Can Lyme Disease Be Mistaken for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)?
Lyme disease and CIDP can share similar neurologic symptoms
Negative Lyme antibody tests may complicate the diagnosis
An unexpected response to treatment should prompt diagnostic reassessment
Can Lyme disease be mistaken for chronic inflammatory demyelinating polyneuropathy (CIDP)? Occasionally, yes. A published case describes a woman initially diagnosed with CIDP after developing progressive weakness, fatigue, and diffuse paresthesias. She received repeated intravenous immunoglobulin treatments but experienced only partial improvement followed by relapse.1
The case illustrates how Lyme disease and CIDP may occasionally produce overlapping neurologic findings. It also highlights the importance of reconsidering the diagnosis when symptoms persist, objective improvement is limited, or the clinical course does not unfold as expected.
A Patient Diagnosed With CIDP
The woman presented with asthenia, weakness, and diffuse paresthesias. Electromyography showed mild demyelination.
Lyme disease was initially considered unlikely because serum and cerebrospinal fluid antibody testing were negative.
She was diagnosed with chronic inflammatory demyelinating polyneuropathy and received intravenous immunoglobulin eight times. Although she experienced a partial response, her neurologic symptoms subsequently relapsed.1
Ten months after the onset of her symptoms, a serum polymerase chain reaction analysis reportedly detected Borrelia at 100 copies/mL. Based on that result and the clinical presentation, the authors diagnosed Lyme disease.1
The woman was treated for six weeks with doxycycline and hydroxychloroquine. The authors reported a dramatic clinical improvement with disappearance of her neurologic signs.1
This is a single published case and does not establish that Lyme disease commonly causes CIDP or that every patient diagnosed with CIDP should receive antibiotic treatment. It does demonstrate how an alternative diagnosis may be reconsidered when a patient does not respond to treatment as anticipated.
What Is CIDP?
Chronic inflammatory demyelinating polyneuropathy is an immune-mediated disorder involving the peripheral nerves and nerve roots. Damage to the myelin sheath interferes with the transmission of nerve signals.3,4
Patients with typical CIDP generally develop progressive or relapsing weakness and sensory impairment over at least eight weeks. Weakness often affects both proximal and distal muscles, while sensory symptoms may include numbness, tingling, painful paresthesias, and impaired balance. Deep tendon reflexes are frequently reduced or absent.4
The diagnosis is based on the pattern and progression of symptoms, neurologic examination, nerve conduction studies, and other supportive findings. No single laboratory test independently confirms every case of CIDP.
Why CIDP Can Be Misdiagnosed
CIDP is a complex diagnosis, and both overdiagnosis and underdiagnosis have been documented. A review by Allen emphasized that atypical presentations, equivocal nerve conduction studies, mildly elevated cerebrospinal fluid protein, and subjective improvement after immunotherapy can contribute to diagnostic error.5
In one tertiary-center study cited in the review, nearly half of patients previously diagnosed and often treated for CIDP were ultimately found not to have the disorder. The alternative explanations varied, and some patients did not have objective evidence of neuropathy.5
These findings do not suggest that CIDP is an invalid diagnosis. Rather, they underscore the importance of applying accepted clinical and electrophysiologic criteria and maintaining an appropriate differential diagnosis.
Objective improvement in weakness, walking ability, grip strength, or other measurable neurologic functions is more useful than improvement in nonspecific symptoms alone when evaluating a response to CIDP treatment.5
Delayed Diagnosis Can Occur in Either Direction
Although CIDP can be overdiagnosed, it can also be missed. Chaudhary and Rajabally reviewed 60 patients ultimately diagnosed with treatment-responsive definite or probable CIDP. An alternative diagnosis had initially been assigned to 68.3% of the patients.6
Among patients with non-Guillain–Barré syndrome alternative diagnoses, the mean delay before the correct CIDP diagnosis was 21.3 months. Electrophysiologic interpretation contributed to underdiagnosis in 85% of those patients.6
The study demonstrates that diagnostic uncertainty works in both directions. A patient with CIDP may initially be given another diagnosis, while a patient with another neurologic illness may initially be labeled as having CIDP.
Careful reassessment is therefore appropriate when the clinical findings, electrodiagnostic results, laboratory data, and treatment response do not align.
How Lyme Disease May Resemble CIDP
Lyme disease can affect the peripheral nervous system. Depending on the presentation, patients may experience weakness, numbness, paresthesias, neuropathic pain, gait difficulty, cranial neuropathy, or radicular symptoms.
CIDP can also cause progressive weakness, sensory loss, paresthesias, impaired balance, and abnormal nerve conduction studies. These overlapping findings may create diagnostic uncertainty, particularly when the illness does not follow a typical pattern.
The differential diagnosis of a demyelinating polyneuropathy can include infectious, inflammatory, metabolic, toxic, malignant, and inherited disorders. One CIDP review specifically notes that cerebrospinal fluid white blood cell counts above the range expected for CIDP should prompt consideration of disorders such as Lyme disease, HIV infection, sarcoidosis, lymphoma, or leukemia.4
Lyme disease remains an uncommon explanation for a CIDP-like presentation. Nevertheless, it may deserve consideration when the exposure history, accompanying symptoms, laboratory findings, or treatment course raise concern for an alternative infectious diagnosis.
Can Negative Lyme Tests Exclude the Diagnosis?
In the published case, Lyme disease was initially ruled out because serum and cerebrospinal fluid serologic tests were negative. The authors argued that negative formal serology may not always be sufficient to exclude Lyme disease in every clinical setting.1
However, the later diagnosis in this case relied on a serum PCR result, and the interpretation of blood PCR testing for Lyme disease remains controversial. The report should therefore be viewed as an instructive case of diagnostic reconsideration rather than proof that negative antibody testing routinely misses Lyme disease in patients diagnosed with CIDP.
Lyme test results should be interpreted in the context of the patient’s symptoms, timing of testing, physical findings, exposure history, and other possible diagnoses. The limitations of testing are discussed further in Why Lyme Tests Can Miss the Diagnosis.
When Should the Diagnosis Be Reconsidered?
A diagnosis may warrant reassessment when a patient:
- does not have the characteristic clinical pattern of CIDP;
- has equivocal or atypical nerve conduction findings;
- fails to show objective improvement with appropriate CIDP therapy;
- experiences repeated relapse despite treatment;
- develops findings that suggest an infectious or systemic illness; or
- has an exposure history compatible with Lyme disease or another tick-borne infection.
Reassessment does not mean assuming that the initial diagnosis was incorrect. It means reviewing the history, examination, electrophysiologic findings, laboratory evidence, treatment response, and alternative explanations together.
Frequently Asked Questions
Can Lyme disease be mistaken for CIDP?
Yes, in uncommon cases. Lyme disease and CIDP may both present with weakness, numbness, paresthesias, gait problems, and abnormal nerve conduction findings. A careful evaluation is needed because these symptoms can also occur in many other neurologic disorders.
Can Lyme disease cause demyelinating neuropathy?
Published reports have described demyelinating findings in patients with Lyme disease, but this appears to be uncommon. A demyelinating nerve conduction pattern is not specific to Lyme disease and should be interpreted alongside the clinical history and other diagnostic findings.
How do doctors distinguish Lyme disease from CIDP?
Doctors consider the pattern and duration of weakness, sensory deficits, reflexes, nerve conduction studies, cerebrospinal fluid findings, Lyme exposure risk, laboratory testing, associated symptoms, and objective response to treatment. No single finding reliably distinguishes every case.
Clinical Takeaway
In my practice, patients with progressive neuropathy who do not respond as expected to treatment warrant a careful reassessment of the diagnosis, including consideration of Lyme disease and other tick-borne illnesses when the clinical history supports it.
Although Lyme disease is an uncommon cause of a CIDP-like presentation, maintaining a broad differential diagnosis may help avoid unnecessary delays in identifying a potentially treatable condition.
When the clinical course and treatment response do not fit the expected diagnosis, taking a second look may be as important as the initial evaluation.
Related Articles
These related articles explore Lyme disease misdiagnosis, neurologic symptoms, neuropathy, and limitations in laboratory testing.
Lyme Disease Misdiagnosis
Lyme Disease Neuropathy
Neurological Symptoms of Lyme Disease
Lyme Disease Test Accuracy
References
- Perronne C, Lacout A, Marcy PY, El Hajjam M. Errancy on Lyme diagnosis. Am J Med. 2017;130(5):e219.
- Cameron DJ. Consequences of treatment delay in Lyme disease. J Eval Clin Pract. 2007;13(3):470-472.
- Dimachkie MM, Barohn RJ. Chronic inflammatory demyelinating polyneuropathy. Curr Treat Options Neurol. 2013;15(3):350-366.
- Allen JA. The misdiagnosis of CIDP: A review. Neurol Ther. 2020;9(1):43-54.
- Chaudhary UJ, Rajabally YA. Underdiagnosis and diagnostic delay in chronic inflammatory demyelinating polyneuropathy. J Neurol. 2021;268(4):1366-1373.
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
I had a positive IGG western blot test in May 2020 after receiving multiple ticks bites in the Dordogne region of France over a period of several years. No rash was ever detected.
Symptoms elevated in the last 3 months seem to be an exact replica of those described in this article, however the doctors in Norway, where my my MRI and lumbar puncture were performed expressed that the mild demyelination that showed was indicative of a “ normal” result for my age (55). Even though borrelia antibodies were found in the spinal fluid it was assessed as being negative for borreliosis. It seems very difficult to confer with a LLMD in Europe and they do not exist in Scandinavia. I am currently still on a two month waiting list with a LLMD in the Netherlands. It would be so helpful to speak with someone who has expertise in this field.
How are you doing now Lisa? Were you able to locate a reputable physician(s) interested in considering your case of CIDP related to Lyme borreliosis? Please be careful regarding so called LLMD’s. They are often self-proclaimed and are prone to self-promotion through dubious methods. Be particularly wary of doctors who demand payment, some in cash, upfront. That’s a clear indicator in the US at least, that the physician probably uses treatment(s) that are considered “alternative” at best and most importantly, have not been subjected to scientific scrutiny. I pray you are doing better.