Commentary

Abstract

Emergency physicians can play an important public health role by accurately diagnosing and treating syphilis to minimize ongoing transmission to others. Patient education, timely and accurate reporting, and prophylaxis for exposed partners are also important in reducing the burden of syphilis in the United States.From 1990 to 2000, syphilis was on a steady decline. Unfortunately, since 2000, syphilis rates have been increasing, particularly among men who have sex with men. Rates of other sexually transmitted diseases also have increased among men who have sex with men, representative of a general increase in unsafe sexual activity. In 2002, a total of 6,862 cases of primary and secondary syphilis were reported to the CDC, an increase of 12.4% over 2001.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar, 2.Brown D.L. Frank J.E. Diagnosis and management of syphilis.Am Fam Phys. 2003; 68: 283-290PubMed Google Scholar, 3.Centers for Disease Control and Prevention Primary and secondary syphilis—United States, 2002.MMWR. 2002; 52: 1117-1120Google Scholar Emergency physicians should try to be aware of the patterns of sexually transmitted infections in their community and should be especially alert for infections in high-risk groups such as men who have sex with men.Syphilis is caused by the spirochete Treponema pallidum and spread through direct contact with infectious lesions or bodily fluids. Patients usually present to the emergency department (ED) with chancre, inguinal lymphadenopathy, or rash. Presentations may overlap, but classically the natural history of syphilis may be divided into 3 stages. Primary syphilis typically manifests as a solitary, painless chancre at the inoculation site that develops on average 3 weeks after exposure. Common signs and symptoms of secondary syphilis include maculopapular rash, especially over the hands and soles, malaise, lymphadenopathy, sore throat, or headache beginning about 4 to 10 weeks after appearance of the chancre. Tertiary syphilis can manifest in any organ system, most seriously as neurosyphilis or syphilitic aortitis. Patients who are infected but asymptomatic are deemed early latent if within 1 year of infection and are deemed late latent phase if greater than 1 year of infection.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar In practice, the duration of infection is rarely known, so most are treated for late latent infection.Treponema pallidum cannot be cultured. Dark-field microscopy can assist with diagnosis but is not a widely available technique. Infection with syphilis leads to antibodies that react with cardiolipin, the basis of diagnosis with traditional nontreponemal serologic tests, the Venereal Disease Research Laboratory and Rapid Plasma Reagin tests.2.Brown D.L. Frank J.E. Diagnosis and management of syphilis.Am Fam Phys. 2003; 68: 283-290PubMed Google Scholar For purposes of diagnosis, positive nontreponemal tests should be confirmed with treponemal-specific tests, either T pallidum particle agglutination or fluorescent treponemal antibodies. False-positive nontreponemal test results occur in 1% to 2% of the population as a result of autoimmune disease, pregnancy, and infections. The Venereal Disease Research Laboratory test and Rapid Plasma Reagin test are equally valid assays, but quantitative results from the 2 tests cannot be compared directly. Nontreponemal titers usually correlate with disease activity and become nonreactive with time after treatment, whereas treponemal tests remain reactive for life. Nontreponemal tests are 78% to 86% sensitive in primary syphilis, nearly 100% sensitive in secondary syphilis, and 95% to 98% in latent syphilis.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar Serologic tests are generally accurate and reliable for the diagnosis of syphilis in HIV-infected individuals. Persons with very high titer Rapid Plasma Reagin or Venereal Disease Research Laboratories tests may have false-negative test results that become positive with serum dilution (prozone phenomenon). The cerebrospinal fluid Venereal Disease Research Laboratory test is the standard serologic test for neurosyphilis and is highly specific, but insensitive; therefore, it should be interpreted in the setting of other tests and clinical suspicion.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar, 4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google ScholarAlthough sexual transmission of T pallidum occurs only when mucocutaneous syphilitic lesions are present, the CDC recommends that persons exposed sexually to a patient with syphilis at any stage should be evaluated clinically and serologically, with presumptive treatment of contacts exposed within 90 days preceding the diagnosis of primary, secondary, or early latent syphilis in a sex partner. Without prophylaxis, up to 50% to 75% of exposed sex partners of persons with primary or secondary syphilis may become infected.5.Garnett G.P. Aral S.O. Hoyle D.V. et al.The natural history of syphilis: implications for the transmission dynamics and control of infection.Sex Transm Dis. 1997; 24: 185-200Crossref PubMed Scopus (150) Google ScholarParenteral administration of penicillin G is the preferred drug of treatment of all stages of syphilis. The recommended adult dose is 2.4 million units intramuscularly of benzathine penicillin G. Patients should be informed about the Jarisch-Herxheimer reaction, an acute febrile reaction that may occur within the first 24 hours after any therapy for syphilis, especially among patients with early syphilis. Treatment of syphilis is similar in HIV-positive and HIV-negative patients, although HIV-positive patients require closer follow-up for monitoring of potential treatment failure.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google ScholarAlternative treatment regimens for primary or secondary syphilis have been sought for patients with penicillin allergies, as well as for issues of patient preference, compliance, and ease of prophylaxis. Regimens listed by the CDC include 100 mg of doxycycline orally twice daily for 14 days, 500 mg of tetracycline 4 times daily for 14 days, 1 g of ceftriaxone daily either intramuscularly or intravenously for 8 to 10 days, or a single dose of 2 grams of azithromycin orally.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google Scholar, 6.Hook W. Martin D.H. Stephens J. et al.A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis.Sex Transm Dis. 2002; 29: 486-490Crossref PubMed Scopus (117) Google Scholar Pilot studies have found comparable rates of efficacy between azithromycin and penicillin G in treatment and prophylaxis of syphilis.7.Hook E.W. Stephens J. Ennis D.M. Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis.Ann Intern Med. 1999; 131: 434-437Crossref PubMed Scopus (80) Google Scholar, 8.Verdon M.S. Handsfield H.H. Johnson R.B. Pilot study of azithromycin for treatment of primary and secondary syphilis.Clin Infect Dis. 1994; 19: 486-488Crossref PubMed Scopus (63) Google Scholar However, no large trials on azithromycin for this indication exist, and the CDC recommends close follow-up of patients treated with alternative regimens. Azithromycin for treatment of primary syphilis and for prophylaxis (single dose of 1 gram) has been viewed as an attractive option because it is an oral, 1-dose regimen that is preferred by patients, easier to administer in the field by public health nurses, and with a cost profile comparable to penicillin. Such a regimen also achieves a higher level of treatment in exposed partners because of higher rates of presentation for medical follow-up.9.Blandford J.M. Gift T.L. The cost-effectiveness of single-dose azithromycin for treatment of incubating syphilis.Sex Transm Dis. 2003; 30: 503-508Crossref Scopus (19) Google Scholar Azithromycin is also currently recommended for treatment of several other sexually transmitted diseases, including chlamydial infections, gonorrhea, nongonococcal urethritis, and chancroid. It is safe for use in children and pregnancy. The above alternative regimens are not suitable for pregnant women with syphilis in any stage with penicillin allergy and patients with neurosyphilis; these patients should be desensitized and treated with penicillin.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google ScholarWhenever the diagnosis of syphilis is considered, it is appropriate to send studies for other sexually transmitted diseases. It is also important to consider testing for syphilis in those who present with other sexually transmitted infections. Because many syphilis cases are asymptomatic or minimally symptomatic, they will only be found by screening patients at risk. Although most EDs do not engage in HIV screening because of concerns about counseling and follow-up, all patients with syphilis need HIV testing and should get appropriate referral. In addition, syphilis is reportable in every state. Accurate reporting assists local health departments in targeting limited resources, identification of at-risk sexual contacts, and generation of robust epidemiologic reports.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google Scholar Emergency physicians can play an important public health role by accurately diagnosing and treating syphilis to minimize ongoing transmission to others. Patient education, timely and accurate reporting, and prophylaxis for exposed partners are also important in reducing the burden of syphilis in the United States. From 1990 to 2000, syphilis was on a steady decline. Unfortunately, since 2000, syphilis rates have been increasing, particularly among men who have sex with men. Rates of other sexually transmitted diseases also have increased among men who have sex with men, representative of a general increase in unsafe sexual activity. In 2002, a total of 6,862 cases of primary and secondary syphilis were reported to the CDC, an increase of 12.4% over 2001.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar, 2.Brown D.L. Frank J.E. Diagnosis and management of syphilis.Am Fam Phys. 2003; 68: 283-290PubMed Google Scholar, 3.Centers for Disease Control and Prevention Primary and secondary syphilis—United States, 2002.MMWR. 2002; 52: 1117-1120Google Scholar Emergency physicians should try to be aware of the patterns of sexually transmitted infections in their community and should be especially alert for infections in high-risk groups such as men who have sex with men. Syphilis is caused by the spirochete Treponema pallidum and spread through direct contact with infectious lesions or bodily fluids. Patients usually present to the emergency department (ED) with chancre, inguinal lymphadenopathy, or rash. Presentations may overlap, but classically the natural history of syphilis may be divided into 3 stages. Primary syphilis typically manifests as a solitary, painless chancre at the inoculation site that develops on average 3 weeks after exposure. Common signs and symptoms of secondary syphilis include maculopapular rash, especially over the hands and soles, malaise, lymphadenopathy, sore throat, or headache beginning about 4 to 10 weeks after appearance of the chancre. Tertiary syphilis can manifest in any organ system, most seriously as neurosyphilis or syphilitic aortitis. Patients who are infected but asymptomatic are deemed early latent if within 1 year of infection and are deemed late latent phase if greater than 1 year of infection.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar In practice, the duration of infection is rarely known, so most are treated for late latent infection. Treponema pallidum cannot be cultured. Dark-field microscopy can assist with diagnosis but is not a widely available technique. Infection with syphilis leads to antibodies that react with cardiolipin, the basis of diagnosis with traditional nontreponemal serologic tests, the Venereal Disease Research Laboratory and Rapid Plasma Reagin tests.2.Brown D.L. Frank J.E. Diagnosis and management of syphilis.Am Fam Phys. 2003; 68: 283-290PubMed Google Scholar For purposes of diagnosis, positive nontreponemal tests should be confirmed with treponemal-specific tests, either T pallidum particle agglutination or fluorescent treponemal antibodies. False-positive nontreponemal test results occur in 1% to 2% of the population as a result of autoimmune disease, pregnancy, and infections. The Venereal Disease Research Laboratory test and Rapid Plasma Reagin test are equally valid assays, but quantitative results from the 2 tests cannot be compared directly. Nontreponemal titers usually correlate with disease activity and become nonreactive with time after treatment, whereas treponemal tests remain reactive for life. Nontreponemal tests are 78% to 86% sensitive in primary syphilis, nearly 100% sensitive in secondary syphilis, and 95% to 98% in latent syphilis.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar Serologic tests are generally accurate and reliable for the diagnosis of syphilis in HIV-infected individuals. Persons with very high titer Rapid Plasma Reagin or Venereal Disease Research Laboratories tests may have false-negative test results that become positive with serum dilution (prozone phenomenon). The cerebrospinal fluid Venereal Disease Research Laboratory test is the standard serologic test for neurosyphilis and is highly specific, but insensitive; therefore, it should be interpreted in the setting of other tests and clinical suspicion.1.Golden M.R. Marra C.M. Holmes K.K. Update on syphilis: resurgence of an old problem.JAMA. 2003; 290: 1510-1514Crossref PubMed Scopus (338) Google Scholar, 4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google Scholar Although sexual transmission of T pallidum occurs only when mucocutaneous syphilitic lesions are present, the CDC recommends that persons exposed sexually to a patient with syphilis at any stage should be evaluated clinically and serologically, with presumptive treatment of contacts exposed within 90 days preceding the diagnosis of primary, secondary, or early latent syphilis in a sex partner. Without prophylaxis, up to 50% to 75% of exposed sex partners of persons with primary or secondary syphilis may become infected.5.Garnett G.P. Aral S.O. Hoyle D.V. et al.The natural history of syphilis: implications for the transmission dynamics and control of infection.Sex Transm Dis. 1997; 24: 185-200Crossref PubMed Scopus (150) Google Scholar Parenteral administration of penicillin G is the preferred drug of treatment of all stages of syphilis. The recommended adult dose is 2.4 million units intramuscularly of benzathine penicillin G. Patients should be informed about the Jarisch-Herxheimer reaction, an acute febrile reaction that may occur within the first 24 hours after any therapy for syphilis, especially among patients with early syphilis. Treatment of syphilis is similar in HIV-positive and HIV-negative patients, although HIV-positive patients require closer follow-up for monitoring of potential treatment failure.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google Scholar Alternative treatment regimens for primary or secondary syphilis have been sought for patients with penicillin allergies, as well as for issues of patient preference, compliance, and ease of prophylaxis. Regimens listed by the CDC include 100 mg of doxycycline orally twice daily for 14 days, 500 mg of tetracycline 4 times daily for 14 days, 1 g of ceftriaxone daily either intramuscularly or intravenously for 8 to 10 days, or a single dose of 2 grams of azithromycin orally.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google Scholar, 6.Hook W. Martin D.H. Stephens J. et al.A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis.Sex Transm Dis. 2002; 29: 486-490Crossref PubMed Scopus (117) Google Scholar Pilot studies have found comparable rates of efficacy between azithromycin and penicillin G in treatment and prophylaxis of syphilis.7.Hook E.W. Stephens J. Ennis D.M. Azithromycin compared with penicillin G benzathine for treatment of incubating syphilis.Ann Intern Med. 1999; 131: 434-437Crossref PubMed Scopus (80) Google Scholar, 8.Verdon M.S. Handsfield H.H. Johnson R.B. Pilot study of azithromycin for treatment of primary and secondary syphilis.Clin Infect Dis. 1994; 19: 486-488Crossref PubMed Scopus (63) Google Scholar However, no large trials on azithromycin for this indication exist, and the CDC recommends close follow-up of patients treated with alternative regimens. Azithromycin for treatment of primary syphilis and for prophylaxis (single dose of 1 gram) has been viewed as an attractive option because it is an oral, 1-dose regimen that is preferred by patients, easier to administer in the field by public health nurses, and with a cost profile comparable to penicillin. Such a regimen also achieves a higher level of treatment in exposed partners because of higher rates of presentation for medical follow-up.9.Blandford J.M. Gift T.L. The cost-effectiveness of single-dose azithromycin for treatment of incubating syphilis.Sex Transm Dis. 2003; 30: 503-508Crossref Scopus (19) Google Scholar Azithromycin is also currently recommended for treatment of several other sexually transmitted diseases, including chlamydial infections, gonorrhea, nongonococcal urethritis, and chancroid. It is safe for use in children and pregnancy. The above alternative regimens are not suitable for pregnant women with syphilis in any stage with penicillin allergy and patients with neurosyphilis; these patients should be desensitized and treated with penicillin.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google Scholar Whenever the diagnosis of syphilis is considered, it is appropriate to send studies for other sexually transmitted diseases. It is also important to consider testing for syphilis in those who present with other sexually transmitted infections. Because many syphilis cases are asymptomatic or minimally symptomatic, they will only be found by screening patients at risk. Although most EDs do not engage in HIV screening because of concerns about counseling and follow-up, all patients with syphilis need HIV testing and should get appropriate referral. In addition, syphilis is reportable in every state. Accurate reporting assists local health departments in targeting limited resources, identification of at-risk sexual contacts, and generation of robust epidemiologic reports.4.Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines 2002.MMWR. 2002; 51: 18-28PubMed Google Scholar