What is the recommended testing and treatment approach for Lyme disease?

Testing for Lyme Disease

Clinical Diagnosis Without Testing

Patients with erythema migrans (EM) in endemic areas should be diagnosed clinically without laboratory testing. 1, 2 Approximately 70-80% of Lyme disease patients present with this characteristic gradually expanding annular lesion >5 cm in diameter, often accompanied by fever, lymphadenopathy, myalgias, or arthralgias. 1

• Testing is unnecessary and potentially misleading in early EM because antibody responses are still developing, resulting in only 30-40% sensitivity during this window period. 1, 2
• Geographic exposure history to endemic areas (northeast and upper midwest United States) is essential—without plausible tick exposure, even highly specific tests produce false-positives. 2

Two-Tiered Serologic Testing Algorithm

For all patients without EM or with suspected disseminated disease, use standard two-tiered testing: first-tier EIA or IFA, followed by reflex Western immunoblot only if the first test is positive or equivocal. 1, 3, 2

When to Order Testing

Test only when specific clinical manifestations are present with appropriate epidemiologic exposure: 3

• Neurologic presentations: meningitis, painful radiculoneuritis, mononeuropathy multiplex, acute cranial neuropathies (especially facial palsy), or spinal cord inflammation with radiculitis
• Cardiac involvement: acute myocarditis or pericarditis of unknown cause in endemic settings
• Articular disease: recurrent large-joint monoarticular or oligoarticular arthritis

Never test patients with nonspecific symptoms (fatigue, cognitive complaints) without characteristic clinical findings and endemic exposure. 3 Do not routinely test patients with psychiatric illness, dementia, Parkinson's disease, or ALS without epidemiologically plausible tick exposure. 3

Test Performance Characteristics

The sensitivity and specificity of two-tiered testing varies dramatically by disease stage: 1, 2

• Early localized disease: 30-40% sensitivity (acute phase), improving to 61% at 3-4 weeks convalescence
• Disseminated disease (neuritis, carditis, arthritis): 70-100% sensitivity, 88-100% for late manifestations
• Specificity: >95% across all disease stages 1

In low-incidence states without endemic exposure, positive predictive value drops to only 10%, and merely 0.7% of patients with arthritis, cranial neuropathies, or meningitis actually have Lyme disease. 2

Critical Testing Pitfalls to Avoid

Never order Western immunoblot as a stand-alone test without first performing EIA/IFA—this dramatically increases false-positive rates. 2 The two-tiered algorithm must be followed sequentially. 1

Only use FDA-cleared, clinically validated tests. 1 Alternative laboratories using unvalidated criteria have demonstrated alarming false-positive rates of 58% in healthy controls. 1 Specifically avoid:

• Urine antigen tests (shown to be inaccurate) 1, 2
• CD57 tests (lack validation) 1, 2
• Unvalidated Borrelia culture methods (results suspicious for laboratory contamination) 1

Do not retest patients after treatment to assess cure. 2 Antibodies persist for months to years after successful treatment and do not indicate active infection or treatment failure. 3

Emerging Alternative Testing Approaches

A novel two-tiered EIA approach (whole-cell sonicate EIA followed by reflex C6 EIA) shows promise with improved early disease sensitivity (61% vs 48%) while maintaining equivalent specificity (99.5%) to standard testing. 1, 4 This approach eliminates the subjectivity of Western immunoblot interpretation and allows for easier automation. 1 However, this remains investigational and standard two-tiered testing with Western immunoblot remains the current recommendation. 1, 3

Diagnostic Imaging Considerations

Do not routinely perform diagnostic imaging for suspected Lyme disease. 5 The diagnosis relies on clinical findings and serologic testing, not imaging. 5

Limited imaging may be appropriate only to exclude alternative diagnoses: 5

• MRI brain/spine for suspected CNS involvement to rule out stroke, tumors, or demyelinating disease
• Joint imaging (X-ray, ultrasound, MRI) to evaluate Lyme arthritis severity or exclude other causes of arthritis—but diagnosis remains clinical and serologic

Ordering imaging as a screening tool leads to incidental findings, patient anxiety, unnecessary costs, and radiation exposure without diagnostic benefit. 5