- Clinical science
Syphilis is a predominantly sexually transmitted bacterial infection with the spirochete Treponema pallidum. The disease presents with four distinct, successive clinical stages if left untreated. Primary syphilis manifests with a painless chancre (primary lesion), typically on the genitals. Secondary syphilis is characterized by a polymorphic, maculopapular rash that also appears on the palms and soles. The first two stages are followed by an asymptomatic phase (latent syphilis), in which the disease may resolve entirely or progress to tertiary syphilis. During the tertiary stage, characteristic granulomas (gumma) may appear, which can cause irreversible organ damage, particularly in the cardiovascular system (syphilitic aortic aneurysm) and the CNS (neurosyphilis). Diagnosis requires serologic analyses, including nontreponemal tests for screening purposes and treponemal tests for confirmation. Further tests may directly detect T. pallidum (dark field microscopy, PCR) if a specimen of infected tissue or blood can be obtained. The first-line treatment for syphilis is penicillin, which should be administered after an infection has been confirmed. , a complication seen in children of women who have syphilis during pregnancy, is discussed in another learning card.
- Treponema pallidum: gram-negative, spiral-shaped bacteria belonging to the family
- Sexual contact (via small mucocutaneous lesions)
Treponema bacteria (particularly during stages I/II) are highly contagious! Sexual contact with a partner who suffers from active syphilis will lead to infection in 30% of cases!
- 10–90 days; on average 21 days
Primary lesion (chancre)
- Typically starts out as a solitary, raised papule (usually on the genitals)
- Evolves into painless, firm ulcer with indurated borders and smooth base
- Resolves spontaneously within 3–6 weeks, typically without scarring
- Regional (usually inguinal) nontender lymphadenopathy
- Begins approx. 8–12 weeks after primary infection; typically lasts 2–6 weeks
- Constitutional symptoms
- Polymorphic rash
- Condylomata lata
- Additional lesions
- No clinical symptoms, despite seropositivity
- May last months, years, or even for the entire life of the patient
- Disease may resolve, reactivate, or progress to tertiary syphilis
Gumma: destructive granulomatous lesions with a necrotic center that tend to ulcerate
- May affect any organ, e.g., skin, internal organs, bones
- Cardiovascular syphilis: , ascending aortic aneurysm (thoracic aortic aneurysm), syphilitic mesaortitis, aortic root dilation
- Asymptomatic neurosyphilis: documented CNS invasion without clinical signs or symptoms
- Acute meningeal syphilis : symptoms of acute
- Meningovascular syphilis : subacute stroke, cranial neuropathies
- Late (parenchymal) neurosyphilis
- General paresis
- (Frontotemporal) dementia, psychosis , cognitive dysfunction, and personality changes
- Argyll Robertson pupil: bilateral miosis; pupils accommodate, but do not react to direct or indirect light
- Tabes dorsalis (syphilitic myelopathy): demyelination of the dorsal columns and the dorsal root ganglia; occurs approx. 25–30 years after infection
During pregnancy: see
Syphilis (also known as “the great imitator”) may have a very broad clinical presentation that mimics many other diseases!
Two separate serological tests are required to establish a diagnosis of syphilis: Nontreponemal tests are used for screening purposes, while treponemal tests confirm the diagnosis. In early primary syphilis, both types of test may be nonreactive. Therefore, direct detection of the treponemes is usually preferred during this stage.
- Indications: screening, evaluation of disease activity , monitoring response to treatment
Commonly used tests
- Rapid Plasma Reagin (RPR): generally the test of choice
- Venereal Disease Research Laboratory (VDRL)
2. Treponemal tests
- Indication: confirmatory test after positive or equivocal nontreponemal test (high positive predictive value)
- Interpretation: positive results indicate active syphilis or persistent antibodies from a prior infection
- Commonly used tests
Direct detection of the pathogen
- Indication: definite tests to detect primary and secondary syphilis when a specimen can be obtained (e.g., exudative chancre, condyloma)
- Interpretation: confirmation of diagnosis, but negative results do not rule out syphilis
- Available tests
In vitro cultivation of Treponema pallidum is not possible!
First-line therapy: benzathine penicillin G
- Primary, secondary, or early latent: IM, single dose is sufficient
- Late latent, tertiary, or date of transmission unknown: weekly IM injections over a 3-week course
- Neurosyphilis: IV penicillin G for 10–14 days
- If allergic to penicillin
- Sexual contacts should also be treated
- Notable complication of treatment: Jarisch-Herxheimer reaction (see “Complications” below)
Penicillin is the drug of choice for treatment of syphilis!
- Definition: : acute, transient, systemic reaction to bacterial endotoxins and pyrogens that are released after initiation of antibiotic therapy
- Epidemiology: Commonly seen during treatment of infections with spirochetes (Borrelia, Leptospira); . In syphilis, the Jarisch-Herxheimer reaction is most often seen if treatment begins in the early phases of the secondary stage.
- Clinical features
- NSAIDs for symptomatic treatment
- May consider meptazinol
We list the most important complications. The selection is not exhaustive.