When Clinical Judgment Overrides Negative Testing

A 6-year-old child presented to her pediatrician with a circular rash on the left side of her face. The pediatrician initially suspected allergic dermatitis and prescribed topical steroids. However, the rash failed to improve, explain Banadyha and colleagues in their case report.

Over the following six weeks, the rash gradually spread to the back of the child’s head. During this time, she developed systemic symptoms, including malaise and a low-grade fever of 37.7 °C. Initial laboratory evaluation included an enzyme-linked immunosorbent assay (ELISA) for Lyme disease, which was negative.

There was no reported history of a tick bite, nor did the child have joint pain or neurologic complaints. Despite these factors, clinicians suspected Lyme disease based on the appearance and progression of the rash and the fact that the child lived in a Lyme endemic region, the authors explain.

Clinical Diagnosis Despite Negative Early Testing

This case highlights a common diagnostic challenge in early Lyme disease. Serologic tests such as ELISA rely on antibody production, which may not be detectable in the early stages of infection. As a result, reliance on laboratory testing alone can delay diagnosis and treatment.

Using clinical judgment, the pediatric team initiated treatment with oral cefuroxime in accordance with International Lyme and Associated Diseases Society (ILADS) treatment guidelines.

Two weeks after starting antibiotics, confirmatory testing revealed a positive IgG Western blot for Lyme disease. The diagnosis of Lyme disease was therefore retrospectively confirmed after treatment had already begun.

“The girl remained asymptomatic even after a 1.5-year follow-up,” the authors report, underscoring the benefit of early clinical treatment.

Why Early Serology Fails in Pediatric Lyme Disease

ELISA testing for Lyme disease detects antibodies—specifically IgM and IgG antibodies produced in response to Borrelia burgdorferi infection. However, antibody production takes time. In early localized Lyme disease, particularly when erythema migrans rash is present, antibodies may not have developed yet.

This creates a diagnostic window where patients are clinically infected but serologically negative. Waiting for antibody seroconversion before treating delays care and allows disease progression.

The child in this case presented with a circular rash that spread over six weeks, developed systemic symptoms including fever and malaise, lived in an endemic region, and had clinical findings compatible with erythema migrans. These factors justified empiric treatment despite negative initial serology.

Two weeks later, Western blot confirmed what clinical judgment already suggested: she had Lyme disease all along. The negative ELISA simply reflected early testing before antibodies developed.

The Tick Bite Requirement Myth

One of the most persistent misconceptions about Lyme disease diagnosis is that a known tick bite is required. This case demonstrates why that requirement is both impractical and harmful.

The child had no reported history of tick bite. Yet she clearly had Lyme disease, confirmed by subsequent Western blot testing and response to treatment.

Why might tick bites go unnoticed in children? Nymphal Ixodes ticks are tiny—smaller than a poppy seed. They feed for 36-72 hours but are easily overlooked, particularly in areas with hair coverage like the scalp. Children may not report tick bites. Parents may miss them during routine bathing. The bite itself is painless.

Requiring documented tick exposure before diagnosing Lyme disease misses the majority of genuine cases. Clinical presentation and geographic risk should guide diagnosis, not whether a parent happened to observe a tiny tick.

Geographic Risk and Endemic Regions

The child lived in a Lyme endemic region. This epidemiologic context influenced clinical decision-making appropriately.

When a child in an endemic area develops a circular expanding rash with fever and malaise—particularly during tick season—Lyme disease should be the primary differential diagnosis even without documented tick bite and even with negative serology.

Geographic risk assessment is part of clinical diagnosis. A circular rash in Connecticut during June carries different diagnostic weight than the same rash in Arizona in December.

This doesn’t mean Lyme disease never occurs outside traditional endemic boundaries. But it does mean clinicians should integrate local epidemiology into diagnostic reasoning.

Treatment Response as Diagnostic Confirmation

The child received oral cefuroxime following ILADS guidelines. She remained asymptomatic at 1.5-year follow-up.

This treatment response provides retrospective diagnostic confirmation independent of serology. When clinical presentation suggests Lyme disease, endemic exposure supports it, empiric treatment is provided, and the patient recovers completely—the diagnosis is confirmed by therapeutic response.

This is fundamentally different from treating with antibiotics “just to see what happens” in patients with non-specific symptoms and no objective findings. The child had objective clinical findings: documented expanding circular rash, fever, malaise, endemic exposure.

Treatment response in this context validates the clinical diagnosis and demonstrates that waiting for serologic confirmation would have delayed necessary care.

Frequently Asked Questions

Can children have Lyme disease without a tick bite?
Yes. Most pediatric Lyme disease cases lack documented tick bite history. Nymphal ticks are tiny and easily missed, particularly in hair-covered areas. Clinical diagnosis based on rash, symptoms, and endemic exposure is appropriate without confirmed tick bite.

Why was the ELISA test negative if the child had Lyme disease?
ELISA detects antibodies, which take time to develop. In early Lyme disease, patients may be infected but not yet seropositive. The child’s negative ELISA reflected early testing before antibody production, not absence of infection.

Should treatment wait for positive test results?
No. When erythema migrans rash is present or clinical presentation strongly suggests Lyme disease in an endemic area, treatment should begin immediately. Waiting for serology delays care and allows disease progression.

How did they confirm the diagnosis if the ELISA was negative?
Western blot performed two weeks after treatment initiation was positive, confirming Lyme disease. Additionally, the child’s complete recovery with antibiotic treatment provided therapeutic confirmation of the diagnosis.

What should parents do if their child has a circular rash but no known tick bite?
Seek medical evaluation immediately, particularly if living in or visiting a Lyme endemic area. The rash may be erythema migrans even without documented tick exposure. Early treatment prevents complications.

Clinical Takeaway

This case demonstrates three fundamental principles of pediatric Lyme disease diagnosis that challenge common misconceptions and testing-dependent approaches. A 6-year-old child developed a circular facial rash that failed to respond to topical steroids. Over six weeks, the rash spread to the back of her head while she developed systemic symptoms including malaise and low-grade fever. Initial ELISA testing was negative. There was no history of tick bite. Despite these factors—negative serology, no documented tick exposure—clinicians recognized the clinical pattern and initiated treatment with oral cefuroxime following ILADS guidelines. Two weeks later, Western blot confirmed positive IgG antibodies for Lyme disease. At 1.5-year follow-up, the child remained asymptomatic. The negative ELISA simply reflected early testing before antibody development. The absent tick bite history reflected the reality that nymphal Ixodes ticks are tiny and easily overlooked, particularly in hair-covered areas of children. Requiring documented tick exposure before diagnosing Lyme disease misses the majority of genuine pediatric cases. The authors’ conclusions deserve emphasis: erythema migrans may precede detectable antibodies, patients with erythema migrans in endemic areas can be diagnosed clinically without laboratory confirmation, and a known tick bite is not required to diagnose Lyme disease. This case validates clinical judgment over rigid adherence to testing protocols. When presentation suggests Lyme disease (expanding circular rash, systemic symptoms, endemic exposure), empiric treatment is appropriate despite negative serology and absent tick bite history. Treatment response provides diagnostic confirmation independent of laboratory testing. The child’s complete recovery after antibiotic therapy confirmed what clinical judgment already suggested: she had Lyme disease all along, despite negative ELISA and no documented tick bite.