Lyme Disease Misdiagnosis: Why It Happens and What to Know

Lyme disease can resemble many other conditions
Symptoms and testing may delay recognition
The diagnostic error can occur in either direction

She was told it was depression. Then fibromyalgia. Then anxiety. It took three years and five doctors before anyone tested her for Lyme disease.

This pattern is familiar in clinical practice. Lyme disease misdiagnosis can occur when symptoms resemble neurologic, rheumatologic, psychiatric, fatigue-related, or other disorders before Lyme disease is considered.

The consequences can be significant: delayed treatment, prolonged symptoms, repeated evaluations, and loss of trust in the medical system.

At the same time, diagnostic error can occur in the opposite direction. Symptoms caused by another medical condition may sometimes be attributed to Lyme disease. Careful evaluation is important because symptom overlap alone does not establish the diagnosis.

This page organizes published reports and clinical patterns showing how—and why—Lyme disease may be misdiagnosed. Understanding these patterns can help patients and clinicians recognize when diagnostic reassessment may be appropriate.

This evolving pattern is closely linked to delayed Lyme disease diagnosis, where early symptoms are misinterpreted before the full clinical picture emerges.

Why Lyme Disease Is So Often Misdiagnosed

Lyme disease can affect multiple body systems. Neurologic, musculoskeletal, cardiac, constitutional, and other manifestations may overlap with symptoms seen in unrelated illnesses.

Several factors can contribute to a missed or delayed diagnosis:

• A tick bite may never be noticed. Ticks can be small, and patients do not always recall an attachment.
• The rash may be absent, unnoticed, or atypical. Erythema migrans does not always resemble the familiar textbook bull’s-eye.
• Testing has limitations. Antibody testing can be negative early in infection before a measurable antibody response develops.
• Symptoms overlap with common conditions. Fatigue, cognitive complaints, pain, numbness, headache, dizziness, and mood symptoms occur in many illnesses.
• The clinical picture may evolve. A diagnosis that initially appears reasonable may become less convincing as new symptoms or objective findings develop.

When multisystem symptoms remain unexplained, diagnostic reassessment may be more useful than assuming that every new symptom belongs to the original diagnosis.

What Is a Common Misdiagnosis of Lyme Disease?

There is no single condition that accounts for every Lyme disease misdiagnosis. Depending on the patient’s presentation, Lyme disease may initially be mistaken for fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), multiple sclerosis, inflammatory or rheumatologic disease, migraine or vestibular disorders, peripheral neuropathy, or a psychiatric disorder.

The reverse diagnostic error also occurs. In a retrospective study of patients referred to an academic center for presumed Lyme disease but lacking evidence of active Borrelia burgdorferi infection, Kobayashi and colleagues found alternative diagnoses including anxiety or depression, fibromyalgia, chronic fatigue syndrome, migraine, osteoarthritis, and sleep disorders. Less common diagnoses included multiple sclerosis, Parkinson’s disease, malignancy, sarcoidosis, and ALS.

That study examined patients in whom Lyme disease had been overdiagnosed, rather than patients whose Lyme disease had initially been missed. It nevertheless illustrates an important point: many disorders share symptoms with Lyme disease, and careful differential diagnosis matters in both directions.

How Lyme Disease Misdiagnosis Evolves

Misdiagnosis in Lyme disease rarely happens all at once. It may follow a pattern:

• Initial symptoms are mild or nonspecific
• Early testing may be negative
• A more common diagnosis is assigned
• Symptoms fluctuate or additional systems become involved
• The original diagnosis is not reconsidered

As the clinical picture evolves, new findings may provide information that was not available during the first evaluation.

How Often Is Lyme Disease Misdiagnosed?

There is no single reliable percentage that describes how often Lyme disease is misdiagnosed across all settings.

The frequency depends on the population being studied, stage of illness, geographic exposure, clinical presentation, whether erythema migrans is recognized, and when laboratory testing is performed.

Published reports document both directions of diagnostic error: patients with Lyme disease may initially receive another diagnosis, while patients with other medical conditions may sometimes be diagnosed or referred for presumed Lyme disease.

Psychiatric Misdiagnoses: When Infection Looks Like Mental Illness

Neurologic Lyme disease can be accompanied by cognitive, behavioral, mood, sleep, and other neuropsychiatric symptoms. Fallon and Nields reviewed neurologic and psychiatric manifestations associated with Lyme disease and emphasized considering Lyme disease in the differential diagnosis of atypical psychiatric presentations in appropriate clinical settings.

This does not mean that depression, anxiety, obsessive-compulsive symptoms, or other psychiatric disorders generally indicate Lyme disease. Rather, an infectious or neurologic contribution may deserve consideration when psychiatric symptoms occur alongside compatible exposure, neurologic findings, or other multisystem manifestations.

Examples and broader discussions include:

• “Just Depression,” They Said — But It Was Lyme Disease
• Lyme Brain Fog and Anxiety: When Psychiatric Symptoms Have a Medical Cause
• Lyme Disease Was Misdiagnosed as OCD
• Conversion Disorder, Guillain-Barré Syndrome, or Neurologic Lyme Disease?
• Neuropsychiatric Lyme Disease: Symptoms, Patterns, Misdiagnosis

Neurologic Misdiagnoses: When Lyme Mimics Neurologic Disease

Neurologic Lyme disease may produce facial palsy, radicular pain, sensory symptoms, cognitive complaints, meningitis, and other neurologic manifestations.

In a classic series of 27 patients with chronic neurologic Lyme disease, Logigian and colleagues described encephalopathy, polyneuropathy, and, less commonly, leukoencephalitis. Symptoms included memory changes, radicular pain, paresthesias, fatigue, headache, and other neurologic complaints.

Because symptoms such as numbness, weakness, cognitive difficulty, dizziness, and pain are not specific to Lyme disease, neurologic disorders must be evaluated on their own merits rather than distinguished by symptoms alone.

Related clinical examples include:

• Lyme Misdiagnosed as MS, Lupus, Fibromyalgia: Why It Happens
• Why Does Lyme Disease Mimic MS or Fibromyalgia?
• ALS Mimicked Lyme Disease: A Case Report
• Subacute Parkinsonism as a Complication of Lyme Disease
• Lyme Disease and Dementia: When Cognitive Decline Has Another Cause
• Numbness and Tingling in Lyme Disease: A Full-Body Case Study

Rheumatologic Misdiagnoses: When Joint Pain Has More Than One Explanation

Lyme disease can produce musculoskeletal symptoms and Lyme arthritis, while fatigue, widespread pain, stiffness, and cognitive complaints may overlap with fibromyalgia, ME/CFS, and rheumatologic illnesses.

However, symptom overlap does not establish that Lyme disease is responsible. Objective joint findings, exposure history, laboratory results, symptom evolution, and the broader clinical picture help distinguish Lyme arthritis from autoimmune or other rheumatologic conditions.

Fibromyalgia is particularly challenging because widespread pain, fatigue, sleep disturbance, and cognitive complaints may occur in both patient populations.

• Lyme Disease and Fibromyalgia: Could It Be Misdiagnosed?

Post-Infectious Confusion: Lyme Disease and Long COVID

Long COVID and Lyme disease can share symptoms including fatigue, cognitive difficulty, dizziness, exercise intolerance, pain, and autonomic complaints.

The presence of overlapping symptoms does not establish which condition is responsible. Timing of illness, exposure history, objective findings, laboratory testing, and other clinical features remain important when considering the differential diagnosis.

• Lyme Disease Misdiagnosed as Long COVID
• Case Study: Lyme Disease in a Patient with Long COVID
• Long COVID and Lyme Disease: Distinguishing Post-Infectious Syndromes

Dermatologic Misdiagnoses: When the Rash Isn’t What It Seems

Erythema migrans may be confused with other skin conditions, particularly when it does not have a classic target or bull’s-eye appearance.

Depending on its appearance and clinical context, a rash may initially be attributed to cellulitis, an insect or spider bite, an allergic reaction, shingles, or another dermatologic condition.

• Lyme Disease Misdiagnosed as Shingles in a 62-Year-Old Man
• Lyme Disease Skin Rash Puzzles Doctors, Leading to Misdiagnosis
• Lyme Disease Rash: What Does It Really Look Like?

Pediatric Misdiagnoses

Children can present additional diagnostic challenges because they may have difficulty describing symptoms such as pain, dizziness, fatigue, sensory changes, or cognitive problems.

Behavioral or school changes may have many possible explanations. Lyme disease should not be assumed to be the cause, but compatible tick exposure and accompanying physical or neurologic findings may warrant appropriate evaluation.

• 7-Year-Old Girl with Lyme Disease Presenting as Attention Deficit Disorder
• Understanding Pediatric Lyme Disease

Cardiac and Co-Infection Misdiagnoses

Lyme carditis can affect the heart’s electrical conduction system and may present with palpitations, dizziness, fainting, shortness of breath, chest discomfort, or conduction abnormalities.

Other tick-borne infections can further complicate the clinical picture. Babesiosis and anaplasmosis, for example, can produce systemic symptoms that may overlap with Lyme disease or occur as coinfections following exposure to infected ticks.

• Case Reports: Lyme Disease Infection Causes Carditis
• Tick Bite with Lyme Disease, Babesia, and Anaplasmosis

Understanding Symptom Patterns and Persistent Illness

Recognizing possible Lyme disease misdiagnosis requires considering the full clinical picture rather than relying on one nonspecific symptom.

Persistent symptoms after appropriately treated Lyme disease present a separate diagnostic challenge. Rebman and Aucott noted that fatigue, cognitive difficulties, and musculoskeletal pain can persist in a subset of patients and that overlapping comorbid conditions can complicate evaluation.

Persistent symptoms therefore require continued clinical assessment rather than automatically being attributed either to ongoing Lyme disease or to an unrelated condition.

When Reassessment May Be Appropriate

Diagnostic reconsideration may be helpful when symptoms evolve over time, objective findings emerge, multiple organ systems become involved, or the working diagnosis no longer adequately explains the clinical picture.

Reassessment should consider both possibilities: Lyme disease or another tick-borne illness may have been overlooked, or another medical condition may better explain symptoms previously attributed to Lyme disease.

Careful history, exposure assessment, examination, appropriate testing, and follow-up remain central to sorting out these overlapping presentations.

Frequently Asked Questions

What is a common misdiagnosis of Lyme disease?

Lyme disease may be mistaken for fibromyalgia, ME/CFS, multiple sclerosis, inflammatory or rheumatologic disease, migraine or vestibular disorders, peripheral neuropathy, or psychiatric conditions because many symptoms overlap. Which diagnosis is considered first often depends on the patient’s dominant symptoms.

What else can mimic Lyme disease?

Many conditions can produce symptoms similar to Lyme disease, including fibromyalgia, ME/CFS, migraine, autoimmune and rheumatologic disorders, peripheral neuropathy, multiple sclerosis, sleep disorders, depression, and anxiety. Symptoms alone may not reliably distinguish these conditions.

Can Lyme disease be misdiagnosed?

Yes. Lyme disease may initially be missed when symptoms are nonspecific, a tick bite or rash was not noticed, testing is performed early, or another diagnosis appears to explain the symptoms. The reverse also occurs: other illnesses may sometimes be incorrectly attributed to Lyme disease.

How often is Lyme disease misdiagnosed?

There is no single reliable percentage that applies across all patient populations. Misdiagnosis rates depend on the stage of illness, clinical presentation, geographic exposure, testing practices, and the population being studied.

What autoimmune disease can mimic Lyme disease?

Rheumatoid arthritis, lupus, Sjögren syndrome, and other inflammatory or autoimmune conditions can share symptoms with Lyme disease. Joint pain, fatigue, neurologic complaints, and other overlapping symptoms require careful evaluation because either condition may be present and some patients may have more than one diagnosis.

How often are Lyme disease tests wrong?

The accuracy of Lyme disease testing depends partly on the stage of illness and the test being used. Antibody tests can be negative early in infection before the immune response has produced detectable antibodies, while positive antibodies do not by themselves establish that every current symptom is caused by active Lyme disease.

Clinical Takeaway

Lyme disease misdiagnosis can occur because its manifestations overlap with numerous neurologic, rheumatologic, psychiatric, infectious, and post-infectious conditions.

The diagnostic problem works in both directions: Lyme disease may be overlooked, while symptoms caused by another condition may sometimes be attributed to Lyme disease.

When the clinical picture changes or no longer fits the original diagnosis, careful reassessment can help determine whether Lyme disease, another condition, or more than one process best explains the patient’s symptoms.

Related Articles

These articles expand on diagnostic overlap and conditions that may be confused with Lyme disease:

Conditions Lyme Disease Can Mimic (And Why It’s Often Misdiagnosed)
Why Is Lyme Disease Hard to Diagnose? Why Your Doctor May Have Missed It
Is It Dementia, Parkinson’s… or Lyme Disease?
Factors That Delay Lyme Disease Diagnosis

References

1. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323(21):1438–1444.
2. Fallon BA, Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994;151(11):1571–1583.
3. Rebman AW, Aucott JN. Post-treatment Lyme disease as a model for persistent symptoms in Lyme disease. Front Med (Lausanne). 2020;7:57.
4. Kobayashi T, Higgins Y, Melia MT, Auwaerter PG. Mistaken identity: Many diagnoses are frequently misattributed to Lyme disease. Am J Med. 2022;135(4):503–511.e5.

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