Syphilis: From Symptoms to Treatment

A 27-year-old man attends a sexual health service after noticing a small ulcer on his penis. It is not painful, so he almost ignored it, but a recent sexual partner has contacted him to say they have been diagnosed with syphilis. He feels well, has no rash and has not noticed any other symptoms.

What might his symptoms suggest?

A painless genital ulcer following a relevant sexual exposure should make us think about primary syphilis, particularly when a partner has already been diagnosed. The classical lesion is called a chancre: usually a single, painless, indurated ulcer with a relatively clean base. Real presentations are not always classical, however. Chancres can be multiple, painful, purulent or located somewhere the patient cannot easily see, including the mouth, anus or rectum.

Syphilis is caused by Treponema pallidum subspecies pallidum, a thin spiral-shaped bacterium known as a spirochaete. A genital ulcer should not be diagnosed from appearance alone. Genital herpes and other causes of ulceration remain part of the differential diagnosis, and the history, examination and laboratory findings need to be considered together.

What is happening and why?

T. pallidum enters through a mucosal surface or a small break in the skin and begins multiplying at the site of entry. The incubation period is typically around three weeks, although BASHH describes a range of approximately 9 to 90 days. The local inflammatory response produces the chancre, while nearby lymph nodes may enlarge. Importantly, the infection does not remain confined to that ulcer. Spirochaetes can enter the lymphatic system and bloodstream early, allowing them to disseminate through the body before the first lesion has necessarily disappeared. (BASHH, 2024)

This is why the natural history of syphilis can be misleading. The chancre usually heals without treatment, but the disappearance of the ulcer does not mean the infection has cleared. If untreated, some people progress to secondary syphilis as disseminated infection produces a much broader inflammatory response. The patient may develop a widespread rash, often involving the palms and soles, generalised lymphadenopathy, fever, malaise, sore throat, patchy alopecia or mucous patches. Broad moist lesions called condylomata lata may occur around the perineal or perianal region and are highly infectious.

Secondary symptoms can also resolve spontaneously. The infection may then enter a latent phase, when the person has reactive syphilis serology but no clinical signs or symptoms attributable to active disease. BASHH classifies latent infection acquired within the previous two years as early latent syphilis. Infection of longer duration, or where the duration cannot be established, is managed as late latent syphilis. This distinction affects treatment and partner notification.

Understanding the four stages of syphilis

The four-stage framework helps make sense of how untreated syphilis can change over time, although not every patient follows a neat sequence and some manifestations can overlap.

1. Primary syphilis begins at the site where T. pallidum entered the body. The characteristic finding is a chancre, usually a painless, firm ulcer, with regional lymph-node enlargement sometimes accompanying it. Because the lesion may be painless or hidden in the mouth, vagina, cervix, anus or rectum, the patient may never realise it was there. It usually heals spontaneously within several weeks, but the organism has not necessarily gone. Dissemination may already have occurred.

2. Secondary syphilis reflects systemic dissemination of the organism. This is the stage in which seemingly unrelated findings begin to make sense together: a widespread rash that may involve the palms and soles, generalised lymphadenopathy, fever, malaise, sore throat, mucous patches, patchy alopecia or condylomata lata. Symptoms may again resolve without treatment, but spontaneous improvement does not mean microbiological cure.

3. Latent syphilis is the asymptomatic stage. The patient has reactive serology but no clinical signs or symptoms attributable to syphilis. BASHH subdivides this into early latent infection, acquired within the previous two years, and late latent infection, acquired more than two years previously or of uncertain duration. That distinction is clinically useful because it changes treatment and partner-notification decisions.

4. Tertiary syphilis describes late clinical disease that can develop years after untreated infection. It may involve the cardiovascular system, particularly the aorta, or produce destructive granulomatous lesions called gummas in tissues such as skin and bone. Late neurological manifestations can also occur.

There is one important qualification to this four-stage picture: neurosyphilis, ocular syphilis and otosyphilis are not simply a fifth or final stage. Neurological, visual or auditory involvement can occur earlier in infection, so symptoms suggesting these complications need assessment whenever they occur. (BASHH, 2024)

Syphilis remains an important infection across the UK, although surveillance is reported separately by the four nations. In Scotland, Public Health Scotland recorded 522 diagnoses of infectious syphilis in 2025, down from a peak of 564 in 2023. Where information was available across 2021 to 2025, 83% of diagnoses occurred among gay, bisexual and other men who have sex with men. These figures describe current Scottish surveillance rather than who can acquire syphilis: anyone exposed to an infectious lesion can become infected. (Public Health Scotland, 2026)

What else would you want to know?

Go back to our patient. We already know about the ulcer and the partner diagnosis, but we need enough history to estimate when infection may have occurred, identify other possible sites of exposure and look for evidence that the infection is already affecting other systems.

A sexual history should explore recent and previous partners, when sexual contact occurred, condom use and whether vaginal, oral or anal sex took place. The anatomical sites of exposure are relevant because a chancre may be oral, genital, anal or rectal. Ask about previous STI testing and diagnoses, particularly any previous syphilis diagnosis, previous serology and treatment. This becomes especially important later when we interpret his blood results, because treponemal antibodies commonly remain detectable after successfully treated infection.

Ask directly about symptoms he may not have connected with the ulcer: rash, including on the palms and soles, swollen lymph nodes, fever, malaise, sore throat or patchy hair loss. Neurological, visual and auditory symptoms deserve particular attention. Headache, cranial nerve symptoms, altered sensation, weakness, cognitive change, visual disturbance, hearing loss, tinnitus or vestibular symptoms may indicate neurological, ocular or otic involvement. Neurosyphilis can occur at any stage; it should not be taught as something that appears only decades after untreated infection. (BASHH, 2024)

Where pregnancy is possible, establish pregnancy status and relevant obstetric history. T. pallidum can cross the placenta, so maternal infection requires specialist management because untreated infection can result in fetal loss, prematurity or congenital syphilis. (BASHH, 2024)

What investigations are recommended?

Syphilis testing is easier to understand if you separate two questions: has this person been infected with T. pallidum? and what does the current serological pattern tell us about activity and response to treatment?

UK laboratories commonly begin with a treponemal test, such as an enzyme immunoassay (EIA) or chemiluminescence immunoassay (CLIA), which detects antibodies directed against T. pallidum. A reactive screening test is confirmed using a different treponemal assay and a second specimen. Treponemal tests usually remain reactive for life, even after successful treatment. A positive result therefore does not, by itself, prove that the patient has new or currently untreated syphilis. Previous results, previous treatment and the clinical history all matter. (BASHH, 2024)

A rapid plasma reagin (RPR) test is different. It is a non-treponemal test and is reported as a titre, for example 1:8, 1:16 or 1:32. Quantitative RPR helps assess disease activity and, importantly, provides a value that can be followed after treatment. A four-fold change means two dilution steps: a fall from 1:32 to 1:8 is a four-fold fall, while a rise from 1:8 to 1:32 is a four-fold rise. A sustained four-fold rise after treatment raises concern about reinfection or treatment failure and must be interpreted alongside the patient's subsequent sexual history and symptoms.

There is another timing issue. Antibodies do not become detectable immediately after infection, so very early syphilis can initially produce negative serology. If a chancre is suspicious but direct testing is negative, BASHH recommends repeat serology after two weeks. Where appropriate expertise is available, polymerase chain reaction (PCR) or dark-ground microscopy can detect T. pallidum directly from a suitable lesion. (BASHH, 2024)

You may occasionally hear about the prozone phenomenon. Very high antibody concentrations can interfere with an undiluted RPR reaction and produce an unexpected false-negative result. If the clinical picture strongly suggests syphilis, the laboratory can repeat the test using diluted serum. It is uncommon, but it is a useful reminder not to let one laboratory result overrule a convincing clinical presentation.

Our patient should also be offered testing for other STIs, including HIV, according to his history and current sexual-health guidance. Examination should be directed by his presentation and may include the ulcer itself, skin including the palms and soles, mouth and lymph nodes, with neurological, ophthalmic or otological assessment when symptoms indicate it.

How could syphilis be managed?

Treatment depends on the stage of infection and whether there is neurological, ocular, otic, cardiovascular or other complicated disease. For primary, secondary and early latent syphilis, BASHH recommends benzathine penicillin G 2.4 million units intramuscularly as a single dose as first-line treatment. Late latent syphilis requires benzathine penicillin G 2.4 million units intramuscularly once weekly for three weeks. Neurosyphilis requires a different regimen capable of treating infection within the central nervous system, so suspected neurological involvement needs specialist assessment rather than simply giving the uncomplicated early-syphilis regimen. (BASHH, 2024)

Pregnancy also requires specialist management under the specific BASHH pregnancy and congenital syphilis guidance. Treatment choice, timing and follow-up affect both maternal and fetal care. (BASHH, 2024)

After treatment, some patients develop a Jarisch-Herxheimer reaction. Within hours they may experience fever, chills, headache, myalgia and a temporary worsening of syphilis symptoms as the inflammatory response changes following rapid killing of spirochaetes. This is not the same as an immediate penicillin allergy. Urticaria, angioedema, bronchospasm or haemodynamic compromise would raise very different concerns and require appropriate emergency assessment.

Treatment also needs a baseline quantitative RPR so that the response can be followed. BASHH recommends clinical and serological follow-up at approximately 3, 6 and 12 months, with further monitoring when indicated until the RPR becomes negative or reaches a stable serofast level. Some adequately treated people remain serofast, with a persistent low stable RPR titre, so follow-up is about the pattern over time rather than expecting every result to become completely non-reactive. (BASHH, 2024)

What should we explain to the patient?

Our patient needs to understand that syphilis is treatable and that the painless ulcer healing would not mean the infection had gone. Explain why blood tests may remain reactive after successful treatment and why future clinicians need an accurate record of his diagnosis, treatment and RPR results. Otherwise, a persistently positive treponemal test years later can be difficult to interpret and may lead to unnecessary concern or treatment.

Partner notification is part of treatment, not an optional extra added afterwards. The relevant look-back period depends on the stage of syphilis. BASHH recommends notifying sexual partners from the previous three months in primary syphilis, while partner notification may extend to two years for secondary syphilis, clinical relapse or early latent infection. Specialist sexual-health teams can support this process without requiring the patient to manage it alone. (BASHH, 2024)

Discuss how transmission can be reduced while treatment and partner management are taking place, when follow-up blood tests are due, and why new symptoms should not simply be waited out. New visual changes, hearing loss, neurological symptoms or significant deterioration require prompt reassessment. Future STI testing, condoms and HIV prevention can be discussed according to the person's individual circumstances without turning the consultation into a lecture.

What could happen if syphilis is not appropriately managed?

Untreated syphilis can remain in the body for years. Late disease is now much less commonly seen where testing and effective treatment are accessible, but it can cause major neurological, cardiovascular and inflammatory damage. Neurosyphilis may produce meningitis, cranial nerve abnormalities, altered sensation, cognitive change or stroke-like presentations. Ocular syphilis can involve structures such as the uvea, optic nerve or retina, while otosyphilis may cause hearing loss, tinnitus or vestibular symptoms.

Late cardiovascular syphilis classically affects the aorta, while gummas are destructive granulomatous inflammatory lesions that can develop in skin, bone or other organs. These are consequences of persistent infection and the host inflammatory response rather than simply a continuation of the original genital ulcer.

Pregnancy creates a further route of harm because T. pallidum can cross the placenta. Congenital infection can have severe consequences, which is why syphilis screening in pregnancy and prompt specialist management of a positive result are so important.

There is also a public-health consequence when early infectious syphilis goes unrecognised. A chancre may be painless and secondary symptoms can disappear without treatment, so someone can reasonably believe the problem has resolved while infection remains. Timely diagnosis, effective treatment, partner notification and follow-up help interrupt transmission and identify reinfection.

References

British Association for Sexual Health and HIV (BASHH) (2024) UK guidelines for the management of syphilis 2024. Available at: BASHH syphilis guideline.

British Association for Sexual Health and HIV (BASHH) (2024) UK guidelines for the management of syphilis in pregnancy and children 2024. Available at: BASHH syphilis in pregnancy guideline.

Peeling, R.W., Mabey, D., Kamb, M.L., Chen, X.S., Radolf, J.D. and Benzaken, A.S. (2017) ‘Syphilis’, Nature Reviews Disease Primers, 3, 17073. doi: 10.1038/nrdp.2017.73.

Public Health Scotland (2026) Sexually transmitted infections in Scotland 2016 to 2025. Available at: Public Health Scotland.