What are the complications and consequences of syphilis?

Complications and Consequences of Syphilis

Untreated syphilis progresses through distinct stages with devastating complications including cardiovascular destruction, neurological damage, congenital transmission, and increased HIV acquisition risk—all of which are preventable with timely penicillin treatment.

Neurological Complications

Neurosyphilis can occur at any stage of infection and represents one of the most serious consequences of untreated disease. 1

• Neurologic manifestations include auditory disease, cranial nerve dysfunction, acute or chronic meningitis, stroke, altered mental status, and loss of vibration sense 2
• Ophthalmic complications such as iritis and uveitis can lead to permanent vision loss 2, 3
• Hearing loss may be permanent if neurosyphilis is not promptly treated 4, 3
• HIV-infected patients face higher risk for neurologic complications and accelerated disease progression 1
• CSF invasion by Treponema pallidum frequently occurs during primary and secondary stages, though overt neurosyphilis develops in only a minority after standard therapy 1

Cardiovascular Complications

Tertiary cardiovascular syphilis, though rare in the antibiotic era, causes life-threatening aortic disease through obliterative endarteritis of the vasa vasorum. 5

• The classic triad includes syphilitic thoracic aortic aneurysm, aortic regurgitation, and coronary ostial stenosis 5
• Syphilitic aortitis results from ischemic injury to the aortic wall, leading to aneurysm formation with involvement of the aortic valve and coronary ostia 5
• Cardiovascular syphilis was formerly a major cause of aortitis and thoracic aortic aneurysms before widespread antibiotic use 5
• Evidence of active tertiary syphilis includes aortitis and gumma formation 2
• Recent population-based studies implicate syphilis in increased long-term cardiovascular risk 5

Tertiary Syphilis Manifestations

Approximately 25% of untreated patients develop tertiary syphilis after 3-12 years of latency, with irreversible organ damage. 1

• Gummatous lesions can affect skin, bones, and internal organs 1
• Tertiary disease occurs years after initial infection and can lead to irreversible neurological or cardiovascular complications 6
• Without treatment, the disease progresses through clinical stages leading to permanent morbidity 6

Congenital Syphilis

In pregnancy, up to 40% of fetuses with in-utero syphilis exposure are stillborn or die from infection during infancy. 4

• Congenital syphilis cases increased by 106% from 2019 to 2023 in the United States 4
• Untreated maternal syphilis causes lifelong morbidity in children born to infected mothers 6
• The disease can be transmitted via the placenta during pregnancy 4

HIV Co-infection and Transmission Risk

Syphilis significantly increases the risk of HIV acquisition and transmission, creating a syndemic effect. 4, 6

• Untreated syphilis increases HIV acquisition risk through mucosal inflammation and immune activation 3
• HIV-infected patients may exhibit atypical serologic patterns, elevated titers, false-negative results, or delayed seroreactivity 1
• Secondary syphilis can mimic acute primary HIV infection with constitutional symptoms and CSF abnormalities 1
• All patients diagnosed with syphilis should be screened for HIV because co-infection is common and influences management 1

Latent Disease Progression

The objective of treating latent syphilis is to prevent progression to tertiary complications, as the disease remains active despite absence of symptoms. 2

• Early latent syphilis (infection within the preceding year) remains infectious, while transmissibility is markedly reduced in late latent infection 1
• Late latent syphilis is defined as infection acquired more than one year ago or of unknown duration 1
• Nontreponemal serologic titers usually are higher during early latent syphilis than late latent syphilis 2

Treatment Failure Consequences

Treatment failure leads to persistent infection with ongoing risk of progression to irreversible complications. 1

• Persistent or recurrent clinical signs and symptoms indicate treatment failure 1
• A sustained ≥4-fold increase in non-treponemal titer signals inadequate treatment response 1
• Failure of non-treponemal titer to decline ≥4-fold within 6 months after therapy for primary or secondary disease requires CSF examination and retreatment 1

Jarisch-Herxheimer Reaction

An acute febrile reaction occurs within 24 hours of initiating syphilis therapy, with specific risks in pregnancy. 1

• The reaction manifests with headache, myalgia, and other systemic symptoms 1
• In pregnant individuals, this reaction can precipitate early labor or fetal distress, but therapy should not be delayed 1
• Antipyretics may provide symptomatic relief, but no proven prophylactic measures exist 1

Common Clinical Pitfalls

• Delayed diagnosis is perilous and associated with worse outcomes, particularly for cardiovascular and neurologic complications 5
• The disease is called "the great imitator" because of its varied manifestations, making diagnosis challenging 5
• Complacency in prevention and diagnosis has occurred due to previously declining rates 7
• Providers should maintain vigilance when evaluating all symptom-less dermatological lesions 7