Small fiber neuropathy has been described in both Lyme disease and COVID-19 patients — causing burning pain, tingling, and autonomic dysfunction that standard nerve tests often miss. The overlap between these two conditions offers important insights into how infections can damage the smallest nerve fibers.
Small Fiber Neuropathy in Lyme Disease
Small fiber neuropathy with autonomic and sensory dysfunction has been reported in Lyme disease patients. A study suggests that small fiber neuropathy may be a viable biomarker of post-treatment Lyme disease syndrome, particularly for patients whose main symptoms involve sensory issues.
Case Report: An 83-Year-Old Woman with Burning Pain
In their article “Resolution of Pain in the Absence of Nerve Regeneration in Small Fiber Neuropathy Following Treatment of Lyme Disease,” the authors describe the case of an 83-year-old woman with a 4-year history of diffuse burning pain in her face, arms, and legs, and muscle spasms in the legs.
Lyme disease testing was positive. She was then treated with a 40-day course of oral antibiotics for Lyme disease with complete resolution of her neuropathic symptoms.
The authors suggest that painful small fiber neuropathy may be a manifestation of Lyme disease, and that antibiotic treatment can result in resolution of the neuropathic pain symptoms.
Small Fiber Neuropathy and COVID-19
Small fiber neuropathy is now being recognized in patients with COVID-19 as well. Investigators described the clinical presentation of small fiber neuropathy associated with COVID-19 in two patients.
Patient 1: A 52-year-old man who contracted SARS-CoV-2 developed moderate respiratory problems. About 3 weeks later, he began experiencing burning pain in the feet that spread up to the knees, associated with imbalance and falls. The pain would wake him at night, impacted his functional capacity, and was associated with allodynia — the experience of pain from stimuli that typically are not painful, such as light touch.
He was diagnosed with small fiber neuropathy based on symptoms and test results. His symptoms were most compatible with a small fiber-predominant sensory neuropathy unmasked by COVID-19 infection. His neuropathic symptoms improved with gabapentin and topical lidocaine cream.
Patient 2: A 67-year-old woman with a 10-year history of mild tingling and burning pain had been diagnosed with small fiber neuropathy associated with psoriatic arthritis based on biopsy results. Her symptoms had been stable for 10 years until she contracted SARS-CoV-2 and developed severe burning pain in her hands and feet. She presented 6 months later with persistent symptoms and occasional orthostasis.
The authors describe this as an example of a chronic pre-existing sensory and small fiber-predominant autonomic neuropathy exacerbated by COVID-19 infection.
Why This Matters for Lyme Patients
The recognition of small fiber neuropathy in COVID-19 patients validates what Lyme disease patients have experienced for years — burning pain, tingling, and autonomic symptoms that standard nerve tests fail to detect. Both conditions appear to trigger small fiber nerve damage through immune-mediated mechanisms.
This parallel strengthens the case that post-infectious small fiber neuropathy is a documented medical phenomenon — not a psychological one. For more on the broader connection between Long COVID and Lyme, see Long COVID and Lyme Disease: What Patients Need to Know.
Why Standard Tests Miss Small Fiber Neuropathy
Standard EMG and nerve conduction studies assess large nerve fibers. Small fiber neuropathy affects the smallest sensory and autonomic fibers, which these tests cannot measure. A skin biopsy measuring intraepidermal nerve fiber density (IENFD) is the most widely accepted diagnostic tool.
When burning pain, tingling, or autonomic symptoms persist but standard nerve tests are normal, small fiber neuropathy should be considered — especially in patients with Lyme disease or post-COVID symptoms. For a deeper look at how neuropathy presents in Lyme disease, see Lyme Disease Neuropathy: Symptoms and What Causes It.
Frequently Asked Questions
Can Lyme disease cause small fiber neuropathy?
Yes. Research has documented small fiber neuropathy in Lyme disease patients, and it may serve as a biomarker for post-treatment Lyme disease syndrome.
Can small fiber neuropathy from Lyme disease be treated?
Yes. In the case described, a 40-day course of antibiotics resulted in complete resolution of burning pain and neuropathic symptoms that had persisted for 4 years.
Does COVID-19 also cause small fiber neuropathy?
Yes. Small fiber neuropathy has been documented in COVID-19 patients, with symptoms including burning pain, tingling, and autonomic dysfunction — strikingly similar to what Lyme patients experience.
Why are my nerve tests normal if I have burning pain?
Standard EMG and nerve conduction studies only assess large nerve fibers. Small fiber neuropathy requires a skin biopsy for diagnosis.
What does small fiber neuropathy feel like?
Patients describe burning pain, tingling, temperature sensitivity, allodynia (pain from light touch), and autonomic symptoms like dizziness or sweating abnormalities.
References
- Johns Hopkins Medicine. Neurology and Neurosurgery. HopkinsMedicine.org.
- Novak P, Felsenstein D, Mao C, et al. Association of small fiber neuropathy and post treatment Lyme disease syndrome. PLoS One. 2019;14(2):e0212222.
- Feuer N, Alaedini A. Resolution of Pain in the Absence of Nerve Regeneration in Small Fiber Neuropathy Following Treatment of Lyme Disease. Neurology. 2013;80(7 Supplement):P06.228.
- Shouman K, Vanichkachorn G, Cheshire WP, et al. Autonomic dysfunction following COVID-19 infection: an early experience. Clin Auton Res. 2021.
Related Reading
- Lyme Disease Neuropathy: Symptoms and What Causes It
- Autonomic Dysfunction, Small Fiber Neuropathy and Lyme Disease
- Femoral Neuropathy and Lyme Disease
- Full Body Numbness and Tingling Due to Lyme Disease
- Long COVID and Lyme Disease: What Patients Need to Know
- Autonomic Dysfunction and Lyme Disease
- CIDP Case Resolved with Antibiotics
My original Lyme symptom was muscle inflammation with terrible pain in head, neck and shoulder. After months of severe pain, I was finally put on Steroids to manage what doctors thought was Polymyalgia Rheumatica (PMR). Oddly enough, the Rheumatologist took a Lyme test and it was totally CDC, all bands positive. Once, I started Doxy, and then a round of IV ceftriaxone, I developed terrible nerve pain, numbness on my left side from headaches, face, neck shoulder, back, sacro and left leg.
Unfortunately, all the antibiotics have not relieved this neuropathy or the pain on my left side. Had Shingles twice since Lyme diagnosis which may be causing some nerve pain as well.
Somehow, I tested positive again for Lyme and Babesia last month – no bite, no rash. I’m on second round of Doxy, Azithromycin and Atovaquone. This new treatment has intensified the nerves and I’m absolutely miserable. Maybe herxing?
Has anyone had nerve pain that still persists after antibiotic treatment? Treatment and/or Detox?
That is exactly what I am dealing with. None of my MD’s even mentioned Lyme when they were examining me. The tingling started a bit and when it was evident all the time, I got a referral to the neurologist. He called it sensory neuropathy. Said to come back in 6 months (to see if it was getting worse or not). It is continual and no, I am not going back as I can’t see how they will have a fix anyway.
Yes, my daughter is dealing with severe neuropathic pain that started during treatment with antibiotics and still last after finishing. She has been prescribed with gabapentin and lipoic acid for the pain. Also she is being tested for SFN and doctors are considering IVIG as well. She still is positive for Lyme on the bands but not with the PCR. Doctors (neuro & reuma) are not sure if continuing antibiotics will benefit her at all. How long a patient should receive antibiotics when PCR is negative but bands are still positive, considering the side effects?
I often have Lyme disease patients with a negative PCR and neuropathy who do well with antibiotic treatment. I have some patients who fail antibiotic treatment for neuropathy. I ask my patients to continue working with their neurologist if their neuropathy persists. Some have benefited from IVIG.
Hi dr Cameron,
I have first the diagnose Sarcoidose, later small fiber neuropathy and 8 years later TBD.
The TBD is a big struggle in the lyme world.
Iam extremely tired with pain also.
Lot of brainfog.
Muscle pain and bone pain.
Sleap problems.
Tninitus.
Dry mouth and tong. Burn mouth syndrom.
Also are mine Interleukine very high
Best regards,
Ed
When small nerve fibers are damaged they become hyperexcitable and you’ll probably find that many antibiotics can cause flare ups in nerve symptoms. While I don’t have lyme (as far as I’m aware), I did develop neuropathy, most likely from B12 deficiency. When I went to treat a UTI, I was unable to tolerate Trimethoprim or Doxycycline as they’d cause severe nerve pain, burning, numbness, tingling, shooting pains. I had no issues at all with these antibiotics prior to developing SFN. Once I stopped the antibiotics , the nerve pains would mostly go away. It seemed that the antibiotics simply unmasked nerve damage, but without a trigger, the level was under the threshold that was obvious. So the strategy was then to allow my nerves to heal somewhat and then try again 9 months later while I treated it naturally to suppress the infection.
I was finally able to tolerate Trimethoprim after 9 months, especially when I added R lipoic acid to my regimen. It seemed that ALCAR, Benfotiamine, Magnesium Glycinate did not prevent the burning pain completely, but it was still around a 3-4 out of 10. Once I added the ALA, it went to a 0 and tolerated Trimethoprim for 2 months. Unfortunately the bacteria eventually become resistant it seems.
I was also getting weird reactions to even things like glycerol, which I guess because it may alter osmolality of the cells and somehow leads to increased nerve pain. But I can toleate this much better now. Also, even Hiprex would cause nerve pain and that has no neurotoxicity that has been documented.
I still have not tried Doxycycline again but that is probably what I will need to take. So I’m hoping my nerves have repaired enough to be less hyperexcitable and the R lipoic will help. I had no idea that I had B12 deficiency when I first tried Doxy. Or that R Lipoic was so helpful.
Whether or not it is a psuedoexacerbation of the the SFN, I am unsure. Hypersensitive nerves can react to even benign things. So it’s not always because of a herx reaction due bugs (in the case of lyme) dying off.
Do many lyme patients just try to tolerate the nerve pain and work through the course? I have wondered how some people with SFN have no issues with antibiotics. Maybe there is genetic differences in sodium ion channel genes. Hopefully new targeted therapies that reduce hyperexcitability by targeting thse Nav genes (some in trials now I think) will enable patients to complete treatment without the serious nerve side effects.
can sfn remit with antibiotics
In 1990, Logigian and colleagues described axonal sensory neuropathy in Lyme disease. some of their patients improved. I have seen some patients whose SFN has improved with antibiotics.
Hi,
I have suffered with small fiber neuropathy for 16 years. In spite of my pain meds, being the only thing that has given me any relief, I still hurt. My pain worsened for months and I blamed it on SFN ect…Then I couldn’t walk, developed a skin infection with bad neck pain. My Dr. tested me for Lyme disease. I was surprised It came back positive! They put me on an antibiotic for 3 weeks. I am only 1 week into taking my antibiotics. I am still in so much leg and foot pain walking is almost impossible! I feel really hopeless! Even at it’s worse with SFN I could walk! Will this ever get better?