Tertiary syphilis is identified by three categories of manifestations: gummatous lesions (rubbery, destructive growths in skin, bone, or organs), cardiovascular disease (most commonly aortitis), and late neurosyphilis (including tabes dorsalis and general paresis). These complications develop 10 to 30 years after the initial infection in roughly 30% to 40% of people who never receive treatment.
Gummatous Lesions
Gummas are the most recognizable tissue-level sign of tertiary syphilis. They appear as firm, non-tender nodules that can form almost anywhere: skin, bone, liver, and other internal organs. On the skin, a gumma typically looks like a crater-shaped plaque with a centrally punched-out ulcer, often covered with crusts and necrotic debris. They can reach several centimeters in diameter. Under a microscope, gummas show a distinctive pattern of tissue death called caseation necrosis, which helps distinguish them from other chronic infections or tumors.
Despite their alarming appearance, gummas are the most treatable form of tertiary syphilis. They generally respond well to antibiotic therapy, and much of the tissue damage can resolve once the infection is cleared.
Cardiovascular Syphilis
Cardiovascular involvement is the most life-threatening tertiary manifestation. The hallmark is syphilitic aortitis, an inflammation of the aorta that damages the elastic tissue in the vessel wall. This weakening occurs because the infection targets tiny blood vessels that supply the aortic wall itself, cutting off its own blood supply from the inside out. The damage concentrates in the ascending and arch portions of the thoracic aorta.
In untreated syphilis, aortitis develops in over 70% of cases, but only about 10% of those become symptomatic. When symptoms do appear, the complications include aortic regurgitation (the aortic valve leaks backward, present in about 85% of symptomatic cardiovascular cases), narrowing of the coronary artery openings (25% to 30%), and aortic aneurysm (5% to 10%). Roughly 90% of syphilitic aneurysms occur in the thoracic aorta rather than the abdominal aorta, which is the opposite pattern from the more common atherosclerotic aneurysms. That distinction itself can be a diagnostic clue.
Late Neurosyphilis
Late neurosyphilis takes two major forms: general paresis and tabes dorsalis. Both represent direct damage to the central nervous system by the syphilis bacterium after years of untreated infection.
General paresis is a progressive decline in mental function. It starts with forgetfulness and subtle personality changes, then worsens over time into severe dementia. In the pre-antibiotic era, general paresis was a leading cause of psychiatric institutionalization.
Tabes dorsalis involves slow degeneration of specific nerve pathways in the spinal cord that carry sensory information. It has the longest latency of any syphilis complication, averaging about 20 years from initial infection. The classic symptoms include lancinating pains (sudden, intense stabbing sensations in the limbs, back, or face that can last minutes to days), progressive loss of balance and coordination, bladder dysfunction, and a gradual loss of pain sensation. On examination, patients typically show decreased reflexes in the lower legs, impaired ability to sense vibration and joint position (affecting nearly 60% of patients), and a positive Romberg test, meaning they sway or fall when standing with their eyes closed because they’ve lost the position-sense feedback their brain relies on for balance.
The Argyll Robertson Pupil
One of the most classic and highly specific physical signs of tertiary syphilis is the Argyll Robertson pupil. This is a distinctive eye finding where both pupils are small and irregular, and they fail to constrict in response to bright light but still constrict normally when focusing on a nearby object. This split behavior is called “light-near dissociation.” The finding develops gradually over months to years and is bilateral. On nursing and medical exams, the Argyll Robertson pupil is considered virtually diagnostic of neurosyphilis.
How Tertiary Syphilis Is Detected
Because tertiary syphilis can involve the brain, spinal cord, heart, and skin in varying combinations, diagnosis often requires both blood testing and, when neurosyphilis is suspected, a spinal tap. Blood tests for syphilis antibodies are typically positive at this stage, though the non-treponemal screening tests can occasionally turn negative in late disease even while the infection persists.
For neurosyphilis specifically, cerebrospinal fluid analysis looks for a combination of inflammation (elevated white blood cell count and protein levels) alongside positive syphilis antibody tests in the fluid. One commonly used spinal fluid test is highly specific for neurosyphilis but catches fewer than 70% of true cases, which means a negative result doesn’t fully rule it out. A different type of antibody test in spinal fluid has strong negative predictive value: if that test comes back negative, neurosyphilis is very unlikely.
Why Tertiary Syphilis Still Occurs
Tertiary syphilis is now extremely rare in countries with widespread access to antibiotics, but it has not disappeared. The infection is easy to miss during its earlier stages. Primary syphilis causes a single painless sore that heals on its own. Secondary syphilis produces a rash and flu-like symptoms that also resolve without treatment. The disease then enters a latent phase with no visible symptoms at all, sometimes lasting decades. During that silent period, the bacterium continues to cause slow, cumulative damage to blood vessels, nerve tissue, and organs. By the time tertiary symptoms appear, the structural harm to the aorta or nervous system may be only partially reversible, even with successful antibiotic treatment.