In United States, syphilis is managed by infectious diseases. Syphilis is a sexually transmitted bacterial infection caused by the spirochete Treponema pallidum, which spreads through direct contact with infectious sores and through the placenta from mother to fetus. United States cases reached 207,255 in 2022 — the highest count since 1950 and a 80% rise over five years — with primary, secondary, and early latent cases now reported in every age band from 15 to 65.
Syphilis (ICD-10: A50-A53) is a chronic systemic infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum, transmitted primarily through sexual contact with an infectious lesion and vertically from a pregnant person to the fetus. The organism is a slow-replicating, microaerophilic spirochete that cannot be grown on standard culture media, which is why diagnosis relies on dark-field microscopy, serology, or molecular methods rather than culture. After inoculation, treponemes disseminate hematogenously within hours, producing a sequence of clinical stages: primary (painless chancre at the site of inoculation, 10-90 days after exposure), secondary (mucocutaneous rash, lymphadenopathy, and systemic symptoms 4-10 weeks later), early and late latent (asymptomatic but seropositive), and tertiary (cardiovascular syphilis, gummatous lesions, neurosyphilis) developing in 25-40% of untreated patients over 10-30 years. Neurologic involvement can occur at any stage, and ocular and otic syphilis are increasingly recognized presentations.
The key symptoms of Syphilis are: A single firm, painless, indurated genital, anal, or oral ulcer (chancre) with raised edges and a clean base, appearing 10-90 days after exposure and persisting 3-6 weeks before healing on its own., Painless regional lymphadenopathy near the chancre, typically inguinal nodes that are firm, mobile, and non-tender., A diffuse non-itchy maculopapular or papulosquamous rash 4-10 weeks later, characteristically involving the palms and soles and sparing the face in most adults., Mucous patches — shallow, painless gray-white erosions on the oral or genital mucosa during secondary syphilis, highly infectious on contact., Condyloma lata — moist, flat, pink-gray wart-like papules in skin folds (perianal, vulvar, axillary) that are teeming with treponemes and highly contagious., Patchy, moth-eaten alopecia of the scalp, eyebrows, and beard during the secondary stage, with hair regrowth after treatment., Generalized lymphadenopathy, low-grade fever, headache, sore throat, malaise, and weight loss accompanying the secondary rash..
Diagnosis combines clinical recognition with serologic testing, since T. pallidum cannot be grown in routine culture. The standard workflow uses two complementary blood tests: a non-treponemal test (RPR or VDRL) that quantifies disease activity through measurable titers, and a treponemal test (FTA-ABS, TP-PA, or chemiluminescent immunoassay) that confirms exposure but remains positive for life. Many US labs now run a reverse algorithm — automated treponemal screening followed by reflex RPR — which catches early infection and late latent disease that non-treponemal tests can miss. Discordant results require a second treponemal assay (TP-PA) to resolve. Direct visualization of treponemes by dark-field microscopy or PCR of swabbed lesion exudate confirms primary or secondary disease when a chancre or mucous patch is accessible. Any reactive serology in a person with new neurologic, ocular, or otic symptoms warrants lumbar puncture and ophthalmologic or audiologic examination. CSF VDRL is the diagnostic test for neurosyphilis; an elevated CSF white cell count and protein in the right clinical context also support the diagnosis. Staging matters because treatment duration differs: a single benzathine penicillin G dose for primary, secondary, and early latent disease, three weekly doses for late latent and tertiary disease without neurologic involvement, and 10-14 days of intravenous aqueous penicillin G for neurosyphilis, ocular, or otic syphilis. The CDC recommends every patient with new syphilis also be tested for HIV, gonorrhea, chlamydia, and hepatitis B and C at the same visit.
With timely benzathine penicillin G, the prognosis for primary, secondary, and early latent syphilis is excellent — over 95% of immunocompetent patients achieve serologic cure within 12 months and have no long-term sequelae. Late latent disease responds in 70-90% of cases, though existing organ damage (aortic aneurysm, neurologic deficits, optic atrophy) does not reverse. Neurosyphilis treated promptly shows clinical improvement in 70-80% of patients, with CSF parameters normalizing over 6-12 months. Reinfection is common in high-risk populations, with reported rates of 10-20% within 2 years of initial cure. Untreated, roughly 25% of infections progress to late latent or tertiary disease over 10-30 years, and roughly one-third of untreated patients develop devastating cardiovascular, neurologic, or gummatous complications. The historic Oslo (1891-1951) and Tuskegee cohort data — though ethically indefensible in their conduct — established that fewer than 10% of untreated patients die directly of syphilis, but many more sustain irreversible end-organ damage. Pregnancy outcomes are dramatic: untreated early maternal syphilis causes stillbirth or neonatal death in up to 40% of cases, while timely treatment reduces this to under 2%.
An infectious disease physician or sexual health specialist should be involved in any syphilis case with neurologic, ocular, or otic symptoms; in HIV co-infection; in pregnancy with confirmed allergy to penicillin; in suspected serologic non-response or reinfection; and in tertiary disease. Primary care and sexual health clinics manage most uncomplicated early infections according to CDC algorithms.
Find specialists →Primary chancre heals within 3-6 weeks of treatment, often faster. Secondary rash and mucosal lesions usually clear within 1-2 weeks. RPR titer should drop fourfold by 6 months and at least eightfold by 12 months. CSF normalization in neurosyphilis takes 6-12 months. Visible aortic or neurologic damage from tertiary disease does not reverse but progression halts. Patients are considered non-infectious 7 days after benzathine penicillin G administration.
No specific restrictions apply for early syphilis once treatment has started. After the first penicillin injection, rest for the day in case of Jarisch-Herxheimer reaction. Resume normal activity once acute symptoms resolve.
Look for a clinician comfortable with the CDC 2021 STI Treatment Guidelines, with access to benzathine penicillin G, and with established referral pathways to ophthalmology, audiology, and neurology. Sexual health clinics and ID departments at academic centers usually offer rapid testing, partner notification support, and HIV/STI bundle screening. Continuity matters because serologic follow-up extends over 12-24 months.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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