CDC Lyme Disease Criteria: Why Some Patients Are Dismissed as “Not Lyme”

What happens when strict criteria are applied to patients with complex, evolving Lyme symptoms?

Kobayashi and colleagues reported that the majority of patients referred for Lyme disease consultation did not have active or convincing prior Lyme disease. However, many of these patients were ultimately labeled as not having Lyme disease based on a chart review—rather than a full clinical reassessment that included the referring physician’s reasoning or the patient’s evolving history.

The issue is not simply who was dismissed—it is how Lyme disease was defined.

CDC Criteria vs Clinical Diagnosis of Lyme Disease

The CDC framework was developed for surveillance and research—not to capture every clinical presentation of Lyme disease.

Importantly, the CDC recognizes that erythema migrans can be diagnosed clinically without laboratory testing. This allows for early diagnosis and treatment based on clinical findings alone.

Yet in practice, stricter interpretations of these criteria may lead to patients being labeled as “not Lyme,” even when symptoms and clinical suspicion remain.

What the Study Found

Out of 1,261 patients, all but one were symptomatic at presentation, with a median duration of symptoms of 558 days, ranging from 1 day to 51 years.

The most common symptoms included arthralgia (71.3%), fatigue/malaise (66.8%), headache (42.1%), myalgia (40.8%), and sleep disturbance (34.3%).

Objective physical findings were uncommon, including rash other than erythema migrans (6.6%), joint swelling (5.9%), tender points (3%), sensory abnormalities (2.1%), and motor weakness (1.5%).

This pattern—significant symptoms with limited exam findings—is commonly seen in Lyme disease and does not exclude it.

What Distinguished Patients Who Actually Had Lyme Disease?

Although many patients were labeled as not having Lyme disease, a meaningful subset did meet criteria for active or recent infection.

These patients were more likely to have:

• Shorter symptom duration
• Objective findings such as joint swelling
• Positive Lyme serologic testing

This highlights an important clinical distinction: Lyme disease may be easier to recognize earlier in its course, while more complex or prolonged presentations may fall outside strict criteria.

Study Conclusions—and Their Limits

The authors concluded that misdiagnosis and unnecessary antibiotic use were common. Many patients had prolonged symptoms, multiple prior tests, and in some cases a history of coinfections or extended antibiotic treatment.

They also found that patients with longer symptom duration, a higher number of subjective symptoms, and multiple prior laboratory evaluations were less likely to meet their criteria for Lyme disease.

However, several limitations should be considered. This was a retrospective, single-center study subject to referral bias, incomplete data, and variability in clinical judgment. The investigators did not interview referring physicians or reassess diagnostic decisions in real time.

Additionally, the inclusion of patients with remote Lyme disease in the comparison group may have influenced the findings, given the potential overlap in symptoms.

This distinction matters in clinical practice, where diagnosis often depends on patterns over time—not just criteria applied retrospectively.

Clinical Takeaway

When strict CDC or IDSA criteria are applied to a broad clinical illness like Lyme disease, many patients may be labeled as “not Lyme”—even when their symptoms remain unexplained.

This is not just a diagnostic issue—it is a clinical gap.

For patients, that gap can mean delayed diagnosis, persistent symptoms, and missed opportunities for treatment.

Reference:

Kobayashi, T., Higgins, Y., Samuels, R., Moaven, A., Sanyal, A., Yenokyan, G., Lantos, P. M., Melia, M. T., & Auwaerter, P. G. (2019). Misdiagnosis of Lyme disease with unnecessary antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic. Open Forum Infectious Diseases, 6(7), ofz299.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention