Peripheral Neuropathy and Lupus

Peripheral neuropathy is nerve damage that impairs of the communication between our central nervous system and the rest of the body. How is this condition implicated in lupus?

Introduction

Our central nervous system (CNS) consists of the brain and spinal cord – the “centers” where we coordinate, regulate and interpret and ultimately control most of our other bodily functions … and occasionally some thinking!  The CNS takes the signals that come from all over the body (the skin, eyes, ears, internal organs and other senses), interprets them and then sends messages back so that the body can move or react appropriately. Our peripheral nervous system (PNS) consists of all of the nerves outside the brain and spinal cord and as such, mediates the CNS with the rest of the body and the outside world.

The peripheral nervous system has two main parts – the somatic nervous system (SNS) and the autonomic nervous system (ANS).

The somatic nervous system is divided into motor (movement) and sensory systems.  As such, it is responsible for most of our voluntary muscle movement (walking, talking, facial expressions), and for processing external stimuli such as the traditional five senses (hearing, sight, taste, smell, touch) as well as all the other “senses” such as motion, position, and equilibrium.  The SNS is also responsible for the involuntary muscle movements we have when we do things such as jerk our hand away when we touch a hot stove or kick our leg when our reflexes are tested.

The autonomic nervous system does most of its work behind the scenes, without our ability to control it very well.  It regulates the organs that tend to “run on their own,” without our conscious effort, such as our intestines, heart, bladder, and lungs.  Our heartbeat, breathing rate and body temperature are regulated by this system.  The ANS is quite often driven by emotion.  So, when we see something beautiful, the pupils of our eyes may dilate. When we get worried, our stomach feels like it gets “tied in knots.” When we are afraid, we start to sweat, and when we are hungry, we might salivate.  All of these reactions are due to the autonomic nervous system.

When an individual has peripheral neuropathy, these somatic and autonomic functions may become impaired.  This happens during or after an illness or infection, trauma or injury.  Also, the impairment may occur for what seems to be no apparent reason at all.  The resulting symptoms can be incredibly diverse.  An individual may feel excruciating pain, or experience tingling or numbness in parts of their body.  They may be unable to maintain their balance or control their bowels or bladder.

Those with systemic lupus erythematosus (SLE) are more prone to developing peripheral neuropathy due to the activity of SLE, the inflammation that can occur throughout the body and/or secondary health conditions from overlap diseases. In a 2011 study published in Seminars in Arthritis and Rheumatism, researchers found that the prevalence of peripheral neuropathy was high in individuals with SLE, especially those with high disease activity and those who already had a compromised central nervous system.  It is important to understand how peripheral neuropathy can affect an individual with lupus and how to communicate with healthcare practitioners to best to treat, manage and cope with this sometimes debilitating condition.

Classifying Peripheral Neuropathy

According to the National Institute of Health (NIH), there are more than 100 neuropathies. For ease of classification, they have been broken down into three general groups depending on which type of nerves are affected:

  • Motor nerves: Motor nerves assist with our ability to walk around the block, grab something off of a shelf and speak about how we are feeling.
  • Sensory nerves: Sensory nerves allow us to feel the pain of a papercut, the chilling cold of an ice cube and the heat from an iron.
  • Autonomic nerves: Autonomic nerves involve the things we cannot control ourselves including our ability to digest pizza, breathe hard after physical exertion and regulate our blood pressure when we are angry.

If an individual experiences peripheral neuropathy in just one nerve, they have mononeuropathy. If more than one nerve is affected, the individual has polyneuropathy. In the 2011 Seminars in Arthritis and Rheumatism study, polyneuropathy was found to be more common than mononeuropathy in individuals with SLE.  The study also found that this neuropathy primarily attacked the sensory nerves.  Subsequently, researchers of a 2014 study published in the journal Arthritis and Rheumatology found that individuals with peripheral neuropathy of the sensory nerves most often had small fiber neuropathy, which is primarily characterized by severe pain in the hands and/or feet.

Many neuropathies are “length-dependent” –  meaning they start from the nerves farthest away from the spine (the toes, the fingertips) and move towards the torso. Some other neuropathies that occur sporadically and in patches and are “non-length dependent.” Length can also determine the severity of the neuropathy.

What are the symptoms of peripheral neuropathy?

The Mayo Clinic and the NIH list the following most common symptoms of neuropathy:

  • Feeling off-balance, uncoordinated and/or losing a sense of position and falling.
  • Tingling, buzzing or that “pins and needles” feeling in the hands and/or feet.
  • Muscle twinges, spasms or cramping.
  • Weakness in the arms, hands, legs and/or feet.
  • Sharp, shooting, burning pain that may start at the fingers or toes and spread towards the torso.
  • The inability to distinguish hot from cold.
  • Extreme sensitivity to hot, cold or touch.
  • The inability to feel pain, vibrations or touch.
  • Pain during normal activities that should not cause pain.
  • Loss of reflexes.
  • Excessive sweating.
  • The inability to swallow and/or eat.
  • Digestive
  • Changes in blood pressure that cause dizziness or lightheadedness.

In the 2014 Arthritis & Rheumatology study, individuals reported neuropathic pain as their most prevalent symptom, especially burning pain. All 2,097 individuals studied who had a form of peripheral neuropathy noted feeling pain as their main symptom. The pain not only occurred in the hands and feet, but sometimes in the face, torso and whole body as well. Others reported muscle weakness, and asymmetric sensory symptoms (no apparent pain pattern) and sensorimotor symptoms (affecting both sensory and motor nerves).

What causes peripheral neuropathy?

Peripheral neuropathy has many causes. The Cleveland Clinic lists the following as the most common triggers for peripheral neuropathy:

  • Diabetes which can cause nerve damage that commonly is felt as pain in the legs and feet.
  • Trauma resulting from injuries or car accidents.
  • Autoimmune diseases such as SLE, Sjögren’s syndrome and rheumatoid arthritis (RA).
  • Infections such as Epstein-Barr virus, herpes and Lyme disease.
  • Medications/toxins such as anti-seizure medications, chemotherapy and radiation, lead or mercury poisoning.
  • Vascular disorders such as vasculitis.
  • Alcoholism, which can decimate levels of thiamine that are essential for nerve function.
  • Vitamin deficiencies such as deficiencies of vitamin E, B1, B6, B12 and niacin.
  • Genetic disorders such as Charcot-Marie-Tooth disease (muscle weakness and atrophy), familial amyloidosis (a protein disorder), and Fabry disease (narrowing of the blood vessels).

When there is no known cause for peripheral neuropathy, it is said to be idiopathic.

Certain types of vasculitis – inflammation of the blood vessels – cause inflammation of the vessels that surround nerves. Since individuals with SLE are at risk of developing vasculitis, they are also more at risk of developing this kind of nerve damage, including a condition called mononeuritis multiplex, a painful neuropathy that can attack multiple nerves in random areas of the body. According to researchers of a 2014 review published in the journal The Lancet, up to 70% of individuals with vasculitis report having symptoms of peripheral neuropathy. They initially reported feeling burning pain around one nerve point, which within weeks, begins to spread to others. The American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) describes mononeuritis not as a disease, but a classification of symptoms of peripheral neuritis that affects two or more nerve groups. Its symptoms include numbness, tingling, lack of or distorted sensation, uncontrollable movement or even the inability to move parts of the body at all. Mononeuritis multiplex can also affect individuals with RA and scleroderma as these individuals are more prone to developing vasculitis as well.

Just as cytokines, the large category of proteins that signal damage and regulate immune and inflammation responses, play a significant role in SLE, they may also play a role in the pain experienced with peripheral neuropathy. Some cytokines produce an anti-inflammatory response and others produce a pro-inflammatory response. Individuals with SLE have an overactive immune system and an excess of the inflammatory cytokines. Researchers of a 2013 article published in the Journal of Pain Research discuss how the cytokine Interleukin 1ß (IL-1ß) is implicated in initiating inflammatory and immune responses during peripheral nerve injury as well. Under normal conditions, IL-1ß is present at low levels in cells, but after peripheral nerve injury, IL-1ß is “upregulated” which can cause the feeling of intense pain. Though these studies were conducted in rats, researchers agree that these studies may lead to exploring ways of treating the pain and discomfort of peripheral neuropathy in humans.

How is peripheral neuropathy diagnosed and treated?

A neurologist typically diagnoses and treats peripheral neuropathy. They should work closely with an individual’s healthcare team especially if the individual has lupus.

Diagnosis

In 1999, the American College of Rheumatology (ACR) recommended guidelines for diagnosing neuropsychiatric SLE. Neuropsychiatric SLE (NPSLE) represents conditions that affect the CNS and the peripheral nervous system in individuals with lupus. These conditions can include everything from anxiety and brain fog to the nerve damage associated with peripheral neuropathy. Approximately 15% of individuals with NPSLE specifically experience peripheral nervous system disturbances.

The ACR guidelines include case definitions for 19 neuropsychiatric syndromes of SLE. An individual may be diagnosed with NPSLE if they meet the case definition of NPSLE and meet three or more of the ACR criteria for diagnosing SLE.

Some of the conditions that case definitions have been developed include:

  • Anxiety, mood disorders and
  • Cognitive dysfunction such as difficulties focusing and remembering.
  • Headache including migraine and benign intracranial hypertension.
  • Demyelinating syndrome, which occurs when there is damage to the myelin sheath around the nerve fibers in the brain and spinal cord.
  • Myelopathy that results when there is severe compression of the spine and ultimately nerve damage.
  • Aseptic meningitis, which can result from inflammation of the meninges, the membrane that covers the brain and spinal cord.
  • Neurologic syndromes of the peripheral nervous system including disturbances of the peripheral nerves, sensorimotor nerves and autonomic nerves.

The NIH lists the following diagnostic tools that further aid a healthcare practitioner in the proper diagnosis and treatment of peripheral neuropathy:

  • A health assessment of an individual’s and family’s medical history.
  • Lab tests such as blood tests to determine organ function (kidney and liver), vitamin levels, the presence of abnormal protein levels and immune cells, infections and other abnormalities.
  • A physical exam that checks for conditions that can cause nerve damage.
  • A neurological exam, which checks for neuropathic disorders as well as the degree of nerve damage.
  • Genetic tests for the inherited conditions mentioned earlier in this article.
  • A physiological test of nerve function or more specifically a nerve conduction velocity test which measures the strength and speed that signals move along a nerve path.
  • Neuropathology tests of nerve appearance which is a biopsy of sensory nerve tissue taken from the leg to detect what kind of nerves and cells are damaged or a skin biopsy which shows nerve fiber endings that may be damaged.
  • Autonomic testing that measures a person’s ability to sweat.
  • Radiology imaging tests including an MRI or CT scan.
  • Muscle and nerve ultrasounds that check for abnormalities related to muscle or nerve disorders.
  • A spinal tap, which may show antibodies, or the presence of protein markers for B-cell activation.

Treatment

A healthcare practitioner will first try to address the cause of the neuropathy and treat any underlying conditions. For example, if an individual has diabetes or is not maintaining a healthy weight, a healthcare practitioner should work with that individual to manage those complications. A healthcare practitioner will also try to rule out other potential reasons or causes for the neuropathy.

The NIH lists the following as the most common types of treatment for neuropathy.  Notice that some are the same as those for treating SLE:

  • Over-the-counter medications such as ibuprofen, naproxen or aspirin for more mild cases.
  • Glucocorticoids, including prednisone.
  • Immunosuppressants such as cyclosporine, azathioprine.
  • Monoclonal antibodies such as Rituximab.
  • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) including duloxetine hydrochloride (Cymbalta). A 2012 review article published in the Journal of Clinical Pharmacology discussed that this class of antidepressants can significantly reduce pain intensity and overall discomfort.
  • Antiseizure therapy including gabapentin, pregabalin, topiramate, lamotrigine.
  • Carbamazepine and
  • Local anesthetics that block nerve conditions and can be applied as patches or creams including lidocaine, capsaicin, bupivacaine.
  • Narcotics including opioids. Note: A healthcare practitioner should work very closely with an individual who may need narcotics to insure they are used in the safest way possible, for the least amount of time.
  • Plasmapheresis: A more invasive procedure, which removes blood, clears it of immune systems cells and antibodies and returns the blood to the body.
  • Braces and splints: These stabilizing measures may be taken if an individual experiences pain from carpal tunnel syndrome, foot pain or severe muscle weakness.
  • Modifying activity: This may include exercise or even just learning how to move in a different way so the affected nerves are not aggravated.
  • Surgery: Surgery is sometimes used as treatment for pinched nerves in the back or neck.
  • Transcutaneous Electrical Nerve Stimulation (TENS): TENS is often used in diabetic neuropathies to relieve pain.
  • Acupuncture: A good acupuncturist will work with an individual as their pain and discomfort changes to make sure their symptoms are being properly managed.
  • Massage therapy: Getting regular massages may not only relieve stiffness and pain, but provide relaxation as well.
  • Herbal medications: It is always important to first discuss the use of herbs when treating any condition, especially if an individual has lupus as there may be drug interactions.

Researchers of a 2018 study published in the Asian Journal of Medical Sciences also found that high-dose vitamin B therapy (B1, B6 and B12) may be effective in the management of mild to moderate peripheral neuropathy symptoms. 399 subjects were studied and showed significant improvement of symptoms within 14 days.

Someone with lupus should work closely with healthcare practitioners to avoid any contraindications and take their limitations, lupus activity and overall health condition into consideration when developing treatment plans.

Managing the Effects of Peripheral Neuropathy

A healthcare practitioner may suggest an individual with neuropathy receive cognitive behavioral therapy (CBT). CBT can help an individual manage their symptoms, especially if they are already trying to manage the symptoms of a chronic illness such as lupus. CBT includes talk therapy and may also include incorporating other management tools that benefit emotional well-being. These other tools may include practicing tai chi or yoga, mindful meditation, journaling, deep breathing and relaxation exercises or other practices that help manage stress.

An individual’s support system can be an invaluable resource of strength and stability when an individual feels down. Being able to rely on and talk to trusted friends and family can strengthen relationships as well as bring a sense of peace and calm.  Support systems can also be there when an individual needs to let loose and have a little fun at times! It is important for an individual experiencing the symptoms of peripheral neuropathy and/or lupus to be honest with themselves and others about how they are feeling and what they need emotionally.

Getting rest and sleep is also important in managing and coping with the effects of peripheral neuropathy. If an individual is not getting proper, quality sleep, they should address the issue and their concerns with a healthcare practitioner who can help them discover ways to get more rest and develop good sleep practices.

Maintaining a healthy diet and drinking plenty of water throughout the day will also help to manage symptoms and provide some relief. An individual can discuss proper nutrition with their healthcare practitioner to make sure they are getting the right vitamins and nutrients into their diet depending on any food allergies or restrictions and eat the right foods that may help ease pain and inflammation.

In Conclusion

Working closely with a healthcare practitioner or team of practitioners will ensure that an individual experiencing the sometimes debilitating pain and discomfort of peripheral neuropathy receives proper care and treatment. Treating the patient holistically – both mind and body – can go far in helping an individual cope with and manage not only pain and physical discomfort, but the stress and fear that often come from wondering what is wrong and waiting to feel better.

 

References
American Association of Neuromuscular & Electrodiagnostic Medicine. (2020). Mononeuritis multiplex. Retrieved January 21, 2020, from https://www.aanem.org/Patients/Muscle-and-Nerve-Disorders/Mononeuritis-Multiplex
Christopher & Dana Reeve Foundation. (2020). How the spinal cord works. Retrieved January 21, 2020, from https://www.christopherreeve.org/living-with-paralysis/health/how-the-spinal-cord-works
Clark, A., Old, E., & Malcangio, M. (2013). Neuropathis pain and cytokines: Current perspectives. Journal of Pain Research. Retrieved January 21, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839806/pdf/jpr-6-803.pdf
Dharmshaktu, P., Tayal, V., & Kalra, B. (2012). Efficacy of antidepressants as analgesics: A review. Journal of Clinical Pharmacology. Retrieved January 21, 2020, from https://accp1.onlinelibrary.wiley.com/doi/pdf/10.1177/0091270010394852
Florica, B., Aghdassi, E., Su, J., Gladman, D., Urowitz, M., & Fortin, P. (2011). Peripheral neuropathy in patients with systemic lupus erythematosus. Seminars in Arthritis and Rheumatism, 203-211. Doi: 10.1016/j.semarthrit.2011.04.001
Gwathmey, K., Burns, T., Collins, M., & Dyck, P. (2014). Vasculitic neuropathies. The Lancet, 2014(13), 67-82.
Hakim, M., Kurniani, N., Pinzon, R., Tugasworo, D., Basuki, M., Haddani, H. …Wuysang, A. (2018). Management of peripheral neuropathy symptoms with a fixed dose combination of high-dose vitamin B1, B6, and B12: A 12-week prospective non-interventional study in Indonesia. Asian Journal of Medical Sciences, 9(1), 32-40. doi: 10.3126/ajms.v9i1.18510
Kivity, S., Agmon-Levin, N. Zandman-Goddard, G., Chapman, J., & Shoenfeld, Y. (2015). Neuropsychiatric lupus: A mosaic of clinical presentations. Medicine. Retrieved January 21, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349748/pdf/12916_2015_Article_269.pdf
Mayo Clinic (n.d.) Peripheral neuropathy. Retrieved January 21, 2020, from https://www.mayoclinic.org/diseases-conditions/peripheral-neuropathy/symptoms-causes/syc-20352061
National Institute of Neurological Disorders and Stroke (2019). Peripheral neuropathy fact sheet. Retrieved January 21, 2020, from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Peripheral-Neuropathy-Fact-Sheet
Oomatia, A., Fang, H., Petri, M., & Birnbaum, J. (2014). Peripheral neuropathies in systemic lupus erythematosus. Arthritis & Rheumatology, 66(4), 1000-1009. doi: 10.1002/art.38302
Popescu, A., & Kao, A. (2011). Neuropsychiatric systemic lupus erythematosus. Current Neuropharmacology. Retrieved January 21, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151599/pdf/CN-9-449.pdf
The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. (1999). Arthritis & Rheumatism, 42(4), 599-607. Retrieved January 21, 2020, from https://onlinelibrary.wiley.com/doi/epdf/10.1002/1529-0131%28199904%2942%3A4%3C599%3A%3AAID-ANR2%3E3.0.CO%3B2-F
U.S. National Library of Medicine (2020). Small fiber neuropathy. Retrieved January 21, 2020, from https://ghr.nlm.nih.gov/condition/small-fiber-neuropathy
University of Washington. (n.d.). Neuroscience for kids. Retrieved January 21, 2020, from https://faculty.washington.edu/chudler/nsdivide.html#cns

 

Author: Liz Heintz

Liz Heintz is a technical and creative writer who received her BA in Communications, Advocacy, and Relational Communications from Marylhurst University in Lake Oswego, Oregon. She most recently worked for several years in the healthcare industry. A native of San Francisco, California, Liz now calls the beautiful Pacific Northwest home.

All images unless otherwise noted are property of and were created by Kaleidoscope Fighting Lupus. To use one of these images, please contact us at [email protected] for written permission; image credit and link-back must be given to Kaleidoscope Fighting Lupus.

All resources provided by us are for informational purposes only and should be used as a guide or for supplemental information, not to replace the advice of a medical professional. The personal views expressed here do not necessarily encompass the views of the organization, but the information has been vetted as a relevant resource. We encourage you to be your strongest advocate and always contact your healthcare practitioner with any specific questions or concerns.