Syphilis Diagnosis and Treatment Guidelines

Diagnostic Approach

The diagnosis of syphilis requires both treponemal and nontreponemal tests, as using only one type of test is insufficient for accurate diagnosis, and treatment should be with parenteral penicillin G, with the preparation, dosage, and length determined by disease stage, as recommended by the Centers for Disease Control and Prevention 1, 2
Darkfield microscopy or direct fluorescent antibody tests of lesion exudate are the definitive methods for diagnosing early syphilis when lesions are present, according to the Centers for Disease Control and Prevention 1
The American Academy of Pediatrics recommends a traditional algorithm: Screen with nontreponemal test (VDRL or RPR), followed by treponemal test confirmation (FTA-ABS, TP-PA) if reactive 3
The Centers for Disease Control and Prevention recommends an alternative algorithm: Screen with treponemal-based enzyme immunoassay (EIA) or chemiluminescent immunoassay, followed by nontreponemal test for confirmation of active disease 4

Nontreponemal tests (VDRL, RPR) correlate with disease activity and should be reported quantitatively, as stated by the Centers for Disease Control and Prevention 2
A fourfold change in titer (two dilutions) indicates a clinically significant difference in disease activity or treatment response, according to the Centers for Disease Control and Prevention and the American College of Physicians 1, 2
Treponemal tests (FTA-ABS, TP-PA) typically remain reactive for life regardless of treatment or disease activity, as noted by the Centers for Disease Control and Prevention 2
False-positive nontreponemal tests can occur, especially in HIV-infected persons, requiring careful interpretation, as warned by the Centers for Disease Control and Prevention 4

Parenteral penicillin G is the preferred drug for all stages of syphilis, as recommended by the Centers for Disease Control and Prevention 2
For neurosyphilis: Aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units IV every 4 hours for 10-14 days, as recommended by the Centers for Disease Control and Prevention 2
HIV-infected persons should be treated with the same regimens as those without HIV infection, according to the Centers for Disease Control and Prevention 4
For penicillin-allergic patients who are not pregnant and do not have neurosyphilis, doxycycline is the recommended alternative, as suggested by the Centers for Disease Control and Prevention 2
Penicillin desensitization is recommended for pregnant women with penicillin allergy, as recommended by the Centers for Disease Control and Prevention 2

Clinical and serologic evaluation should be performed 6 and 12 months after treatment, as recommended by the Centers for Disease Control and Prevention 2
A fourfold decline in nontreponemal test titers indicates adequate treatment response, according to the American College of Physicians and the Centers for Disease Control and Prevention 1
Patients with persistent or recurrent signs/symptoms, or a sustained fourfold increase in titer, should be evaluated for treatment failure or reinfection, as recommended by the Centers for Disease Control and Prevention 2

The Centers for Disease Control and Prevention recommends testing for HIV in all patients with confirmed syphilis due to high co-infection rates 5
The Centers for Disease Control and Prevention recommends treating primary, secondary, or early latent syphilis with Benzathine penicillin G 2.4 million units IM as a single dose 5
Treatment should not be delayed in pregnant women once diagnosis is confirmed, as untreated syphilis causes severe fetal complications including stillbirth 6, 7
Pregnant women with penicillin allergy require desensitization, as there are no acceptable alternatives to penicillin in pregnancy 6, 7, 8

Treatment failure is defined by persistent/recurrent symptoms, sustained fourfold increase in nontreponemal titers, or failure of titers to decline fourfold by 6 months 5
The Centers for Disease Control and Prevention recommends monitoring nontreponemal titers at 3, 6, 9, 12, and 24 months after treatment to expect a fourfold decline in titers within 6-12 months as evidence of adequate treatment response 5