Syphilis (overview) A53.9

History: Syphilis first appeared in 1495 during the siege of Naples by the French King Charles VIII. Thereafter, within five years, a syphilis epidemic swept across Europe. The course of its spread can be seen from the names given to it by the different peoples, depending on where they thought the source of the infection was:

• Italy: French or Celtic disease.
• France: Italian or Neapolitan disease.
• Germany: French disease
• Japan: Chinese celestial disease.

According to the Columbus theory, syphilis was introduced by Christopher Columbus or his sailors when he returned to Europe in 1495 after discovering America. This theory has since been disproved. There is evidence that syphilis existed in a more harmless form, as a skin disease, as early as ancient Greece or pre-Columbian America. The name "syphilis" derives from a poem published in 1530 by the Venetian scholar Girolamo Fracastoro, which is the story of the infected shepherd Syphilus.

The pure cultivation of the syphilis pathogen was first achieved by the Japanese bacteriologist Noguchi Hideyo in 1911.

Worldwide spread infectious disease(venereal disease: in Germany - non-named notification directly to the RKI in case of laboratory evidence), caused by Treponema pallidum.

A distinction is made according to the mode of infection, duration and organ manifestation:

• Congenital syphilis(syphilis connata): only occasionally found in industrialized countries.
• Acquired syphilis (syphilis acquisita)
  • Early syphilis (syphilis I and syphilis II)
  • Late syphilis (syphilis III - tertiary stage)
    • Neurosyphilis (late syphilis of the CNS)

Pathogen: Treponema pallidum (Spirochaeta pallida). A spirochaeta which, due to its sensitivity, is only transmitted in a warm and humid environment and thus almost exclusively via sexual intercourse.

Syphilis progresses in 3 stages with different clinics and disease activities, which are interrupted by latency phases of varying length.

• Early syphilis: the infectious phase of the disease (affects the 1st year of untreated syphilis infection) is referred to as early syphilis (primary and secondary stage).
• Late syphilis: The non-infectious stage is called the tertiary stage (neurosyphilis). This stage is only rarely reached in industrialized countries.

In 2015, the nationwide incidence was 8.5 cases/100,000 inhabitants/year. In Berlin, the incidence was 31/100,000 inhabitants, in Hamburg 19.7/100,000. In 2014, the average incidence in Europe (29 countries) was 5.1 cases/100,000 inhabitants/year. The lowest incidence was found in Italy (0.6/100,000), the highest in Malta (11.5/100,000 inhabitants/year).

The proportion of female syphilis cases reported in Germany was 6.2%.

Syphilis infections are more common in men who have sex with men ("men who have sex with men" MSM). The highest growth rates have been recorded in this group in recent years.

Up to 15% of those infected in Germany also suffer from an HIV infection, and up to 80% of those infected with HIV are TPHA-positive(no significant difference in the clinical course).

A distinction is made between search, confirmation and progression reactions:

• Search reactions: TPPA test, TPHA test, VDRL.
• Confirmatory reactions: FTA test, FTA-Abs test (gold standard of confirmatory test procedures), IgM/IgG ELISA or IgG/IgM Western blot.
• Activity control: Assessment of the activity of the infection and titer determination can be carried out using VDRL (Veneral Disease Research Laboratory) or Cardiolipin-KBR. The detection of IgM antibodies against Treponema pallidum can also be carried out by IgM FTA-Abs test or by 19S IgM-FTA test.
• Follow-up: VDRL/RPR with the aim of a drop of 3-4 titer levels after adequate therapy within approx. one year. 19-S-IgM-FTA-ABS in case of re-infection, normal drop after 3-24 months.

Clinically relevant test procedures:

• TPHA test (Treponema pallidum hemaglutination test): Screening test with high specificity (0.2% false reactive findings). Detection of IgM and IgG antibodies. Reaction in all phases of the disease. Positive from the 3rd post-infectious week. Low titers persist for life.
• TPPA test:
• FTA test (Flurescence treponema pallidum antibody absorption test): High specificity and sensitivity (false reactive findings in 1%). The 19S IgM-FTA-Abs test can be used to diagnose fresh infections from the 2nd post-infectious week.
• VDRL (= Venereal Disease Research Laboratory test): Non-specific but can be quantitatively evaluated to assess activity and success. Titres >1:4 are positive and indicate active syphilis. Positive reactions from the 5th week post infection. Time course and correlation with the clinic.
• Note! In the serological diagnosis of syphilis, non-specific tests should always be combined with specific tests, such as the VDRL test and/or the TPHA test as a screening test in combination with the FTA-Abs test as a confirmatory test.

CSF serology for the assessment of neurosyphilis: detection of syphilis antibodies in the CSF. A negative result of the specific tests in the CSF rules out neurosyphilis. Detection of IgG antibodies does not prove neurosyphilis, as these antibodies are soluble in the CSF. The detection of IgM antibodies in the CSF confirms the diagnosis.

CSF serology in HIV: Co-infections are not uncommon. The prevalence of false negative results in the primary or secondary phase is higher than in patients without prior HIV infection. The prozone effect increases the risk of false negative tests. The European guidelines recommend closer and longer follow-up care for HIV-coinfected patients, especially with ^CD4+ cell counts ^<350mm3 and/or without retroviral therapy (Cebolla-Verdugo M et al. 2025)

Primary stage: 10-14 days after infection, usually in the genital area (also extragential: lips, tongue, anal area, rectum, tonsils, fingers) Development of a deep red, slightly painful nodule as a sign of the primary infection. The nodule ulcerates (ulcus durum) between the 18th and 30th day after infection. Painless swelling of the regional lymph nodes.

Direct detection of spirochetes from the irritant serum is possible using the dark field technique(no longer of practical relevance). TPHA test becomes positive 1 week after the ulcer develops.

Secondary stage: exanthema stage with the typical clinical changes. Detection of Treponema pallidum-AK (VDRL >1:4, detection of IgG and IgM-AK in the FTA-Abs and TPHA test)

Tertiary stage: Detection of Treponema pallidum-AK

Neurosyphilis: Detection of IgM-AK in the CSF

See below syphilis early syphilis, late syphilis syphilis connata.

History of treatment methods: Until the beginning of the 20th century, syphilis was treated with highly toxic mercury, which was applied to large areas of the patient's body, usually resulting in the complete loss of body hair and all teeth and the rapid deterioration of all bodily functions. The South American natives had a combined syphilis therapy, which usually also cured them, as the disease was less severe in them than in Europeans. They used decoctions made from the wood or bark of the guaiac tree (Guaiacum officinale and G. sanctum) or sarsaparilla roots (Smilax regelii and other species) in combination with a sweat bath and a fasting cure. The sweat bath that the indigenous people of South America underwent after taking guaiac consisted of targeted hot steaming of the external genitals. Ulrich von Hutten tested this method himself and described it in his work 'De guajaci medicina et morbo gallico liber unus', published in 1519. The treatment did indeed lead to a temporary improvement. Around 1900 it was discovered that Treponema pallidum does not survive temperatures of > 41 °C. As a result, syphilis patients were infected with malaria. The high malaria fever attacks were often sufficient to kill the syphilis pathogen (malaria therapy). In 1909, Paul Ehrlich developed Salvarsan, a less toxic but effective arsenical remedy.

See also p. 10 and 11 of the current guidelines of the German STI Society(guidelines for syphilis)

Treatment of syphilis acquisita

History: Syphilis first appeared in 1495 during the siege of Naples by the French King Charles VIII. A syphilis epidemic then spread throughout Europe within five years. The course of its spread can be recognized by the names given to it by the various peoples, depending on where the source of the infection was thought to be:

• Italy: French or Celtic disease
• France: Italian or Neapolitan disease
• Spain: French disease
• England: French disease
• Scotland: English disease
• Germany: French disease
• Poland: German disease
• Hungary: French disease
• Russia: Polish disease
• Mongolia: Russian disease
• Japan: Chinese celestial cancer.

According to the Columbus theory, syphilis was introduced by Christopher Columbus or his sailors when he returned to Europe in 1495 after discovering America. The Columbus theory has since been challenged. There is evidence that syphilis already existed in a more harmless form, as a skin disease, in ancient Greece or in pre-Columbian America. The name syphilis goes back to a poem published in 1530 by the Venetian scholar Girolamo Fracastoro, which tells the story of the shepherd Syphilus, who suffered from this disease.

The Japanese bacteriologist Noguchi Hideyo was the first to succeed in cultivating the syphilis pathogen in 1911.

1. Adam B (2001) The punishment of Venus. A cultural history of venereal diseases. Orbis, Munich
2. Cebolla-Verdugo M et al. (2025) Syphilis in people living with HIV: Diagnostic challenges. J Dtsch Dermatol Ges 23: 887-888.
3. Nenoff P et al. (2017) Nonviral sexually transmitted infections-epidemiology, clinical manifestations,
   diagnostic workup, therapy: Part 3: Treponemes, Gardnerella and trichomonads. Dermatology 68:136-148.