Syphilis: comprehensive clinical diagnosis and management
Syphilis is a chronic, systemic infection caused by the motile spirochaete Treponema pallidum. It spreads mainly through sexual contact with an infectious lesion and crosses the placenta. The disease evolves through primary, secondary, latent and tertiary stages, but stages can overlap and neurosyphilis or ocular disease may occur at any time. A painless ulcer that has healed does not exclude infection.
Every patient with syphilis needs HIV testing, a sexual-exposure history, neurological/ocular review, pregnancy assessment where relevant, and a plan for partner notification.
Learning objectives
- Recognise the stages and infectiousness of syphilis.
- Interpret treponemal and non-treponemal tests, including titre changes after treatment.
- Diagnose and manage neurosyphilis, ocular/otosyphilis and congenital syphilis.
- Choose stage-appropriate penicillin treatment and manage allergy, pregnancy and follow-up.
- Prevent reinfection through partner management, safer sex and antenatal screening.
Organism, transmission and pathogenesis
T. pallidum enters through microscopic breaks in skin or mucosa. It multiplies locally, spreads through lymphatics and blood, and can persist in tissues for decades. Infectiousness is highest during primary and secondary disease and early latent infection. Transmission occurs through vaginal, anal or oral sex, direct contact with mucous patches or condylomata lata, and vertically across the placenta. Fomites are not an important route because the organism is fragile outside the body.
| Stage | Key findings | Infectiousness |
|---|---|---|
| Primary | Solitary or multiple chancre with regional nodes | High at lesion |
| Secondary | Generalised rash, mucous patches, condylomata lata, systemic symptoms | Very high |
| Early latent | No symptoms, infection acquired recently | Meaningful sexual/vertical risk |
| Late latent | Asymptomatic infection of longer duration | Low sexual risk, ongoing fetal risk |
| Tertiary | Gummas, cardiovascular disease, neurosyphilis | Usually not sexually infectious |
Clinical stages
Primary syphilis
After an incubation of roughly 10–90 days, a chancre appears at the inoculation site: classically painless, indurated and clean-based, with non-tender regional lymphadenopathy. Rectal, cervical, oral or vaginal chancres may be hidden or mistaken for trauma, herpes or malignancy. It heals spontaneously in two to six weeks without eradication of infection.
Secondary syphilis
Haematogenous dissemination produces fever, malaise, headache, generalised lymphadenopathy and a diffuse rash that characteristically involves palms and soles but may be subtle in dark skin. Mucous patches, broad moist condylomata lata, patchy alopecia, hepatitis, nephritis, uveitis and meningitis can occur. Symptoms may relapse if untreated.
Latent syphilis
There are no clinical signs, but serology remains positive. Classify as early or late using documented symptoms, previous negative testing or a credible recent exposure; if timing is uncertain, manage as late latent/unknown duration.
Tertiary and late complications
Gummatous disease causes destructive granulomas in skin, bone or viscera. Cardiovascular disease includes aortitis, aneurysm and aortic-valve insufficiency. Neurosyphilis can cause meningitis, meningovascular stroke, tabes dorsalis, general paresis, sensory ataxia and psychiatric/cognitive change.
Neurosyphilis, ocular and otic disease
Suspect neurosyphilis with cranial-nerve palsy, meningitis, stroke in a young adult, altered cognition, sensory ataxia, lightning pains or unexplained psychiatric change. Ocular syphilis causes uveitis, retinitis, optic neuritis or vision loss; otosyphilis causes tinnitus, vertigo or sensorineural hearing loss. These are treated as neurosyphilis, with urgent ophthalmology or ENT input. Do not delay treatment while awaiting cerebrospinal-fluid results when sight or hearing is threatened.
History and examination
- Ask about ulcers, rash, mucous lesions, hair loss, visual/hearing symptoms, headache, neuropathy and previous treatment.
- Record all sexual sites and partners, condom use, gender of partners, recent STI, HIV/PrEP status and exposure timing.
- Examine skin including palms/soles, mouth, genital/perianal area, lymph nodes, eyes, cranial nerves, gait, reflexes and cognition.
- Determine pregnancy status and assess newborn risk if pregnant.
Diagnosis
- Use both a non-treponemal test (RPR or VDRL) and a treponemal test (TPPA/TPHA or EIA/CLIA). One test alone is insufficient for staging and treatment decisions.
- RPR/VDRL titres reflect activity and are used for follow-up; treponemal tests usually remain positive for life.
- Dark-field microscopy or lesion PCR, where available, can confirm early disease but a negative result does not exclude it.
- Perform lumbar puncture when neurological signs, ocular/otic disease, tertiary disease or treatment failure raises concern; interpret CSF cell count, protein and CSF-VDRL with serum results.
- Test for HIV and other STIs, check pregnancy, and evaluate hepatitis or renal disease when clinically indicated.
Differential diagnosis
Genital herpes, chancroid, lymphogranuloma venereum, donovanosis, traumatic ulcer, aphthosis, drug eruption, pityriasis rosea, psoriasis, viral exanthem, HIV-associated disease, autoimmune vasculitis and malignancy.
Management
Primary, secondary or early latent
Benzathine penicillin G intramuscularly as the recommended single-dose regimen in current national guidance. Use the appropriate local formulation and needle technique.
Late latent or unknown duration
Benzathine penicillin G intramuscularly in three weekly doses. If a dose is substantially delayed, restart according to guideline; document every dose.
Neurosyphilis/ocular/otic disease
Use an aqueous crystalline penicillin G intravenous regimen for the recommended duration, followed by specialist-directed follow-up. Ocular disease requires urgent ophthalmology; do not substitute routine benzathine penicillin alone.
Penicillin allergy
In non-pregnant patients with confirmed early disease, a guideline-approved alternative may be used only when neurosyphilis is excluded. Penicillin desensitisation is required in pregnancy and for neurosyphilis.
Pregnancy and congenital syphilis
Penicillin is the only proven treatment that prevents congenital syphilis. Screen at the first antenatal visit and repeat later in pregnancy or at delivery according to national policy and risk. Treat promptly; do not wait for a partner. Ultrasound may show fetal anaemia, hepatomegaly, placentomegaly or hydrops, but a normal scan does not exclude fetal infection. Evaluate exposed infants with paediatrics, including examination, quantitative serology and treatment based on maternal stage, treatment timing and infant findings.
Jarisch–Herxheimer reaction
Within 24 hours of therapy, fever, chills, myalgia, headache or transient rash may occur due to cytokine release. It is not penicillin allergy. Provide fluids, antipyretics and observation. In pregnancy it may precipitate contractions or fetal distress; treat syphilis promptly and monitor obstetrically rather than withholding therapy.
Follow-up and partner management
- Repeat quantitative RPR/VDRL at guideline-defined intervals; compare using the same test and laboratory where possible.
- Assess for a fourfold titre decline, persistent symptoms, treatment failure and reinfection. Re-test HIV if risk continues.
- Partners exposed during the infectious period need confidential notification, examination, serology and presumptive treatment when indicated.
- Advise abstinence until lesions have healed and partners have been assessed/treated; condoms reduce but do not eliminate risk because lesions may be outside covered areas.
Exam pearls
- A painless indurated chancre is classic but not universal.
- Palms-and-soles rash plus lymphadenopathy and mucous patches strongly suggests secondary syphilis.
- Treponemal tests remain positive; use RPR/VDRL titres to monitor response.
- Pregnancy is never a reason to withhold penicillin—desensitise if necessary.
- Ocular syphilis is a treatment emergency and is managed like neurosyphilis.
References
- SlideShare: Syphilis lecture.
- Uganda Clinical Guidelines: Syphilis.
- WHO and current national STI guidance.
Safety note: Confirm current Uganda dosing, laboratory algorithms and congenital-syphilis protocols before prescribing.
