What are the different stages of syphilis and their characteristic clinical presentations?

Types of Syphilis and Clinical Presentations

Syphilis progresses through distinct stages—primary, secondary, latent (subdivided into early and late), and tertiary—each with characteristic clinical features that guide diagnosis and treatment.

Primary Syphilis

Primary syphilis presents as a painless chancre at the inoculation site, typically appearing 2-8 weeks after exposure. 1, 2

• Classic presentation: Single, painless ulcer (chancre) with indurated borders at the site of T. pallidum entry 1, 3
• Regional lymphadenopathy accompanies the chancre 1, 4
• Multiple or atypical chancres may occur in HIV-coinfected patients 5
• The chancre appears after an incubation period of approximately 2-8 weeks following initial exposure 2
• Most infectious stage along with secondary syphilis 6

Secondary Syphilis

Secondary syphilis develops 2-8 weeks after primary infection and is characterized by disseminated mucocutaneous lesions, often with generalized lymphadenopathy. 1, 2

Dermatologic Manifestations

• Diffuse maculopapular rash that typically starts on the trunk and spreads peripherally 5, 3
• Palmar and plantar involvement is pathognomonic for secondary syphilis 5, 4
• Lesions may be macular, maculopapular, or pustular 5
• Condyloma lata: moist, wart-like lesions in genital or intertriginous areas 5, 4

Systemic Manifestations

• Generalized lymphadenopathy 1, 3
• Constitutional symptoms: fever, malaise, anorexia 5, 4
• Arthralgias and headache 5
• Symptoms may persist for days to weeks before spontaneously resolving 5

Important Caveat

• Must differentiate from acute HIV infection, as both can present with constitutional symptoms and similar CSF abnormalities 5
• Acute syphilitic meningitis can occur during this stage 5

Latent Syphilis

Latent syphilis is asymptomatic infection detected only by serologic testing, subdivided by duration into early, late, and unknown categories. 1

Early Latent Syphilis

• Infection acquired within the previous 12 months 1
• No clinical signs or symptoms but positive serology 1
• Still potentially infectious 5
• Diagnosed based on: 1
  • Documented seroconversion or fourfold titer increase in past 12 months
  • History of primary/secondary symptoms in past 12 months
  • Sexual exposure to confirmed early syphilis partner
  • Reactive tests with exposure only in preceding 12 months

Late Latent Syphilis

• Infection occurred more than 1 year previously 1
• Asymptomatic with positive serology 1
• Relapses of secondary manifestations can occur, most commonly within 1-4 years after infection 5

Latent Syphilis of Unknown Duration

• Cannot establish timing of infection 1
• Classified when patient is aged 13-35 years with nontreponemal titer ≥32 1

Tertiary (Late) Syphilis

Tertiary syphilis develops in approximately 25% of untreated patients after 15-30 years, manifesting as gummatous disease, cardiovascular complications, or late neurologic involvement. 1, 5

Clinical Manifestations

• Gummas: granulomatous inflammatory lesions affecting skin, bone, and internal organs 1, 5
• Cardiovascular syphilis: inflammatory lesions of the cardiovascular system 1, 5
• Skeletal involvement: bone lesions 1, 5
• Rare sites: respiratory tract, eyes, abdominal organs (including liver), reproductive organs, lymph nodes, skeletal muscle 1, 5
• Typically becomes clinically manifest 15-30 years after untreated infection 1, 5

Neurosyphilis

Neurosyphilis can occur at any stage of syphilis and represents CNS infection with T. pallidum. 1, 5

Diagnostic Criteria

• Confirmed: reactive serologic test for syphilis AND reactive VDRL in CSF 1
• Probable: negative CSF VDRL but elevated CSF protein or leukocyte count plus clinical symptoms consistent with neurosyphilis 1

Clinical Forms

• Asymptomatic neurosyphilis: CSF abnormalities (elevated protein, lymphocytic pleocytosis, positive serology) without symptoms 5
• Symptomatic neurosyphilis: meningitis, meningovascular disease, or parenchymal disease 5
• Uveitis and concurrent meningitis may be more common in HIV-coinfected patients 5

Critical Consideration

• CSF analysis is necessary when evaluating late syphilis with clinical manifestations 1

Congenital Syphilis

Congenital syphilis results from in-utero transmission and has a wide spectrum of severity, with up to 40% of exposed fetuses resulting in stillbirth or neonatal death. 1, 5, 3

Early Manifestations (Infants <2 years)

• Hepatosplenomegaly 1, 5
• Rash and condyloma lata 1, 5
• "Snuffles" (syphilitic rhinitis) 1, 5
• Jaundice (nonviral hepatitis) 1, 5
• Pseudoparalysis, anemia, edema 1, 5

Late Stigmata (Older Children)

• Interstitial keratitis 1, 5
• Nerve deafness 1, 5
• Skeletal abnormalities: anterior bowing of shins, frontal bossing 1, 5
• Dental abnormalities: Hutchinson teeth, mulberry molars 1, 5
• Saddle nose, rhagades, Clutton joints 1, 5

Special Considerations in HIV-Coinfected Patients

• More pronounced clinical lesions and accelerated disease progression 2, 5
• Multiple or atypical chancres in primary stage 5
• Increased risk of concurrent uveitis and meningitis 5
• All patients with syphilis should be tested for HIV 2, 5
• Clinical manifestations in advanced immunosuppression are generally similar to HIV-negative patients 5

Common Diagnostic Pitfalls

• Syphilitic alopecia (occurring 2-8 weeks after infection during secondary stage) can mimic alopecia areata, telogen effluvium, or tinea capitis 7
• Secondary syphilis must be differentiated from acute HIV infection due to overlapping presentations 5
• Serologic testing may be negative during early incubation, necessitating presumptive treatment for recent exposures 2