Small Fiber Neuropathy in Lyme Disease and COVID-19: Why Nerve Pain Persists
Small fiber neuropathy can cause burning pain, tingling, and autonomic symptoms—even when standard nerve tests are normal. This condition has been described in both Lyme disease and COVID-19, offering insight into how infections can affect the smallest nerve fibers.
The overlap between Lyme disease and COVID-19 highlights a broader 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 reported in Lyme disease.
One study suggests that small fiber neuropathy may serve as a biomarker of post-treatment Lyme disease syndrome, particularly in patients with sensory symptoms.
Case Report: Burning Pain Linked to Lyme Disease
An 83-year-old woman experienced four years of diffuse burning pain affecting her face, arms, and legs, along with muscle spasms.
Testing confirmed Lyme disease.
After a 40-day course of oral antibiotics, her neuropathic symptoms completely resolved.
This case suggests that small fiber neuropathy may, in some patients, reflect an infection-related process rather than permanent nerve damage.
Small Fiber Neuropathy and COVID-19
Small fiber neuropathy has also been described after COVID-19 infection.
In one report:
- A 52-year-old man developed burning pain in his feet that spread to his knees, along with imbalance and allodynia
- A 67-year-old woman experienced worsening neuropathy and persistent symptoms months after infection
Researchers concluded that COVID-19 may trigger new neuropathy or worsen existing nerve dysfunction.
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” results.
A skin biopsy measuring intraepidermal nerve fiber density (IENFD) is currently the most reliable diagnostic method.
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 include burning pain, tingling, and autonomic dysfunction
- Standard nerve tests may be normal
- Specialized testing may be required
Recognizing this pattern can prevent misdiagnosis and guide appropriate care.
Frequently Asked Questions
Can Lyme disease cause small fiber neuropathy?
Yes. It has been documented and may be linked to persistent symptoms.
Can it improve with treatment?
In some cases, symptoms improve significantly with appropriate treatment.
Does COVID-19 cause this condition?
Yes. It may trigger new or worsen existing neuropathy.
Why are tests normal?
Standard tests do not detect small fiber involvement.
What are common symptoms?
Burning pain, tingling, sensitivity, and autonomic symptoms.
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?