D3.382 - Safety and outcomes of penicillin desensitization during pregnancy: experience from a tertiary referral center

The rising prevalence of syphilis in pregnancy combined with self-reported penicillin allergy has increased the need for penicillin desensitization, as benzathine penicillin remains the only effective treatment to prevent congenital syphilis. Desensitization is considered safe in pregnancy; however, reactions may occur. The aim was to describe clinical history characteristics, allergy test results, and adverse reactions during penicillin desensitization in pregnant women with syphilis.

Retrospective cross-sectional study including all pregnant women with syphilis and a history of penicillin allergy referred to a tertiary allergy center (June 2016–December 2025). Clinical history, PENFAST score, skin testing, basophil activation test (BAT), route of desensitization, and adverse events were analyzed.

A total of 242 pregnant women were referred; desensitization was indicated in 120 cases. Mean age was 24.2 ± 7.7 years and mean gestational age 15.7 ± 8.0 weeks. Benzathine penicillin was implicated in 83% of index reactions, occurring 8.5 ± 9.0 years before evaluation. Immediate reactions were reported by 60%, with mean PENFAST 2.8 ± 1.7. Skin tests were positive in 9.2%. Intravenous desensitization was performed in 27% (currently the exclusive route). Eight patients reacted during desensitization: 6 anaphylaxis episodes and 2 cases of significant cough/throat clearing with spontaneous resolution. Reactions occurred early in 4 patients, and one after benzathine penicillin administration. One of the  anaphylatic patients discontinued treatment; another reacted during the second benzathine penicillin dose. Mean PENFAST among reactors was 3.25; only 3 had positive skin tests. One patient with PENFAST classified as low risk (score 0)and negative skin test had positive BAT and reacted during drug provocation, requiring desensitization.

Benzathine penicillin exposure, history of immediate reaction, and a moderate-risk PENFAST profile were the main characteristics of this population. Reactions during desensitization were mild to moderate. In addition, the skin test showed low sensitivity, and BAT appears to be an efficient tool for identifying penicillin allergy. Validation of clinical history information combined with BAT is essential for safely indicating desensitization, particularly in pregnant women.