Syphilis management for latent stage

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2]Aysha Anwar, M.B.B.S[3]; Nate Michalak, B.A.

Overview

Latent syphilis is defined as syphilis characterized by seroreactivity without other evidence of disease. Patients who have latent syphilis and who acquired syphilis during the preceding year are classified as having early latent syphilis. An asymptomatic person should be considered to have late latent syphilis or syphilis of unknown duration. Nontreponemal serologic titers usually are higher during early latent syphilis than late latent syphilis but are not necessarily diagnostic of early or latent syphilis. The CDC recommends a Benzathine penicillin G regimen for treatment of syphilis. Patients allergic to penicillin may be treated with Doxycycline or tetracycline regimens but efficacy of these alternatives is not well documented. Patients diagnosed with latent syphilis who demonstrate neurologic or ophthalmic signs or symptoms, evidence of tertiary syphilis, or serologic treatment failure should have a prompt CSF examination.

Management for Latent Stage Syphilis

• Latent syphilis is defined as syphilis characterized by seroreactivity without other evidence of disease.

• Patients who have latent syphilis and who acquired syphilis during the preceding year are classified as having early latent syphilis. Patients' conditions can be diagnosed as early latent syphilis if, during the year preceding the evaluation, they had:

• A documented seroconversion of fourfold or greater increase in titer of a nontreponemal test.
• Unequivocal symptoms of primary or secondary syphilis.
• A sex partner documented to have primary, secondary, or early latent syphilis.
• For persons whose only possible exposure occurred during the previous 12 months, reactive nontreponemal and treponemal tests are indicative of early latent syphilis.

• In the absence of these conditions, an asymptomatic person should be considered to have late latent syphilis or syphilis of unknown duration.

• Nontreponemal serologic titers usually are higher during early latent syphilis than late latent syphilis. However, early latent syphilis cannot be reliably distinguished from late latent syphilis solely on the basis of nontreponemal titers.

• All patients with latent syphilis should have careful examination of all accessible mucosal surfaces (i.e., the oral cavity, perianal area, perineum and vagina in women, and underneath the foreskin in uncircumcised men) to evaluate for internal mucosal lesions.

• All patients who have syphilis should be tested for HIV infection.

CDC Recommendations: Pharmacotherapy

• Because latent syphilis is not transmitted sexually, the objective of treating patients with this stage of disease is to prevent complications.

• Although clinical experience supports the effectiveness of penicillin in achieving this goal, limited evidence is available to guide choice of specific regimens.

• Available data demonstrate no enhanced efficacy of additional doses of penicillin G, amoxicillin, or other antibiotics in early syphilis, regardless of HIV status.
• Recommendations for children:

• Infants and children aged more than 1 month who have been diagnosed with syphilis should have a CSF examination to exclude neurosyphilis.

• Birth and maternal medical records should be reviewed to assess whether children have congenital or acquired syphilis.

• Older children with acquired latent syphilis should be evaluated as described for adults and treated using the following pediatric regimens.

Recommended Regimen for Adults

The following regimens are recommended for penicillin nonallergic patients who have normal CSF examinations (if performed):

• Early Latent Syphilis:

• Benzathine penicillin G 2.4 million units IM in a single dose.

• Late Latent Syphilis or Latent Syphilis of Unknown Duration:

• Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals.

Recommended Regimen for Infants and Children

The following regimens are for penicillin non-allergic children who have acquired syphilis and who have normal CSF examination results (if performed):

• Early Latent Syphilis:

• Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose.

• Late Latent Syphilis or Latent Syphilis of Unknown Duration:

• Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units, administered as 3 doses at 1-week intervals (total 150,000 units/kg up to the adult total dose of 7.2 million units).}}

Other Management Considerations

• Patients diagnosed with latent syphilis who demonstrate any of the following criteria should have a prompt CSF examination:

• Neurologic (e.g., auditory disease, cranial nerve dysfunction, acute or chronic meningitis, stroke, acute or chronic altered mental status, and loss of vibration sense) or ophthalmic signs or symptoms (e.g., iritis and uveitis)

• Evidence of active tertiary syphilis (e.g., aortitis and gumma)

• Serologic treatment failure

• If a patient misses a dose of penicillin in a course of weekly therapy for late syphilis, the appropriate course of action is unclear.

• Pharmacologic considerations suggest that an interval of 10-14 days between doses of benzathine penicillin for late syphilis or latent syphilis of unknown duration might be acceptable before restarting the sequence of injections.

• Missed doses are not acceptable for pregnant patients receiving therapy for late latent syphilis.

• Pregnant women who miss any dose of therapy must repeat the full course of therapy.

Special Considerations

Penicillin Allergy: Alternative Regimen

• The effectiveness of alternatives to penicillin in the treatment of latent syphilis has not been well documented.

• Non-pregnant patients allergic to penicillin who have clearly defined early latent syphilis should respond to therapies recommended as alternatives to penicillin for the treatment of primary and secondary syphilis.

• The only acceptable alternatives for the treatment of late latent syphilis or latent syphilis of unknown duration are:

• Doxycycline (100 mg orally twice daily) or
• Tetracycline (500 mg orally four times daily), both for 28 days.

• These therapies must be used in conjunction with close serologic and clinical follow-up.

• Based on biologic plausibility and pharmacologic properties, ceftriaxone might be effective for treating late latent syphilis or syphilis of unknown duration. However, the optimal dose and duration of ceftriaxone therapy have not been defined.

• Some patients who are allergic to penicillin also might be allergic to ceftriaxone; in these circumstances, use of an alternative agent might be required.

• The efficacy of these alternative regimens in HIV-infected persons has not been well studied.

Pregnancy

Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin.

Follow-Up

• Quantitative nontreponemal serologic tests should be repeated at 6, 12, and 24 months.

• A CSF examination should be performed if:

• Titers increase fourfold
• An initially high titer (greater than 1:32) fails to decline at least fourfold (i.e., two dilutions) within 12-24 months of therapy
• Signs or symptoms attributable to syphilis develop

• In such circumstances, even if the CSF examination is negative, re-treatment for latent syphilis should be initiated.

• In rare instances, despite a negative CSF examination and a repeated course of therapy, serologic titers may fail to decline. In these circumstances, the need for additional therapy or repeated CSF examinations is unclear.

References

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