Lyme Disease Serology With Reflex: Understanding What It Really Means

Lyme disease is a tick-borne infection that can mimic other autoimmune conditions. Generally, Lyme disease can result in clinical manifestations, such as musculoskeletal pain, brain fog, erythema migrans, facial nerve paralysis, etc. 

The diagnosis can become challenging due to overlapping clinical symptoms. Here comes the role of serologic testing that plays a major role in guiding the treatment plan. How does a simple blood test help in confirming an infection? Let’s explore together how Lyme disease serology with reflex can aid in confirming the diagnosis and treatment plans. 

Is it possible to diagnose Lyme disease based on clinical symptoms?

Initially, the majority of Lyme disease cases are misdiagnosed. The clinical manifestations of Lyme disease include fatigue, fever, and musculoskeletal pain. One of the early recognizable clinical signs include erythema migrans (bull’s eye rashes). 

The expanding red lesion can be considered a sign of Lyme disease. It is also important to understand that skin rashes may not appear in all cases. Sometimes, blisters can be seen in the center of the rash and can be misdiagnosed as a spider bite.

Later stages of Lyme disease:

In later stages, the bacteria can reach the bloodstream and travel to distant body parts. The bacteria can reach the nervous system, cardiovascular system, etc. The clinical manifestations can include,

• Joint tenderness
• Cardiovascular problems
• Facial nerve paralysis
• Lyme arthritis

How is Lyme disease diagnosed?

To confirm the infection, serological tests can be used. A blood test or CSF test can be used to detect the infection. The healthcare professional can obtain the blood sample from the vein, using a needle. You might feel a slight pain at the site where the needle was inserted. 

If you experience a tingling sensation or numbness, CSF test can be conducted. To get the CSF sample, lumbar puncture or spinal tap can be performed.

Lumbar puncture:

• The patient can lie on the side or sit on a table.
• A numbing cream will be applied on the back region. To avoid the pain during the procedure, an anesthetic will be injected into the skin.
• A thin, hollow needle will be inserted between the two vertebrae in the lower spine.
• A small amount of CSF will be withdrawn for testing, which will take approximately 5 minutes.
• It is also important to take 1-2 hours of rest after the procedure.

Interpretation of the CSF test:

Polymerase chain reaction (PCR): This test detects the presence of bacterial DNA in the spinal fluid or blood. However, this test is not reliable as the DNA won’t stay in the blood for a longer duration. 

Antigen detection: It is an experimental test that mainly focuses on urine. This test evaluates the presence of bacterial proteins.

What is the role of Lyme disease serology with reflex in diagnosing the infection?

Lyme disease serology with reflex comprises a stepwise approach that can be used for confirming Lyme disease. Let’s discuss the two-step process, which is used to detect the presence of antibodies against the bacteria.

The Center for Disease Control and Prevention recommends a 2-step serologic testing process for confirming the diagnosis. It takes a few weeks for the antibodies to form against the bacteria. Hence, serologic testing is not reliable during the initial weeks of infection. 

Initially, Enzyme-linked immunosorbent Assay (ELISA) or immunofluorescent antibody assay can be used to detect the serum antibodies against Borrelia burgdorferi. If this test is negative, further testing is not suggested. If ELISA is positive or equivocal, a Western blot test will be conducted to confirm the results. 

Interpretation of the blood tests:

Western blot test:

This test indicates the presence of IgG or IgM antibodies that confirms recent infection. IgG tests are more specific, when compared to IgM tests. Hence, IgM is not considered for confirming the infection. 

Risks associated with the blood tests:

• Risks related to blood tests can include,
• Giddiness or fainting
• Accumulation of blood under the skin (Hematoma)
• Excessive bleeding
• If there is a break in the skin, infection can occur.

What are the treatment strategies for Lyme disease?

Early stages of Lyme disease can be treated with oral antibiotics. Amoxicillin or doxycycline are the major antibiotics that are administered to manage the clinical symptoms. If the bacteria has spread to nervous system or cardiovascular system, intravenous administration of antibiotics is required. The pain or inflammation can be managed with nonsteroidal anti-inflammatory drugs and corticosteroids.

Apart from antibiotic therapy, supportive strategies can help manage the symptoms. These strategies comprises,

• Stress relaxation techniques, such as meditation or yoga
• Consuming nutrient-rich foods
• Managing mental health problems, such as anxiety or depression
• Regular exercises

Conclusion:

• Due to overlapping clinical symptoms, the diagnosis of Lyme disease can be challenging.
• The two-step approach, starting with ELISA and Western blot, provides an accurate method to confirm the infection.
• Once the diagnosis is confirmed, the treatment can be initiated at an early stage that can lead to better treatment outcomes. 

References:

Johns Hopkins Lyme Disease Research Center. Diagnosis of Lyme disease [Internet]. Baltimore (MD): Johns Hopkins University; [cited 2025 Jul 24]. Available from: https://www.hopkinslyme.org/lyme-disease/diagnosis-of-lyme-disease/

MedlinePlus. Lyme disease tests [Internet]. Bethesda (MD): U.S. National Library of Medicine; [updated 2024 Jan 17; cited 2025 Jul 24]. Available from: https://medlineplus.gov/lab-tests/lyme-disease-tests/

McPherson RA, Pincus MR. Lyme Disease. In: Henry's Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. Philadelphia (PA): Elsevier; 2017 [cited 2025 Jul 24]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431066/

Columbia University Irving Medical Center. Diagnosis of Lyme disease [Internet]. New York (NY): Columbia University Irving Medical Center; [cited 2025 Jul 24]. Available from: https://www.columbia-lyme.org/diagnosis