Tertiary Syphilis

Tertiary syphilis is the third and final stage of syphilis, a sexually transmitted disease (STD) that progresses through different stages if left untreated.  

 Syphilis has been called “The Great Pretender”, as its symptoms can mimic many other diseases. The first stage is called primary syphilis, and it usually starts 1 to 3 weeks after the initial infection. This stage is characterized by the formation of a painless sore at the inoculation site, called a chancre. The following stage, secondary syphilis, occurs about 6 to 12 weeks after the initial infection. During this stage, the infection spreads through the bloodstream and causes a variety of different symptoms involving the skin, mucous membranes, and lymph nodes. Common symptoms include fever, sore throat, weight loss, hair loss, and headache. More specifically, generalized lymph node enlargement (lymphadenopathy) may occur, as well as a maculopapular rash affecting the palms of the hands and soles of the feet, consisting of small, raised or flat bumps. If left untreated, secondary syphilis typically progresses to a latent phase, where the disease becomes dormant and the affected individual is asymptomatic, although serologic tests (blood tests that detect antibodies or antigens) remain positive. This phase can be classified as early latent, if it occurs within a year of infection, and late latent, if it occurs after a year. Finally, late or tertiary syphilis develops in untreated individuals years or decades after the initial infection. 

Signs and symptoms of tertiary syphilis can be classified into three different forms: gummatous syphilis, late neurosyphilis, and cardiovascular syphilis.  

In gummatous syphilis, granulomatous lesions called gummas develop in the skin, bones, and organs. These lesions are a result of inflammation and contain different types of immune cells surrounded by fibrous tissue.  

In late neurosyphilis, progressive damage to the posterior part of the spinal cord results in a loss of vibration sensation and proprioception (i.e., sense of the position of joints and other body parts, like the hands and feet). This type of neurological involvement is typical of the tertiary stage and is known as tabes dorsalis. In other cases, the blood vessels that supply the brain and spinal cord can be damaged, resulting in slurred speech, altered behavior, memory loss, difficulty coordinating muscle movements, and paralysis.  

Finally, common manifestations of cardiovascular syphilis include inflammation of the aortic walls, which can lead to aortic aneurysms, as well as dilation of the aortic root. Dilation can cause aortic valve regurgitation (i.e., when blood leaks back through the valve leading into the aorta).  

It’s important to note that although tertiary syphilis is part of the natural history of the disease, it only develops in around one-third of individuals who don’t receive appropriate treatment. In addition, tertiary syphilis has become rare in recent years due to the effectiveness of antibiotic treatment.

Diagnosis of tertiary syphilis begins with a thorough medical history and physical examination. Because syphilis lesions are often asymptomatic and can occur in areas of the body where they might go unnoticed, not all infections are diagnosed in their early stages.  

 If tertiary syphilis is suspected, the diagnosis is confirmed through blood tests that look for antibodies against Treponema pallidum (i.e., serological tests). These are divided into non-treponemal tests (e.g., RPR or VDRL), which detect nonspecific antibodies, and treponemal tests (e.g., FT-ABS, TPPA, MHA-TP), which detect antibodies specific to Treponema pallidum. Testing for syphilis typically begins with a non-treponemal test; if negative, syphilis may be ruled out. A positive non-treponemal test should be confirmed with a treponemal test to exclude false positive results. If the treponemal test is also positive, then the diagnosis of syphilis is confirmed. In cases of neurosyphilis, diagnosis can also be made by detecting a high leukocyte count in the cerebrospinal fluid (CSF) collected through a lumbar puncture, along with a positive CSF-VDRL test, which detects antibodies in the CSF.