creation date: 2025-12-26 22:53
tags: Pathologies Incomplete
Syphilis
Background
Definitions
Syphilis is a systemic bacterial infection that his highly prevalent worldwide. It is considered a sexually transmitted disease but can be acquired by nonsexual contact (skin-to-skin or direct blood transfer).
Primary syphilis: initial local reaction to infection and asymptomatic systemic dissemination.
Secondary syphilis: untreated primary syphilis may progress (1/4) to systemic manifestations.
Latent syphilis: resolution of secondary syphilis without treatment which may progress to tertiary syphilis (1/3).
Tertiary syphilis: late symptomatic syphilis that may manifest even decades after initial infection. Manifestations include cardiovascular syphilis, neurosyphilis, or gummatous syphilis.
Congenital syphilis refers to syphilis from transplacental transmission or through contact with infectious lesions during birth. This can occur at any stage and may result in stillbirth or neonatal congenital infections.
Etiology and Pathogenesis
Syphilis is a result of infection from the spirochete Treponema pallidum. Other Treponema spp. can cause nonsexual infection but venereal syphilis is through T. pallidum.
Early infection
Following initial contact by sexual contact or non-direct transfer, T. pallidum gains access to the subcutaneous tissues through micro-abrasions. An early ulcerative lesion (the chancre) is formed following an incubation period of 3-90 days (median: 21 days).
Despite a relatively long 30 hour doubling time, T. pallidum infiltrates regional draining lymph nodes and disseminates. A number of immune responses are elicited which leads to a variety of antibodies that can be detected early in the disease course.
Despite seemingly efficacious immune response, widespread dissemination within weeks to a few months results in subsequent inflammation associated with secondary syphilis.
Late infection
A number of mechanisms may contribute to the resurgence of syphilis following a latent period. Theories include waning immunity with aging allowing recurrence or partial immune hypersensitivity reaction resulting in a chronic inflammatory response.
Involvement of the ascending thoracic aorta and subsequent vasculitis leads to weakening and cardiovascular symptoms.
Gummas, a late benign syphilis involving the skin, viscera, or other tissue result from granulomas as a result of cellular hypersensitivity.
Clinical Presentation
Signs & Symptoms
Early syphilis
Primary syphilis manifests as a solitary skin lesion, initially as a typically painless papule which ulcerates, termed a chancre:
- 1-2 cm ulcer
- Raised, indurated margin
- Nonexudative base
- Resolves spontaneously within 3-6 weeks
- Painless
Mild to moderate regional lymphadenopathy may be present. In some cases, multiple chancres may occur, especially in patients with HIV.
Secondary syphilis develops weeks to a few months following the chancre. A wide variety of manifestations occur (hence its namesake “the great imitator and mimicker”).
Generalized symptoms:
- Constitutional symptoms (fever, headache, malaise, anorexia, sore throat, myalgia, weight loss)
- Adenopathy (epitrochlear nodes particularly suggestive)
Dermatologic findings: - Rash in any form (classically diffuse, symmetric macular or papular eruption involving entire trunk and extremities)
- Mucosal patches and whitish erosions
- Alopecia (“moth-eaten”)
Gastrointestinal findings: - Syphilitic hepatitis (characterized by high-serum ALP)
- Extensive infiltration or ulceration of GI tract
Neurologic findings: - Headache from invasion of CSF
- Meningitis, cranial nerve deficits, meningovascular disease, stroke
Visual/auditory findings: - Ocular syphilis (uveitis, vision loss)
- Otosyphilis (tinnitus, vertigo, sensorineural hearing loss)
Others: - MSK abnormalities
- Renal abnormalities (transient albuminuria, nephrotic syndrome, acute nephritis)
Late syphilis
Tertiary syphilis occurs in 25-40% of patients with untreated syphilis 1-30 years following primary infection. The exact manifestations can vary significantly but the most common are as follows.
Cardiovascular syphilis:
- Insidious onset
- Asymptomatic murmur or left heart failure
- Ascending aortic aneurysm
- Calcification of the aorta
Gummatous syphilis - Gummas (granulomatous nodules with rubbery texture and necrotic centres)
- Found on skin, liver, testes, brain, heart, bone
Neurosyphilis: - Meningitis and associated meningeal symptoms
- Syphilitic paresis from chronic meningoencephalitis
- Tabes dorsalis (degeneration of posterior column) - unsteady gait, balance issues, stabbing pains, bladder dysfunction, paresthesias, loss of proprioception
Congenital syphilis
If infected with syphilis, placentas tend to enlarge beyond normal range. Prenatal ultrasonography following week 18 gestation may find:
- Hepatomegaly
- Placental enlargement
- Hydrops fetalis
Neonates are typically asymptomatic at birth but develop symptoms within first 3 months:
- Generalized bullous rash
- Anemia
- Jaundice
- Hepatosplenomegaly
- Nasal cartilage destruction
- Frontal bossing
- Bowing of the tibia
- Measles-like or bullous rash
- Rhinitis
- Sterile joint effusion
- Peg-shaped upper central incisors
History & Physical Exam
Risk factors
Screening is typically indicated for high risk asymptomatic individuals:
- Patients with sexual partner who has early syphilis
- Sexually active men who have sex with men
- Individuals with HIV or receiving PrEP
- Patients engaging in high-risk sexual behaviours
- Individuals with history of incarceration or commercial sex work
Diagnosis
Criteria
Work-up
Screening
Screening is done for asymptomatic adults and adolescents at high risk for infection. Additionally, testing is done during pregnant patient’s first prenatal visit.
Nontreponemal (lipoidal antigen) test, which are less specific, are often used for initial screen due to low cost and ease:
- Rapid plasma reagin (RPR)
- Venereal disease research laboratory (VDRL)
- Toluidine red unheated serum test (TRUST)
In some regions, treponemal antibody testing can be used for screening and diagnosis simulataneously.
Differential
Numerous conditions can have signs and symptoms similar to syphilis owing to the broad spectrum of manifestations syphilis may have.
Red Flags / Complications
If left untreated, syphilis may develop to later stages which can be fatal.
Congenital syphilis is associated with spontaneous abortions, stillbirth, and infant mortality. Without treatment during pregnancy, syphilis is almost always transmitted to the fetus.