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Date Reviewed | 25 April 2023 |
Subject | Diagnosis and Treatment of Syphilis in Urgent Care |
Patient Population | Sexually active immunocompetent male and female patients |
Rationale | Patients with active syphilis and those with incidental positive lab results for syphilis are presenting with increasing frequency to Urgent Care centers throughout the United States. Urgent Care providers should have a working knowledge of tests available for syphilis, the interpretation of those test results, and the appropriate treatment for each stage of syphilis. |
Introduction | Syphilis is a systemic, sexually transmitted disease caused by the spirochete T. pallidum. This disease is divided into three stages based on clinical findings which guide treatment and follow-up. Patients may present in one of three ways: with symptoms, as asymptomatic exposures, or as asymptomatic with a positive test during routine screening for STIs. Syphilis has become an increasingly common concern in UC over the last few years. Thought to be near eradication in 2000, since then the incidence has climbed steadily, with a 52% increase from 2016 to 2020 and an incidence of 12.6 cases per 1000 population. Approximately 80% of new cases of syphilis occur in men. Men who have sex with men (MSM) are disproportionately impacted. Risk factors for primary and secondary syphilis in this group are methamphetamine use and acquiring a new sexual partner through social media. In women and men who have sex with women (MSW), risk factors include use of methamphetamine and injection drugs including heroin. |
Evidence-Based Guideline | Walensky RP, Houry D, Jernigan DB, et. al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021;70, No. 4, 41-62. |
Discussion | Clinical Presentation Primary syphilis is characterized by a single painless ulcer, or chancre, at the site of inoculation. Rarely it may present with multiple, atypical, or painful lesions. Secondary syphilis has been called the great masquerader, as the typical rash does not always appear typically. Patients may have a generalized or localized skin rash, mucocutaneous lesions, and lymphadenopathy. Untreated cases may become tertiary syphilis, which is characterized by cardiac involvement, gummatous lesions, tabes dorsalis, and general paresis. This is called neurosyphilis. Latent syphilis is the term for those patients who lack clinical manifestations but test positive on serologic testing. If acquired within the previous year, it is considered early latent, if more than one year, the infection is considered late latent, or latent syphilis of unknown duration. Early neurosyphilis may occur at any stage of infection and may include meningitis, cranial nerve dysfunction, stroke, acute altered mental status, ocular syphilis or otosyphilis. Late neurosyphilis, including tabes dorsalis, and general paresis, may cause personality changes, psychiatric disorders, and dementia. Late neurosyphilis occurs 10 to 30+ years after initial infection. Rare cases may occur sooner. Congenital syphilis occurs when transmission occurs from an infected mother to the fetus during pregnancy. The rates of reported congenital syphilis in the U.S. has been increasing dramatically since 2012. In 2019 the national rate of 48.5 cases per 100,000 live births has increased 477% since 2012. Laboratory Testing Early detection and treatment are essential to prevent the spread of disease and the late-stage complications of syphilis. Screening of at-risk individuals is the best way to accomplish this. Patients should be screened with a nontreponemal test, and if positive, should be confirmed by a second, treponemal test. (See Figure 1 and 2.) Treatment Penicillin G administered parenterally is the preferred drug for treating all stages of syphilis. The type of penicillin, dosage, and length of treatment depends on the stage and clinical manifestations present. (See Figure 3.) Latent and tertiary syphilis requires longer treatment. Benzathine penicillin, commercially known as Bicillin L-A is recommended standard treatment in the US. A similarly named combination long and short acting benzathine-procaine penicillin, commercially known as Bicillin C-R, should NOT be used. These recommendations are based on clinical trials, observational studies, and many decades of clinical experiences. Patients with a true allergy to penicillin can be alternately treated with doxycycline or ceftriaxone or desensitized to penicillin and then treated. Parenteral penicillin G is the only therapy with documented efficacy for syphilis during pregnancy. Pregnant women with syphilis with a penicillin allergy should be desensitized by an allergist and then treated with penicillin. The Jarisch-Herxheimer reaction is an acute febrile reaction including headache, myalgia, and fever that occurs within 24 hours of treatment of syphilis, most commonly early syphilis. The incidence is approximately 10-35% (Yang). It can occur with any treatment, not just penicillin. Although the mechanism is not completely understood, it is thought to be due to an immune response to the release of lipoproteins, cytokines, and immune complexes from killed organisms. The reaction cannot be prevented, but is generally self-limited, resolving within 12-24 hours. Patients should be warned of the possibility of reaction. Treatment with NSAIDs and acetaminophen is generally all that is required. Sexual Partners Sexual partners of patients with syphilis should be evaluated clinically and serologically. Sexual transmission occurs from the mucocutaneous lesions and is uncommon after the first year of infection. Patients exposed within 90 days of the partner’s diagnosis should be treated regardless of serologic results. Patients exposed more than 90 days after the partner’s diagnosis should be treated based on serology results. (See the complete guideline for in-depth treatment recommendations of partners.) All patients who have a confirmed diagnosis of syphilis should be tested for HIV. PrEP should be considered if HIV testing is negative. Most states require health department notification of positive syphilis test. Contact your local health department to determine what is required in your area. Many areas have government-sponsored sexually transmitted disease clinics that can follow-up and treat these patients in the long term. |
Summary | Patients presenting to Urgent Care with concerns of syphilis infections and exposures should be evaluated to determine if their risk for primary, secondary, or latent syphilis. A non-treponemal test should be performed. If positive, the result should be confirmed with a treponemal test. Positive results in patients without past infection should be determined to have a current infection. Patients with previous infection should have their current results compared to previous results to determine if the infection is new.
Patients requiring treatment should be treated with long-acting parenteral penicillin G, with duration dependent upon stage of infection. Doxycycline is an alternative in patients with a history of penicillin allergy. Pregnant patients cannot be treated with doxycycline and should be desensitized to and treated with penicillin by an allergist. Syphilis is a health department reportable disease. Many areas have sexually transmitted disease clinics that can follow-up and treat these patients in the long term. |
References |
Walensky RP, Houry D, Jernigan DB, et. al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021;70, No. 4, 41-62. https://www.uptodate.com/contents/syphilis-epidemiology-pathophysiology-and-clinical-manifestations-in-patients-without-hiv?search=syphilis&source=search_result&selectedTitle=3~150&usage_type=default&display_rank=3 , accessed 4/25/2023 Yang CJ, Lee NY, et. al. Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the hiv infection epidemic: incidence and risk factors. Clin Infect Dis. 2010 Oct;51(8):976-9. |
Reviewers | Tracey Q. Davidoff, MD, FCUCM, Sean McNeeley, MD, FCUCM |
Figure 1.
Screening for syphilis in adults without prior infection: Initial nontreponemal test
This algorithm addresses syphilis screening in asymptomatic, nonpregnant adults without a history of syphilis.
* Nontreponemal tests include the rapid plasma reagin (RPR), the Venereal Disease Research Laboratory (VDRL), and the toluidine red unheated serum test (TRUST).
Treponemal tests include the fluorescent treponemal antibody absorption (FTA-ABS), the Treponema pallidum particle agglutination (TPPA), the T. pallidum enzyme immunoassay (TP-EIA), or chemiluminescence immunoassay (CIA). These different tests target different antigens.
Δ Treatment of syphilis depends upon the clinical manifestations and the stage of disease (e.g., early, late, neurosyphilis). Asymptomatic patients are considered to have latent syphilis and should be treated for early latent (patient has serologic evidence of T. pallidum infection that was acquired within the last 12 months) or late latent disease (the initial infection occurred more than 12 months ago). If the timing of an infection is not known, late latent syphilis is presumed. Refer to UpToDate topic on the treatment and monitoring of syphilis for information on treatment regimens.
◊ False-positive nontreponemal tests can be seen in the setting of pregnancy, an acute event (e.g., febrile illness, endocarditis, rickettsial disease), or recent immunization. Test abnormalities attributed to these conditions are usually transitory and typically last for six months or less. Other etiologies include chronic conditions, such as autoimmune disorders (particularly systemic lupus erythematosus), intravenous drug use, chronic liver disease, and underlying HIV disease.
https://www.uptodate.com/contents/image?imageKey=ID%2F134584&topicKey=ID%2F7588&search=syphilis&rank=1~150&source=see_link, accessed online 12/30/22
Figure 2.
Screening for syphilis in adults with prior infection*
This algorithm addresses syphilis screening in asymptomatic, nonpregnant adults with prior syphilis.
* It is important to ensure that all patients with prior syphilis have been adequately treated.
Nontreponemal tests include the rapid plasma reagin (RPR), the Venereal Disease Research Laboratory (VDRL), and the toluidine red unheated serum test (TRUST).
Δ Treponemal tests include the fluorescent treponemal antibody absorption (FTA-ABS), the Treponema pallidum particle agglutination (TPPA), the T. pallidum enzyme immunoassay (TP-EIA), or chemiluminescence immunoassay (CIA). These different tests target different antigens.
◊ Treatment of syphilis depends upon the clinical manifestations and the stage of disease (e.g., early, late, neurosyphilis). For those with prior syphilis, results of prior nontreponemal tests are also used to guide treatment decisions. Refer to the UpToDate topic on treatment of syphilis.
If a patient with prior treated syphilis had an initial treponemal test performed, this pattern (reactive treponemal test/nonreactive nontreponemal test) is expected.
https://www.uptodate.com/contents/image?imageKey=ID%2F134584&topicKey=ID%2F7588&search=syphilis&rank=1~150&source=see_link, accessed online 12/30/22
Figure 3.
Recommended Treatment Regimens for Syphilis Infections
