
    4. Systemic manifestations
      1. Hepatitis
      2. Periostitis
      3. Nephropathy
      4. Uveitis or Iritis
    5. Diagnostic Test Sensitivity in Secondary Syphilis
      1. Dark-field Exam of chancre: 80%
      2. Non-Treponemal tests (e.g. RPR): 100%
      3. Treponemal tests (e.g. FTA-ABS): 100%
  6. Stages: Latent Syphilis
    1. No clinical signs of Syphilis (CSF Normal)
    2. Early Latency (First year after infection)
    3. Late Latency (Latent infection >1 year)
      1. Only infectious in pregnancy and transfusion
    4. Diagnostic Test Sensitivity in Latent Syphilis
      1. Non-Treponemal tests (e.g. RPR): 95-100%
      2. Treponemal tests (e.g. FTA-ABS): 97-100%
  7. Stages: Tertiary Syphilis
    1. Late benign Syphilis (Gumma)
      1. May form 1 to 10 years after initial infection
      2. Destructive Granulomatous lesions affect any area
      3. Responds rapidly to treatment
    2. Cardiovascular Syphilis
      1. Begins 5 to 10 years after initial infection
      2. Clinically seen 20-30 years after infection
      3. Obliterative endarteritis of vasa vasorum
      4. Ascending aorta develops
        1. Aortic Insufficiency
        2. Aortic aneurysm
    3. Neurosyphilis (Occurs in 10% of untreated Syphilis)
      1. Symptoms
        1. Slow mental deterioration
        2. Headaches
        3. Personality change
      2. Signs
        1. Tremor of lips, Tongue or hands
        2. Argyll Robertson Pupil
        3. Seizures
        4. Ataxia
        5. Aphasia
        6. Hyperreflexia
        7. Cognitive changes
      3. Types
        1. Asymptomatic (Cerebrospinal Fluid positive VDRL)
        2. Meningovascular
          1. Begins 5 to 10 years after initial infection
          2. Acute or subacute Aseptic Meningitis
        3. Tabes dorsalis
          1. Onset 20 to 30 years after initial infection
          2. Progressive degeneration of spinal cord
            1. Posterior roots
            2. Posterior Columns
          3. Charcot's Joints
          4. Argyll-Robertson pupil (Prostitute pupil)
            1. Accommodates but does not react
        4. Syphilitic paresis (Dementia paralytica)
          1. Chronic meningoEncephalitis
          2. Evolves into Psychosis
    4. Diagnostic Test Sensitivity in Tertiary Syphilis
      1. CSF evaluation required (see below)
      2. Non-Treponemal tests (e.g. RPR): 71-73%
      3. Treponemal tests (e.g. FTA-ABS): 94-96%
  8. Differential Diagnosis: Syphilis chancre or condyloma
    1. See Genital Ulcer
    2. Genital Herpes
    3. Chancroid
    4. Venereal Wart
    5. Lymphogranuloma venereum
  9. Diagnosis
    1. Dark-field Microscopy
      1. Most specific if chancre or condyloma is present
      2. Accuracy varies with experience of technician
    2. Syphilis Serology
      1. Screening
        1. VDRL (Venereal Disease Research Lab Test)
        2. RPR (Rapid Plasma Reagin test)
      2. Negative test with lesions present
        1. Repeat screening in 3 weeks
      3. Confirmation of positive Screening Test
        1. Fluorescent Treponemal Antibody (FTA-ABS)
    3. Neurosyphilis CSF Evaluation
      1. Screening
        1. CSF VDRL (high Specificity)
        2. CSF white cell count >10/mm3
        3. CSF Protein >50 mg/dl
      2. Retesting if CSF VDRL negative
        1. Treponemal specific CSF tests (e.g. TPHA)
          1. High false positive rate
          2. Consider TPHA index (compares CSF to serum titer)
        2. Spirochete DNA PCR from CSF sample
          1. Higher Specificity than TPHA
          2. Not yet widely available
  10. Management
    1. Incubation stage (post-exposure prophylaxis)
      1. Ceftriaxone 250 mg IM and
      2. Doxycycline 100 mg for 14 days
      3. Azithromycin (Zithromax) 1 gram PO x1 dose
    2. Primary, secondary, early latent (under one year)
      1. Benzathine Penicillin G
        1. Adult: 2.4 MU IM for 1 dose
        2. Child: 50,000 units/kg IM for 1 dose (max: 2.4 MU)
      2. Aqueous Procaine Penicillin G 0.6 MU IM qd for 8 days
      3. Jarisch-Herxheimer Reaction may occur
      4. If Penicillin allergic
        1. Ceftriaxone 1 gram IM or IV for 10 days
        2. Tetracycline 500 mg PO qid for 14 days
        3. Doxycycline 100 mg PO bid for 14 days
    3. Late latent, Cardiovascular (over 1 year)
      1. Benzathine Penicillin G 2.4 MU IM qWeek for 3 weeks
      2. If Penicillin allergic
        1. Tetracycline 500 mg PO qid for 4 weeks
        2. Doxycycline 100 mg PO bid for 4 weeks
    4. Neurosyphilis
      1. Aqueous crystalline Penicillin G
        1. Dose: 3-4 MU IV q4 hours for 10-14 days
        2. Alternative: 0.75 to 1 MU/hour continuous IV
      2. Procaine Penicillin (only in compliant patients)
        1. Dose 2.4 MU IM qd for 14 days
        2. Use with Probenecid 500 mg qid for 14 days
      3. Penicillin Allergy
        1. Desensitize and treat with Penicillin
        2. Ceftriaxone 2 g IM/IV qd for 14 days
    5. Pregnancy
      1. Treat with Penicillin as above
      2. Desensitize and treat with Penicillin if allergic
  11. Follow-up: 6 months after treatment (Stage 1-2)
    1. Repeat quantitative nonTreponemal test titers
    2. Repeat clinical evaluation
  12. References
    1. (2002) MMWR Morb Mortal Wkly Rep 51(RR-6):18
    2. Brown (2003) Am Fam Physician 68(2):283
    3. Hook (1999) Ann Intern Med 131:434
    4. Larsen (1995) Clin Microbiol Rev 8:1

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