After an incubation period averaging 2–6 weeks, a primary lesion appears—often associated with regional lymphadenopathy—and then resolves without treatment
Primary stage
with generalized mucosal and cutaneous lesions and generalized lymphadenopathy, also resolves spontaneously and is followed by a latent period of subclinical infection lasting years or decades
Secondary stage
characterized by destructive mucocutaneous, skeletal, or parenchymal lesions; aortitis; or late CNS manifestations
Tertiary syphilis
The histopathologic features of secondary maculopapular skin lesions include
hyperkeratosis of the epidermis, capillary proliferation with endothelial swelling in the superficial dermis, and—in the deeper dermis—perivascular infiltration by CD8+ T lymphocytes, CD4+ T lymphocytes, macrophages, and variable numbers of plasma cells
In the preantibiotic era, about one-third of patients with untreated latent syphilis developed clinically apparent tertiary disease, the most common types being
the gumma (a usually benign granulomatous lesion);
cardiovascular syphilis (usually involving the vasa vasorum of the ascending aorta and resulting in aneurysm);
and late symptomatic neurosyphilis (tabes dorsalis and paresis
single painless papule that rapidly erodes and becomes indurated, with a characteristic cartilaginous consistency on palpation of the edge and base of the ulcer
Typical primary chancre
Early latent vs Late latent syphilis
Early latent syphilis is limited to the first year after infection, whereas late latent syphilis is defined as that of ≥1 year’s (or unknown) duration
patients who lack neurologic symptoms and signs but who have CSF abnormalities, including mononuclear pleocytosis, increased protein concentration, or reactivity in the CSF VDRL test
Asymptomatic neurosyphilis
present as headache, nausea, vomiting, neck stiffness, cranial nerve involvement, seizures, and changes in mental status in a patient with syphilis
Meningeal syphilis
reflects meningitis together with inflammatory vasculitis of small, medium, or large vessels. The most common presentation is a stroke syndrome involving the middle cerebral artery of a relatively young adult
Menigovascular syphilis
In syphilis:
reflect widespread late parenchymal damage and include abnormalities corresponding to the mnemonic paresis:
General paresis
personality,
affect,
reflexes (hyperactive),
eye (e.g., Argyll Robertson pupils),
sensorium (illusions, delusions, hallucinations),
intellect (a decrease in recent memory and in the capacity for orientation, calculations, judgment, and insight), and
speech
presents as symptoms and signs of demyelination of the posterior columns, dorsal roots, and dorsal root ganglia, including ataxia, foot drop, paresthesia, bladder disturbances, impotence, areflexia, and loss of positional, deep-pain, and temperature sensations
Tabes dorsalis
In syphilis,
produce indolent, painless, indurated nodular or ulcerative lesions that may resemble other chronic granulomatous conditions
Gumma
Transmission from syphilitic woman to her fetus may occur at any stage of pregnancy, but fetal damage generally does not occur until after the
4th month of gestation (treat before 16weeks to prevent fetal damage) an treat before 3rd trimester to treat infected fetus
Classic stigmata of congenital syphilis
Hutchinson’s teeth (centrally notched, widely spaced, peg-shaped upper central incisors), “mulberry” molars (sixth-year molars with multiple, poorly developed cusps), saddle nose, and saber shins
test of choice for rapid serologic diagnosis in a clinical setting in syphilis
RPR test
standard for examining CSF and is superior to the RPR for this purpose
VDRL test
CSF in neurosyphilis
for mononuclear pleocytosis (>5 white blood cells/4L), increased protein concentration (>45 mg/dL), or CSF VDRL reactivity
demonstrated to distinguish between neurosyphilis and HIV-related CSF abnormalities
CXCL13
Syphilis patients that would benefit most from CSF examination
High risk for neurosyphilis
RPR titers of ≥1:32 as are HIV-infected patients with CD4+ T-cell counts of <350/uL
Drug of choice of syphilis and prophylaxis
Penicillin G
Efficacy of treatment should be assessed by clinical evaluation and monitoring of the quantitative VDRL or RPR titer for
Fourfold decline
The activity of neurosyphilis (symptomatic or asymptomatic) correlates best with _____ and this measure provides the most sensitive index of response to treatment
CSF pleocytosis
