From the Guidelines
Syphilis is a complex, multi-staged disease caused by the spirochete bacterium Treponema pallidum, which enters the body through mucous membranes or skin abrasions during sexual contact, leading to a range of clinical manifestations from primary to tertiary syphilis. The pathophysiology of syphilis progresses through distinct stages, starting with primary syphilis, where the bacterium multiplies at the entry site, causing a painless ulcer (chancre) as the organism triggers a local inflammatory response 1. The bacteria then disseminate through the bloodstream and lymphatics, leading to secondary syphilis characterized by widespread mucocutaneous lesions, lymphadenopathy, and systemic symptoms as the immune system responds to spirochete antigens. Without treatment, the infection enters a latent phase where symptoms resolve but bacteria persist in tissues. Years later, tertiary syphilis may develop in approximately 30% of untreated individuals, causing destructive granulomatous lesions (gummas) in various organs, cardiovascular damage (particularly aortitis), or neurosyphilis with meningeal inflammation and neuronal damage 1.
Key Stages of Syphilis
- Primary syphilis: characterized by a painless ulcer (chancre) at the site of infection
- Secondary syphilis: widespread mucocutaneous lesions, lymphadenopathy, and systemic symptoms
- Latent syphilis: symptoms resolve but bacteria persist in tissues
- Tertiary syphilis: destructive granulomatous lesions, cardiovascular damage, or neurosyphilis
The pathology results from both direct bacterial invasion and the host's immune response, with T. pallidum's ability to evade immune detection contributing to its persistence. Treatment with penicillin G remains highly effective, with dosing and duration dependent on the stage of infection - a single dose of benzathine penicillin G 2.4 million units IM for early syphilis, and three weekly doses for late or unknown duration syphilis 1.
Clinical Manifestations
- Macular, maculopapular, papulosquamous, or pustular skin lesions
- Generalized lymphadenopathy and fever, malaise, anorexia, arthralgias, and headache
- Condyloma lata, moist, flat, papular lesions in warm intertrigenous regions
- Neurosyphilis, cardiovascular syphilis, and gummatous syphilis in late stages 1
From the Research
Pathophysiology of Syphilis
The pathophysiology of syphilis is a complex process involving the infection of the host by Treponema pallidum, a sexually transmitted bacterium. The disease progresses through several stages, each with distinct clinical manifestations.
Clinical Stages
- Primary syphilis: characterized by a painless and indurated ulcer at the contact site, known as the primary chancre, accompanied by regional lymph node swelling 2.
- Secondary syphilis: marked by fever, malaise, generalized lymphadenopathy, and a variety of skin and mucosal lesions, including non-pruritic transient exanthems and condylomata lata 2.
- Tertiary syphilis: characterized by granulomatous skin reactions, such as superficial nodular syphilids and gummas, and potential involvement of the bones, cardiovascular, and central nervous systems 2.
- Metasyphilis: a late stage of the disease, occurring 10 to 30 years after primary infection, characterized by severe and sometimes lethal neurological symptoms, including tabes dorsalis and progressive paralysis 2.
Immune Response
The host's immune response to T. pallidum infection is complex and involves both humoral and cell-mediated immunity. However, the bacterium has developed mechanisms to evade the immune system, including:
- Antigenic variation of the TprK protein, allowing it to evade the host's immune response 3.
- Paucity of integral outer membrane proteins, making it difficult for the immune system to recognize the bacterium 3.
- Potential production of immunosuppressive substances, inhibiting the proper function of lymphocytes and macrophages 4.
Chronicity and Persistence
T. pallidum is able to survive for decades in the untreated host, leading to the chronic nature of the disease. The bacterium's ability to evade the immune system and persist in the host is thought to be due to a combination of its unique biology and the host's immune response 3, 5.