Syphilis: The great pretender
Dermatologists are encouraged to take a closer look as U.S. cases rise.
Over the past decade, there has been a surge in syphilis cases in the United States, with an 80% increase in total cases in the past five years. There is a strong connection between syphilis and social determinants of health, with disproportionate effects on sexual/gender minorities, racial/ethnic minorities, and people experiencing homelessness, incarceration, and opioid or methamphetamine use disorder.
The March 9 session, U077 – Sex, Sores, Science, and Surveillance: Syphilis in the 21st Century, delved into the details, with an emphasis on clinical presentation, workup, and management. Session director Erin H. Amerson, MD, FAAD, professor of dermatology at the University of California San Francisco, led a discussion of the latest clinical and epidemiologic trends in syphilis in the U.S. and abroad, including screening for clinical complications, lab diagnosis and monitoring, and treatment. Dr. Amerson was joined by speakers Sarah Jane Coates, MD, FAAD, and Kieron S. Leslie, MBBS.
“Syphilis is truly a great mimicker and can look like a lot of different dermatologic diseases,” Dr. Amerson said. “Given that syphilis is resurgent in the U.S. in the last decade, dermatologists should consider syphilis whenever a patient presents with a new rash, and not just in young people — I have diagnosed a few cases in people in their 70s.”
Looking through the lens
Although the morphology of secondary syphilis is classically papulosquamous, Dr. Amerson said, the condition can appear morbilliform, targetoid, nodular, or crusted/ecthyma-like, just to name a few. Additionally, she reminded dermatologists to look for alopecia, mucosal involvement, and genital involvement, and to remember that the chancre of primary syphilis can occur on other body sites besides the genitals (mouth, anus, etc.).
The “can’t-miss complication” of syphilis, she said, is neurosyphilis, which can present at the same time as primary and secondary syphilis and requires different treatment than uncomplicated primary/secondary syphilis (intravenous rather than intramuscular penicillin). Neurosyphilis most often affects cranial nerves II and VIII (optic and vestibulocochlear nerves, respectively) and may present with decreased or blurry vision, a red or painful eye, and tinnitus or decreased hearing, Dr. Amerson said.
Global epidemiologic trends
According to Dr. Amerson, the steepest inclines in the prevalence of syphilis are occurring among the Native American population.
“South Dakota had the highest rate of syphilis per capita in the nation last year, followed by New Mexico, concentrated in the Native populations in those states,” she said.
Although modern-day syphilis remains primarily a disease of men who have sex with men, Dr. Amerson noted that it has become much more common in women. The male-to-female ratio has dropped from a high of about 12 men for every one woman infected in 2013 to a ratio of about three-to-one in 2023.
“Unfortunately, when women get syphilis, the rate of congenital syphilis also goes up, and there has been a 10-fold increase in cases of congenital syphilis in the past decade,” she said. “If left untreated, congenital syphilis results in miscarriage, stillbirth, or infant death about half the time, and if the infant survives, it may have neurologic and/or skeletal defects for life.”
Aside from its prevalence in the U.S., Dr. Amerson said syphilis is an even bigger problem in the developing world and is the second-leading cause of preventable stillbirths worldwide, behind malaria.
Testing, treating, and monitoring
Dr. Amerson underscored the importance of taking a patient’s sexual history and maintaining a low threshold to test all patients with a new, unexplained rash. Additionally, screening is advised in patients at increased risk (people living with HIV or people with an opioid or methamphetamine use disorder) regardless of symptoms. According to Dr. Amerson, the reverse sequencing testing algorithm is increasingly being used in many hospitals. Reverse sequencing differs from the traditional algorithm, which used an RPR (rapid plasma reagin) to screen and a treponemal test to confirm.
“With reverse sequencing we do it the opposite way, with a (cheaper) treponemal test first, followed by an RPR to confirm if the treponemal test is positive,” she said. “However, clinicians should know that patients with a history of having been treated for syphilis will continue to have a positive treponemal test even if appropriately treated. As such, there may be more false positives, making it important to ask the patient if they have ever had syphilis treated before.”
To monitor treatment efficacy, Dr. Amerson said the goal is to see a four-fold decline in the RPR titer by one year.
“It’s important to get another RPR titer the day of treatment if you’re not treating the same day you’re testing, so you can appropriately monitor,” she said.
Dr. Amerson reminded attendees that the Centers for Disease Control and Prevention (CDC) now recommends the use of doxycycline post-exposure prophylaxis (PEP) for high-risk patients, which is prescribed for preventing sexually transmitted infections.
“There is a lot more syphilis out there than we are used to seeing in recent memory,” she said. “Dermatologists need to be on the lookout, so we don’t miss it.”
