Syphilis

Background

• Syphilis is caused by the spirochete Treponema pallidum.
• Usually sexually transmitted
• Causes a wide range of systemic manifestations that are characterized by episodes of active disease interrupted by periods of latency
• Approximately 30% of asymptomatic contacts examined within 30 days of exposure have infection

Pathogenesis

• Spirochetes penetrate intact mucous membranes or microscopic dermal abrasions.
• Transmission through sexual contact with infectious lesions, infection in utero, blood transfusion, and organ transplantation
• Blood from a patient with incubating or early syphilis is infectious.
• Characterized by multiple stages separated by periods of latency: primary, secondary, latent and tertiary

Clinical Features

Primary syphalis on penile shaft

Primary Syphilis

• Primary lesion appears after an incubation of 2-6 weeks
  • Single painless papule that becomes eroded and indurated, cartilaginous consistency on palpation
  • Minority of patients can have multiple lesions or atypical appearance
  • Occurs at point of contact: penis, rectum, mouth, external genitalia, cervix, or labia
  • Heals in 4-6 weeks
• Regional lymphadenopathy that is painless and firm

Secondary Syphilis

• Characterized by generalized mucocutaneous lesions and lymphadenopathy but can also be found in other tissues
• Skin lesions are usually maculopapular, pale red or pink, non-pruritic, discrete, and distributed on the trunk and proximal extremities. They may be subtle.
• They progress to more wide spread papular lesions that frequently involve the palms and soles.
  • Appears 6-8 weeks after the chancre heals and subsides within 2-6 weeks
  • Healing chancre may still be present in ~15% of cases. The stages may overlap more frequently in HIV patients.
  • In intertriginous areas, papules can enlarge to produce broad, moist, pink or gray-white infectious lesions called condylomata lata
• CSF abnormalities are detected in as many as 40% during this stage. CNS involvement can be symptomatic or asymptomatic.
• Constitutional symptoms may accompany or precede secondary syphilis. Can include: sore throat, fever, weight loss, malaise, anorexia, headache, and meningismus
• Less common complications include: hepatitis, nephropathy, gastritis, proctitis, rectosigmoid mass arthritis, periositis, optic neuritis, iritis, uveitis, pupillary abnormalities

Latent Syphilis

• Detectable by serologic testing only
• May intermittently be present in the bloodstream and transmitted through blood transfusion or organ donation
• Spontaneous cure is rare

Tertiary Syphilis

• Characterized by progressively destructive mucocutaneous, musculoskeletal, or parenchymal lesions, aortitis or CNS manifestations
• The most common manifestation in the US today is neurosyphilis in HIV infected persons.
• Historical manifestations:
  • Gumma: granulomatous lesion
  • Cardiovascular syphilis: involves the vasa vasorum of the ascending aorta and can result in aneurysm formation
  • Late symptomatic neurosyphilis: tabes dorsalis and paresis

Differential Diagnosis

• Ulcerative STDs
• Proctitis
• Genital Herpes
• Chancroid
• Behcet’s Disease
• Lymphogranuloma Venereum
• Gonorrhea
• Candidiasis
• Chlamydia
• Granuloma Inguinale
• HIV
• Bacteremia
• Aortic Insufficiency
• Dementia
• Diabetic Retinopathy
• Sepsis
• Alopecia
• Tuberculosis
• Immunodeficiency
• Rocky Mountain Spotted Fever
• Myocarditis
• Measles
• Rubella
• Meningitis
• Tularemia
• Lyme Disease

Workup

Nontreponemal Tests:

• Rapid Plamsa Reagin (RPR)*
  • Faster and easier to perform
• Venereal Disease Research Laboratory (VDRL)*
  • Standard for CSF examination
• Toludine Red Unheated Serum Test (TRUST)

Most commonly in the ED, the VDRL and RPR will be the ordered screening test

Treponemal Test:

• Fluorescent treponemal antibody absorption (FTA-ABS)
• Microhemagglutination test for antibodies to Treponema pallidum (MHA-TP)
• Treponemal pallidum particle agglutination assay (TP-PA)
• Treponema pallidum enzyme immunoassay (TP-EIA)

CSF

• Pleocytosis (>5 WBC/uL), increased protein (>45 mg/dL) or VDRL reactivity
• May be confounded by HIV infection
• CSF VDRL test is highly specific but is relatively insensitive. Further testing with treponemal antibodies may be necessary.

HIV-infected patients

• All newly diagnosed HIV patients should be tested for syphilis and vice versa
• RPR titer and CD4 count can be used to identify patients at higher risk for neurosyphilis for lumbar puncture

Management

Treatment is primary with penicillin with dosing and type of penicillin determined by the stage of disease Treatment requires antimicrobial therapy. Advanced stages require a prolonged course due to the slow growth time of T. pallidum.

Early Stage

This is classified as primary, secondary, and early latent syphilis less than one year.

Treatment Options:

• Penicillin G Benzathine 2.4 million units IM x 1
  • Repeat dose after 7 days for pregnant patients and HIV infection
• Doxycycline 100mg oral twice daily for 14 days as alternative

Late Stage

Late stage is greater than one year duration, presence of gummas, or cardiovascular disease

Treatment Options:

• Penicillin G Benzathine 2.4 million units IM weekly x 3 weeks
• Doxycycline 100mg oral twice daily for 4 weeks as alternative

Neurosyphilis

There are 3 Major options with none showing greater efficacy than others:

• Penicillin G 3-4 million units IV every 4 hours x 10-14 days
• Penicillin G 24 million units continuous IV infusion x 10-14 days
• Penicillin G Procaine2.4 million units IM daily + probenecid 500mg oral every 6 hours for 10-14 days.
• Alternative:
  • Ceftriaxone 2gm IV once daily for 10-14 days

• Desensitization to the penicillin allergy is still the preferred method of treatment for patients with early and late stage disease (especially during pregnancy)

Disposition

• Primary and late stage syphilis can be discharge however close followup should be provided for each
• Neurosyphilis should be admitted

See Also

• Ulcerative STDs