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Small Fiber Neuropathy and Autonomic Dysfunction in Lyme Disease
Small fiber neuropathy may help explain burning pain, sensory changes, and autonomic symptoms in some patients with persistent symptoms following Lyme disease.
A retrospective study of 10 patients diagnosed with post-treatment Lyme disease syndrome found objective evidence of small fiber neuropathy, autonomic dysfunction, and abnormal cerebral blood flow.
A newer 2026 review of the evaluation of small fiber neuropathy reinforces an important clinical point: identifying small fiber nerve damage is only part of the diagnosis. Clinicians must also consider why the neuropathy developed and look for potentially treatable underlying conditions.
Study Design
Novak and colleagues at the Brigham and Women’s Faulkner Hospital Autonomic Laboratory performed autonomic testing on 10 patients between 2016 and 2018.
The authors aimed to:
- Identify small fiber neuropathy as a potential biomarker
- Evaluate autonomic dysfunction
- Assess cerebral blood flow related to cognitive symptoms
Patients met the Aucott criteria for post-treatment Lyme disease syndrome, including persistent fatigue, cognitive symptoms, and widespread pain for at least 6 months following treatment.
Autonomic Dysfunction and Sensory Symptoms
The 10 patients presented with a broad range of autonomic and sensory symptoms. The most common included:
- Lightheadedness (8 of 10)
- Dry mouth or dry eyes (8 of 10)
- Pale or blue feet (6 of 10)
- Cold feet relative to body temperature (6 of 10)
- Decreased sweating (5 of 10)
Pain symptoms were also prominent:
- Aching pain (10 of 10)
- Burning pain, numbness, and tingling (8 of 10)
- Lancinating pain (6 of 10)
- Allodynia (6 of 10)
Additional symptoms included gastrointestinal issues, urinary changes, and erectile dysfunction.
Key Findings
- All 10 patients had evidence of small fiber neuropathy on skin biopsy
- All demonstrated abnormalities on autonomic testing
- 7 of 10 had reduced cerebral blood flow velocity
Reduced cerebral blood flow was measured using transcranial Doppler of the middle cerebral artery. While the study did not establish that Lyme disease caused these abnormalities, the findings provide objective evidence that may help explain symptoms such as pain, sensory disturbances, autonomic complaints, and brain fog.
Why the Cause of Small Fiber Neuropathy Matters
Small fiber neuropathy is not a single disease. It describes damage or dysfunction involving small sensory and autonomic nerve fibers. These fibers help transmit pain and temperature sensations and regulate involuntary functions such as sweating and other autonomic responses.
A 2026 review by Lefaucheur and colleagues emphasized that confirming small fiber neuropathy does not identify its underlying cause. The authors recommend looking for metabolic, endocrine, nutritional, immune, inflammatory, infectious, and other potential explanations.
Interestingly, the review summarized an earlier cohort of patients evaluated for small fiber neuropathy in which Lyme disease was identified in 8.7% of patients. This finding should be interpreted cautiously. It does not mean that Lyme disease caused 8.7% of all cases of small fiber neuropathy, nor does a positive Lyme test by itself establish the cause of a patient’s neuropathy.
The authors emphasize a broader principle: finding an abnormal laboratory result or risk factor does not necessarily prove that it caused the small fiber neuropathy. The patient’s history, symptoms, examination, laboratory findings, and other evidence must fit together.
For patients with a history or clinical features suggestive of Lyme disease, this distinction is particularly important. Lyme disease may belong in the differential diagnosis of neuropathic symptoms in the appropriate clinical setting, but the diagnosis should not be based on an isolated laboratory result.
What This Means for Patients
Small fiber neuropathy and autonomic dysfunction may help explain persistent symptoms such as burning pain, tingling, numbness, abnormal sensitivity, lightheadedness, sweating abnormalities, and temperature dysregulation.
One reason small fiber neuropathy can be frustrating for patients is that routine nerve conduction studies and EMG primarily evaluate larger nerve fibers. These tests may therefore be normal even when small nerve fibers are affected.
Objective testing can help document that neurologic or autonomic abnormalities are present. But the next question is equally important: What is causing them?
The 2026 review reinforces the importance of investigating underlying conditions rather than simply labeling the neuropathy “idiopathic” without an appropriate evaluation.
For more on how medical dismissal affects Lyme patients, see that article.
Important Limitations
The original Lyme study was small, involving only 10 patients, and was retrospective. It was not designed to determine whether Lyme disease directly caused the small fiber neuropathy or whether additional antibiotic treatment would improve these abnormalities.
The 2026 paper is also not a new Lyme disease study. It is an expert review proposing a structured approach to investigating the causes of small fiber neuropathy. The authors acknowledge that it is neither a systematic review nor a meta-analysis.
I have been reluctant to rely on the term “post-treatment Lyme disease syndrome” until there is a reliable test to rule out persistent infection.
Regardless of terminology or the mechanism responsible for persistent symptoms, objective evidence of small fiber nerve abnormalities and autonomic dysfunction can be clinically meaningful.
For a broader view, see Lyme disease neuropathy and autonomic dysfunction in Lyme disease.
Clinical Takeaway
Small fiber neuropathy may provide an objective explanation for burning pain, sensory disturbances, and autonomic symptoms in some patients with a history of Lyme disease. However, identifying small fiber neuropathy is not the end of the evaluation. Clinicians should consider possible underlying causes and interpret Lyme testing together with the patient’s exposure history, clinical presentation, and other findings.
Frequently Asked Questions
What is small fiber neuropathy?
Small fiber neuropathy affects small sensory and autonomic nerve fibers involved in pain, temperature sensation, and involuntary body functions.
Can Lyme disease be associated with small fiber neuropathy?
Yes. Small fiber neuropathy has been reported in patients with persistent symptoms following Lyme disease. However, an association does not by itself prove that Lyme disease caused the neuropathy.
What symptoms can small fiber neuropathy cause?
Symptoms can include burning pain, tingling, numbness, abnormal sensitivity to touch, and autonomic symptoms such as lightheadedness, abnormal sweating, and temperature dysregulation.
Can EMG and nerve conduction studies be normal?
Yes. These tests primarily evaluate larger nerve fibers and can be normal in patients with small fiber neuropathy.
How is small fiber neuropathy diagnosed?
Evaluation may include skin biopsy and specialized testing of small sensory or autonomic nerve function, depending on the patient’s symptoms and clinical setting.
Does finding small fiber neuropathy tell you what caused it?
No. Small fiber neuropathy has many possible causes. Identifying the underlying condition requires consideration of the patient’s history, examination, laboratory findings, and other clinical evidence.
References
- Novak P, Felsenstein D, Mao C, Octavien NR, Zubcevik N. Association of small fiber neuropathy and post treatment Lyme disease syndrome. PLoS One. 2019;14(2):e0212222. doi:10.1371/journal.pone.0212222.
- Lefaucheur JP, Gendre T, Sène D. A structured list of laboratory tests for screening the possible causes of small fiber neuropathy in clinical practice. Front Neurol. 2026;16:1679316. doi:10.3389/fneur.2025.1679316.
Related Reading
- Lyme Disease Neuropathy: Symptoms and Causes
- Small Fiber Neuropathy in Lyme Disease
- Can Lyme Disease Cause Neuropathy?
- Numbness and Tingling in Lyme Disease
- Autonomic Dysfunction in Lyme Disease
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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
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Lyme is real! We need treatments that work. We need people to take us seriously.
Marker? you gotta be kidding me. What about systemic autoimmune diseases like Sjogren’s that cause SFN (and evven POTS) in youth without sicca and without positive antibodies,…how can SFN be a marker for Lyme.
That is the problem with any biomarker. Small fiber neuropathy can be seen in Lyme disease but may reflect the effects on the immune system. Other illnesses also affect the immune system. POTS is seen in Lyme disease through its effect on the autonomic nervous system. POTS can also have more than one cause.
Then I guess I have the definition of ‘marker’ wrong. I thought it means you have that specific disease.
Biomarkers offer clues for the disease or how active the disease is. They are often not diagnostic on their own.
I have for as long as I remember some kind of PANS, and dysautonomia (heat sensations in my feet, soon neuropathies), then from puberty prob POTS, Hashimoto too. My Lyme diagnosis was clinical, based on high positive Elispot/LTT, but only p83 on Western blot. I never had antibiotics for 20+ years of being symptomatic. Until 5 years ago when I had massive herx from just doxy, azithromycin, monotherapy. The herxing following 2 years made POTS worse and my ANA turned positive, with weak positive SSA. My POTS antibodoies (adrenergic and muscarinic receptors) were record high /700% increased../. I have family history of Sjogrens. Even though antibiotics got rid of many sympotms (facial neuropathy, some neuropsychiatric), seems like they further enhanced autoimmune component and in the end I got even Sjogren’s with classical sicca part. …… What baffles me is that research on Sjogren’s antibodies (early Sjo ) says 41% of POTS patients who have dryness but negative ANA/sjogrens (mind you, I was in the group without dryness!!!) has early Sjo antibodies,, so almost half patient with POTS if you count in those with official Sjogrens/lupus. At the same time I hear ILADS doctors saying that 50% of Lyme patients have POTS. Seems like neuro-Sjogrens, without sicca, often present in youth, is almost undistiguishable from Lyme. Another interesting thing that nobody speaks about is if 50% of Lyme patients have POTS, and 90% of POTS patients have alpha1 adrenergic (and some muscarinic) antibodies, would that mean there is strong connection of Lyme with adrenergic antibodies. As they recently published 1st appear Adrenergic in POTS, and later patients get muscarinic too (Sjogrens), and seems like that is how it was in me, 20 years of POTS and only then Sjogren’s. Dr Cameron, how often you see ANA test or even specific antibodies for lupus or Sjogrens, go negative from Lyme treatment? I am unsure if i should continue in that direction because I think antibiotics wreaked my gut, 2 years ago Rocephine caused severe damage to gut and then to brain too, and I got more neuroinflammation, still recovering 2 yrs later, I think it was leaky gut.
POTS is common in Lyme disease. I am sure the percentage. Rheumatologic diseases and Lyme disease overlap, in part, because they are both driven by an overactive immune status. We are only scratching the surface on what happens to the immune system during a tick-borne infection.
Dr. Cameron ,
Have you observed erratic blood pressure, with orthostatic hypertension, in your Lyme patients ? If so, has antibiotic treatment resolved this complex issue ?
Can POTS be reversed when the Lyme and Co Infections are treated? If Lyme & Co infections are the underlying condition?
I find POTS can be a frustrating part of Lyme disease and can be difficult to treat. I find treatment for Lyme along with POTS treatment quite helpful.
How do you go about diagnosing and treating SFN in post Lyme Disease treatment disorder?
I rely on a neurologist to diagnosed SFN. I am not always sure what the cause of SFN is. I have had patients in my practice with presumed PSLDS with SFN who have improved with antibiotics. You have to work with your doctor or doctors.
My SFN never went away with treatment
I have patients who have failed treatment with IVIG. I have patients improved by changing up their antibiotic schedule. I also advise my a patients to followup with a neurologist.
I have changed several antibiotics (doxycycline, minocycline, bactrim, rifampin) over 7 months. My condition got even worse, I kept worsening and my biopsy showed severe damage so I was put on IVIG.
I also have treatment failures in my practice. I lean on the neurologist for these cases. I also have some patients who have benefited from treatment for Babesia.
How do I follow up with neurologists when they don’t believe in Lyme Disease ? I am in severe pain 24/7 for three years and not one Doctor has helped me. I can not explain the pain I am in each day. It is inhumane and it has crippled me in just a few years. They laugh in my face, they downplay my pain. Pain Management says there is nothing wrong with me and refuse to treat my pain. I wish you all could be in my body just for one day. You all would cry like babies.
I have patients in severe pain despite everything their neurologist and pain management can offer. Some of them improve if their Lyme disease is treated. I also have patients who reports some gains under the care of a neurologist when prescribed IVIG. I also have patients who have found ketamine helpful.
Hi Joe,
I am sorry that you are going through this pain. I have been in pain for 3 years. I also had numbness, tingling, cold feet, spasmed muscles in my neck and left leg. I have done all sort’s of treatments with no change. Doctors did not believe me and many said that it is in my head.
6 months ago I went to Lyme Naturopathic doctor who did Igenex Lyme test which finally showed that I have Lyme. I also did skin/muscle/nerve biopsy which showed small fiber neuropathy. I treated Lyme with 3 different antibiotics 3 times a day for three months. My paid decreased from 10 to 6 but I had many bad side effects from antibiotics. Then I tried 2 weeks of IV antibiotics every day which my body handled better. After that I started taking herbal antimicrobals, antifungul, immunes support, vitamins… I am taking about 20-30 pills (herbs, Chinese medicine, vitamins). I am also doing hydro peroxide and high dose vitamin C IVs once a week. My pain level is down to 3-4 now.
All 5 neurologists that I visited with SFN issue still say that Lyme does not exist in Oregon and that it is in my head. Please don’t give up and keep looking for a right doctor. Try naturopath with Lyme experience.
How is the IVIG going? I too have SFPN for 5 + years. Out out my many symptoms my #1 issue are all day headaches.
I have been trying to get IVIG since I was diagnosed Idiopathic in 2020 from famous NYC Hospital. I was tested negative for Limes 3 times. I also was tested for just about everything else possible including Genetic testing. So finally after not getting a Dr to prescribe IVIG w/o a cause I ordered did my own lab work art Vibrant America Labs (my dietitian was the provider) it came back 3 weeks ago positive for Lyme disease “a bad case” . I just started antibiotics this week. So I really hope that IVIG is working for your symptoms and like to know more about your experience with it.
Do you think babesia only could cause sfn?
I have had patients with small fiber neuropathy (SFN) that have improved with treatment for Babesia.
How do I find treatment as thorough as you do here in Ohio? Or should I travel in these Covid Times?
My Hudson Valley tick bite with EM 26 years ago, misdiagnosed as bipolar illness. IGenX positive for bartonella at year 21 and some, but not enough bands for burgdorfi through care with a naturopath. Bartonella Sjgroens, POTS, neuropathy, neurological are all taking their course, despite continued nutritional and herbal anti viral support.
I am so tired of trying to get adequate antibiotic treatment again, having to put up with the MDs who are in need of continuing education on this. I could even help design the curriculum and train the trainers if I wasn’t so darn sick and tired of being so sick and tired. And the neuropathy is making it difficult to play my fiddle!
I would keep looking. It is always better if you find someone in your area to facilitate treatment if needed. I always advise my patients to include other specialists at the same time for POTS and neuropathy to avoid missing another diagnosis.
Please send me the web addresses for any studies And/Or antidotal information from doctors or researchers on Small Fiber Neuropathy AND Chronic aka Post Treatment Lyme Disease?
Thank you for your time and consideration.
DA Vietnam Veteran
Any links to articles or audio/videos on agent orange and SFN would be appreciated? Please keep my information private.
That is tall order. You might find my blogs on the subject on the search bar of my website at https://danielcameronmd.com/. The web including Pubmed may help. I advise my patients to include a neurologist.
Is Lyme disease associated with Eczema?