A 24-year-old man arrived at a respiratory clinic in Tianjin, China, with two weeks of cough, thick yellow sputum and low-grade fever, plus a month of back and flank pain that a prescription painkiller hadn't relieved. His blood showed a surge of eosinophils, immune cells tied to allergies and certain autoimmune diseases, and his lung scan showed patchy shadows and small nodules.
The picture pointed toward a rare autoimmune disorder that is treated with steroids and other drugs that suppress the immune system. Instead, routine blood screening and genetic testing of fluid washed from his lungs pointed to syphilis, with no rash, no sores and no swollen glands to give it away. Doctors described the case Sept. 3 in Frontiers in Medicine.
A Textbook Picture of the Wrong Disease
The man's symptoms and tests closely resembled eosinophilic granulomatosis with polyangiitis, or EGPA, a form of blood vessel inflammation that often involves the lungs and high eosinophil counts. He also had a history of allergic rhinitis triggered by cat dander, as well as gout.
Eosinophils made up 15.7% of his white blood cells, well above the lab's normal range of up to 8%. His level of immunoglobulin E, an antibody linked to allergic reactions, was 1,290 IU/mL, more than 12 times the upper limit of normal. A chest CT showed hazy and dense areas in both lungs, along with multiple small nodules in the upper lobes.
Doctors examined him carefully for signs of syphilis, including the palms and soles, where its rash often appears, and his mouth, throat, and genitals. They found nothing. He also initially denied any unprotected sexual contact.
The Blood Test That Changed Everything
On his second day in the hospital, routine screening before a planned bronchoscopy came back positive for syphilis. A second blood test, called the rapid plasma reagin (RPR) test, showed a high level of 1:128. When doctors asked again, confidentially, the man acknowledged high-risk sexual exposures.
Doctors then analyzed fluid from his lungs using targeted next-generation sequencing, a technique that searches for the genetic material of many microbes at once. It detected 11,732 genetic reads of Treponema pallidum, the bacterium that causes syphilis. It also picked up a rhinovirus, a common cold virus, which the authors considered an active co-infection; pneumococcal bacteria, which they judged a secondary infection; and Epstein-Barr virus, which they attributed to reactivation of a dormant infection.
ANCA antibody tests, which are associated with EGPA, came back negative, as did tests for tuberculosis and fungal infection. The authors wrote that his overall immune profile looked more like an infection-driven response than a primary autoimmune disease. That distinction matters because the 2022 EGPA classification criteria require doctors to rule out infections that mimic the disease.
The authors described this as, to their knowledge, the first use of this targeted sequencing method to diagnose syphilis in the lungs. An earlier case had used a broader form of sequencing, described in a 2022 report.
The stakes were high. Treating presumed EGPA with steroids or other immune-suppressing drugs could have let the infection spread unchecked, with potentially fatal effects on the nervous system or heart, the authors warned.
A Drug Shortage and a Workaround
The standard treatment for syphilis, benzathine penicillin G, was temporarily unavailable. Because doctors couldn't rule out nervous system involvement, and the patient declined a spinal tap, they gave two weeks of intravenous ceftriaxone, a recommended alternative. When penicillin became available, he received three weekly injections to complete treatment.
The antibiotic also covered the pneumococcal bacteria found in his lungs. His fever, cough and back pain resolved within about two weeks. Curiously, his eosinophil count climbed further, to 18.1%, before it fell. His RPR level dropped steadily, reaching 1:2 by day 100, and a repeat CT showed the lung shadows had almost completely cleared without any steroids. The small nodules stayed about the same, and doctors couldn't determine whether syphilis caused them or they had been there before.
Lung involvement in secondary syphilis is rare, with fewer than 30 cases documented in the English-language literature, according to the authors. They acknowledged a key limitation: no lung biopsy was performed, so the bacterium was never directly seen invading lung tissue. They argued that the high bacterial load in his lung fluid, his blood test results and his full recovery on antibiotics alone together gave enough confidence to guide treatment.
The shortage also raised a broader point. Because the world relies so heavily on one injectable form of penicillin for syphilis, treatment is vulnerable to supply disruptions, the authors wrote.
Why Stigma Can Delay a Diagnosis
The patient said the stigma around sexually transmitted infections was why he didn't share his sexual history at first. He emphasized the value of non-judgmental, repeated questioning, and he was relieved to learn he had an infection with a clear, time-limited treatment rather than a disease requiring long-term immunosuppression.
Syphilis has long been nicknamed "the great imitator" because its symptoms can resemble many other conditions. In the United States, the CDC's most recent national surveillance data, provisional figures for 2024, showed primary and secondary syphilis cases fell nearly 22% from 2023. But congenital syphilis, passed from mother to baby, rose for the 12th straight year to nearly 4,000 cases, up nearly 700% since 2015.
The case involves a single patient in China, and most syphilis infections will never involve the lungs. But the authors urged clinicians to consider syphilis when unexplained eosinophilia and lung shadows appear, even without a rash. The CDC's STI treatment guidelines outline testing and treatment, and anyone who may have been exposed should ask a clinician about screening.
Key Questions Answered
What happened in this case?
A 24-year-old man with cough, fever, back pain, and high eosinophils appeared to have a rare autoimmune disease, EGPA. Testing pointed instead to syphilis affecting his lungs.
Why was syphilis so hard to spot?
He had no rash, sores, or swollen lymph nodes, the classic clues, and he initially did not disclose his sexual history.
How was syphilis identified?
Syphilis blood tests came back positive, and genetic sequencing of fluid from his lungs detected large amounts of the syphilis bacterium. No lung biopsy was performed.
Why did the correct diagnosis matter?
EGPA is treated with steroids and immune-suppressing drugs, which could have allowed the infection to spread dangerously.
Did he recover?
Yes. After antibiotics, his symptoms resolved, his syphilis blood marker fell sharply and his lung shadows nearly cleared without steroids.
Can syphilis be cured?
Yes. Syphilis is treatable with antibiotics, and people who may have been exposed should talk with a clinician about testing.
