What are the potential risks of the Jarisch-Herxheimer reaction in pregnant women?

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Elsevier ClinicalKey Drug Monograph

Content last updated: January 4, 2024.

Adverse Reactions The Jarisch-Herxheimer reaction is a self-limiting systemic reaction that has been reported in the setting of spirochete infections, such as Lyme disease, syphilis, relapsing fever, and leptospirosis, after the initiation of antimicrobial therapy. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. Less commonly, symptoms may include meningitis, pulmonary failure, hepatic and renal dysfunction, myocardial injury, premature uterine contractions in pregnant patients, and worsening cerebral function as well as strokes and seizures. The reaction has been noted in up to 30% of patients with early Lyme disease. The timing of the reaction varies by underlying infection but typically presents within a few hours after the initiation of antibiotics. For Lyme disease, the reaction usually begins within 1 to 2 hours after starting therapy and disappears within 12 to 24 hours. The reaction after treatment in syphilis usually starts at 4 hours, peaks at 8 hours, and subsides by 16 hours whereas it starts at about 1 to 2 hours, peaks at 4 hours, and subsides by 8 hours after treatment in relapsing fever. The pathogenesis of this reaction is unknown but may be due to the release of spirochetal heat-stable pyrogen. Fluids and antipyretics can be used to alleviate symptoms and duration of the reaction if severe. Although this reaction may induce early labor or cause fetal distress in pregnant women, according to guideline recommendations, this concern should not prevent or delay therapy for syphilis.

2.

Elsevier ClinicalKey Drug Monograph

Content last updated: May 2, 2024.

Contraindications And Precautions Human experience with penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. Animal reproduction studies have also not revealed any evidence of impaired fertility or harmful fetal effects. However, there are no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of penicillins on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, use penicillin G in pregnant women only if clearly needed. The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache, myalgia, and other symptoms that usually occurs within the first 24 hours after any therapy for syphilis, most often among patients who have early syphilis. Antipyretics may be used, but they have not been proven to prevent this reaction. The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress in pregnant women; this concern should not prevent or delay therapy.

Pregnancy Human experience with penicillins during pregnancy has not shown any positive evidence of adverse effects on the fetus. Animal reproduction studies have also not revealed any evidence of impaired fertility or harmful fetal effects. However, there are no adequate and well-controlled studies in pregnant women showing conclusively that harmful effects of penicillins on the fetus can be excluded. Because animal reproduction studies are not always predictive of human response, use Pfizerpen in pregnant women only if clearly needed. The Jarisch-Herxheimer reaction is an acute febrile reaction frequently accompanied by headache, myalgia, and other symptoms that usually occurs within the first 24 hours after any therapy for syphilis, most often among patients who have early syphilis. Antipyretics may be used, but they have not been proven to prevent this reaction. The Jarisch-Herxheimer reaction may induce early labor or cause fetal distress in pregnant women; this concern should not prevent or delay therapy.

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Sato, Alice I., Davies, H. Dele (2025). Syphilis (Treponema pallidum). In Nelson Textbook of Pediatrics (pp. 1866). DOI: 10.1016/B978-0-323-88305-4.00264-9

When clinical or serologic findings suggest active infection or when the diagnosis of active syphilis cannot be excluded with certainty, treatment is indicated. The goals of treatment of the pregnant person include eradication of maternal (parental) disease, prevention of parent-to-child transmission, and treatment of fetal infection. Patients should be treated immediately with the penicillin regimen appropriate for the pregnant person’s stage of syphilis. Those who have beenadequately treated in the past do not require additional therapy unless quantitative serology suggests evidence of reinfection(fourfold elevation in titer). Penicillin G is the only agent known to be effective for treating fetal infection and for prevention of congenital infection. Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin. If doses for late latent syphilis are delayed beyond 9 days from the prior dose, the full course of therapy needs to be repeated. Additional therapy may be considered for pregnant persons with primary, secondary, or early latent syphilis or when syphilis is diagnosed during the second half of pregnancy and sonographic evidence of fetal or placental syphilis is noted. In these cases, a second dose of benzathine penicillin G (2.4 million units IM given 1 week after the initial dose) may decrease the risk of vertical transmission. Jarisch-Herxheimer reaction in the second half of pregnancy may induce premature labor or fetal distress, and patients with reactions should seek obstetric attention promptly.