Syphilis

What is syphilis?

Syphilis is a complex sexually transmitted infection (STI) caused by the bacteria Treponema pallidum. Episodes of active disease occur, followed by latent periods, when the person remains infected but there are no signs or symptoms.

Initially syphilis appears as a painless sore (ulcer) where the infection entered (usually around the genitals, anus or mouth) and may go unnoticed. The sore is known as a chancre and this phase is known as primary syphilis.

Widespread rash and ‘flu-like symptoms appear next (secondary syphilis).

If left untreated, tertiary syphilis may develop years later and cause a variety of problems affecting the brain, eyes, heart and bones.

Who is at risk of syphilis and how is it spread?

Reported cases of syphilis have increased in New Zealand over the last few years, particularly among men who have sex with men (MSM).

Sexually active people may be at risk of syphilis. It is passed from person to person through direct contact with syphilis ulcers or infected blood through microtraumas during unprotected sexual intercourse. Syphilis ulcers are most commonly on the genitals and anal area but may also be found on the lips or mouth. Hence, vaginal, anal or oral sex is the main way of passing the infection from one individual to another.

Syphilis can also be passed on through:

Infected products eg blood transfusions, if donors are not screened
The placenta to an unborn baby.
If a pregnant woman has syphilis, the outcome for her baby is dependent on the stage of pregnancy and of the disease, and whether appropriate treatment was received.

Men and women are equally at risk of syphilis. The peak incidence arises between the age of 15 and 34 years.

What are the signs and symptoms of syphilis?

Once infected there is an incubation period of anywhere from 10-90 days (on average 21 days) before any signs become apparent.

Stage	Features
Primarysyphilis	Single small firm red painless papule quickly ulcerates (chancre). Heals within 4-8 weeks without treatment, and within 1 to 2 weeks with appropriate treatment. Sores may be inside the vagina or anus and often go unnoticed. Unilateral enlargement of lymph nodes close to the ulcer develops about 5 weeks after acquiring infection. Inguinallymphadenopathy arises in men with ulcers on the genitals and cervical lymphadenopathy in patients with ulcers in the mouth. If a syphilis ulcer is located in the vagina or rectum, the lymphadenopathy can be only detected by pelvic ultrasound examination.

Stage

Features

Primarysyphilis

Single small firm red painless papule quickly ulcerates (chancre). Heals within 4-8 weeks without treatment, and within 1 to 2 weeks with appropriate treatment. Sores may be inside the vagina or anus and often go unnoticed.
Unilateral enlargement of lymph nodes close to the ulcer develops about 5 weeks after acquiring infection. Inguinallymphadenopathy arises in men with ulcers on the genitals and cervical lymphadenopathy in patients with ulcers in the mouth. If a syphilis ulcer is located in the vagina or rectum, the lymphadenopathy can be only detected by pelvic ultrasound examination.

Secondary syphilis

Patient is very infectious during this stage.
If left untreated or treatment has failed, about 3 weeks to 3 months after the 1st stage, a widespread skin rashoccurs.
Rash may be subtle or appear as rough, red or reddish brown papules or patches. Occurs typically on the trunk and frequently affects palms and soles. May be mistaken for other conditions. The rash does not itch. It can appear more obvious with physical activity or heat. It resolves spontaneously within several weeks but can recur during the following 2 years.
Corymbose syphilis describes a cluster of erythematous papules around a central scaly plaque (resembling a flower).
Patchy hair loss.
Raw and red mucosal surfaces such as inside the mouth, throat, genital area, vagina and anus (mucous patches).
Unilateral tonsilitis, which may be ulcerated and accompanied by cervical lymph node enlargement. Can be mistaken for common tonsilitis but does not respond to usual oral antibiotics.
Greyish-white moist raised patches in the groin, inner thighs, armpits, umbilicus, or under breasts (condyloma lata).
Other symptoms include fever, tiredness, muscle and joint pains, headache and swollen lymph glands.
Other affected organs may include liver, kidneys, central nervous system (CNS), joints and eyes (resulting in visual impairment).

Early latentsyphilis (first 2 years)	Patient is infectious and can pass the infection on to partner. Usually normal,i.e. no signs on clinical examination. Continued infection found by positive treponemal antibody tests.
Late latentsyphilis (after 2 years)	Patient is non-infectious. Usually normal,i.e. no signs on clinical examination. Continued infection found by positive treponemal antibody tests
Tertiary syphilis	Signs and symptoms may develop 3 to 10 years after initial infection, and corresponds with immunologicalresponse to the infection. Tertiary syphilis is very rare in developed countries. Solitary granulomatous lesions (gummas) may be found on the skin, in the mouth and throat or occur in bones. Small or large nodules or ulcers may persist for years. Skin lesions may be painless but gummas in long bones cause a deep boring pain that is worse at night. Brain involvement (neurosyphilis) may cause headaches, dizziness, blurred vision, mental disturbances, paralysis and dementia (general paresis). This occurs 10–30 years after infection. Spinal cord disease results in unsteady gait, bladder disturbance, impotence and sensory changes (tabes dorsalis) resulting in collapsed joints (Charcot’s joints) and foot ulcers. Other internal organs such as the heart, blood vessels, eyes, liver and blood may be damaged by infection.
Congenitalsyphilis	Congenital syphilis can be prevented by treatment prior to 16 weeks gestation. The risk to the fetus is greatest with early untreated maternal syphilis Miscarriage or stillbirth may occur. In the first few weeks of life, effects resemble secondary syphilis including blisters, scaly rash, mucous patches and condyloma latum (very infectious). Snuffles, inflamed bones, swollen liver and lymph glands are common. Blood changes include anaemia, reduced platelets, and increased white cells. Late congenital syphilis often affects eyes (interstitial keratitis), ears, joints and CNS. Characteristic signs include Hutchinson’s teeth, typical facial appearance and bowed sabre shins.

Differential diagnosis of clinical symptoms of syphilis

Ulcers

Genital ulcers: genital herpes, trauma, cancer; and less commonly, tuberculosis, chancroid
Anal ulcers: genital herpes, anal fissure, bacterial infections, trauma, inflammatory bowel disease
Mouth ulcers: herpes simplex (cold sore), aphthous ulcers, trauma

Rash

Drug eruption
Pityriasis rosea
Psoriasis
Eczema/dermatitis

Laboratory tests for syphilis

Syphilis can be detected during the early infectious stages by a dark-field microscopy examination of tissue or tissue fluid taken from a primary ulcer (chancre) or condylomata lata.

Blood for serological tests is necessary for diagnosis. Serological tests turn positive about 5 to 6 weeks after acquiring the infection. In some cases, cerebrospinal fluid can be tested to confirm neurosyphilis.

Non-specific non-Treponemal tests eg Rapid plasma reagin (RPR), Venereal disease research laboratory (VDRL)
- May cross-react resulting in low-level false-positive tests during pregnancy, other infections, drug abuse, connective tissuedisease and aging.
- Levels usually relate to disease activity and are used for monitoring treatment.
- After effective treatment of syphilis, these tests usually become negative but in some people, may remain positive at low levels
Specific anti-treponemal antibody tests eg Treponenam pallidum particle agglutination assay (TPPA), enzyme immunoassays (EIA or AIA), fluorescent treponemal antibody absorption (FTA-ABS), microhaemagglutination assay (MHA-TP) and Western Blot (WB).
- These detect antibody due to past or present infection with T. pallidum or another Treponema species (eg yaws or pinta).
- They cannot distinguish between different types of Treponemal infection eg yaws or syphilis or the duration of infection.
- Most people with reactive treponemal tests will continue to have reactive tests for the remainder of their lives, regardless of treatment or disease activity.
- An EIA test is sometimes used as a screening test, as it avoids the false positives found when RPR or VDRL are used.
- Skin biopsy may or may not show characteristic histopathological features. Molecular testing using polymerase chain reaction(PCR) can confirm the presence of genetic material from the bacteria in ulcers, on the skin surface, in blood, lymph nodes and other tissue.

Test results in syphilis
Test	Primary chancre	Secondary syphilis	Tertiary syphilis
Dark field	+	–	–
RPR	+/-	+	+/-
VDRL	+/-	+	+/-
TPPA	–	+	+
AIA	–	+	+
FTA	–	+	+
CSF: VDRL	+/-	+/-	+/-

Other tests that may be required include X-ray, heart examination (ECHO), neurological and eye examinations.

Genital ulcer disease eg syphilis and chancroid, increases the risk of HIV infection so HIV testing should be undertaken as well.

What is the treatment for syphilis?

For detailed and up to date guidelines for treatment of syphilis, refer to the WHO guidelines for the treatment of Treponema pallidum (syphilis)(2016)

Penicillin by injection is still the mainstay of treatment for all stages of syphilis. Other antibiotics are less reliable but tetracyclines, erythromycin or cephalosporins may be used in those allergic to penicillin. Pregnant woman who are allergic to penicillin should be desensitised and treated with penicillin. People who also have HIV infection may respond less well to treatment so careful follow-up is needed.

Treatment failures can occur at any stage of the infection, so close follow-up with repeated serology tests for one to two years is important. In some countries patients with syphilis are followed up lifelong. Asymptomatic (latent) syphilis should be treated to prevent occurrence of late complications (tertiary syphilis). The response to treatment for those with tertiary syphilis is variable, particularly if the person has had the infection for a long time.

All sexual activity should be refrained from until all syphilis sores or lesions are completely healed and treatment is completed.

Can syphilis be prevented?

There is no vaccine available for syphilis.

Syphilis can be acquired repeatedly; antibodies and treatment do not protect against a new infection.

Early treatment of syphilis has very good outcomes and prevent later complications. However, treatment in advanced stages can leave irreversible consequences, for example neurological or visual problems.

If you think you are infected, stop all sexual contact and see your doctor or sexual health clinic. Notify all sexual contacts immediately so they can be checked for infection and treated appropriately.

Other measures to prevent the spread of syphilis include:

Limiting the number of sex partners
Using condoms
Regular blood tests if sexual behaviour is high risk

What is syphilis?

Who is at risk of syphilis and how is it spread?

What are the signs and symptoms of syphilis?

Differential diagnosis of clinical symptoms of syphilis

Ulcers

Rash

Laboratory tests for syphilis

What is the treatment for syphilis?

Can syphilis be prevented?

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