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Medical Alliance for the Preservation of the Lower Extremity
The majority of the ulcers described on this website arise from neuropathy. So it's important to understand a little about this topic.
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On this page we discuss what neuropathy is and
some of the conditions that may cause it.
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We discuss the clinical effects of neuropathy in
greater detail here, but let's start with some
definitions.
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What is Neuropathy?
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Simply put, the word "neuropathy" describes
a disorder in the nerves that causes abnormal
nerve function.
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Many people assume neuropathy refers specifically to the loss of sensation. And certainly, this is the major issue with how neuropathic ulcerations form, because when we can't feel pain, we cannot feel when excessive pressure, friction and damage starts to cause pathology.
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But neuropathy affects other nerves in the body as well. Motor nerves, the nerves that send signals to our muscles to move us, may be affected by neuropathy. And autonomic nerves, the nerves that control the things in our body we don't think about, like heart rate and blood pressure, are affected too. We discuss this in more detail here.
Scanning electron micrograph of cultured human neuron (nerve cell).
Photo credit: Mark Ellisman and Thomas Deerinck, National Center for Microscopy and Imaging Research, UC San Diego
"When pain is over, the remembrance of it often becomes a pleasure."
--Jane Austen, Persuasion
How many Diabetics Will Get Peripheral Neuropathy (loss of sensation in the feet)?
About half to two thirds. ​
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This study from the US, Canada, UK, Saudi Arabia and India, found at least 50% of individuals with diabetes developed diabetic neuropathy.
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Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, Bril V, Russell JW, Viswanathan V. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun 13;5(1):41. doi: 10.1038/s41572-019-0092-1. PMID: 31197153.
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In this 2023 study from China of 25,710 patients, 57.2% had peripheral neuropathy.
Li C, Wang W, Ji Q, Ran X, Kuang H, Yu X, Fang H, Yang J, Liu J, Xue Y, Feng B, Lei M, Zhu D. Prevalence of painful diabetic peripheral neuropathy in type 2 diabetes mellitus and diabetic peripheral neuropathy: A nationwide cross-sectional study in mainland China. Diabetes Res Clin Pract. 2023 Apr;198:110602. doi: 10.1016/j.diabres.2023.110602. Epub 2023 Mar 4. PMID: 36871876.
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In this 2023 study from China, 14,908 patients were examined and the prevalence as peripheral neuropathy (affecting the feet) was 67.6% with 47.7% having mild neuropathy, 33.% having moderate neuropathy, and 19.3% having severe neuropathy. Men (69%) and women (66.6%) were equally represented. Neuropathy was worse with age and time of disease. Neuropathy was lower with lower body mass index (weight) and education level.
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Wang W, Ji Q, Ran X, Li C, Kuang H, Yu X, Fang H, Yang J, Liu J, Xue Y, Feng B, Lei M, Zhu D. Prevalence and risk factors of diabetic peripheral neuropathy: A population-based cross-sectional study in China. Diabetes Metab Res Rev. 2023 Nov;39(8):e3702. doi: 10.1002/dmrr.3702. Epub 2023 Jul 25. PMID: 37490047.
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Yet over 90% of people with diabetic peripheral neuropathy are unaware they have it.
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Bongaerts BW, Rathmann W, Heier M, Kowall B, Herder C, Stöckl D, Meisinger C, Ziegler D. Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy: the KORA F4 study. Diabetes Care. 2013
May;36(5):1141-6. doi: 10.2337/dc12-0744. Epub 2012 Dec 28. PubMed PMID: 23275355; PubMed Central PMCID: PMC3631873.
This meta-analysis (a study combining the results of multipel studies) found that 46.7% developed painful neuropathy, that is not sensory loss but burning, electrical, stabbing pain not caused by a stimulus.
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Tao Y, Zhang HY, MacGilchrist C, Kirwan E, McIntosh C. Prevalence and risk factors of painful diabetic neuropathy: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2025 Apr;222:112099. doi: 10.1016/j.diabres.2025.112099. Epub 2025 Mar 17. PMID: 40107621.
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What are the Causes of Neuropathy?
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There are dozens of possible causes of neuropathy. And they may tend to cause varying types of symptoms involving both sensory, motor, and autonomic nerves. ​​
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Diabetes is far and away the most common cause
of neuropathy. In fact, diabetes is more common
than all other causes of neuropathy combined.
Diabetes is so common as a cause of neuropathy
that it often erroneously assumed that any
individual with neuropathy must have diabetes.
The effect of diabetic neuropathy on the foot can
be seen in a variety of nerves. It can affect the
autonomic nerves, leading to dry skin and altered
circulation. It can affect motor nerves, leading to
deformities in the foot, such as contracted toes (hammertoes). And it can affect the sensory nerves, leading to ulcers (holes in the skin).
The combination of these effects may lead
to infections, amputations and even premature
death. For more on diabetes, click here.
Alcoholic toxicity is the second most common cause of neuropathy, with 25-50% of chronic drinkers affected. Alcohol neuropathy can mimic diabetic neuropathy and can lead to loss of sensation and ulceration. It can be very difficult to differentiate the cause in a diabetic patient who has a history of heavy drinking.
Above: The foot of a diabetic with neuropathy, chronic ulcerations that have resulted in the amputation of two toes.
Spinal abnormalities technically produce radiculopathy, which is often grouped in with neuropathy. This may come as a result of trauma, compressions, degenerative disc disease, and malformations like spina bifida. In addition to neuropathic symptoms, these often result in chronic pain, chronic absence of pain, muscle wasting, weakness and dysfunction.
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Vitamin deficiencies involving vitamins B-1, B-6, B-12, folate, vitamin E, and niacin may be the second most common cause of neuropathy. However, vitamin deficiencies don't typically create the level of pathology such as ulcerations that many of these other conditions do.
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Autoimmune and connective tissue diseases are a broad category of overlapping diseases that may also cause neuropathy. Rheumatoid arthritis (RA, seen below left), lupus, Sjogren’s syndrome, multiple sclerosis (MS), Necrotizing Vasculitis, Chronic Inflammatory Demyelinating Polyneuropathy, and Guillain–Barré Syndrome (below right) are the most common examples.
Above: The classic appearance of a foot with rheumatoid arthritis, with misaligned toes drifting laterally (away from the midline of the body) and the prominent rheumatoid nodule (the lump on the bottom of the foot). When accompanied by sensory loss, these nodules may ulcerate.
Above: The collapse of this foot in stance is a result of the loss of function of the motor nerve to the posterior tibial muscle, which supports the arch and pushes off in gait. This is a result of Guillain–Barré disease.
The two classic examples of an Infection causing neuropathy are leprosy (Hansen's disease) and syphilis. In fact, before the advent of antibiotics that can treat these conditions, and before the advent of insulin and other medications that helped diabetics live longer, leprosy and syphilis were the most common cause of neuropathic ulcerations. We still see leprosy in India, Brazil, Indonesia and parts of Africa, where antibiotic therapy can be expensive and hard to come by. But other than for immigrants, leprosy is largely a thing of the past in Canada and the first world. Today the most common infections causing neuropathy are Lyme disease, Shingles, HIV, Epstein Barr, Diphtheria, and Hepatitis C. ​​​
​​Genetic conditions like Charot-Marie-Tooth
(CMT) disease can cause neuropathy. An
example of the motor CMT neuropathy,
characterized by high arches and contracted
toes is seen to the right. ​Less common examples of genetic disorders that can cause neuropathy are porphyria and Refsum's disease.
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​​Circulation disorders Peripheral nerves depend upon a circulation delivering oxygen and nutrients. Any condition that impairs blood flow, causes inflammation or occlusion or vessel wall damage can result in nerve ischemia.
Examples of conditions that can disrupt blood flow to nerves include general atherosclerosis, peripheral artery disease, Lipoprotein A disease, Raynaud's disease, Pernio (Chilblains), hypercoagulation, and vasculitis.​
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Repetitive motion injuries like carpal tunnel disease and tarsal tunnel disease in the foot can irritate nerves, creating neuropathy. In the hand this may result in tingling to burning pain, weakness and dysfunction. In the foot this may lead to similar symptoms and make it difficult to
walk.
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​Neoplasms (tumors), both malignant and benign can exert pressure on nerves, causing neuropathy. One example is seen to the right.
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​​Medications for things like chemotherapy
and HIV infections can be toxic to nerves
and result in damage that may result in
numbness, pins and needles sensations,
burning and weakness.
Chronic disease of the liver and kidney
can also cause neuropathy. In fact, the treatment for severe kidney disease, dialysis, can be a cause of neuropathy in and of itself.
The manifestations of renal disease exhibited
in the foot has become a specialty of the author
of this web page. An example is seen to the
right.
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​​Miscellaneous causes of neuropathy include
a tight cast, particularly the peroneal nerve,
amyloidosis, hypothyroidism, and exposure to
heavy metals and chemicals.
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Idiopathic neuropathy refers to a condition that develops without an identifiable cause despite appropriate evaluation. Some 20% of sensory neuropathy cases are idiopathic—with no known cause.
While many of these are statistically like to be undiagnosed diabetes, along with other known causes of neuropathy that have not been identified, it is also possible that there are either more potential causes of neuropathy than we know.
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Because diabetes accounts for more cases of
neuropathy and wounds than all other causes
combined, we have a page devoted to diabetes.
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To learn more about the effects of neuropathy, click here.
Above: The typical high arch and contracted digits seen with the motor neuropathy of Charcot-Marie Tooth Disease. This can lead to a jarring gait, and pressure spots in the ball of the foot and in the tips of the toes.
Above: A rare neoplasm known as mycosis fungoides, a lymphoma of the skin. These can create issues with the sensory nerves and may ulcerate. In this case, the neoplasm was fatal.
Above: Three ulcers of a dialysis patient with chronic, end-stage renal disease. These lesions all healed, and the patient was able to walk with
custom-made shoes.
To return to the top of the page,
click on the maple leaf to the right.
This page written by Dr. S A Schumacher
Podiatric Surgeon
Surrey, British Columbia Canada
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Unless otherwise indicated, all clinical
photographs owned and provided by
Dr. S A Schumacher.
They may be reproduced for educational
purposes with attribution to:
Dr. S A Schumacher
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