Syphilis

See Also

Epidemiology

Resurgence of Syphilis since HIV epidemic onset in 1980s
Worldwide: 5 Million new cases per year
Syphilis Incidence in U.S. (primary and secondary) is increasing
1. 2000: 2.1 cases per 100,000 persons (5979 new cases in U.S.)
2. 2005: 2.9 cases per 100,000 persons (8724 new cases in U.S.)
3. 2010: 4.5 cases per 100,000 persons (13,774 new cases in U.S.)
4. 2014: 6.3 cases per 100,000 persons (19,999 new cases in U.S.)
  1. Men account for 91% of cases (of whom 83% are Gay Men)
5. 2015: 8.0 cases per 100,000 persons (23,872 new cases in U.S.)
6. 2018: 10.8 cases per 100,000 persons (35,063 new cases in U.S.)
Gender
1. Syphilis infections in women is increasing as of 2021
  1. High risk of Congenital Syphilis for women who are infected with Syphilis during pregnancy
  2. Screen high risk patients in pregnancy at intake, 28 weeks and at delivery
2. Males account for 90% of cases
  1. Men who have Sex with Men account for 82% of cases in men
  2. More common in men of color under age 30 years
  3. HIV and Syphilis infection are associated
Reinfections
1. Reinfection accounts for 15-20% of new Syphilis cases each year

Causes

Caused by Spirochete Treponema pallidum
In addition to Syphilis, Treponema pallidum also causes yaws and pinta

Pathophysiology

Transmission via mucous membranes, non-intact skin, transfusions, and vertical transmission (transplacental)

Risk factors
Cohorts with highest Prevalence in U.S.

HIV Infection
Men who have Sex with Men (most common)
Incarceration
Sex Worker History
Males
Southern and Western U.S,
Urban centers
Age 20 to 35 years (esp. under age 30 years old)
Race and ethnicity
1. African americans
2. Hispanics
3. American Indians
4. Alaskan and Hawaiian natives
5. Pacific Islanders

Signs
By Stage

Early Syphilis
1. Primary Syphilis
  1. Solitary Chancre (hallmark ulcer of Primary Syphilis)
    1. Genital lesion present in 95% of cases (Oral Mucosa ulcer in remainder of cases)
    2. Single, painless, well-demarcated ulcer
    3. Clean base
    4. Indurated border
  2. Nonsuppurative, mildly tender Regional Lymphadenopathy (uncommon)
2. Secondary Syphilis
  1. Nickel and dime-size pale, pink to red discrete round, ScalingMacular to papular lesions
    1. Distributed over trunk, flexors, palms, soles
  2. Condyloma Lata (painless, wart-like lesions)
    1. Distributed over mouth, genitalia and intertriginous areas (perineum, axilla, between toes)
  3. Syphilitic Alopecia (Alopecia with moth-eaten appearance)
Late Syphilis
1. Latent Syphilis
  1. Latent, asymptomatic period of 3-20 years
  2. Infectious only in pregnancy and Blood Transfusion
  3. One third will progress to Tertiary Syphilis
2. Tertiary Syphilis
  1. Syphilitic Gumma (Granulomas and Psoriasis-like Plaques)
    1. Diffusely distributed soft ulcerative lesions, with firm necotic center
  2. Cardiovascular Syphilis (thoracic aneurysm)
  3. Neurosyphilis (Tabes Dorsalis, Meningitis, Dementia)

Differential Diagnosis

Labs

See Syphilis Testing
HIV Screening
Other Sexually Transmitted Infection sceening
1. Gonorrhea PCR
2. Chlamydia PCR
3. Trichomonas PCR (or Wet Prep)

Precautions

Test in pregnancy at intake
1. Risk of Congenital Syphilis
2. Repeat testing at 28 weeks and after delivery in high risk patients
Syphilis requires a high index of suspicion
1. Widely variable presentations
2. Resurgence in the last 10 years
3. Insidious and delayed onset with painless primary lesions that may easily be missed
Syphilis course is complex
1. Neurologic complications may occur at any stage of illness
2. Latent periods of infection are common (despite ongoing infection)
3. Late Syphilis (latent and Tertiary Syphilis) are high risk if Syphilis is not treated in the first year of infection

Management
General

Precautions
1. Do NOT use Bicillin CR (short acting preparation) to treat Syphilis
2. Evaluate for ear, eye or neurologic findings (requires admission and IV Penicillin for 14 days)
Incubation stage (Post-exposure Prophylaxis)
1. Gonorrhea and Syphilis Prophylaxis
  1. Ceftriaxone 500 mg IM/IV for 1 dose (1 gram IM/IV if weight > 150 kg, dose increased in 2020)
2. Chlamydia and Syphilis Prophylaxis
  1. Doxycycline 100 mg twice daily for 7 days (preferred as of 2020)
3. References
  1. Cyr (2020) MMWR Morb Mortal Wkly Rep 69(50): 1911-6 [PubMed]
    1. https://www.cdc.gov/mmwr/volumes/69/wr/mm6950a6.htm
Primary, secondary, early latent (under one year)
1. Benzathine Penicillin G (Bicillin LA)
  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 daily for 8 days
3. Jarisch-Herxheimer Reaction may occur
  1. Acute febrile reaction (due to Spirochete lysis) in first 24 hours of Syphilis treatment
  2. Manifests as fever, Headache, rash exacerbation
4. If Penicillin allergic
  1. Ceftriaxone 1 to 2 gram IM or IV for 10-14 days
  2. Tetracycline 500 mg orally four times daily for 14 days
  3. Doxycycline 100 mg orally twice daily for 14 days
  4. Avoid Azithromycin
    1. Previously dosed at Azithromycin 2 grams orally once
    2. High risk of resistance (esp. pregnancy, Men who have Sex with Men)
    3. Was used only if Penicillin allergic and unable to take doxycyline, Minocycline or Ceftriaxone
Late latent, Cardiovascular Syphilis (duration over 1 year)
1. Benzathine Penicillin (Bicillin LA) G 2.4 MU IM weekly for 3 weeks
2. If Penicillin allergic
  1. Tetracycline 500 mg orally four times daily for 4 weeks OR
  2. Doxycycline 100 mg orally twice daily for 4 weeks
Neurosyphilis
1. See Neurosyphilis
Pregnancy
1. Screen all patients in early pregnancy (and consider rescreening in third trimester)
2. Identifying maternal Syphilis before 4 months gestation prevents Congenital Syphilis
3. Treat with Penicillin as above
  1. If Penicillin allergic, admit, desensitize and treat with Penicillin
4. Consider hospital admission for start of treatment
  1. Risk of Preterm Labor associated with Jarisch-Herxheimer Reaction
Congenital Syphilis
1. CDC STD management booklet
  1. http://www.cdc.gov/mmwr/pdf/rr/rr5912.pdf
Sexual partners
1. Treat all sexual contacts from prior 90 days

Management
Follow-up at 6 months after treatment

Prior Syphilis does not result in significant Immunity to prevent reinfection
1. If exposure risks remain unchanged, reinfection is common
Repeat quantitative nontreponemal test titers at 6 and 12 months after treatment (all patients)
1. Expect a four-fold decrease in RPR or VDRL titers over subsequent 3-6 months following treatment
2. Four-fold increase in titers over prior level suggests recurrent Syphilis and these patients should be re-treated
3. Decrease in titers may be slower in patients who have had more than one Syphilis infection
4. Seronegative conversion may occur if original titers were low or in cases treated early (stage 1-2)
Repeat clinical evaluation
1. Persistent symptoms and signs despite treatment should prompt Syphilis re-treatment
Extended follow-up for late Syphilis (latent, tertiary) and neurologic complications
1. Additional follow-up at 12 and 24 months for latent and Tertiary Syphilis
2. Additional follow-up at 3 months, and continue every 6 months until CSF labs normalize
  1. Until CSF WBC Count normal
  2. Until CSF VDRL normal

Complications

Unteated pregnancy (even if acquired up to 4 years before pregnancy)
1. Congenital Syphilis (fetal infection risk 80%)
2. Stillbirth or Miscarriage: 40%
Untreated Secondary Syphilis
1. Lues Maligna (Ulceronodular Syphilis, Malignant Syphilis)
  1. Severe form of Secondary Syphilis (especially in immunosuppressed patients)
2. Hepatitis
3. Periostitis
4. Nephropathy
5. Uveitis or Iritis
Untreated Tertiary Syphilis
1. Thoracic Aortic Aneurysm (from ascending aortitis)
2. Neurosyphilis complications
HIV Transmission
1. Syphilis related Genital Ulcers (Chancre of Primary Syphilis) facilitate HIV Transmission
2. Chancres are laden with Lymphocytes which allow for both HIV Transmission and entry

Prevention

Personal Protection Equipment (PPE)
1. Use contact precautions
2. T. pallidum infects host via mucous membranes and nonintact skin (as well as hematologic)
3. Chancre (Primary Syphilis) and Condyloma Lata (Secondary Syphilis) are contagious lesions
Screen all high risk patients at least annually
1. Screen more often in Men who have Sex with Men, not in monogamous relationships
Screen in pregnancy
1. Screen at least once in pregnancy (typically with initial pregnancy labs, and consider repeat at 28 weeks)
2. Repeat screening in high risk groups and in regions of high syphilis Prevalence

References

Green, Cohen, Billington (2016) Crit Dec Emerg Med 30(11): 4-10
Kirk, McHugh and Parnell (2023) Crit Dec Emerg Med 37(8): 23-9
(2002) MMWR Recomm Rep 51(RR-6):1-78 +PMID: 12184549 [PubMed]
Brown (2003) Am Fam Physician 68(2):283-90 [PubMed]
Hook (1999) Ann Intern Med 131:434-7 [PubMed]
Mattel (2012) Am Fam Physician 86(5): 433-40 [PubMed]
Ricco (2020) Am Fam Physician 102(2): 91-8 [PubMed]
Workowski (2010) MMWR Recomm Rep 59(RR-12): 1-110 [PubMed]
Workowski (2021) MMWR Recomm Rep 70(4): 1-187 [PubMed]