Syphilis

Overview

Microbiology

• Very few surface antigens - outer membrane contains only ~1% as many antigens as E. coli, helping the organism evade immune detection
• Rapid dissemination - enters the bloodstream within hours of inoculation; reaches the brain within 18 hours
• Antigen variation - outer membrane proteins mutate rapidly, generating subpopulations with different surface antigens
• Low metabolic capacity - its genome is only one quarter the size of most bacteria; sensitive to temperature changes
• Andrews' Diseases of the Skin, p. 4724-4728

Clinical Stages

Primary Syphilis

• Occurs after an incubation period of 10-90 days (average 3 weeks) following sexual exposure
• Classic lesion: the chancre - a solitary (can be multiple in 32-47% of cases), painless, indurated round-to-oval ulcer with sharply demarcated, raised, regular borders and a clean base; feels cartilaginous ("hard ulcer" / ulcus durum)
• Location: usually genital mucosa, but can be oral, anorectal, or any site of inoculation
• Accompanied by painless regional lymphadenopathy
• The chancre heals spontaneously in 3-6 weeks even without treatment - but the spirochetes have already disseminated
• Darkfield examination or direct fluorescent antibody testing of the chancre is diagnostic; serology can be negative in up to 30% of primary cases
• Fitzpatrick's Dermatology, Vol. 1-2, p. 3177-3179

Primary chancre - note the sharp edge and raw base

Secondary Syphilis

• Develops in 60-90% of persons with untreated primary syphilis, typically 3-12 weeks after the chancre
• Results from hematogenous dissemination of treponemes throughout the body
• Rash is present in nearly all cases:
  • Erythematous macules or maculopapules symmetrically on trunk and extremities (40-70%)
  • Classically involves palms and soles (hyperpigmented, scaly papules)
  • Biett collarette - white scaly ring on papulosquamous lesions; characteristic of syphilis
  • Usually NOT pruritic
  • Face is typically spared, but seborrheic dermatitis-like lesions at the hairline (Corona of Venus) can occur
• Condylomata lata - moist, flat, warty lesions in anogenital or skin fold areas; highly infectious
• Mucous patches - shallow, painless ulcerations of the oral or genital mucosa
• Alopecia - patchy "moth-eaten" pattern on the scalp
• Systemic symptoms: fever, generalized lymphadenopathy, headache, sore throat, arthralgias, malaise
• Organ involvement (less common): CNS, eyes, liver, kidneys (immune-complex glomerulonephritis)
• Secondary syphilis is the stage with the highest serologic sensitivity: RPR is ~99% sensitive, MHA-TP ~100% sensitive
• Fitzpatrick's Dermatology, p. 3180-3186; Textbook of Family Medicine 9e, p. 2592

Maculopapular lesions of secondary syphilis on the palms

Latent Syphilis

• Defined by reactive serologic tests in the absence of any clinical signs or symptoms
• Early latent: acquired within the preceding 12 months; up to 25% may relapse into secondary syphilis
• Late latent: acquired more than 12 months ago; much lower risk of relapse
• Treatment differs between early and late latent stages

Tertiary (Late) Syphilis

• Neurosyphilis and ocular syphilis can occur at any stage of infection, not only tertiary
• Textbook of Family Medicine 9e, p. 2592-2594

Congenital Syphilis

• Transmission rates from untreated mothers: 70-100% in primary syphilis, 40% in early latent, 10% in late latent
• Fetal infection can occur at any stage of pregnancy; leads to stillbirth in 30-40% of cases
• Early congenital syphilis (<2 years): fever, rash, hepatosplenomegaly, "snuffles" (persistent rhinitis), osteochondritis causing pseudoparalysis of Parrot
• Late congenital syphilis: Hutchinson teeth (notched incisors), interstitial keratitis, VIII nerve deafness (Hutchinson triad), saddle-nose deformity, saber shins
• Routine serologic screening in early pregnancy is standard; should be repeated in the last trimester for high-risk women
• Fitzpatrick's Dermatology, p. 3187; Sherris & Ryan's, p. 1416

Diagnosis

Direct Detection

• Darkfield microscopy: gold standard for primary chancre and moist secondary lesions; identifies characteristic corkscrew morphology and motility. NOT valid for oral or anal lesions (commensal treponemes present)
• Direct fluorescent antibody (DFA): confirms T. pallidum in lesion exudate; more specific than darkfield
• PCR: available in specialized centers; high sensitivity/specificity

Serologic Tests

• Detect antibodies to cardiolipin-lecithin-cholesterol antigen (reagin)
• Used for screening and monitoring treatment response
• Titers correlate with disease activity; a fourfold fall after treatment = adequate response
• RPR sensitivity: ~79% in primary, 99% in secondary, 87% in latent, 73% in tertiary syphilis
• False positives occur with pregnancy, autoimmune disease, viral infections (EBV, HIV, hepatitis), Lyme disease, and narcotic addiction

• Detect antibodies against T. pallidum antigens
• Higher sensitivity in primary and late stages; higher specificity overall
• Remain positive for life even after successful treatment in most people (15-25% become nonreactive 2-3 years after treatment of primary syphilis)
• Used to confirm a reactive nontreponemal test
• NOT used to monitor treatment response (titers do not correlate with activity)

• Fitzpatrick's Dermatology, p. 3190-3195

CSF Examination (Lumbar Puncture) - Indications

• Neurologic, ophthalmic, or otologic signs or symptoms
• Evidence of active tertiary syphilis
• Treatment failure

Treatment

• Jarisch-Herxheimer reaction: fever, headache, myalgias occurring 2-8 hours after the first dose of treatment; results from cytokine release due to rapid spirochete killing. Manage with antipyretics; do NOT discontinue treatment.
• Treatment response is monitored by fourfold fall in nontreponemal titer (e.g., 1:32 to 1:8) within 6-12 months of therapy. Failure to achieve this is considered treatment failure.
• Textbook of Family Medicine 9e, p. 2598; Fitzpatrick's Dermatology, p. 3197-3200

Key Points Summary