The patient: An 83-year-old man in Belgium
The symptoms: The man sought medical attention at a hospital because the muscles on one side of his face had weakened suddenly, causing it to droop — a condition called unilateral peripheral facial-nerve palsy. He had also recently had a fever, which had since resolved.
The man’s liver abnormalities hadn’t resolved by one week later, but his facial-nerve palsy cleared following a 10-day course of a strong corticosteroid. But then, over the next month, the man’s knees and ankles became stiff and painful, and his legs and feet — and occasionally his face, arms and hands — began to swell. He reported feeling generally unwell, he had gained 11 pounds (5 kilograms), and his urine had darkened even though he had been drinking more water than usual. All of these signs pointed to problems with his kidney function.
Besides the conditions uncovered on his recent medical examinations, the patient had long-standing high blood pressure, high cholesterol, an enlarged prostate and chronic obstructive pulmonary disease (COPD), for which he was taking medications. He had also been diagnosed with rectal cancer 20 years beforehand and received various treatments over the years. He and his wife of 50 years had been sexually inactive since that cancer treatment, he told his doctors.
What happened next: After weeks spent in and out of the hospital, the man went to an emergency room after his skin suddenly became intensely itchy. He had a red, scaly rash on his calves. A neurological exam revealed “normal motor strength, sensation, reflexes, coordination, and gait,” the doctors wrote in a report of the case.
At the ER, the patient was questioned further about his medical history, at which point he told doctors that, during his military service as a young man, he’d had unprotected sex with multiple casual partners. He reported being treated for various sexually transmitted infections (STIs) during that time but had forgotten the specific diagnoses.
Tests revealed that the patient was anemic and that his urine contained blood and an abnormal amount of protein. Additionally, a test for autoimmune diseases found abnormally high levels of antinuclear antibodies, which target the control centers of cells that house DNA. Because the patient had recently had facial-nerve palsy, the doctors analyzed his cerebral spinal fluid — the clear fluid that surrounds the brain and spinal cord. This revealed elevated levels of white blood cells, which hinted at an active infection.
The diagnosis: While tests for HIV and tuberculosis came back negative, an assay for Treponema pallidum, the bacterium that causes syphilis, was positive, confirming that the patient had an active syphilis infection.
Syphilis infections can progress through four stages, each with different symptoms. If an infected person doesn’t get effective treatment during the primary and secondary stages, the bacteria can go latent, sometimes for decades. And in a minority of cases, latent syphilis can awaken and cause a late, or tertiary, infection.
A more recent, unreported exposure must be considered.
Based on his positive T. pallidum test, rash, general unwell feeling, abnormal liver results, high urinary protein count, leg swelling, facial drooping and swollen lymph nodes, the man’s doctors diagnosed him with secondary syphilis with early neurosyphilis, in which the bacteria attack the nervous system.
The treatment: The patient had been given a single injection of penicillin before the test results confirmed that his infection had neurological involvement. He was subsequently given a 14-day course of intravenous penicillin, which is the recommended treatment for neurosyphilis, according to the case report.
The severe itching was treated with antihistamines, and he was prescribed diuretics to reduce the swelling in his legs. The rash, itching and swelling had improved by his one-month follow-up appointment, and his liver tests and urinary output had normalized.
Public health authorities were informed of the patient’s diagnosis, and his wife was referred for testing. The case report does not note whether his wife tested positive for syphilis.
What makes the case unique: Secondary syphilis normally occurs within the first year of an untreated infection and only rarely develops after four years have passed. Normally, smooth, hard sores appear on the mouth or genitals during primary syphilis, and once those sores disappear, secondary syphilis sets in within months, if left untreated.
“Although the patient’s history of multiple sexually transmitted infections as a young man prompted testing for syphilis, an exposure from that period would not be expected to explain his current presentation,” his doctors wrote.
There’s a possibility that the man had a latent infection that recently reactivated, perhaps due to the immune-suppressing effect of his recent steroid treatment. But you’d expect the reactivation to cause only symptoms of tertiary syphilis — like nervous system problems — not symptoms associated with secondary syphilis, like fever, rash and weight loss.
Therefore, exactly when the man contracted the infection is uncertain. “A more recent, unreported exposure must be considered,” the doctors wrote.
It is also rare for syphilis to affect the liver and kidneys, occurring in less than 10% of cases, according to the case report.
For more intriguing medical cases, check out our Diagnostic Dilemma archives.
This article is for informational purposes only and is not meant to offer medical advice.
Van Den Eynde, J., Van Der Pluijm, C., Schellekens, P., Vanhoutte, T., & Bammens, B. (2025). Spiraling into a Distant Past. New England Journal of Medicine, 393(18), 1844–1850. https://doi.org/10.1056/nejmcps2507868
