Copyright Ars Technica
Syphilis can be a tricky disease to diagnose—especially when a patient may not be sharing the whole story. Doctors in Belgium met with a real head-scratcher when an 83-year-old married man came in with a rare form of secondary syphilis—the second of four stages of the sexually transmitted bacterial infection that has been called a “master of disguise.” The man told doctors up front that he was in a monogamous 50-year-long marriage and had been sexually inactive in recent years following treatment for cancer. In a Clinical Problem-Solving report published today in the New England Journal of Medicine, doctors laid out the step-by-step tests and reasoning they used to get to the right diagnosis, which still didn’t answer all their questions. The case began when the elderly man showed up at an emergency department complaining of severe itchiness. They noted that a month prior, he had been seen by specialists for paralysis on one side of his face. At that time, doctors found that liver enzymes in his blood were also elevated. They assumed it was all caused by a viral infection, but he had tested negative for a variety of them, including HIV, Epstein-Barr, cytomegalovirus, and Hepatitis A, B, C, and E. The paralysis eventually cleared up with a steroid treatment, but the abnormal liver tests persisted. By the time he wound up in the emergency department, he had also developed joint pain in his knees and ankles, malaise, loss of appetite, and swelling in his feet, legs, and occasionally in his face, arms, and hands. With those nonspecific symptoms, there were a lot of possible culprits. Medications—particularly in elderly patients—can cause liver problems, possibly explaining his abnormal enzymes. His other symptoms could be explained by inflammation, infections, autoimmune disorders, or diseases involving buildups of various substances, like clumps of immune cells. They looked for additional symptoms that could help narrow down the possibilities, but on a physical exam, his heart, lungs, and abdomen all seemed fine. He passed a neurological exam. They did notice there was a scaly, red rash on his legs, though. They did more lab work, confirming the liver abnormalities while also finding that he was anemic and had abnormal levels of protein in his urine. A computed tomography (CT) scan found thickening of the gallbladder wall and biliary duct, which point to some sort of inflammatory or infectious liver disease—fitting with the blood work. The combination of swelling, protein in the urine, and liver abnormalities could point to a kidney problem. They speculated that an autoimmune disease attacking the kidneys could be the source of his problems. However, the test for that was negative; further tests found no other biomarkers for autoimmune diseases. A historical hint At this point, they needed more to go on and went back to the patient with questions—particularly about his history of infections and exposures. He revealed that when he was young and in the military, he was a bit promiscuous and had been treated for several sexually transmitted infections (STIs), though he couldn’t remember which ones. They began testing him for various STIs, and he tested positive for syphilis. Given his recent facial palsy, they also did a lumbar puncture to test for neurosyphilis, but that was negative. In the end, his combination of rash, malaise, liver and kidney problems, facial paralysis, and swelling all fit with syphilis. However, syphilis that affects the liver is rare, occurring in less than 10 percent of cases, which made the diagnosis particularly difficult. Doctors think the infection was likely in the second stage. In the first stage, people just develop a chancre at the site of the infection. The chancre develops usually around a month after an exposure, is painless, and resolves on its own. Then the second stage emerges with the bacterial infection going systemic, usually with rash, malaise, loss of appetite, joint pain, swelling, fevers, and sore throat—similar to the man’s symptoms. After that, the infection can become latent (third stage) before reemerging in the tertiary (late stage), which can manifest in various ways, including with the destruction of the heart, central nervous system, and organs. While late-stage syphilis can show up years or even decades after an initial infection, the secondary stage doesn’t, the doctors note. “Secondary syphilis typically emerges within the first year after untreated primary infection and only rarely beyond 4 years,” they wrote in the report. It’s possible an immunosuppressing drug, like the steroid he took for his facial paralysis, could reactivate a latent infection, but once reactivated, it would be a late-stage infection, not a secondary one. Although the man’s STI history decades ago led the doctors to the right diagnosis, it doesn’t explain the current infection. A “more recent, unreported exposure must be considered,” the doctors wrote, but, ultimately, the timing and source of the infection remain unknown. With a treatment of antibiotics, the man made a full recovery. His doctors note that local health authorities would be contacted to track down and notify the man’s actual sexual partners. How things went with the man’s wife also remains unknown.
