When a 21-day-old infant developed a fever and rapid heartbeat just hours after receiving antibiotics for Lyme disease, doctors were faced with a critical question: Was it sepsis—or something else? Could it possibly be a Herxheimer reaction?

This case highlights a rare but important phenomenon: a Herxheimer reaction can even occur in a newborn infant. Without careful observation, this response could easily be mistaken for a serious complication.

What Is a Herxheimer Reaction?

The Jarisch-Herxheimer reaction (JHR) is a temporary inflammatory response that can occur during antibiotic treatment for certain bacterial infections—especially those caused by spirochetes like Borrelia burgdorferi, the bacterium responsible for Lyme disease.

This reaction typically involves the sudden onset of new symptoms or worsening of existing ones shortly after beginning treatment. It is thought to result from the release of bacterial components during die-off, which triggers a surge in inflammatory cytokines.

Common symptoms include:

1. Fever
2. Chills
3. Headache
4. Muscle and joint pain
5. Tachycardia
6. Worsening of pre-existing symptoms

A Case of Herxheimer Reaction in an Infant

In a 2020 case report in The Pediatric Infectious Disease Journal, Prodanuk and colleagues describe a 21-day-old infant who presented with:

1. Poor feeding

2. Decreased activity

3. Abdominal distension

The infant had an erythema migrans (EM) rash at the site of a recently removed engorged tick, leading to a presumptive diagnosis of early localized Lyme disease. Intravenous ceftriaxone was started.

Just two hours later, the infant developed:

1. Fever
2. Tachycardia
3. General clinical deterioration

These symptoms were consistent with a Herxheimer reaction, prompting close monitoring.

The Lyme Test Was Negative—But That’s Not Unusual

In this case, Lyme testing returned negative—a result that can be expected in early disease or in neonates whose immune systems are not mature enough to produce detectable antibodies.

This underscores an important point: Lyme disease is primarily a clinical diagnosis – we don’t rely on a positive test, especially in the presence of an EM rash and known tick exposure.

Recognizing Herx in Newborns

Although rare, Herxheimer reactions can occur in infants, and recognition is critical. Clinicians must differentiate this response from more serious complications such as sepsis or allergic reactions. The Herx reaction is self-limiting and typically resolves within hours to a day as treatment continues.

Key points to consider:

• Newborns may be more vulnerable to Herx reactions due to their underdeveloped immune systems.

• Early Lyme disease can still cause significant systemic responses during treatment.

• Monitoring and supportive care are essential, but antibiotic therapy should not be discontinued unnecessarily.

The Science Behind the Reaction

Although once believed to be caused by endotoxins, current understanding points to a cytokine storm triggered by bacterial die-off. This inflammatory cascade includes TNF-alpha and various interleukins that contribute to systemic symptoms.

In newborns, this immune reaction can appear sudden and severe but often resolves with appropriate management.

Takeaway

This case serves as a reminder that:

• Herxheimer reactions can happen in newborns

• Early recognition can prevent misdiagnosis

• EM rash and clinical judgment are more reliable than testing in early Lyme

• Continued awareness among clinicians is essential when treating infants with suspected Lyme disease

References
Prodanuk M, et al. Lyme Disease in a Neonate Complicated by the Jarisch–Herxheimer Reaction. Pediatric Infectious Disease Journal, 2020.

Nykytyuk O, et al. Insights into the Pathophysiology of the Jarisch-Herxheimer Reaction. Infect Dis Rev, 2020.