A Jarisch-Herxheimer reaction (JHR) is a transient inflammatory response that can occur during antibiotic treatment of spirochetal infections. The reaction was first described in patients treated for syphilis but has also been reported in other spirochetal diseases including leptospirosis, relapsing fever, and Lyme disease.

Jarisch-Herxheimer reactions typically develop within several hours after starting antimicrobial therapy and are characterized by fever, tachycardia, chills, and a temporary worsening of existing symptoms. Although usually self-limited, the reaction can be clinically concerning, particularly in vulnerable populations such as newborns.

Lyme disease in neonates is uncommon, but clinicians should remain aware of possible exposure when a tick bite and erythema migrans rash are documented.

Prodanuk and colleagues described a neonatal case of Lyme disease complicated by a Jarisch-Herxheimer reaction in The Pediatric Infectious Disease Journal.

Clinical Presentation

A 21-day-old infant presented to the hospital with the following symptoms:

• Decreased activity
• Poor feeding
• Abdominal distension

The parents reported removing an engorged tick from the infant’s forearm five days prior to admission. An erythema migrans rash was noted at the bite site, strongly suggesting early localized Lyme disease.

Given the erythema migrans lesion at the site of the tick bite, clinicians made a presumptive diagnosis of Lyme disease and initiated intravenous ceftriaxone therapy.

Development of the Herxheimer Reaction

Within two hours of starting intravenous ceftriaxone, the infant developed:

• Fever
• Tachycardia
• Symptoms consistent with a Jarisch-Herxheimer reaction

The infant was closely monitored and the symptoms gradually resolved as treatment continued. Laboratory testing for Lyme disease returned negative, which can occur early in infection or in neonates with immature immune responses.

Three Key Discussion Points

1. Awareness of JHR in Neonates
   Clinicians should be aware that Jarisch-Herxheimer reactions may occur during treatment of spirochetal infections, even in very young infants.
2. Risk of Disseminated Lyme Disease
   Neonates may be at greater risk for disseminated infection due to immature immune defenses.
3. Broad Range of Symptoms
   Jarisch-Herxheimer reactions can involve a range of systemic symptoms including:

• Fever
• Chills
• Tachycardia
• Hypotension
• Muscle and joint pain
• Nausea
• Headache
• Temporary worsening of existing symptoms

Pathophysiology of the Herxheimer Reaction

The exact mechanism of the Jarisch-Herxheimer reaction remains uncertain.

Early theories suggested endotoxin release, but spirochetes do not produce biologically active endotoxins. Current evidence indicates that rapid destruction of spirochetes during antibiotic therapy triggers release of bacterial components that stimulate a pro-inflammatory cytokine response.

This inflammatory cascade involves mediators such as tumor necrosis factor-alpha (TNF-α) and interleukins, leading to the systemic symptoms observed during the reaction.

Management of JHR is generally supportive while antibiotic therapy continues.

Video: Understanding the Herxheimer Reaction

The following short video explains how a Jarisch-Herxheimer reaction can occur during treatment of Lyme disease.

Conclusion

This neonatal case illustrates the complexity of diagnosing and managing Lyme disease in very young infants. Awareness of the Jarisch-Herxheimer reaction can help clinicians distinguish a temporary inflammatory response from clinical deterioration during antibiotic therapy.

Learn more about Lyme disease symptoms and how early recognition may guide treatment decisions.

References

1. Nykytyuk O, et al. Insights into the Pathophysiology of the Jarisch-Herxheimer Reaction. Infectious Disease Review. 2020.
2. Prodanuk M, et al. Lyme Disease in a Neonate Complicated by the Jarisch-Herxheimer Reaction. Pediatric Infectious Disease Journal. 2020.