Syphilis

Syphilis develops in stages. Primary syphilis appears as a painless chancre at the inoculation site, typically 3–90 days after exposure. Secondary syphilis, weeks to months later, features a diffuse rash, mucous membrane lesions, and lymphadenopathy. Latent syphilis is asymptomatic and detected only by serology. Tertiary syphilis, occurring years later, can involve the cardiovascular system, central nervous system, and gummatous lesions.¹

Neurosyphilis can occur at any stage, with manifestations ranging from asymptomatic cerebrospinal fluid abnormalities to general paresis and tabes dorsalis. Congenital syphilis results from transplacental transmission, leading to stillbirth, neonatal death, or stigmata such as Hutchinson's teeth and interstitial keratitis.²

Diagnosis relies on dark-field microscopy for early lesions and serological tests, including nontreponemal (VDRL, RPR) and treponemal (FTA-ABS, TP-PA) assays. A positive nontreponemal test is confirmed by a treponemal test to avoid false positives from conditions like autoimmune diseases.³

Penicillin G remains the treatment of choice for all stages, with doxycycline or tetracycline as alternatives for penicillin-allergic patients. The Jarisch-Herxheimer reaction, a febrile response to treatment, occurs in up to 50% of patients with early syphilis. Management of congenital syphilis requires intravenous penicillin in the neonate.⁴

Syphilis is a major global health issue, with an estimated 7.1 million new cases in 2020. Incidence is highest in sub-Saharan Africa and among men who have sex with men in high-income countries. The disease increases the risk of HIV transmission and acquisition.

Public health measures include screening in pregnancy, partner notification, and surveillance. The WHO aims to eliminate congenital syphilis as a public health problem. Despite progress, syphilis rates have risen in many countries since the early 2000s, particularly among marginalized populations.⁵

Syphilis has a long and controversial history. The Columbian hypothesis suggests it was brought to Europe from the Americas, while the pre-Columbian hypothesis argues it existed in Europe earlier. The disease has influenced art and literature, with suspected cases among historical figures like Oscar Wilde and Al Capone.⁶

In the 20th century, the Tuskegee Study (1932–1972) withheld treatment from African American men, leading to ethical reforms in research. The disease also inspired the term "syphilophobia" and has been linked to the development of the Wassermann test, one of the first serological tests.⁷

Chancre

A painless ulcer at the site of infection, characteristic of primary syphilis.

Jarisch-Herxheimer reaction

A transient febrile reaction that occurs within hours of starting treatment for syphilis.

Tabes dorsalis

A late manifestation of neurosyphilis affecting the spinal cord, causing ataxia and sensory loss.