Syphilis cases climb

The United States appeared to be winning the fight against syphilis only decades ago. But the trend reversed and the dangerous sexually transmitted disease has resurged.

“Dermatologists know that syphilis is the great mimicker of many diseases. But it turns out it’s also the come-back kid. Syphilis has been on the rise in the U.S. for 15 years, particularly among men who have sex with men and people living with HIV,” says Kenneth A. Katz, M.D., M.Sc., M.S.C.E., a dermatologist at the Kaiser Permanente San Francisco Medical Center, San Francisco Calif.

Dermatologists are among the frontline providers who might encounter syphilis and have the opportunity to screen especially high risk populations, as outlined in newly updated syphilis screening recommendations released by the U.S. Preventive Services Task Force and published in the Journal of the American Medical Association(JAMA).

A rollercoaster ride of prevalence

In his editorial “Syphilis Screening in the 21st Century,” published July 2016 in JAMA Dermatology, Dr. Katz notes that a mere 60 years ago, the journal Archives of Dermatology and Syphilology shortened its name to Archives of Dermatology. The editor-in-chief at the time explained the move by saying the diagnosis and treatment of syphilis was no longer an important aspect of dermatology practice. The American Board of Dermatology and Syphilology followed suit, becoming the American Board of Dermatology.

Thanks to penicillin and public health measures in the mid-20th Century, new cases of primary and secondary syphilis plummeted from a high of nearly 95,000 in 1946 to about 7000 in 1954, according to the editorial.

In 1999, the CDC announced its plan to eliminate syphilis in the United States. But that confidence soon waned, as new cases of primary and secondary syphilis climbed year after year, and are still increasing today.

In 2014, 19,999 cases of primary and secondary syphilis were reported in the United States, which represents a 15.1% increase compared with 2013 and a 40% increase compared with 2010, according to the CDC.

Syphilis 101

Caused by the bacterium T. pallidum, syphilis is a systemic infectious disease. Untreated syphilis can go from primary to secondary, latent and tertiary disease. At any stage of syphilis, the infection can affect the nervous system, which is neurosyphilis, or the eyes, which is known as ocular syphilis.

There are many important reasons to treat syphilis early. Left untreated, about 15% of those with syphilis will progress to late-stage disease. That can lead to the development of inflammatory lesions throughout the body, which can result in cardiovascular or other organ dysfunction. Being infected with syphilis also increases one’s risk for acquiring or transmitting HIV infection, according to the recommendations in JAMA.

The update to the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for syphilis infection in nonpregnant adults recommends at least annual screening for sexually active men who have sex with men, as well as at least annual screening for people living with HIV. Those are the two populations at highest risk for syphilis infection, according to CDC. The CDC also recommends syphilis screening in correctional facilities on the basis of the local area and institutional prevalence and has a separate recommendation, issued in 2009, which highly recommends syphilis screening for all pregnant women.

Accurate screening tests are available and effective treatment (which is also widely available) can prevent progression to late-stage disease, according to the 2016 recommendations. According to CDC, syphilis screening is generally a two-step process, starting traditionally with a nontreponemal test (RPR or VDRL) or, in increasingly common “reverse-sequence” screening algorithms, starting with a treponemal test (for example, enzyme immunoassay). If an initial nontreponemal test is positive, it should be followed by a treponemal test; similarly, if an initial treponemal test is positive, it should be followed by a non-treponemal test. A positive result on both tests (and in some cases in only the treponemal test) is consistent with syphilis infection, although the blood tests themselves can’t tell a doctor whether the infection has already been treated or not. Skin biopsies can also be used to help determine whether syphilis is present, according to Dr. Katz.

What dermatologists need to know - and do

The USPSTF updated screening recommendations can help combat this syphilis epidemic by identifying syphilis early in infected individuals before it can be transmitted to others, Dr. Katz says. Those recommendations, he writes in the editorial, should influence dermatology practice in three important ways.

“The first is for dermatologists to follow the screening recommendations. If you have a patient who is a man who has sex with men or a person living with HIV or a pregnant woman, then screen them for syphilis,” he says. “The second is keep in mind that syphilis has never left us and is at levels that are unprecedented in the past 15 years. So, it’s worthwhile keeping it in the clinical differential diagnosis, especially if you know a patient is a man who has sex with men or a person living with HIV, or is part of another group at higher risk for syphilis as outlined in USPSTF recommendations. The third point is that really knowing whether a person is at risk for syphilis requires taking a sexual history, including ascertaining the gender or genders of a patient’s sex partners, as well as a person’s medical history-whether they are someone living with HIV.”

Dermatologists should consider syphilis when they encounter patients with a number of skin manifestations. Skin manifestations of syphilis at each stage of the disease can mimic other skin conditions. For example, on the early stage, syphilis can present as ulcer-like lesions in genital or non-genital areas, fooling providers into thinking patients might have herpes, according to Dr. Katz.

Skin manifestations associated with secondary syphilis, include spots on the palms of hands and soles of feet; a rash on the trunk; hair loss; or white spots in the mouth.

“And these can mimic diseases from acute HIV infection to pityriasis rosea, for the trunk rash,” he says.

Treating the disease depends on the stage of syphilis and whether neurosyphilis or ocular syphilis is present, according to Dr. Katz. Recommended treatment for all stages of syphilis is benzathine penicillin G and the dose depends on the stage, he says.

According to the CDC, a single intramuscular injection of long-acting benzathine penicillin G (2.4 million units) typically cures primary, secondary or early latent syphilis, as long as neurosyphilis or ocular syphilis is not present. For patients with late latent syphilis or latent syphilis of unknown duration, the CDC recommends three doses of long acting Benzathine penicillin G (2.4 million units, administered intramuscularly) at weekly intervals.

Providers must add aqueous crystalline penicillin G to treatment when neurosyphilis or ocular syphilis is present, according to Dr. Katz.

“Along with the rise in syphilis over the past 15 years, in the last year or so, there has been an uptick in ocular syphilis, which can present with visual disturbances that require special treatment. So every patient with syphilis should have a review of systems for neurologic and ocular symptoms and should have a targeted neurologic exam, as well,” he says.

While there has never been a case of syphilis known to be resistant to penicillin, there is widespread resistance to what used to be a staple second-line treatment, according to Dr. Katz.

“The second line treatment, which can be used in non-pregnant women and as an alternative to penicillin is doxycycline. There has been a widespread emergence in the U.S. and in many developed countries of resistance of Treponema pallidum … to the macrolide class of antibiotics-specifically, azithromycin,” he says. “Azithromycin is no longer a reliable alternative in the U.S. or in many countries for syphilis treatment.”

Dermatologists should keep in mind that treating syphilis means treating the infection, not just the cutaneous manifestations.

“… it’s important to understand exactly what’s going on with the person besides the skin. It doesn’t stop with the skin,” Dr. Katz says.

When addressing the sensitive topic with patients, Dr. Katz says he might say something like: “I ask people who have a rash like this a number of sensitive questions in order for me to be able to take care of you. And that includes some questions about your sexual and medical history.’ I think as long as patients understand that, and you ask in a respectful way, it’s fine.”

Disclosure: Dr. Katz reports no relevant conflicts.