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Syphilis

BASICS

  • Definition: Chronic systemic infection caused by Treponema pallidum
  • Transmission:
  • Sexual (direct contact with lesion)
  • Vertical (maternal-fetal)
  • Blood transfusion (rare)
  • Stages (overlapping):
  • Primary: Painless chancre (10–90 days after exposure, heals in 3–6 weeks)
  • Secondary: 2–8 weeks after chancre; nonpruritic rash (palms/soles), mucous lesions, lymphadenopathy, fever, alopecia
  • Latent: Seroreactive, asymptomatic; early (<1yr), late (>1yr)
  • Tertiary (late): Gumma, cardiovascular, neurosyphilis (may be fatal)
  • Neurosyphilis: CNS involvement possible at any stage (psychosis, delirium, dementia)

EPIDEMIOLOGY

  • Incidence:
  • All stages: 53/100,000
  • Congenital: 78/100,000 live births
  • Increased rates since 2000, especially in MSM
  • Prevalence:
  • Primary/secondary: Male (78%) > Female (22%)
  • Highest in MSM

ETIOLOGY AND PATHOPHYSIOLOGY

  • T. pallidum enters via mucous membranes/broken skin → systemic spread via lymphatics
  • Highly infectious: 50% risk with exposure to as few as 60 spirochetes

RISK FACTORS

  • MSM
  • Multiple sexual partners
  • Exposure to infected fluids
  • Injection drug use
  • Transplacental transmission
  • High-risk sexual behavior
  • People living with HIV (PLWH)

GENERAL PREVENTION

  • Safe sex education
  • Condom use (reduces, but does not eliminate risk)

COMMONLY ASSOCIATED CONDITIONS

  • HIV, hepatitis B, other STIs

DIAGNOSIS

HISTORY

  • "Great imitator": high index of suspicion
  • Sexual contact, high-risk behavior
  • Primary: Genital lesion (chancre)
  • Secondary: Rash, alopecia, malaise, headache
  • Tertiary: Neurocognitive changes

PHYSICAL EXAM

  • Primary: Single/multiple painless ulcer, regional adenopathy (spontaneous healing in 4–8 wks)
  • Secondary: Nonpruritic rash (palms/soles), condylomata lata, alopecia, fever, lymphadenopathy
  • Tertiary: Focal neurologic findings, gummas

DIFFERENTIAL DIAGNOSIS

  • Primary: Chancroid, LGV, granuloma inguinale, HSV, Behçet, carcinoma, trauma, fungal infection
  • Secondary: Pityriasis rosea, psoriasis, drug eruption, lichen planus, viral exanthem, SJS

DIAGNOSTIC TESTS & INTERPRETATION

  • Initial:
  • Dark-field microscopy (T. pallidum in lesion exudate/biopsy, gold standard but low sensitivity)
  • Nontreponemal tests: VDRL/RPR (screening, positive within 7 days of exposure, quantify titers)
    • False-positives/negatives common; prozone phenomenon possible (check diluted serum)
    • 4-fold titer change significant; monitor titers post-treatment for response
  • Treponemal tests: FTA-ABS, TP-PA (confirmatory, positive for life post-treatment, titers not useful)
  • Lumbar puncture (LP):
  • Indications: neuro, ocular, auditory findings; late latent if nonpenicillin therapy; children
  • VDRL on CSF (specific, not sensitive); FTA-ABS/MHA-TP on CSF (negative excludes neurosyphilis)
  • Special notes:
  • Pregnancy, autoimmune disease, mononucleosis, malaria, leprosy, viral pneumonia, HIV, elderly: can alter serology results

TREATMENT

GENERAL MEASURES

  • Notify/avoid sexual contact until treatment is complete
  • Test for HIV, screen/treat partners per CDC guidelines

MEDICATION

  • First Line:
  • Penicillin G (drug of choice; regimen based on stage/manifestations)
    • Primary, secondary, early latent (<1yr): Benzathine penicillin G 2.4M U IM x1
    • Penicillin-allergic: doxycycline 100 mg BID x14d or ceftriaxone 1–2g IM/IV x10–14d
    • Late latent/tertiary (no neurosyphilis): Benzathine penicillin G 2.4M U IM weekly x3
    • Allergy: desensitization or doxycycline 100 mg BID x28d
    • Neurosyphilis/ocular: Aqueous crystalline penicillin G 3–4M U IV q4h x10–14d
    • Alternative: penicillin G procaine 2.4M U IM daily + probenecid 500 mg QID x10–14d
    • Allergy: desensitization preferred; ceftriaxone 2g/day IM/IV x10–14d
    • Congenital/children:
    • Aqueous crystalline penicillin G 50,000 U/kg/dose IV (dose/frequency by age) x10d
    • Benzathine/procaine regimens possible in select cases
    • If >1 day missed, restart course
    • Pregnancy:
    • Same as nonpregnant; consider extra dose in 3rd trimester/early latent
    • Allergy: desensitize and treat with penicillin
  • ALERT: Use Bicillin L-A, NOT Bicillin C-R
  • Precautions:
  • PLWH/pregnant: higher failure rates, consider IV for treatment failures
  • Do not use benzathine/procaine penicillin IV

RETREATMENT

  • For persistent/recurrent signs, 4-fold rise in titers, or lack of 4-fold drop at 6–12mo
  • Neurosyphilis: repeat LP every 6mo for CSF normalization

ONGOING CARE

  • Follow-up:
  • Clinical/serologic evaluation at 6–12mo after tx; at 24mo if >1yr duration
  • PLWH: 3, 6, 9, 12, 24mo after tx
  • Monitor with same nontreponemal test and same lab
  • Patient Education:
  • No intimate contact until 4-fold titer drop

PROGNOSIS

  • Excellent if treated early
  • Poorer in late syphilis/PLWH

COMPLICATIONS

  • Membranous glomerulonephritis
  • Paroxysmal cold hemoglobinemia
  • Neurosyphilis (meningitis, tabes dorsalis)
  • Cardiovascular: aneurysms, valvular disease, irreversible organ damage
  • Jarisch-Herxheimer reaction:
  • Fever, chills, myalgias, new rash post-tx (esp. primary/secondary)
  • NOT a drug allergy—treat supportively

REFERENCES

  1. Ghanem KG, Ram S, Rice PA. N Engl J Med. 2020;382(9):845-854.
  2. CDC. Sexually Transmitted Disease Surveillance 2021.
  3. Workowski KA, Bachmann LH, Chan PA, et al. MMWR Recomm Rep. 2021;70(4): 1-187.

ICD-10

  • A52.71 Late syphilitic oculopathy
  • A51.0 Primary genital syphilis
  • A52.74 Syphilis of liver/other viscera

CLINICAL PEARLS

  • Screen all PLWH and high-risk individuals for syphilis
  • Penicillin is the treatment of choice
  • Syphilis rates are rising—highest prevalence in MSM