Small Fiber Neuropathy in Lyme Disease and COVID-19: Why Nerve Pain Persists
Small fiber neuropathy Lyme disease symptoms may include burning pain, tingling, sensitivity to touch, dizziness, and autonomic dysfunction—even when EMG and nerve conduction studies are normal.
The overlap between Lyme disease and COVID-19 highlights a broader neurologic pattern: infections can trigger persistent nerve dysfunction that standard testing may miss.
Small Fiber Neuropathy in Lyme Disease
Small fiber neuropathy affecting both sensory and autonomic nerves has been described in Lyme disease patients.
One study suggests that small fiber neuropathy may serve as a biomarker of post-treatment Lyme disease syndrome, particularly in patients whose primary symptoms involve sensory dysfunction.
These findings support growing interest in the relationship between neuropathy, autonomic dysfunction, and persistent Lyme disease symptoms.
Case Report: Burning Pain Linked to Lyme Disease
In their article, “Resolution of Pain in the Absence of Nerve Regeneration in Small Fiber Neuropathy Following Treatment of Lyme Disease,” Feuer and Alaedini describe an 83-year-old woman with a four-year history of diffuse burning pain involving her face, arms, and legs, along with muscle spasms.
Testing confirmed Lyme disease.
She was treated with a 40-day course of oral antibiotics and experienced complete resolution of her neuropathic symptoms.
This case suggests that small fiber neuropathy may, in some patients, reflect an infection-related process rather than permanent nerve damage.
The authors concluded that painful small fiber neuropathy may be a manifestation of Lyme disease and that treatment may improve symptoms in selected patients.
Small Fiber Neuropathy and COVID-19
Small fiber neuropathy has also been described following COVID-19 infection.
Investigators reported two patients with neuropathic symptoms after SARS-CoV-2 infection.
- A 52-year-old man developed burning pain in his feet that spread to his knees, along with imbalance, falls, and allodynia
- A 67-year-old woman experienced worsening neuropathy, persistent symptoms, and occasional orthostasis months after infection
Allodynia refers to pain caused by stimuli that are not normally painful, such as light touch.
The authors suggested COVID-19 may have unmasked underlying small fiber neuropathy in one patient and exacerbated pre-existing autonomic neuropathy in another.
Researchers emphasized that the study was observational and could not establish causation.
Why This Matters
These findings support what many Lyme disease patients have reported for years:
- Burning pain
- Tingling
- Autonomic symptoms
- Normal nerve tests
This pattern reflects a biologic process—not a psychological condition.
For more, see Long COVID and Lyme disease.
Why Standard Tests Often Miss Small Fiber Neuropathy
Standard nerve conduction studies and EMG tests evaluate large nerve fibers.
Small fiber neuropathy affects the smallest sensory and autonomic fibers—which these tests cannot detect.
This explains why symptoms can be severe despite “normal” test results.
A skin biopsy measuring intraepidermal nerve fiber density (IENFD) is currently considered one of the most reliable diagnostic methods.
For more on neuropathy patterns, see Lyme disease neuropathy.
Clinical Takeaway
Small fiber neuropathy is a recognized complication of both Lyme disease and COVID-19.
- Symptoms may include burning pain, tingling, sensitivity, and autonomic dysfunction
- Standard nerve tests may remain normal
- Specialized testing may be required for diagnosis
Recognizing this pattern may prevent misdiagnosis and support more appropriate neurologic evaluation.
Frequently Asked Questions
Can Lyme disease cause small fiber neuropathy?
Yes. Small fiber neuropathy has been described in Lyme disease patients and may contribute to persistent sensory and autonomic symptoms.
Can small fiber neuropathy improve with treatment?
In some patients, neuropathic symptoms improve significantly after treatment.
Can COVID-19 trigger small fiber neuropathy?
Yes. COVID-19 infection has been associated with new or worsening small fiber neuropathy symptoms.
Why are EMG and nerve conduction studies normal?
Standard nerve tests evaluate large fibers and often miss small fiber involvement.
What symptoms are common?
Burning pain, tingling, sensitivity to touch, dizziness, orthostasis, and autonomic symptoms are commonly reported.
Related Articles
- Autonomic dysfunction, small fiber neuropathy and Lyme disease
- Femoral neuropathy and Lyme disease
- Chronic inflammatory demyelinating polyneuropathy resolved with antibiotics
- Long COVID and Lyme disease
References
- Neurology and Neurosurgery. Johns Hopkins Medicine.
- 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.
- 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 Suppl):P06.228.
- Shouman K, Vanichkachorn G, Cheshire WP, et al. Autonomic dysfunction following COVID-19 infection: an early experience. Clin Auton Res. 2021;31(3):385-394.
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
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?