Small Fiber Neuropathy in Lyme Disease and COVID-19
Small fiber neuropathy has been described in both Lyme disease and COVID-19 patients. This condition can cause burning pain, tingling, and autonomic dysfunction that standard nerve tests often fail to detect. The overlap between these infections provides insight into how infectious diseases may damage the smallest sensory and autonomic nerve fibers.
Small Fiber Neuropathy in Lyme Disease
Small fiber neuropathy involving both sensory and autonomic dysfunction has been reported 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 disturbances.
Case Report: Burning Pain Linked to Lyme Disease
In the article
“Resolution of Pain in the Absence of Nerve Regeneration in Small Fiber Neuropathy Following Treatment of Lyme Disease”
, investigators described the case of an 83-year-old woman with a four-year history of diffuse burning pain affecting her face, arms, and legs, along with muscle spasms.
Testing confirmed Lyme disease. The patient received a 40-day course of oral antibiotics, after which her neuropathic symptoms completely resolved.
The authors concluded that painful small fiber neuropathy may represent a manifestation of Lyme disease and that antibiotic treatment may relieve neuropathic symptoms in certain patients.
Small Fiber Neuropathy and COVID-19
Small fiber neuropathy has also been reported in individuals following COVID-19 infection. Investigators described the clinical features of small fiber neuropathy associated with COVID-19 in two patients.
Patient 1: A 52-year-old man who developed moderate respiratory symptoms from SARS-CoV-2 later experienced burning pain in the feet that gradually spread to the knees. The symptoms were associated with imbalance, falls, and allodynia—pain caused by normally non-painful stimuli such as light touch.
He was diagnosed with small fiber neuropathy based on clinical findings and testing. Treatment with gabapentin and topical lidocaine improved his symptoms.
Patient 2: A 67-year-old woman with a prior diagnosis of small fiber neuropathy related to psoriatic arthritis experienced a significant worsening of burning pain in her hands and feet after contracting COVID-19. Six months later she continued to report persistent symptoms and occasional orthostatic intolerance.
Researchers concluded that COVID-19 may either trigger new small fiber neuropathy or worsen pre-existing neuropathic conditions.
Why This Matters for Lyme Disease Patients
Recognition of small fiber neuropathy in COVID-19 patients supports what many Lyme disease patients have reported for years—persistent burning pain, tingling, and autonomic symptoms that standard nerve studies may fail to detect.
Both infections appear capable of triggering immune-mediated injury to small nerve fibers. This growing body of research strengthens the evidence that post-infectious small fiber neuropathy is a real biological phenomenon rather than a psychological condition.
For more on the connection between these two illnesses, see Long COVID and Lyme Disease: What Patients Need to Know.
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.
A skin biopsy measuring intraepidermal nerve fiber density (IENFD) is currently considered the most reliable diagnostic method.
When patients experience burning pain, tingling, or autonomic symptoms despite normal nerve tests, small fiber neuropathy should be considered—particularly in individuals with Lyme disease or post-COVID symptoms.
For additional information about neuropathy in Lyme disease, see
Lyme Disease Neuropathy: Symptoms and Causes
.
Frequently Asked Questions
Can Lyme disease cause small fiber neuropathy?
Yes. Studies have 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 improve with treatment?
In the case described, a 40-day course of antibiotics resulted in complete resolution of neuropathic symptoms that had persisted for several years.
Does COVID-19 cause small fiber neuropathy?
Yes. Small fiber neuropathy has been documented in some COVID-19 patients, producing symptoms such as burning pain, tingling, and autonomic dysfunction.
Why are nerve tests normal when symptoms are severe?
Standard EMG and nerve conduction tests evaluate large nerve fibers. Small fiber neuropathy requires specialized testing such as skin biopsy.
What symptoms occur with small fiber neuropathy?
Common symptoms include burning pain, tingling, temperature sensitivity, allodynia, and autonomic symptoms such as dizziness or abnormal sweating.
References
- Novak P, Felsenstein D, Mao C, et al. Association of small fiber neuropathy and post treatment Lyme disease syndrome. PLoS One. 2019.
- Feuer N, Alaedini A. Resolution of Pain in the Absence of Nerve Regeneration in Small Fiber Neuropathy Following Treatment of Lyme Disease. Neurology. 2013.
- Shouman K, Vanichkachorn G, Cheshire WP, et al. Autonomic dysfunction following COVID-19 infection. Clin Auton Res. 2021.
Related Reading
- Lyme Disease Neuropathy: Symptoms and Causes
- Autonomic Dysfunction, Small Fiber Neuropathy and Lyme Disease
- Femoral Neuropathy and Lyme Disease
- Full Body Numbness and Tingling in Lyme Disease
- Long COVID and Lyme Disease
- Autonomic Dysfunction and Lyme Disease
- CIDP Case Resolved with Antibiotics
Small fiber neuropathy has been described in both Lyme disease and COVID-19 patients. This condition can cause burning pain, tingling, and autonomic dysfunction that standard nerve tests often fail to detect. The overlap between these infections provides insight into how infectious diseases may damage the smallest sensory and autonomic nerve fibers.
Small Fiber Neuropathy in Lyme Disease
Small fiber neuropathy involving both sensory and autonomic dysfunction has been reported 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 disturbances.
Case Report: Burning Pain Linked to Lyme Disease
In the article
“Resolution of Pain in the Absence of Nerve Regeneration in Small Fiber Neuropathy Following Treatment of Lyme Disease”
, investigators described the case of an 83-year-old woman with a four-year history of diffuse burning pain affecting her face, arms, and legs, along with muscle spasms.
Testing confirmed Lyme disease. The patient received a 40-day course of oral antibiotics, after which her neuropathic symptoms completely resolved.
The authors concluded that painful small fiber neuropathy may represent a manifestation of Lyme disease and that antibiotic treatment may relieve neuropathic symptoms in certain patients.
Small Fiber Neuropathy and COVID-19
Small fiber neuropathy has also been reported in individuals following COVID-19 infection. Investigators described the clinical features of small fiber neuropathy associated with COVID-19 in two patients.
Patient 1: A 52-year-old man who developed moderate respiratory symptoms from SARS-CoV-2 later experienced burning pain in the feet that gradually spread to the knees. The symptoms were associated with imbalance, falls, and allodynia—pain caused by normally non-painful stimuli such as light touch.
He was diagnosed with small fiber neuropathy based on clinical findings and testing. Treatment with gabapentin and topical lidocaine improved his symptoms.
Patient 2: A 67-year-old woman with a prior diagnosis of small fiber neuropathy related to psoriatic arthritis experienced a significant worsening of burning pain in her hands and feet after contracting COVID-19. Six months later she continued to report persistent symptoms and occasional orthostatic intolerance.
Researchers concluded that COVID-19 may either trigger new small fiber neuropathy or worsen pre-existing neuropathic conditions.
Why This Matters for Lyme Disease Patients
Recognition of small fiber neuropathy in COVID-19 patients supports what many Lyme disease patients have reported for years—persistent burning pain, tingling, and autonomic symptoms that standard nerve studies may fail to detect.
Both infections appear capable of triggering immune-mediated injury to small nerve fibers. This growing body of research strengthens the evidence that post-infectious small fiber neuropathy is a real biological phenomenon rather than a psychological condition.
For more on the connection between these two illnesses, see Long COVID and Lyme Disease: What Patients Need to Know.
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.
A skin biopsy measuring intraepidermal nerve fiber density (IENFD) is currently considered the most reliable diagnostic method.
When patients experience burning pain, tingling, or autonomic symptoms despite normal nerve tests, small fiber neuropathy should be considered—particularly in individuals with Lyme disease or post-COVID symptoms.
For additional information about neuropathy in Lyme disease, see
Lyme Disease Neuropathy: Symptoms and Causes
.
Frequently Asked Questions
Can Lyme disease cause small fiber neuropathy?
Yes. Studies have 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 improve with treatment?
In the case described, a 40-day course of antibiotics resulted in complete resolution of neuropathic symptoms that had persisted for several years.
Does COVID-19 cause small fiber neuropathy?
Yes. Small fiber neuropathy has been documented in some COVID-19 patients, producing symptoms such as burning pain, tingling, and autonomic dysfunction.
Why are nerve tests normal when symptoms are severe?
Standard EMG and nerve conduction tests evaluate large nerve fibers. Small fiber neuropathy requires specialized testing such as skin biopsy.
What symptoms occur with small fiber neuropathy?
Common symptoms include burning pain, tingling, temperature sensitivity, allodynia, and autonomic symptoms such as dizziness or abnormal sweating.
References
- Novak P, Felsenstein D, Mao C, et al. Association of small fiber neuropathy and post treatment Lyme disease syndrome. PLoS One. 2019.
- Feuer N, Alaedini A. Resolution of Pain in the Absence of Nerve Regeneration in Small Fiber Neuropathy Following Treatment of Lyme Disease. Neurology. 2013.
- Shouman K, Vanichkachorn G, Cheshire WP, et al. Autonomic dysfunction following COVID-19 infection. Clin Auton Res. 2021.
Related Reading
- Lyme Disease Neuropathy: Symptoms and Causes
- Autonomic Dysfunction, Small Fiber Neuropathy and Lyme Disease
- Femoral Neuropathy and Lyme Disease
- Full Body Numbness and Tingling in Lyme Disease
- Long COVID and Lyme Disease
- Autonomic Dysfunction and Lyme Disease
- CIDP Case Resolved with Antibiotics
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?