Syphilis

Essentials

• Suspected syphilis should be verified with serological tests and the patient should be treated with the most efficient antimicrobial drug available.
• Syphilis is a notifiable infectious disease. Its treatment and contact tracing should be centralized to specialist STD centres or to other experts. Find out about local policies.

Aetiology and transmission

• Syphilis is caused by Treponema pallidum bacteria.
• Easily transmitted sexually and also from the mother to the foetus
• The contagiousness is high (30-60%) both in primary and secondary stages.
• Untreated syphilis is contagious for about 2 years.
• Untreated syphilis in a pregnant woman may infect the foetus in all stages of the disease.

Epidemiology

• Globally, there were almost 50 million prevalent cases in 2019, with an increase of almost 61% from 1990 http://www.nature.com/articles/s41598-023-38294-4. The highest prevalence was found in regions with low sociodemographic index.
• In Europe, over 35 000 cases were found in 29 EU/EEA Member States in 2022, with a 41% increase from 2018 http://www.ecdc.europa.eu/en/publications-data/syphilis-annual-epidemiological-report-2022. Of cases with information on transmission category, about 3 out of 4 were in category men who have sex with men (MSM).
• In countries with low syphilis prevalence, screening of pregnant women may yield positive findings. These may represent serological scars of an earlier, already treated disease, or they may be a sign of a latent infection, especially in mothers who come from countries with high prevalence of syphilis.

Clinical picture

• Asymptomatic incubation period lasts for 3-4 weeks after which two thirds of the patients have visible symptoms.

1. Primary symptoms (local infection)
   • An indurated non-tender ulcer (picture 1) in the genital region, sometimes also in the anus or the oral region
   • Local non-tender lymph node enlargement
2. Secondary stage 6-8 weeks after transmission (general infection)
   • General symptoms include malaise, low-grade fever and enlarged lymph nodes.
   • Roseola rash (picture 2) resembles widely spread viral exanthema or drug eruption.
   • Syphilides, i.e. formations of papules are found in the hands (picture 3) and feet (picture 4) or spread all over the body. These may be large, cauliflower-like formations (condylomata latum) around the anus or necrotic ulcerations in patients with a poor immune response (e.g. HIV).
   • Syphilitic alopecia, "moth-eaten" spotty baldness in some patients
3. Late symptoms occur in about one third of untreated patients in 10-30 years. The most important are neurological (atypical psychosis, paralytic dementia) and vascular symptoms (aortic aneurysm, valvular disease).

Differential diagnosis

• Primary syphilis
  • Genital herpes Genital Herpes. Incubation time is short in primary infection, lesions occur in groups and they are painful. Lymph node enlargement is less pronounced, and the nodes are tender.
  • Infected coital or other traumas
  • Other chancres (ulcus molle, soft chancre)Rare Sexually Transmitted Diseases: Chancres
• Secondary syphilis
  • Roseola may resemble pityriasis rosea Pityriasis Rosea or exanthemas (eruptive skin rashes) Exanthem (Eruptive Skin Rash) caused by drugs Hypersensitivity to Drugs or viruses Measles, Mumps and Rubella (MMR).
  • Syphilides (picture 5) resemble papular lichen ruber planus, psoriasis, scabies or infectious eczema of the feet (e.g. tinea). Condyloma latum may resemble condyloma acuminata Human Papillomavirus (HPV) Infection.

Diagnosis

• Clinical picture
• Serology
  • Determination of Treponema pallidum antibodies is the primary screening test. The enzyme immunoassay test is specific and sensitive.
    • The test becomes positive within 3-4 weeks after infection.
    • The test identifies Treponema antibodies also in previously treated or latent cases in which the cardiolipin test remains negative.
    • Remember always to ask whether the patient has been treated for syphilis earlier.
    • A positive result is verified by immunoblotting.
    • The cardiolipin test becomes positive 3-4 weeks after infection. A low titre may suggest a serological scar of an earlier treated infection or latent syphilis.
  • TPHA (Treponema Pallidum hemagglutination) test is used to confirm the cardiolipin test.
    • Becomes positive slightly later than the cardiolipin test.
    • Specific (almost 100%)
  • FTA-abs (fluorescent treponemal antibody absorption) is a specific syphilis test used in special cases (neurosyphilis, suspicion of neonatal syphilis) as it detects also IgM antibodies.
• Nucleic acid detection methods are not in routine use.

Treatment Antibiotics for Syphilis during Pregnancy, Penicillin and Ceftriaxone for Early Syphilis

• Benzathine penicillin 2.4 million IU i.m. as a single dose (primary and secondary syfilis) or once a week for 3 weeks (latent syphilis) Penicillin and Ceftriaxone for Early Syphilis.
• Neurosyphilis is treated with i.v. penicillin.
• For patients allergic to penicillin, ceftriaxone injections (1 g/day for 10-21 days) are an alternative Penicillin and Ceftriaxone for Early Syphilis.

Follow-up and contact tracing

• After antimicrobial therapy the cardiolipin test is performed at 1, 3 and 6 months, and if necessary at 12 months. In primary stage infection, the cardiolipin becomes negative in most cases, in other recent infections the titre falls by at least two dilutions when the treatment has been successful.
• All sexual partners who have been exposed to infection should be screened with the Treponema pallidum antibody test. If the result is negative, the test should be repeated after 2-3 months.
• The infection is reported to the health authorities according to the local regulations.