1. My Clinical Approach to Syphilis
At my clinic in Rhodes, I often see patients worried about a suspicious ulcer that went unnoticed, or who discover a positive VDRL/RPR or TPHA result incidentally on a routine STI panel, without recalling any lesion at all.
Syphilis is an infection with many “faces” — correct interpretation never relies on a single test alone, but combines treponemal and nontreponemal tests, history, and the likely stage.
In practice, I always follow these steps:
- Combining treponemal and nontreponemal testing before any diagnosis.
- Determining the likely stage before choosing treatment.
- Evaluating for neurological, ocular, or otologic signs at every stage, not only in "late" syphilis.
- Scheduling correct follow-up with VDRL/RPR titres, separate from TPHA/TPPA.
The goal of this guide is a medically accurate, non-stigmatising picture of syphilis — clear, but without oversimplifications that could lead to misinterpreting test results.
2. What Is Syphilis
Syphilis is caused by the bacterium Treponema pallidum and is transmitted mainly through sexual contact, as well as through direct contact with an infectious lesion. It can also be transmitted vertically from mother to fetus during pregnancy.
The infection progresses through different stages with different clinical manifestations, can remain latent without symptoms, is treated effectively when correctly diagnosed, but does not leave permanent immunity — reinfection is possible.
3. How Is It Transmitted
Transmission can occur through:
- Vaginal sexual contact
- Anal sexual contact
- Oral sexual contact
- Direct contact with an infectious ulcer or lesion
- Vertical transmission from mother to fetus during pregnancy
Sexual transmission is thought to occur mainly when active mucocutaneous lesions are present — this is particularly relevant during early stages of the infection, becoming less common after the first year.
Is it transmitted through toilet seats, towels, or swimming pools?
No, syphilis is not usually transmitted through toilet seats, swimming pools, shared objects, or ordinary everyday contact. Transmission generally requires appropriate direct exposure to an infectious lesion.
4. Stages of Syphilis
Primary Syphilis
- A syphilitic ulcer (chancre) at the site of entry
- Often painless
- Can appear on the penis, vulva, cervix, anus, mouth, or other sites
- Can go unnoticed
The disappearance of the ulcer does not mean the infection has been cured.
Secondary Syphilis
Skin rash
Possible involvement of palms and soles
Lymphadenopathy
Fever
Malaise
Mucous membrane lesions
Condylomata lata, where relevant
Latent Syphilis
There are no visible symptoms, but serologic tests remain reactive — diagnosis is made exclusively through laboratory testing. Per current guidelines (CDC), it is classified as early latent (infection acquired within the preceding year) and late latent or of unknown duration (all other cases).
Tertiary Syphilis
Can appear years after untreated infection and affect the cardiovascular system, the nervous system, and other organs.
It is not an inevitable outcome of every untreated infection.
5. Neurosyphilis
Neurological involvement (neurosyphilis) can appear at different stages of the infection — not only in “late” or tertiary syphilis. Possible symptoms include:
Headache
Meningeal symptoms
Neurological deficits
Changes in cognitive function
Sensory or motor disturbances
This list is not a diagnostic checklist — symptoms are always evaluated by a physician, often with cerebrospinal fluid (CSF) analysis when clinical signs are present.
6. Ocular & Otosyphilis
The following symptoms require immediate medical evaluation:
- Visual disturbances
- Blurred vision
- Eye pain or inflammation
- Sudden or new hearing loss
- Tinnitus / vestibular symptoms, where relevant
Ocular syphilis and otosyphilis can appear at any stage, often early on, and without timely treatment can cause permanent loss of vision or hearing.
7. How Diagnosis Is Made
A confirmed diagnosis of syphilis generally requires two types of laboratory tests:
Nontreponemal Tests
RPR (Rapid Plasma Reagin), VDRL (Venereal Disease Research Laboratory)
Treponemal Tests
TPHA, TPPA, EIA/CIA, or other equivalents depending on the laboratory
Using only one type of test is not sufficient — a combination of treponemal and nontreponemal testing is typically used for a reliable diagnosis.
8. VDRL / RPR & Titre
- Used for diagnosis in the right clinical context, never in isolation.
- The titre can be used to monitor response to treatment.
- False-positive results can occur (e.g., other infections, autoimmune conditions, vaccination, pregnancy, older age).
- Should never be interpreted without treponemal testing and a full history.
VDRL and RPR are equally valid methods, but their quantitative results cannot be directly compared with each other — which is why sequential follow-up tests should use the same method, ideally at the same laboratory.
9. TPHA / TPPA — Why It Stays Positive
Treponemal tests (TPHA, TPPA) help confirm past or current infection, but they often remain positive for a very long time or even for life after treatment — only about 15–25% of those treated during the primary stage revert to a nonreactive result after 2–3 years.
A positive TPHA after successful treatment does not necessarily mean active infection.
Treponemal vs Nontreponemal: The Key Difference
Treponemal test (TPHA/TPPA) → often remains positive, does not predict treatment response, and is not used for that purpose.
RPR/VDRL titre → often used to monitor treatment response, since titres usually decrease over time.
You should not expect the RPR/VDRL to become negative in everyone — some treated patients may retain a low, stable titre (a state known as “serofast”), without this automatically meaning treatment failure.
10. When Does Testing Become Positive
There is no universal “window period” that applies with certainty to every case. Very early infection may not be immediately detected by all serologic tests.
If exposure is very recent and the initial test is negative, repeat testing may be needed depending on the clinical context and your physician’s advice.
If there is a suspicious lesion or significant exposure, a very early negative result should not be used as an absolute rule-out without a full clinical evaluation.
11. How Syphilis Is Treated
Penicillin (administered parenterally) is the preferred treatment for syphilis at all stages, per CDC guidelines. The exact preparation, dosage, and duration of treatment depend on:
The stage of infection
The duration of infection
Possible pregnancy
Presence of neurological / ocular involvement
Previous treatment history
The treatment regimen depends on the stage of syphilis — there is no single dose appropriate for every form.
Late latent syphilis, syphilis of unknown duration, and tertiary syphilis usually require a longer treatment duration than early stages. Where the active substance benzathine penicillin G is mentioned, this is done purely for informational purposes, in line with clinical guidelines — not as an individualised prescription.
Penicillin Allergy
In selected non-pregnant patients with a genuine penicillin allergy, alternative approaches exist, but these depend on the stage of infection and require close medical monitoring. Pregnancy is a special case — see the next section.
12. Jarisch–Herxheimer Reaction
After starting appropriate treatment, some patients may temporarily experience, within the first 24 hours:
Fever
Chills
Headache
Myalgia
Temporary worsening of symptoms
This is a reaction to treatment, not an allergy to penicillin, and it occurs more frequently in early stages of infection. In pregnancy, special caution is needed, since per guidelines it can rarely trigger early labour or fetal distress — however, this should not prevent or delay starting appropriate treatment.
13. Syphilis & Pregnancy
Untreated maternal syphilis can be transmitted to the fetus and cause serious fetal or neonatal complications. Treatment during pregnancy has specific recommendations, with penicillin playing a central role according to clinical guidelines — it is the only treatment with documented efficacy for syphilis in pregnancy.
In cases of a genuine penicillin allergy during pregnancy, guidelines recommend specific management with desensitisation and treatment with penicillin, rather than simply switching to another antibiotic. The decision belongs exclusively to the treating obstetrician/gynaecologist, in collaboration with a specialist.
14. How Do We Know It Was Cured
Monitoring treatment response is based on:
- Clinical progress
- Nontreponemal test titre (VDRL/RPR)
- The stage of infection
- Scheduled follow-up
A useful indicator is a fourfold change in titre, i.e. a change of two dilutions — for example, from 1:32 to 1:8. This is not a universal deadline for every patient, but an indicator of clinically significant response evaluated by the physician.
The exact follow-up frequency varies depending on the stage, HIV status, possible pregnancy, clinical response, and the likelihood of reinfection — determined by the treating physician per current guidelines.
15. Treatment Failure vs Reinfection
A new rise in titre or new symptoms may raise the question: is this reinfection or an inadequate treatment response? In either case, reassessment of history and repeat testing by a physician is required.
Can I Get Syphilis Again?
Yes.
Syphilis is curable, but a new infection can occur after a new exposure. Successful treatment does not create protective immunity.
16. Partner & Resuming Sexual Activity
Should My Partner Be Tested?
Yes — evaluating and notifying recent sex partners (partner notification) is a key part of management. Per the CDC, the period for which recent partners should be evaluated depends on the stage:
- Primary syphilis: contact within 3 months plus duration of symptoms
- Secondary syphilis: contact within 6 months plus duration of symptoms
- Early latent syphilis: contact within 1 year
In some cases, partners with recent exposure (e.g., within 90 days) may receive presumptive treatment even with negative tests, while partners with more distant exposure are evaluated clinically and serologically — the exact approach is determined by a physician.
When Can I Have Sex Again?
Appropriate completion of treatment, evaluation and management of partners, and absence of any infectious lesions where relevant are all required — without a single fixed number of days that applies to every case. Discuss with your physician when it is safe in your specific situation.
17. Syphilis & HIV
A syphilis diagnosis is often accompanied by a recommendation for HIV evaluation, per clinical guidelines. The two infections can coexist, and the presence of syphilis can, in the appropriate context, increase the likelihood of transmitting or acquiring HIV.
HIV can also affect certain aspects of follow-up (e.g., interpretation of cerebrospinal fluid tests) — for most patients with HIV, syphilis serologic tests remain reliable.
18. Testing for Other STIs
Depending on history and exposure, evaluation may be needed for:
HIV
Gonorrhoea
Chlamydia
Hepatitis
Other STIs depending on risk profile
The exact same full panel is not recommended for everyone without exception — it is individualised by the treating physician. See also our guide on Chlamydia.
19. Syphilis vs Herpes & Other Ulcers
Syphilis (primary chancre)
- Often single or limited
- Painless
- A relatively clean ulcer
Genital Herpes
- More often painful lesions
- Vesicular / multiple
- Recurrent
The appearance of the lesion alone is not always enough for diagnosis — clinical examination and laboratory confirmation are needed. See our guide on Genital Herpes.
For unusual or persistent genital ulcers, differential diagnosis from other, rarer causes (e.g., chancroid) may also be needed — clinical assessment determines the necessary work-up.
20. Prevention
- Correct condom use
- STI testing according to risk profile
- Prompt treatment when infection is diagnosed
- Partner notification
- Avoiding contact with active lesions
Condoms significantly reduce risk but cannot always cover all potentially infectious lesions on the skin or mucous membranes.
21. When to Seek Immediate Medical Care
- Vision problems
- Sudden hearing loss
- Neurological symptoms
- Severe headache with other neurological signs
- Syphilis during pregnancy
- Symptoms suggestive of neurosyphilis or ocular syphilis
Step-by-Step Diagnostic Pathway
22. Frequently Asked Questions
What are the first symptoms of syphilis?
The first finding is usually a single, often painless ulcer (chancre) at the site where the infection entered — the penis, vulva, cervix, anus, mouth, or another site depending on exposure. It can, however, go unnoticed.
Is the ulcer always painful?
No. The primary syphilis chancre is classically painless, although it can less commonly present in an atypical or painful form, or with multiple lesions.
Can I have syphilis without symptoms?
Yes. In latent syphilis there are no visible symptoms, but serologic tests remain reactive — diagnosis is made only through laboratory testing.
How soon after exposure can I get tested?
There is no universal timeframe that applies with certainty to everyone. Very early infection may not be immediately detected by all serologic tests, so discuss the appropriate testing timing for your exposure with your physician.
What does a positive VDRL or RPR mean?
VDRL/RPR are nontreponemal tests used for diagnosis in the right clinical context and for monitoring treatment response via the titre. They can produce false-positive results, which is why they are always confirmed with a treponemal test.
Why does TPHA remain positive after treatment?
Treponemal tests (TPHA/TPPA) often remain positive for a very long time, or even for life, even after successful treatment. They are not used to monitor treatment response — that is done with the RPR/VDRL titre.
Is syphilis fully curable?
Yes, it is treated effectively with appropriate antibiotic therapy when correctly diagnosed and managed. Treatment, however, does not create permanent immunity.
How do we know treatment worked?
Response is monitored mainly through the nontreponemal test titre (VDRL/RPR), looking for a fourfold decrease in titre (e.g., from 1:32 to 1:8), together with clinical progress and scheduled follow-up.
Can I get syphilis again?
Yes. Successful treatment does not create protective immunity, and a new exposure can lead to a new infection.
Should my partner be tested too?
Yes, evaluating recent sex partners is a key part of management. The exact timeframe for which partners should be evaluated depends on the stage of the infection, according to current clinical guidelines.
Related Topics
Suspicious Genital Ulcer or Positive VDRL/RPR/TPHA?
Syphilis diagnosis does not rely on a single test. Correct interpretation combines treponemal and nontreponemal tests, history, and the likely stage of infection. Book an appointment at our clinic in Rhodes for a comprehensive evaluation.
References
- CDC Sexually Transmitted Infections Treatment Guidelines, 2021 (last reviewed 2024) — Syphilis — cdc.gov
- EAU Guidelines on Urological Infections — uroweb.org
- IUSTI (International Union against Sexually Transmitted Infections) — European Guidelines — iusti.org
Medical Review
Dr. Marinos Vasilas
Urological Surgeon – Andrologist
Dr. Marinos Vasilas applies an individualised approach to investigating and managing sexually transmitted infections at his clinic in Rhodes, following the guidelines of the EAU, the CDC, and IUSTI.
Meet the DoctorThe content of this page is for informational purposes only and does not replace an individualised medical evaluation. Treatment depends on the stage of infection and specific factors. Antibiotics should never be taken arbitrarily. Suspicious neurological, ocular, or otologic symptoms require immediate medical evaluation.