2.5.7 Syphilis

Grading & Level of Importance: B


W. Burgdorf, Munich; R. Woolf, J. McGrath, London
Revised by A. Salava, E. Hiltunen-Back, A. Ranki, Helsinki






World Health Organization (WHO) estimates that in 2017 6 million new cases occurred among adolescents and adults aged 15–49 years worldwide.  In Europe, almost 30 000 syphilis cases (6.1 /100 000) and still congenital syphilis cases were reported. The reported syphilis rates were eight times higher in men than in women and peaked among 25-34-year-old men. Two-thirds of the syphilis cases with information on transmission were among men who have sex with men (MSM).


Mainly sexually transmitted systemic infection by Treponema pallidum.

Aetiology & Pathogenesis

Syphilis is a systemic infection caused by Treponema pallidum spirochete, and has four stages; primary, secondary, latent and tertiary syphilis. The incubation period from infection to the primary stage is 10-90 days. Secondary syphilis develops in 30 % of untreated patients 2-3 months after the onset of chancre. Tertiary syphilis is rare and develops in 10 % of untreated patients. Syphilis is mostly considered as a sexually transmitted infection (STI), but a fetus of the untreated mother can get congenital syphilis. The European Centre for Disease Prevention and Control (ECDC) defines early or infectious syphilis as an infection acquired ≤1 year earlier and it includes primary, secondary and early latent syphilis stages. Late syphilis, which is divided to late latent and tertiary stages, has been acquired more than a year earlier.  Patients are considered infectious during the first year (primary and secondary syphilis). Later transmission vertically.

Signs & Symptoms

The typical symptom of primary syphilis is a single, painless, indurated ulcer (chancre) at the inoculation site, mainly in the anogenital area but can also be detected extragenitally, such as  in the oral area. Regional lymphadenopathy is usually observed.

The primary stage may be asymptomatic or chancres, which are difficult to detect if located in the vagina or rectum.  The typical feature of secondary syphilis is a non-itching skin rash (roseola) on the trunk and later, papular syphilids on the palms and soles and mucocutaneous lesions. Constitutional symptoms like fever, chills, malaise, generalized lymphadenopathy, myalgias and arthritis occur due to  bacteremia. During the secondary stage of syphilis symptoms of early neurosyphilis, like uveitis, retinitis, otitis, meningitis, and cranial nerve dysfunction may occur.

Latent syphilis is clinically asymptomatic.

The symptoms of tertiary syphilis are  like erosive cutaneous or mucosal lesions (gumma), neurological (late neurosyphilis) and cardiovascular (aortic aneurysm) disorders. 


Stage I: anogenital, oral or elsewhere, draining lymph node enlarged.

Stage II: all over the body, localised and generalised, general lymphodenopathy.

Stage III: all over the body, localised and generalised, central and periferal nerve system, cardiovascular.


Syphilis stages are clinically defined, and they may overlap each other.

Primary stage: ulcer (ulcus durum) at the inoculation site; regional lymphadenopathy.

Secondary stage: eruptive skin rash (roseola exanthem); papular syphilids on palms and soles; mucocutaneous lesions; fever with generalized lymphadenopathy.

Tertiary: plaque-like lesions (gumma), neurological (late neurosyphilis) and cardiovascular (aortic aneurysm) disorders.

Laboratory & other workups

The direct verification of the spirochete is done with Darkfield examination by microscopy in the early chancre. Serological tests for syphilis (STS) are obligatory, additionally they are used for screening and follow-up. Both treponemal tests (TT) and non- treponemal tests (NTT) are available. NTTs like the Venereal Diseases Research Laboratory test (VDRL) and the Rapid Plasma Reagin test (RPR) become positive 10-15 days after the onset of the primary chancre (i.e. around 6 weeks after infection).  After a previously adequately treated syphilis, the STS often stay positive. A person with a positive STS should be asked about earlier treatments of syphilis and treated as for syphilis if not known.

Titres of NTT correlate with the disease activity, and are used to monitor disease activity and efficacy of treatment.


Usually not necessary. In cutaneous  secondary and tertiary stages a biopsy may become essential to exclude differential diagnoses such as viral exanthemas, hand eczema, psoriasis, cutaneous pseudolymphoma and malignant lymphomas.


Untreated cases run according to classification and symptoms (see above).


Comorbidity with HIV and other sexually transmitted infections is frequent. The clinical picture and disease course can be be severe (disseminated ulcerative skin lesions, severe constitutional symptoms, neurosyphilis, aortic aneurysm) in immunocompromised patients (lues maligna). HIV infection increases the propensity of syphilis to progress  into neurosyphilis and  ocular syphilis.


The diagnosis of syphilis is done by a thorough case history, clinical picture and laboratory test (see above) for correct staging. A biopsy should be done in several differential diagnoses (see below).

Differential diagnosis

Primary chancres may be atypical, multiple, painful, deep and indistinguishable from genital and oral herpes. In the female the chancre may be misdiagnosed as Bartholinitis. Roseola can mimic other dermatological exanthemas (drug reactions, viral infections) and eruptive papulosquamous dermatoses (e.g. guttate psoriasis, pityriasis rosea, pityriasis lichenoides). Pseudolymphomas and malignant lymphomas have to be ruled out in nodular and infiltrated plaque lesions (gumma).

Prevention & Therapy

The first line therapy for the early syphilis is single dose of benzathine penicillin G (BPG) 2.4 million units intramuscularly (im). The treatment of late latent syphilis is benzathine penicillin G (BPG) 2.4 million units im weekly on day 1, 8 and 15.  In case the patient is allergic to penicillin or refuses the parenteral treatment, oral doxycycline 200 mg daily (2x100) can be used for 14 days (early syphilis) and for 21–28 days (late latent). Benzyl penicillin 18–24 million units intravenously daily, (3–4 million units every 4 h) during 10–14 days is the first choice of treatment for neurosyphilis, ocular and auricular syphilis. Consider Herxheimer reaction.


NTTs are used for monitoring the effectiveness of treatment at 1, 3 and every 6 months thereafter, until it becomes negative or attains a low plateau (1:1-1:4).


All syphilis cases should be reported and contact tracing performed according to the local communicable disease legislation.

Mark article as unread
Article has been read
Mark article as read


Be the first one to leave a comment!