SYPHILIS (Last Revision: May )

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1 SYPHILIS (Last Revision: May ) Discuss all cases of suspected or proven syphilis with the attending physician prior to treatment, regardless of the stage or duration of infection. A. Diagnosis A serologic test for syphilis (STS) should be performed on all patients who have not been tested within the preceding 3 months and on any patient with undiagnosed genital lesions, regardless of time since the previous serology. Obtain a stat RPR for all patients with genital or perianal ulcerations that are not typical of genital herpes, warts that are not typical for condylomata acuminata, any undiagnosed general skin rash, or a patient who is a sexual contact of a partner with syphilis. It may be necessary in some cases to dilute the serum 1:8 to detect a positive RPR (prozone phenomenon). Perform a darkfield (DF) examination of any genital, anal, or perianal ulcerative lesion not typical of genital herpes. Staging is as follows: 1. Primary: Dark Field positive material from a chancre-like lesion, with positive serology (RPR+/FTA+ or RPR-/FTA+) and no past history of syphilis. In principal, primary syphilis should not be diagnosed without a positive darkfield microscopy. 2. Secondary: signs of systemic infection (bilaterally symmetric macular/ papular/papulosquamous/pustular skin lesions, alopecia, loss of eyelashes and lateral eyebrows, condylomata lata, mucous patches, generalized lymphadenopathy, fever and malaise) with positive serology (RPR+/FTA+). 3. Early latent: patient without symptoms/signs of syphilis with positive serology (RPR+/FTA+) known to have had in the past year: a) negative STS, b) symptoms of primary or secondary syphilis, c) exposure to known case of early (primary, secondary, or early latent) syphilis, or d) > 4-fold increase in titer on serial RPR. 4. Late latent: patient without symptoms/signs of syphilis with positive serology (RPR+/FTA+) and no prior treatment for syphilis who does not meet definition of early latent disease. 5. Establishing a diagnosis of syphilis in a patient with a prior history of treated syphilis requires a positive DF exam or > 4-fold rise in RPR titer. 6. Persistent infection is suggested by persistent/recurrent signs or symptoms of syphilis, a > 4-fold increase in RPR titer, or the failure of a high-titer RPR (> 1:32) to decrease > 4-fold within 12 months. 7. In ALL stages of syphilis, patients should be interviewed about possible neurologic symptoms (headache, photophobia, dizziness, memory loss,

2 weakness or numbness of arms or legs, seizures, difficulty concentrating, problems with vision or hearing). Those with any suggestion of neurologic problems should have a neurologic exam by the attending physician. A CSF exam should be considered, in consultation with the clinic physician, if any of the following are present: a) Neurologic or ophthalmologic signs or symptoms b) Documented treatment failure (recurrent symptoms or 4-fold-rise in absence of likely re-infection) c) Other evidence of active syphilis (aortitis, gumma, iritis) d) HIV infection 8. All patients with active syphilis should be advised to have an HIV test and a follow-up HIV test in 3 months. B. Treatment For all stages of syphilis, IM penicillin G is the treatment of choice, and is the only therapy with documented efficacy for neurosyphilis or syphilis in pregnancy. If doxycycline or erythromycin are given, it is extremely important to counsel the patient firmly about adherence to the regimen, since missing only a few doses will significantly increase the failure rate. 1. Early syphilis (primary, secondary, and early latent syphilis) a) Long-acting benzathine penicillin G (LAB) 2.4 million units IM b) Doxycycline 100 mg BID PO for 14 days; use only if patient is allergic to penicillin. Note 1: All penicillin injections should be given in a divided dose, half of the recommended dose to the upper outer quadrant of each hip. The patient should be asked to wait minutes, before leaving the clinic, in case of allergic response to the medication. Note 2: The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache and myalgia, and other symptoms that usually occurs within the first 24 hours following treatment for early syphilis. Patients should be informed about this possible adverse reaction. Note 3: The use of alternative treatments, including azithromycin and ceftriaxone may be considered in certain cases, but should be discussed with the attending physician. 2. Late latent syphilis a) LAB 2.4 million units IM weekly for 3 doses (total 7.2 million units) b) Doxycycline 100 mg PO BID x 28 days; use only if patient is allergic to penicillin.

3 Note: If a patient misses a dose of penicillin in the course of weekly therapy for late syphilis, the sequence of injections must be restarted. 3. Neurosyphilis, both symptomatic and asymptomatic Patient with neurosyphilis need to be managed in combination with the AIDS/ID clinic or inpatient medicine service. There are no satisfactory alternatives to penicillin for treatment of neurosyphilis and those with a history of penicillin allergy should be skin-tested and, if necessary, desensitized. a) The treatment of choice is hospitalization for penicillin G, million units IV daily for 14 days, followed by weekly injections of LAB 2.4 million units for 3 weeks. b) Procaine penicillin G 2.4 million units IM daily plus probenecid 500 mg PO qid, both for days, followed by weekly injections of LAB 2.4 million units for 21 days. 4. Syphilis in pregnancy: Penicillin is the only treatment known to be effective in preventing or treating syphilis in the fetus. In case of penicillin allergy, refer for penicillin desensitization and treatment. Treatment of early syphilis in women in the second half of pregnancy should be undertaken with obstetrical consultation as the Jarisch-Herxheimer reaction may lead to premature labor and fetal distress. C. Follow-up Treatment failure is common in all stages of syphilis, even with recommended treatment regimens. In addition to resolution of signs and symptoms, the serological response is used to define cure. Most patients should be seen on the following schedules (although visits may be individualized by the clinic physician): 1. Early syphilis (primary, secondary, early latent): a. Clinic examination after 1 week. b. Repeat serology (quantitative RPR) 6 and 12 months after treatment. 2. Late syphilis: a. Repeat serology (quantitative RPR) 6, 12 and 24 months after treatment. b. Evaluate for neurosyphilis if the RPR titer increases 4-fold, an initially high titer ( 1:32) fails to fall 4-fold in months, or if signs or symptoms of syphilis develop. 3. Neurosyphilis:

4 a. Repeat serology (quantitative RPR) at 6, 12 and 24 months after treatment b. Follow-up CSF examination at 6-month intervals until cell count is normal. D. Management of contacts Refer all patients with syphilis to CDPHE DIS staff for partner notification interview. 1. To determine risk of partners, the time periods before treatment are a) 3 months plus duration of symptoms for primary syphilis; b) 6 months plus duration of symptoms for secondary syphilis; and c) 1 year for early syphilis 2. Contacts of patients with primary, secondary, or early latent syphilis: Routine history, examination, and syphilis serology, including stat RPR; administer epidemiologic treatment for all contacts within the preceding 3 months, regardless of syphilis serology (LAB 2.4 million units IM x 1). Treponomal test (FTA) should be performed for all contacts to syphilis, since they may be positive when non-treponomal tests (RPR, VDRL) are still negative in early syphilis. 3. Contacts of patients with late syphilis: serology (RPR, FTA) in all longterm contacts, and for the children of infected women; treat only if positive. 4. Contacts of patient with latent syphilis of unknown duration (no prior serologic test) should be managed as are contacts of early latent syphilis even though the source contact patient is typically treated for possible late latent infection. 5. For purposes of partner notification and presumptive treatment of exposed sex partners, patients with syphilis of unknown duration who have high treponemal serologic tests (i.e., >1:32) can be assumed to have early syphilis. However, serologic tests should not be used to differentiate early from latent syphilis for the purpose of treatment. 6. Advise sexual abstinence for 1 week after one-time penicillin for early syphilis therapy or until completion of treatment with other regimens. E. Syphilis in HIV-Infected Patients 1. Clinic physician should see all HIV-positive syphilis patients to assess the presence of neurologic problems. 2. Patients with primary, secondary, and confirmed early latent syphilis should be treated with LAB 2.4 million units once, as for HIV-negative patients. Those with late latent syphilis, or syphilis of unknown duration, should have a CSF exam prior to treatment, especially if neurologic symptoms or signs, treatment failure, or low CD4 count (<200) are

5 present. If the patient has a normal CSF exam then he/she should be treated with LAB 2.4 mu weekly x 3; if the patient has CSF consistent with neurosyphilis then he/she should be managed the same as patients with neurosyphilis. Depending on the patient s circumstances, the attending physician has the discretion to authorize starting treatment prior to CSF exam. 3. Penicillin regimens should be used whenever possible for all stages of syphilis in HIV-infected patients. Penicillin-allergic patients should be skin-tested and, if positive, considered for desensitization. The efficacy of alternative non-penicillin regimens in HIV-infected persons has not been studied. 4. In order to detect early treatment failure, it is important that HIV-infected patients with early syphilis have follow-up serology performed at 3, 6, 9, 12, and 24 months, while those with late latent syphilis should have follow-up serology performed at 6, 12, 18, and 24 months after therapy. Patients with late latent syphilis who develop symptoms consistent with syphilis, a 4-fold increase in RPR titer, or whose RPR fails to decline 4-fold should have a repeat CSF examination and re-treatment for late latent syphilis. Patients with early syphilis whose titers increase or fail to decrease 4-fold within 6 months should undergo a CSF exam and be retreated as for late latent syphilis.