Algorithm to guide re-exposure to penicillin in allergic pregnant women with syphilis: Efficacy and safety

Background: Gestational syphilis is underdiagnosed and undertreated, leading to stillbirth, prematurity, low birthweight, neonatal death, and congenital syphilis. Most patients who label as allergic to penicillin are misdiagnosed. Objective: To assess the efficacy and safety of an algorithm to guide re-exposure to penicillin in pregnant women with syphilis and reporting allergy to the antibiotic. Methods: We performed a prospective study assessing pregnant women with syphilis and labeled as allergic to penicillin. Based on clinical history, patients were divided in two groups: high-risk and low-risk to penicillin allergy. Low-risk patients with negative skin testing and negative serum specific IgE to penicillin underwent drug provocation test. The remaining patients underwent desensitization. Results: Ninety-one patients were enrolled. Allergy to penicillin was confirmed in 7.69% of pregnant women with syphilis and clinical history of allergy to penicillin; in all cases the diagnosis was made through intradermal testing, which predicted 100% of the breakthrough reactions observed during rapid drug desensitization (p < 0.001). Risk stratification based on the initial clinical reaction and skin testing to guide penicillin re-introduction through drug challenge or desensitization was safe (97.8%) and effective (97.8%). Conclusion: We developed and showed the efficacy and safety of an algorithm to guide re-exposure to penicillin in pregnant women with syphilis and labeled as allergic to this drug. Intradermal test is an excellent biomarker in the diagnosis of immediate hypersensitivity reaction to penicillin and to predict breakthrough reaction during rapid drug desensitization. Further studies may confirm the greater safety of the intravenous protocol compared to the oral protocol