The Jarisch-Herxheimer reaction and fetal monitoring changes in pregnant women treated for syphilis

doi:10.1016/S0029-7844(98)00271-3

Obstetrics & Gynecology

Volume 92, Issue 5, November 1998, Pages 859-864

https://doi.org/10.1016/S0029-7844(98)00271-3 Get rights and content

Abstract

Objective: To estimate the incidence of the Jarisch-Herxheimer reaction in pregnant women undergoing treatment of syphilis and the incidence of changes in uterine activity or fetal heart rate (FHR).

Methods: Pregnant women of at least 24 weeks’ gestation diagnosed as needing treatment of syphilis were reviewed retrospectively. Patients were admitted for their first dose of benzathine penicillin, and the FHR was recorded continuously before and for 24 hours after injection. The occurrence of the Jarisch-Herxheimer reaction was noted, and all available FHR records for this admission were reviewed. Evaluations for changes in the FHR pattern and uterine activity were made. Statistical comparisons used Student t, Fischer exact, and χ² tests, when applicable (significance P < .05).

Results: We reviewed 50 charts and 31 available FHR records. The average gestational age was 30.8 weeks. We found 20 cases of probable Jarisch-Herxheimer reaction (40%). Thirteen of 31 patients (41.9%) developed regular uterine contractions, median onset, 10 hours. All resolved within 24 hours of treatment. Patients with uterine contractions had a greater mean increase in temperature (1.15F versus 0.68F, P < .008). Twelve of 31 women (38.7%) developed recurrent variable decelerations, median onset, 8 hours. All patients but one had their contractions resolve within 24 hours of treatment. Lower gestational age was associated with the occurrence of recurrent variable decelerations (29.6 weeks versus 32.3 weeks, P < .05). No patients required delivery at the time of treatment.

Conclusion: The incidence of Jarisch-Herxheimer reaction in treated syphilitic pregnancies is about 40%; similar proportions of patients develop regular uterine contractions and recurrent variable decelerations.

Section snippets

Materials and methods

From 1991 to 1996, our hospital treatment protocol for syphilis infected women with pregnancies greater than 24 weeks’ gestation was for admission with continuous monitoring both before and after treatment. The continuous monitoring after treatment was for a minimum of 24 hours. Patients were admitted for their initial penicillin dose only. We studied 50 such pregnancies. These women had been admitted to the antepartum step-down unit at the University of Illinois at Chicago from 1991 to 1996.

Results

With our medical record search, we found 50 patients who fulfilled the study criteria, and had been admitted for continuous FHR monitoring at the time of initial treatment of syphilis. The demographic breakdown of these patients is included in Table 1. No perinatal deaths occurred. Five infants were born before 34 weeks. No patient delivered during this hospitalization. The average temperature change was 0.76F. Although 25 of 50 patients’ temperature spiked to 99.0F or above, no patient had a

Discussion

The Jarisch-Herxheimer reaction has been described in medical literature for over 100 years. Because of the changes in uterine activity and FHR tracings observed by ourselves and others, possibly an extension of the Jarisch-Herxheimer reaction, the description of the Jarisch-Herxheimer reaction in the obstetrical literature may require refinement. Bowan et al described two cases of fetal death within 24 hours of treatment.8 He hypothesized that this was because of some sort of fetal

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In addition to a 30% to 40% stillbirth risk, newborns of infected mothers are often born preterm or with low birthweight (10%–40%).18,62 Fetuses exposed in utero often have significant hematologic abnormalities, hepatobiliary dysfunction (33%–100%), blistering skin rashes (40%), and potential neurologic and orthopedic sequelae (75%), all of which result in prolonged neonatal intensive care unit stay, with significant morbidity and adverse long-term outcomes.18–20,47,62–64 The most serious complication is CNS involvement, which occurs in up to 40% of newborns with symptomatic CS.
Syphilis is a treponemal infection that can be acquired sexually, hematogenously, or via vertical transmission from mother to infant. Despite evidence-based curative treatment options with penicillin, it remains a public health threat with increasing prevalence over recent years. Congenital syphilis, a condition where a fetus acquires the infection during pregnancy, can lead to stillbirth, miscarriage, preterm birth, birth defects, and lifelong physical or neurologic changes. Congenital syphilis rates in the United States increased by 261% from 2013 to 2018 and continue to increase in 2021. The only recommended treatment for syphilis in pregnancy is benzathine penicillin G because evidence of decreased risk of congenital syphilis with other modalities is lacking. Testing for syphilis is complex and includes either the reverse-sequence algorithm or the traditional algorithm. Determination of the clinical stage of syphilis includes incorporation of the previous treatment sequence and physical examination. The goal of this review was to discuss the current evidence about optimal treatment and testing during pregnancy to optimize maternal health and prevent congenital syphilis.
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The JH reaction occurs in up to 44% of pregnant women and can precipitate preterm labor, fetal heart rate abnormalities, and stillbirth.75,78,80-85 It occurs in 100% of primary disease, 60% of secondary disease, and more than half of patients with syphilis of unknown duration.80 Pregnancy-specific complications include uterine contractions (56-67%), decreased fetal movement (67%), and fetal heart rate decelerations (50%).75,78,80
Syphilis remains the most common congenital infection worldwide and has tremendous consequences for the mother and her developing fetus if left untreated. Recently, there has been an increase in the number of congenital syphilis cases in the United States. Thus, recognition and appropriate treatment of reproductive-age women must be a priority. Testing should be performed at initiation of prenatal care and twice during the third trimester in high-risk patients. There are 2 diagnostic algorithms available and physicians should be aware of which algorithm is utilized by their testing laboratory. Women testing positive for syphilis should undergo a history and physical exam as well as testing for other sexually transmitted infections, including HIV. Serofast syphilis can occur in patients with previous adequate treatment but persistent low nontreponemal titers (<1:8). Syphilis can infect the fetus in all stages of the disease regardless of trimester and can sometimes be detected with ultrasound >20 weeks. The most common findings include hepatomegaly and placentomegaly, but also elevated peak systolic velocity in the middle cerebral artery (indicative of fetal anemia), ascites, and hydrops fetalis. Pregnancies with ultrasound abnormalities are at higher risk of compromise during syphilotherapy as well as fetal treatment failure. Thus, we recommend a pretreatment ultrasound in viable pregnancies when feasible. The only recommended treatment during pregnancy is benzathine penicillin G and it should be administered according to maternal stage of infection per Centers for Disease Control and Prevention guidelines. Women with a penicillin allergy should be desensitized and then treated with penicillin appropriate for their stage of syphilis. The Jarisch-Herxheimer reaction occurs in up to 44% of gravidas and can cause contractions, fetal heart rate abnormalities, and even stillbirth in the most severely affected pregnancies. We recommend all viable pregnancies receive the first dose of benzathine penicillin G in a labor and delivery department under continuous fetal monitoring for at least 24 hours. Thereafter, the remaining benzathine penicillin G doses can be given in an outpatient setting. The rate of maternal titer decline is not tied to pregnancy outcomes. Therefore, after adequate syphilotherapy, maternal titers should be checked monthly to ensure they are not increasing four-fold, as this may indicate reinfection or treatment failure.
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Infections may be hazardous to the health of the mother, the course of pregnancy, and the unborn child. They can lead to premature labor or premature rupture of membranes and thereby increase the risk for spontaneous abortion and prematurity. Furthermore, certain germs can pass to the unborn child and harm it directly. Therefore, an anti-infective treatment which should be both effective and safe for the mother and the unborn child is often required. The use of penicillines and older cephalosporines is well documented and considered to be safe. Consequently, they are the drug of choice during pregnancy. In selected cases of bacterial resistance or intolerance to first-line antibiotics, other anti-infective agents might be recommended. Especially for life-threatening infections, a therapy with not so well-tried agents might be needed. The potential benefit of treatment in such cases most often outbalances the potential risk for the unborn child.
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Original ArticlesThe Jarisch-Herxheimer reaction and fetal monitoring changes in pregnant women treated for syphilis

Abstract

Section snippets

Materials and methods

Results

Discussion

Am J Obstet Gynecol

Therapeutic veruche bei syphilis

Wein Med Wochenschr

The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy

Obstet Gynecol

Adverse reactions in syphilis therapy

J Am Vener Dis Assoc

Doppler systolic-diastolic ratios in pregnancies complicated by syphilis

Obstet Gynecol

Original Articles
The Jarisch-Herxheimer reaction and fetal monitoring changes in pregnant women treated for syphilis