Desensitization for Syphilis in Pregnancy: One-Time Protocol
Pregnant patients with syphilis and a severe IgE-mediated penicillin allergy require desensitization only once before initiating the penicillin treatment course, not before each individual dose. 1, 2
Desensitization Protocol Structure
Desensitization is performed as a single procedure that temporarily induces tolerance to penicillin, allowing the entire treatment regimen to be completed without repeating the desensitization process. 2, 3
After successful desensitization, all subsequent penicillin doses (whether single-dose for early syphilis or three weekly doses for late latent disease) can be administered without additional desensitization. 2, 3
The desensitization effect persists throughout the treatment course as long as penicillin administration is not interrupted for more than 10–14 days; if treatment is delayed beyond this window, re-desensitization may be necessary. 2
Why Desensitization Is Mandatory in Pregnancy
Penicillin is the only antimicrobial proven to prevent congenital syphilis and reliably cure fetal infection; no acceptable alternatives exist during pregnancy. 1, 2, 3
Tetracyclines cause maternal hepatotoxicity and fetal bone/tooth staining, while erythromycin and azithromycin fail to reliably treat the fetus and should never be substituted. 1, 2, 4
Ceftriaxone lacks sufficient data to recommend for preventing congenital syphilis in pregnancy. 1
Pre-Desensitization Assessment
Confirm penicillin allergy status with skin testing before proceeding to desensitization; some patients with reported allergy will have negative skin tests and can receive penicillin directly. 1, 2, 5
Skin testing should include both major determinants (penicilloyl-polylysine) and minor determinant mixtures when available; a negative skin test significantly reduces (but does not eliminate) the risk of immediate hypersensitivity. 1, 5
If initial skin testing is negative but clinical suspicion for allergy remains high, consider repeating skin testing 1–2 weeks later, as sensitization may not be detectable on first evaluation. 5
Desensitization Setting and Monitoring
Perform desensitization in a monitored setting with immediate access to resuscitation equipment, epinephrine, antihistamines, corticosteroids, and airway management tools. 2, 6
For viable pregnancies beyond 20 weeks gestation, administer the first dose of benzathine penicillin G in a labor and delivery unit with continuous fetal and uterine contraction monitoring for at least 24 hours to detect Jarisch-Herxheimer reaction. 2, 7
Oral desensitization protocols are safe, feasible, and cost-effective; they can be performed in an outpatient obstetric emergency setting with intensive care backup available. 6
Treatment Regimen After Desensitization
For primary, secondary, or early latent syphilis: administer benzathine penicillin G 2.4 million units IM as a single dose, with some experts recommending a second dose one week later, particularly in the third trimester or for secondary syphilis. 2, 3, 4
For late latent or unknown-duration syphilis: administer benzathine penicillin G 2.4 million units IM weekly for three consecutive weeks (total 7.2 million units). 2, 3, 4
Each weekly injection should be spaced exactly 7 days apart; if a pregnant patient misses a dose, the entire three-dose series must be restarted. 2
Jarisch-Herxheimer Reaction Precautions
Instruct patients to seek immediate obstetric care if they experience fever, uterine contractions, or decreased fetal movements within 24 hours after any penicillin dose. 1, 2, 3
The Jarisch-Herxheimer reaction occurs in up to 44% of pregnant women treated for syphilis and can precipitate premature labor, fetal distress, or rarely stillbirth, especially when ultrasound shows fetal hepatomegaly or hydrops. 1, 7
Never delay treatment due to fear of this reaction; untreated maternal syphilis poses far greater fetal risk than the reaction itself. 2, 3, 4
Critical Pitfalls to Avoid
Do not substitute non-penicillin antibiotics (azithromycin, ceftriaxone, erythromycin, tetracyclines) for syphilis treatment in pregnancy—they do not prevent congenital infection. 1, 2, 4
Do not assume desensitization is needed for every dose; this misconception leads to unnecessary procedures and delays in treatment. 2, 3
Do not discharge a newborn without documented evidence that the mother was screened for syphilis at least once during pregnancy. 1, 2, 3
Ensure treatment is completed at least 4 weeks before delivery for optimal prevention of congenital syphilis. 2, 3