CDC Lyme Disease Criteria: Why Some Patients Do Not Meet Diagnostic Criteria

CDC surveillance criteria are often confused with diagnosis
Erythema migrans may be diagnosed clinically without testing
Some Lyme presentations may not fit narrow diagnostic frameworks

CDC surveillance criteria for Lyme disease are often misunderstood and may be confused with clinical diagnosis.

Importantly, CDC guidance states that patients with erythema migrans who live in or have traveled to endemic regions may be diagnosed clinically without laboratory confirmation. This distinction between surveillance criteria and clinical diagnosis can create confusion when evaluating symptomatic patients.

Because erythema migrans may be diagnosed clinically, a patient can receive a Lyme diagnosis even when laboratory testing is negative or not recommended.

Why CDC criteria and clinical diagnosis are not always the same

Kobayashi and colleagues concluded that nearly 3 out of 4 patients referred to the clinic did not have Lyme disease using CDC criteria for Lyme disease. They did not interview the referring physicians at Johns Hopkins University School of Medicine. Instead, they conducted a chart review.

However, to be included in the study, patients had to meet Infectious Diseases Society of America (IDSA) guidelines or CDC criteria for Lyme disease.

The authors found that out of 1,261 patients, all but one were symptomatic when they presented to the clinic, with a median duration of complaints of 558 days, ranging from 1 day to 51 years.

“The 5 most commonly identified symptoms were arthralgia (71.3%), fatigue/malaise (66.8%), headache (42.1%), myalgia (40.8%), and sleep disturbance (34.3%),” writes Kobayashi.

Only a few patients had abnormal physical findings. “The 5 most common abnormal physical findings were rash other than erythema migrans (6.6%), joint swelling (5.9%), tender points (3%), objective sensory abnormality (2.1%), and motor weakness (1.5%),” the authors explain.

Clinical presentations that may be underrecognized

These manifestations may be overlooked because surveillance definitions and referral-center criteria may not capture the full range of Lyme presentations seen in clinical practice.

Several neurologic, autonomic, psychiatric, and co-infection presentations may be underrecognized when applying narrow diagnostic frameworks.

Neurologic manifestations such as neurologic Lyme disease and autonomic complications including POTS and Lyme disease may not always fit neatly into traditional diagnostic frameworks.

The researchers did not report several clinical presentations that can occur in Lyme disease, including:

1. Lyme encephalopathy [2]
2. Lyme neuropathy [2]
3. Neuropsychiatric Lyme disease [3]
4. Pediatric neuropsychiatric disorders – PANS [4]
5. Lyme carditis [5]
6. Autonomic dysfunction – POTS [6]
7. Post-treatment Lyme fatigue – post-Lyme disease [7]
8. Neuropathic pain [8]
9. Persistent symptoms after Lyme disease [9]
10. Lyme disease with co-infection, including Babesia [10]

It may be that many physicians do not recognize or document these manifestations, given that the authors did not discuss these presentations.

Approximately 1 in 10 patients had a history of co-infections. “Although 139 (11%) co-infections were diagnosed before evaluation at the infectious diseases clinic, none of these infections were confirmed or treated based upon the evaluations performed in this study,” writes Kobayashi.

“Of these 139 putative co-infections, 61 (44%) were said to be caused by Babesia microti or B. duncani, 40 (29%) by Epstein-Barr virus, 30 (22%) by Bartonella, 11 (8%) by Ehrlichia spp., and 32 (23%) were attributed to other infectious agents,” writes Kobayashi.

Frequently Asked Questions

Can Lyme disease be diagnosed without testing?

Yes. CDC guidance allows clinical diagnosis without laboratory testing when a patient has erythema migrans in an endemic area.

Does erythema migrans require laboratory testing?

CDC guidance states that erythema migrans in an appropriate clinical setting may be diagnosed clinically without laboratory confirmation.

Are CDC Lyme disease criteria used for diagnosis?

CDC surveillance criteria were developed primarily for public health reporting. Clinicians may consider symptoms, exposure history, examination findings, and laboratory data together.

Why do some patients not meet CDC criteria?

Patients may present early, have atypical symptoms, lack documented erythema migrans, or have manifestations not emphasized in surveillance definitions.

Can co-infections complicate diagnosis?

Yes. Co-infections such as Babesia or Bartonella may contribute additional symptoms and complicate interpretation.

Clinical Takeaway

CDC Lyme disease criteria can help standardize surveillance, but some patients with Lyme-compatible illness may not fit neatly into surveillance definitions or testing frameworks.

Clinical diagnosis, exposure history, erythema migrans recognition, symptom patterns, and evolving presentations remain important when evaluating possible Lyme disease.

Related Articles

Lyme rash misdiagnosis and bull’s-eye rashes
Autonomic dysfunction and Lyme disease
Persistent Lyme disease symptoms

References

1. Takaaki Kobayashi, Yvonne Higgins, Roger Samuels, Aurasch Moaven, Abanti Sanyal, Gayane Yenokyan, Paul M Lantos, Michael T Melia, Paul G Auwaerter. Misdiagnosis of Lyme Disease With Unnecessary Antimicrobial Treatment Characterizes Patients Referred to an Academic Infectious Diseases Clinic. Open Forum Infectious Diseases. Volume 6, Issue 7, July 2019.
2. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323(21):1438-1444.
3. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151(11):1571-1583.
4. Sigra S, Hesselmark E, Bejerot S. Treatment of PANDAS and PANS: a systematic review. Neurosci Biobehav Rev. 2018;86:51-65.
5. Muehlenbachs A, Bollweg BC, Schulz TJ, et al. Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis. Am J Pathol. 2016.
6. Kanjwal K, Karabin B, Kanjwal Y, Grubb BP. Postural orthostatic tachycardia syndrome following Lyme disease. Cardiology Journal. 2011;18(1):63-66.
7. Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. 2003;60(12):1923-1930.
8. Simons LE. Fear of pain in children and adolescents with neuropathic pain and complex regional pain syndrome. Pain. 2016;157 Suppl 1:S90-97.
9. Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85-92.
10. Krause PJ, Telford SR III, Spielman A, et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA. 1996;275(21):1657-1660.

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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