DESCRIPTION

• Sexually transmitted disease
• 12 million new cases diagnosed annually worldwide
• Acquired via mucous membranes/disrupted skin
• Divided into 3 stages:
  • Primary syphilis:
    • Painless chancre or ulcer
  • Secondary syphilis:
    • Replication and hematogenous spread
    • Begins 3–6 wk after primary lesion
    • Late latent secondary phase
  • Tertiary or late syphilis:
    • Very uncommon
    • Cardiovascular and neurologic symptoms

ETIOLOGY

Treponema pallidum:

• Spirochete bacteria

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

Primary (Early) Syphilis

• 21-day incubation period
• No constitutional symptoms
• Chancre:
  • Painless papule at site of inoculation
  • Clean-based, circular, sharply defined borders:
    • Solitary lesions
    • Commonly on penis, vulva, and rectum
    • Bilateral regional lymphadenopathy
  • Heals spontaneously in 3–6 wk
• Rectal chancre:
  • Painful or painless
  • Rectal irritation/discharge
  • Painless enlargement of lymph nodes

Secondary (Early) Syphilis

• Occurs 3–6 wk after primary lesion
• Disseminated stage
• Rash (most common):
  • Symmetric, diffuse, polymorphous, papular, or maculopapular rash
  • Rash may be diverse and not fit a pattern
  • Starts on trunk and flexor extremities
  • Spreads to involve palms and soles:
    • Discrete, red/reddish-brown
    • 0.5–2 cm in diameter
• Condyloma lata:
  • Large raised gray/white lesions, painless, moist
  • Mucous membranes:
    • Oral cavity and perineum
    • Very contagious
    • Intertriginous areas
    • Flat rectal warts
• Systemic symptoms:
  • Fever, headache, malaise, anorexia, sore throat, myalgias, and weight loss
• Diffuse lymphadenopathy:
  • Palpable nodes at inguinal, axillary, posterior cervical, femoral, and/or epitrochlear regions
  • Painless, firm, and rubbery
• Less common:
  • "Moth-eaten" alopecia
  • Syphilitic meningitis
  • Scleritis
• Loss of lateral 3rd of eyebrows
• Painless mucosal lesions (mucous patches)
• Secondary stage resolves spontaneously in 1–2 mo

Latent Secondary Syphilis

• Begins after primary and secondary symptoms resolve.
• Period of no symptoms but positive serology:
  • CSF normal
• Late latent stage not infectious except for fetal transmission in pregnant women
• Persists for lifetime or develops into tertiary syphilis

Tertiary (Late) Syphilis

• Occurs in about 15% of patients with untreated latent secondary syphilis
• Can appear 10–20 yr after initial infection
• Neurologic and cardiovascular involvement:
  • Destructive stages of disease
• Neurosyphilis (most common):
  • Asymptomatic:
    • Positive CSF – Venereal Disease Research Laboratories (VDRL)
    • CSF pleocytosis (10–100 lymphocytes)
    • Elevated CSF protein at 50–100 mg/dL
  • Meningitis:
    • Aseptic; CSF with positive VDRL, higher protein, and lower glucose (compared with above)
    • Cranial nerve palsy, including isolated 8th nerve palsy
  • General paresis:
    • Loss of cortical function
    • Argyll Robertson pupils (small fixed pupils that do not react to strong light, but do react to accommodative convergence)
  • Tabes dorsalis (peripheral neuropathy)
• Degeneration of posterior columns/posterior or dorsal roots of spinal cord
• Dementia
• Paresthesias, abnormal gait, and lightning (sudden, severe) pain of extremities/trunk
• Progressive loss of reflexes, vibratory/position sensation
• Positive Romberg sign
• Vision: Optic atrophy
• Pupils: Argyll Robertson pupils
• Urinary incontinence
• Gummas:
  • Late benign syphilis of cutaneous skin/viscera:
    • Bone, brain, abdominal viscera, etc.
• Granulomatous, cellular hypersensitivity reaction:
  • Round, irregular, or serpiginous shape
  • "Great pox"
• Cardiovascular:
  • Thoracic aortic aneurysm (ascending most common):
    • Dilated aorta and aortic valve regurgitation
    • Aortic valve insufficiency
    • Coronary thrombosis
    • Destructive lesions of skeletal structures or skin
• HIV-infected:
  • Strong association with syphilis
• Increased incidence of neurosyphilis

Congenital Syphilis

• In utero infection:
  • Age < 2 yr:
    • Hepatosplenomegaly, rash, condyloma lata, rhinitis (snuffles), jaundice (nonviral hepatitis), osteochondritis
• Older children (syphilis stigmata):
  • Interstitial keratitis, nerve deafness, anterior bowing of shins, frontal bossing, mulberry molars, Hutchinson teeth, saddle nose, etc.

ESSENTIAL WORKUP

Rapid plasma reagin (RPR)

DIAGNOSIS TESTS & INTERPRETATION

Lab

• Serology:
  • Nontreponemal test:
    • RPR
    • VDRL
    • Positive 14 days after chancre appears
    • Early false negatives, especially ≤7 days after primary chancre
    • Repeat negative test in 2 wk and correlate with disease activity
    • False positives in 1–2% of general population
    • 4-fold change in titer clinically significant
    • 100% sensitivity in secondary syphilis
    • Nonreactive after successful treatment
  • Treponemal antibody test:
    • Fluorescent treponemal antibody absorption (FTA–ABS)
    • Hemagglutination assay for antibody to T. pallidum (MHA–TP)
    • More sensitive and specific
    • 1% false-positive rate
    • Confirmatory test
    • Reactive for patient's lifetime
    • More costly and harder to perform
  • Dark-field microscopy:
    • Identifies treponemes from primary and secondary lesions
    • Suspicious early lesions with negative serology (early primary syphilis)
    • False negatives with ointments, creams
    • Oral specimen unsuitable
  • CSF analysis for tertiary neurosyphilis:
    • Tertiary syphilis
    • Positive VDRL/RPR
    • Lymphocytes > 5/mL
    • Protein > 45 mg/dL
    • Decreased glucose

DIFFERENTIAL DIAGNOSIS

• Genital ulcer:
  • Chancroid (painful)
  • Genital herpes:
    • Vesicular, multiple lesions
  • Lymphogranuloma venereum
  • Granuloma inguinale
  • Superficial fungal infection
  • Carcinoma
• Secondary and tertiary syphilis:
  • Pityriasis rosea
  • Drug-induced rash
  • Acute febrile exanthems
  • Psoriasis
  • Lichen planus
  • Scabies
  • Infectious mononucleosis
  • Viral illness
  • Bacteremia
  • Tertiary syphilis:
  • Psychosis
  • Dementia
  • Multiple sclerosis
  • Meningitis
  • Encephalitis
  • Delirium
  • Unknown overdose

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

INITIAL STABILIZATION/THERAPY

Lower BP and establish IV access for aortic dissection.

ED TREATMENT/PROCEDURES

• Treatment other than penicillin with increased relapse rate:
  • Desensitize those allergic to penicillin.
• Pregnancy:
  • Treat with penicillin even in latent syphilis.
  • If patient allergic to penicillin, admit for desensitization.
• Jarisch–Herxheimer reaction:
  • Transient febrile reaction to therapy
  • May be owing to antigen liberation from spirochetes or activation of complement cascade
  • Peaks at 8 hr, resolves in 24 hr
  • Symptoms:
    • Fever, headache, malaise, worsening rash
  • Treat with antipyretics
  • No serious sequelae
• Recommended testing:
  • Sexual partners
  • Concomitant sexually transmitted diseases including HIV
  • Repeat serology test in 6 and 12 mo.

MEDICATION

• Early primary, secondary, early latent (< 1 yr):
  • Benzathine penicillin G: 2.4 million U IM
  • Doxycycline: 100 mg PO BID for 14 days
  • Tetracycline: 500 mg PO QID for 14 days
• Late latent (> 1 yr) except neurosyphilis:
  • Benzathine penicillin G: 2.4 million U IM 3 times over 2 wk on days 0, 7, and 14
  • Doxycycline: 100 mg PO BID for 4 wk
  • Tetracycline: 500 mg PO QID for 4 wk
• Neurosyphilis:
  • Penicillin G: 3–4 million U IV q4h for 10–14 days
  • Procaine penicillin: 2.4 million U IM daily +
  • Probenecid: 500 mg PO QID for 10–14 days
• Congenital syphilis:
  • Penicillin G: 50,000 U/kg IM q8–12h for 10–14 days; or
  • Procaine penicillin: 50,000 U/kg IM daily for 10–14 days

[Outline]

• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

• Neurosyphilis requires IV antibiotics
• Pregnant women allergic to penicillin requiring desensitization

Discharge Criteria

Follow-up care:

• Measure for falling titers in 6 mo and 1 yr after treatment.
• Tertiary/latent (> 1 yr):
  • Measure for falling titers in 3, 6, 12, and 24 mo after treatment.

Issues for Referral

Infectious disease consultation for secondary and tertiary syphilis as well as congenital and neurosyphilis

FOLLOW-UP RECOMMENDATIONS

Titers must be monitored.

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• Syphilis is known as the "great imitator."
• In patients presenting with unknown rash, think of syphilis and ask about history of genital lesions.
• Be sure to examine mucous membranes of all patients presenting with rash.
• Think of tertiary syphilis with neurologic symptoms of unknown etiology.

ICD9

• 091.2 Other primary syphilis
• 091.9 Unspecified secondary syphilis
• 097.9 Syphilis, unspecified

ICD10

• A51.0 Primary genital syphilis
• A51.49 Other secondary syphilitic conditions
• A53.9 Syphilis, unspecified

[Outline]

• ICD9
• ICD10

• Centers for Disease Control and Prevention (CDC). Primary and secondary syphilis–United States, 2003–2004. MMWR Morb Mortal Wkly Rep. 2006;55(10):269–273.
• Domantay-Apostol GP, Handog EB, Gabriel MT. Syphilis: The international challenge of the great imitator. Dermatol Clin. 2008;26(2):191–201, v.
• Grange PA, Gressier L, Dion PL, et al. Evaluation of a PCR test for detection of treponema pallidum in swabs and blood. J Clin Microbiol. 2012;50:546–552.
• Hook EW 3rd, Peeling RW. Syphilis control – a continuing challenge. N Engl J Med. 2004;351:122–124.
• Schacter J. Classification of latent syphilis. Sex Transm Dis. 2005;32:143.
• Sparling PF. Diagnosis of neurosyphilis: New tools. Sex Transm Dis. 2010;37:288–289.
• Timmermans M, Carr J. Neurosyphilis in the modern era. J Neurol Neurosurg Psychiatry. 2004;75:1727–1730.
• Tramont EC. Treponema pallidum (syphilis). In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2009, Chapter 238.

Jessica Freedman