by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
March 17, 2020
Ghanem, KG et al. The Modern Epidemic of Syphilis. N Engl J Med 2020; 382:845-854. DOI: 10.1056/NEJMra190159
With the continued increase in STIs seen in the U.S. over the past few years, I have decided to cite an excellent review article on Syphilis and have included- several key points below.
There continues to be an increase in rates of 1° and 2° syphilis in the U.S. with men accounting for 86% of cases. More than > 50% are in MSM of whom 42% are HIV infected. Rates of 1° and 2° syphilis among women doubled between 2014 and 2018.
Treponema pallidum disseminates within days after infection to distant tissues, including the CNS. Primary syphilis is manifested as a solitary ulcerative chancre. Findings with 2° syphilis include a nonpruritic rash, often on the palms and soles. Many cases of early latent syphilis (< 1-year cutoff) often go unnoticed or are misdiagnosed.
Syphilis cases are diagnosed by serologic testing. Two algorithms are used and require two-stage testing. Standard screening is with a non-treponemal test (RPR or VDRL), and reactivity is confirmed with specific treponemal test. Some labs use a reverse screening algorithm with a treponemal test done initially and reactive samples are reflex-tested with the non-treponemal test. The non-treponemal test provides a titer needed for clinical management.
Routine CSF examination for persons with early syphilis even with HIV-infection in not recommended unless neurologic signs are present. Risk factors for neurosyphilis in HIV-infected patients include an RPR titer of > 1:32, a CD4 count of 350 cells or lower, and absence of ART.
Penicillin is the drug of choice for all stages of syphilis and resistance has not been observed. A single IM dose of 2.4 million units of penicillin G benzathine is recommended and sustains drug levels for 7 to 10 days. Late-latent syphilis should be treated with 3 doses of PCN given weekly. Ceftriaxone has similar efficacy to PCN but data are restricted to observational studies.
Goal of treatment for syphilis is clinical and serologic cure. Serologic cure is a decline in RPR titer by a factor of 4 or more by 6 to 12 months for early syphilis and 12 to 24 months after therapy for late syphilis.
A vaccine for prevention of syphilis is likely years away. Recent data from two small studies provided preliminary evidence that a biomedical approach to prevention may be possible. Doxycycline given prophylactically (100 mg qd) reduced combined odds of syphilis, gonorrhea, and chlamydia infection by 73% in a small study HIV-infected MSM. An open-label study in 116 MSM found PEP with doxycycline (200 mg 24 hours after a sexual encounter) produced a 73% reduction in the risk of syphilis over a mean follow-up about 9 months.
I would strongly encourage review of the full content of the cited article. Syphilis screening at least annually is recommended for the majority of our HIV-infected patients as well as those on PrEP. Fortunately, PCN remains highly effective as primary treatment. There remains nuances regarding follow-up titers including a discussion regarding the need for CSF analysis via LP, “sero-fast” status and what constitutes treatment failure (this is rare).
The author has no conflicts of interest to disclose.
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