Neuropathy, Back Problems, Or Both. How Getting The Right Diagnosis Can Be A Minefield

Today's interesting post from heraldtribune.com (see link below) is a question and answer post about how a patient with particular symptoms has had trouble getting the right diagnosis. The patient has been determined to have no neuropathy but possible Sjogren's syndrome and fibromyalgia (both of which could be argued to be neuropathic conditions). However, it illustrates what happens to many patients with these sorts of symptoms, with the key being...it depends on who you go to to find out what's wrong with you. The answer provided by the doctor here is probably very sensible:- go to a neurologist first to try to get a nerve-related answer and then move forward to treatment depending on the answers given. It shows how complex reaching a diagnosis can be but with over 100 sorts of nerve damage and over 100 possible causes...that's hardly surprising. If you're not happy with a diagnosis, ask for a second opinion and then armed with sufficient information, come to a conclusion along with your doctors. It can make a difference between having complex surgery or living with medication and various therapies. The point is; never be afraid to ask.

Lack of neuropathy puts neurosurgeon, rheumatologist at odds
Posted Mar 5, 2019 

Dear Dr. Roach: 
I have weakness, numbness and the feeling of pins and needles in my hands, legs and feet. I have been diagnosed with both Sjogren’s syndrome and fibromyalgia. I was working full time as a library assistant when my legs and knees collapsed a few times. I went to a neurosurgeon, who sent me for scans of my lumbar region. It showed no neuropathy, but a severe spinal stenosis and spondylolisthesis. He recommended lumbar surgery. But since I was not having pain in my buttocks or legs, he ordered scans of my neck and upper back too. Again, no neuropathy, but he is now recommending anterior cervical discectomy and fusion. He thinks this cervical surgery needs to be done before the lumbar surgery.

My rheumatologist, whom I have been seeing for over 10 years, maintains that the negative neuropathy test results indicate that the numbness I suffer from is related to my autoimmune illnesses, but the surgeon says that it means the numbness and other symptoms are being caused by the spinal nerve impingement.

Who do I believe, and what should I do now? I am 64 and had to resign from my job because the county would not extend my medical leave. — B.R.

Dear B.R.: There’s a lot going on, so let’s look at each issue separately.

Fibromyalgia, a systemic disease of unknown cause, most frequently brings on widespread pain and fatigue, but it also may cause cognitive problems (often referred to as “fibro fog”), psychiatric symptoms (depression and anxiety, in particular) and numbness and tingling, especially in the arms and legs. Although these symptoms certainly are real, the diagnostic studies may appear normal.

Sjogren’s syndrome, an autoimmune inflammatory disorder, also may cause pain, numbness and tingling through a wide variety of neuropathies. Depending on the particular person, these symptoms may or may not show up on electromyography studies (also called an EMG, a test of the nerves and muscles using electrodes).

Spinal stenosis is the compression of the spinal cord or a nerve root of the cord by the bones and other hard tissues in the spinal column. This almost always can be diagnosed by the EMG, and surgery is the only effective treatment when the degree of impingement is severe. Spondylolisthesis is a misalignment of one spinal bone on top of another one. This also can stretch and impinge on the spinal cord. Severe spondylolisthesis may require surgery, whereas mild disease may be monitored.

With that in mind, the apparently normal findings you report from the EMG make me think that your rheumatologist is right and that your symptoms are more due to the fibromyalgia or Sjogren’s syndrome. However, anytime a neurosurgeon says an operation is needed, I take it seriously.

I think you don’t have enough information to make the most informed decision, and I would recommend you consult a neurologist, who is in the best position to provide guidance on whether the current symptoms are more due to the spinal stenosis and spondylolisthesis that your neurosurgeon is concerned about, or due to the Sjogren’s syndrome and fibromyalgia that the rheumatologist thinks are the cause.

It is certainly possible that you have spinal stenosis and spondylolisthesis, but it can be very hard to guess how much of your symptoms are due to which condition. You don’t want to go through major surgery expecting improvement if improvement is unlikely. However, you don’t want to delay neurosurgery if it’s truly necessary. That’s why I’d recommend a neurology visit.

https://www.heraldtribune.com/news/20190305/lack-of-neuropathy-puts-neurosurgeon-rheumatologist-at-odds

Neuropathy, Peripheral Neuropathy, Or Small Fiber Neuropathy: Pretty Much A Rose By Any Other Name

Today's post from mdedge.com (see link below) is one of those articles that can easily serve as an A to Z of neuropathy - it's that extensive and extremely useful for all neuropathy patients wondering about their condition, how it works and how it's treated. Granted, it was written in 2009 so some of the ideas regarding treatment options have changed, or been modified to suit the times (although most doctors will be basing their diagnoses and treatments on almost everything that's mentioned here). You may be wondering what the difference is between small fiber neuropathy and peripheral neuropathy but the fact is, there's very little difference in terms of what you feel and how it's treated. Basically small fiber neuropathy is peripheral neuropathy that affects the smallest nerve fibers in the body but to all intents and purposes, most neuropathy patients experience the same sensations either way. So if you've been diagnosed with neuropathy, peripheral neuropathy, or large and/or small fiber neuropathy, you're living with pretty much the same disease and will undergo pretty much exactly the same treatment. Don't worry, this article applies to you whatever the specifics of the diagnosis and is definitely worth a read - you'll learn a great deal about your condition.
 

Small fiber neuropathy: A burning problem 
Cleveland Clinic Journal of Medicine. 2009 May;76(5):297-305
Author(s): Jinny Tavee, MD Lan Zhou, MD, PhD
Author and Disclosure Information


ABSTRACT

 Small fiber neuropathy is increasingly being recognized as a major cause of painful burning sensations in the feet, especially in the elderly. Although strength remains preserved throughout the course of the disease, the pain and paresthesias are often disabling. Diabetes mellitus is the most common identifiable cause of small fiber neuropathy, and impaired oral glucose tolerance and individual components of the metabolic syndrome are often associated with it. Some cases, however, are idiopathic. Skin biopsy (with an evaluation of the density of intraepidermal nerve fibers) and tests of autonomic nerve function are useful for the diagnosis. Management involves controlling pain and identifying and aggressively treating the underlying cause.

PDF Download


KEY POINTS
Symptoms of small fiber neuropathy typically start with burning feet and numb toes.
Causes and associated conditions can be found in over 50% of cases. These include glucose dysmetabolism, connective tissue diseases, sarcoidosis, dysthyroidism, vitamin B12 deficiency, paraproteinemia, human immunodeficiency virus infection, celiac disease, neurotoxic drug exposure, and paraneoplastic syndrome.
Findings on routine nerve conduction studies and electromyography are typically normal in this disease.
Management includes aggressively identifying and treating the underlying cause, advising lifestyle modifications, and alleviating pain.



Figure 1. Symptoms are pain, burning, numbness, and autonomic dysfunction (lack of sweating) in the hands and feet in a stocking-glove distribution. Strength is not affected. Tendon reflexes are normal, as are nerve conduction studies. An estimated 15 to 20 million people in the United States over age 40 have some type of peripheral neuropathy.1 In many, the impairment is purely or predominantly in small nerve fibers, and the clinical presentation consists of pain, burning, tingling, and numbness in a length-dependent or stocking-glove distribution. (“Length” refers to distance from the trunk; distal fibers are affected first.) Symptoms typically begin in the feet and slowly ascend to the distal legs, at which point the hands may also be affected (Figure 1).

In many of these patients, the findings on neurologic examination, nerve conduction studies, and electromyography are normal, although some may show signs of mild distal sensory loss on physical examination. The lack of objective findings on routine nerve conduction studies and electromyography may lead many physicians to attribute the symptoms to other disorders such as plantar fasciitis, vascular insufficiency, or degenerative lumbosacral spine disease.

The past 2 decades have seen the development of specialized tests that have greatly facilitated the diagnosis of small fiber neuropathy; these include skin biopsy to evaluate the density of nerve fibers in the epidermis and studies of autonomic nerve function. Common etiologies have been identified for small fiber neuropathy and can be specifically treated, which is critical for controlling progression of the disease. Pain management is becoming easier with more available options but is still quite challenging.

WHAT IS SMALL FIBER NEUROPATHY?


Figure 2. Small fiber neuropathy is a disorder of the peripheral nerves that primarily or exclusively affects small somatic fibers, autonomic fibers, or both, resulting in sensory changes and autonomic dysfunction when both types are involved (Figure 2).2


Peripheral nerve fibers can be classified according to size, which correlates with the degree of myelination.
Large nerve fibers are heavily myelinated and include A-alpha fibers, which mediate motor strength, and A-beta fibers, which mediate vibratory and touch sensation.
Medium-sized fibers, known as A-gamma fibers, are also myelinated and carry information to muscle spindles.
Small fibers include myelinated A-delta fibers and unmyelinated C fibers, which innervate skin (somatic fibers) and involuntary muscles, including cardiac and smooth muscles (autonomic fibers). Together, they mediate pain, thermal sensation, and autonomic function.

Small fiber neuropathy results from selective impairment of small myelinated A-delta and unmyelinated C fibers.

Sensory symptoms: Pain, burning, tingling, numbness

Damage to or loss of small somatic nerve fibers results in pain, burning, tingling, or numbness that typically affects the limbs in a distal-to-proximal gradient. In rare cases, small fiber neuropathy follows a non-length-dependent distribution in which symptoms may be manifested predominantly in the arms, face, or trunk.

Symptoms may be mild initially, with some patients complaining of vague discomfort in one or both feet similar to the sensation of a sock gathering at the end of a shoe. Others report a wooden quality in their feet, numbness in their toes, or a feeling as if they are walking on pebbles, sand, or golf balls. The most bothersome and fairly typical symptom is burning pain in the feet that extends proximally in a stocking-glove distribution and is often accompanied by stabbing or aching pains, electric shock-like or pins-and-needles sensations, or cramping of the feet and calves.

Symptoms are usually worse at night and often affect sleep. Some patients say that their feet have become so exquisitely tender that they cannot bear having the bed sheets touch them, and so they sleep with their feet uncovered. A small number of patients do not have pain but report a feeling of tightness and swelling in their feet (even though the feet appear normal).

Examination often reveals allodynia (perception of nonpainful stimuli as being painful), hyperalgesia (perception of painful stimuli as being more painful than expected), or reduced pinprick and thermal sensation in the affected area. Vibratory sensation can be mildly reduced at the toes. Motor strength, tendon reflexes, and proprioception, however, are preserved because they are functions of large nerve fibers.

Autonomic symptoms

When autonomic fibers are affected, patients may experience dry eyes, dry mouth, orthostatic dizziness, constipation, bladder incontinence, sexual dysfunction, trouble sweating, or red or white skin discoloration.2 Examination may show orthostatic hypotension and skin changes. The skin over the affected area may appear atrophic, dry, shiny, discolored, or mildly edematous as the result of sudomotor and vasomotor abnormalities.

WHAT CAUSES SMALL FIBER NEUROPATHY?

Small fiber neuropathy has been associated with many medical conditions, including glucose dysmetabolism,3 connective tissue disease,4,5 dysthyroidism,6 vitamin B12 deficiency, paraproteinemia, human immunodeficiency virus (HIV) infection,7 hepatitis C virus infection, celiac disease,8 restless legs syndrome,9 neurotoxic drug exposure, hereditary diseases, and paraneoplastic syndrome. While most of these conditions cause a length-dependent small fiber neuropathy, others (Sjögren disease, celiac disease, and paraneoplastic syndrome) can cause a form of small fiber neuropathy that is not length-dependent.4,8,10
Diabetes and prediabetes

Glucose dysmetabolism, including diabetes and prediabetes with impaired oral glucose tolerance (a glucose level 140–199 mg/dL 2 hours after a 75-g oral dextrose load), is the most common identifiable associated condition, present in about one-third of patients with painful sensory neuropathy11 and in nearly half of those with otherwise idiopathic small fiber neuropathy.12–14


Research findings strongly suggest that even prediabetes is a risk factor for small fiber neuropathy, and that so-called “impaired glucose tolerance neuropathy” may represent the earliest stage of diabetic neuropathy. Several recent studies have found a high prevalence of impaired glucose tolerance in patients with sensory peripheral neuropathy,12–14 with a rate of up to 42% in cases initially thought to be idiopathic14 compared with 14% in the general population.15 Also, a dose-response relationship between the severity of hyperglycemia and the degree of neuropathy was demonstrated in one study, in which patients with impaired glucose tolerance more often had small fiber neuropathy, whereas those with diabetes more often had polyneuropathy involving both small and large fibers.14 And studies in animals and cell cultures have shown that intermittent hyperglycemia, which can be seen in patients with impaired glucose tolerance, caused sensory neuron and nerve fiber damage and increased spontaneous C-fiber firing, resulting in neuropathic pain.8,16,17

Metabolic syndrome

Insulin resistance with prediabetes and diabetes is a part of the metabolic syndrome, which also consists of hypertension, hyperlipidemia, and obesity. The individual components of the metabolic syndrome have been implicated as risk factors not only for cardiovascular and cerebrovascular disease but also for small fiber neuropathy.


One study in 548 patients with type 2 diabetes showed that those with the metabolic syndrome were twice as likely to have neuropathy as those without.18 Another study showed that in 1,200 patients with type 1 diabetes without neuropathy at baseline, hypertension, hyperlipidemia, and increased body mass index were each independently associated with a higher risk of developing neuropathy.19

A recent study of 219 patients with idiopathic distal symmetrical peripheral neuropathy and 175 diabetic patients without neuropathy found a higher prevalence of metabolic syndrome in patients with neuropathy than in normal populations. The prevalence of dyslipidemia (high levels of total and low-density lipoprotein cholesterol and triglycerides and low levels of high-density lipoprotein cholesterol), but not hypertension or obesity, was higher in patients with neuropathy than in patients with diabetes but no neuropathy.20 The findings linked dyslipidemia to neuropathy and showed the need for further studies of the potential pathogenic role of dyslipidemia in neuropathy.

Hereditary causes

Hereditary causes of small fiber neuropathy are rare and include Fabry disease, Tangier disease, hereditary sensory autonomic neuropathy, and hereditary amyloidosis.

HOW DO YOU EVALUATE PATIENTS WITH SUSPECTED SMALL FIBER NEUROPATHY?

A thorough history should be taken to obtain details regarding onset and features of neuropathy symptoms, exacerbating factors, and progression. It is also important to ascertain whether the patient has any associated conditions as mentioned above, a family history of neuropathy, risk factors for HIV or hepatitis C virus infection, or a history of neurotoxic drug exposure.

Clinical suspicion of small fiber neuropathy should be high if a patient presents with predominant small fiber symptoms and signs with preserved large fiber functions.

Nerve conduction studies and electromyography

For diagnostic testing, routine nerve conduction studies and electromyography assess the function of large nerve fibers only and are thus normal in small fiber neuropathy. These tests should still be ordered to rule out subclinical involvement of large fibers, which may affect the diagnostic evaluation, prognosis, and treatment plan. However, if the results of these tests are normal, specialized studies are needed to evaluate small fibers.

Although several tests are available to evaluate somatic and autonomic small fibers, the two that have the highest diagnostic efficiency for small fiber neuropathy and that are used most often are skin biopsy, to evaluate intraepidermal nerve fiber density, and quantitative sudomotor axon reflex testing (QSART), to assess sudomotor autonomic function.21–23
Skin biopsy

Skin biopsy is a minimally invasive procedure in which 3-mm-diameter punch biopsy specimens are taken from the distal leg, distal thigh, and proximal thigh of one lower limb. The procedure takes only 10 to 15 minutes.

Biopsy specimens are immunostained using an antibody against protein gene product 9.5, which is a panaxonal marker. Small nerve fibers in the epidermis are counted under a microscope, and intraepithelial nerve fiber densities are calculated and compared with established normative values. The diagnosis of small fiber neuropathy can be established if the intraepidermal nerve fiber density is lower than normal (Figure 1). Nerve fiber density may be normal in the early stage of small fiber neuropathy, but in this setting skin biopsy often shows abnormal morphologic changes in the small fibers, especially large swellings,24 and repeat biopsy in 6 to 12 months may be considered.

The diagnostic efficiency of skin biopsy is about 88%.21,23 For diagnosing small fiber neuropathy, it is more sensitive than quantitative sensory testing21,25 and more sensitive and less invasive than sural nerve biopsy.26 Intraepidermal nerve fiber density also correlates well with a variety of measures of severity of HIV distal sensory neuropathy and thus may be used to measure the severity and treatment response of small fiber neuropathy.27

Quantitative sudomotor axon reflex testing

QSART is an autonomic study that measures sweat output in response to acetylcholine, which reflects the function of postganglionic sympathetic unmyelinated sudomotor nerve fibers. Electrodes are placed on the arms and legs to record the volume of sweat produced by acetylcholine iontophoresis, in which a mild electrical stimulation on the skin allows acetylcholine to stimulate the sweat glands. The output is compared with normative values.

One prospective study showed that 67 (72.8%) of 92 patients with painful feet had abnormal results on QSART, ie, low sweat output.28 A retrospective study found that 77 (62%) of 125 patients with clinical features of distal small fiber neuropathy had a length-dependent pattern of QSART abnormalities.22 QSART abnormalities were detected in some patients without autonomic symptoms.

If these tests are not available

Skin biopsy and QSART are objective, reproducible, sensitive, and complementary in diagnosing small fiber neuropathy. One or both can be ordered, depending on whether the patient has somatic symptoms, autonomic symptoms, or both. However, these two tests are not widely available. Only a few laboratories in the country can process skin biopsy specimens to evaluate intraepidermal nerve fiber density. Nevertheless, it is easy to learn the skin punch biopsy procedure, and primary care physicians and neurologists can perform it after appropriate training. (A concern is avoiding damage to the epidermis.) They can then send specimens to one of the cutaneous nerve laboratories (but not to a routine reference laboratory).

A special technique, including unique fixative and cryoprotectant, is used to fix and process the biopsy specimens, because routine techniques for processing dermatologic punch biopsy specimens often result in lower intraepidermal nerve fiber densities. Therefore, it is very important to contact the laboratory regarding fixative and processing before performing a biopsy.

QSART requires specialized equipment and must be performed on site. In addition, the test is very sensitive to drugs that can affect sweating, such as antihistamines and antidepressants, and such drugs must be discontinued 48 hours before the study.

Basic laboratory tests to find the cause

Once the diagnosis of small fiber neuropathy is established, the next important step is to order a battery of laboratory tests to search for an underlying cause. The tests should include the following:

Complete blood cell count
Comprehensive metabolic panel
Lipid panel
Erythrocyte sedimentation rate
Thyroid-stimulating hormone level
Free thyroxine (T4) level
Antinuclear antibody
Extractable nuclear antigens
Angiotensin-converting enzyme (ACE) level
Serum and urine immunofixation tests
Vitamin B12 level
2-hour oral glucose tolerance test.

Oral glucose tolerance testing is much more sensitive than measuring the hemoglobin A1c and fasting glucose levels in detecting diabetes and prediabetes. These two conditions were detected by oral glucose tolerance testing in more than 50% of patients with otherwise idiopathic sensory-predominant peripheral neuropathy and normal hemoglobin A1c and fasting glucose levels.13,14 Therefore, every patient with small fiber neuropathy without a known history of diabetes or prediabetes should have an oral glucose tolerance test.
Special laboratory tests in special cases
If there is a history of gastrointestinal symptoms or herpetiform-like rash, then testing for gliadin antibody and tissue transglutaminase antibodies as well as small-bowel biopsy may be pursued to evaluate for celiac sprue.
Serologic tests for HIV or hepatitis C should be ordered if the patient has risk factors.
If there is a significant family history, further genetic testing should be considered.
Lip biopsy or bone marrow biopsy should be considered if clinical suspicion is high for Sjögren disease, seronegative sicca syndrome, or amyloidosis.
The serum ACE level has a low sensitivity and specificity; therefore, if sarcoid is suspected clinically, additional confirmatory testing, such as computed tomography of the chest, should be ordered despite a normal ACE value.

HOW DO YOU TREAT SMALL FIBER NEUROPATHY?

Treatment of small fiber neuropathy should target the underlying cause and neuropathic pain. Cause-specific treatment is a key in preventing small fiber neuropathy or slowing its progression.
Glucose control, weight control, and regular exercise

As glucose dysmetabolism is the condition most often associated with small fiber neuropathy (and since individual components of the metabolic syndrome are potential risk factors for it), tight glycemic control and lifestyle modification with diet control, weight control, and regular exercise are of paramount importance in patients with these conditions.

The Diabetic Prevention Program,29 a study in 3,234 people with prediabetes, found that diet and exercise were more effective than metformin (Glucophage) in preventing full-blown diabetes. At an average of 2.8 years of follow-up, the incidence of diabetes was 11.0 cases per 100 patient-years in a group assigned to receive placebo, compared with 7.8 in those assigned to receive metformin (31% lower), and 4.8 (58% lower) in those who were assigned to undergo a lifestyle intervention that included at least 150 minutes of physical activity per week with a weight-loss goal of 7%. Put another way, to prevent one case of diabetes over 3 years, 6.9 patients would have to undergo the lifestyle intervention program, or 13.9 would have to receive metformin. Since impaired glucose tolerance neuropathy may represent the earliest stage of diabetic neuropathy, the neuropathy at this stage may be reversible with lifestyle intervention and improvement of impaired glucose tolerance.

This concept is supported by a 3-year study in 31 people, which showed that lifestyle intervention significantly improved impaired glucose tolerance, reduced the body mass index, and lowered total serum cholesterol levels.30 Changes in these metabolic variables were accompanied by significant improvement of neuropathy as evidenced by significantly increased intraepidermal nerve fiber density, increased foot sweat volume, and decreased neuropathic pain.30


Treatment of other diseases

It has also been reported that treatment of sarcoidosis, autoimmune diseases, and celiac disease improved the symptoms of small fiber neuropathy resulting from these conditions.8,31 Therefore, it is important to identify the cause and treat it to prevent and slow the progression of small fiber neuropathy, and doing so may improve the disease in some mild cases.

Pain management

Pain management is crucial in the treatment of small fiber neuropathy, as neuropathic pain can be debilitating and can cause depression. Pain management often requires a multidisciplinary team, including a primary care physician, a neurologist, a pain specialist, and a psychiatrist. Medications include antidepressants, anticonvulsants, and topical anesthetics (Table 1) as well as narcotic and non-narcotic analgesics and antiarrhythmics. Nonpharmacologic management includes transcutaneous electrical nerve stimulation (TENS), heat, ice, and massage of painful areas (reviewed by Chen et al32 and Galluzzi33).

First-line choices of pain medications are the anticonvulsants gabapentin (Neurontin) and pregabalin (Lyrica), the tricyclic antidepressants amitriptyline (Elavil) and nortriptyline (Aventyl), a 5% lidocaine patch (Lidoderm), and the semisynthetic opioid analgesic tramadol (Ultram). These can be used alone or in combination.

Gabapentin is relatively well tolerated, but drowsiness can occur, especially with high starting doses. We usually start with 300 mg daily and increase it by 300 mg every week up to 1,200 mg three times a day as tolerated. Most patients need 600 to 900 mg three times a day.


Pregabalin is a newer antiepileptic drug, similar to gabapentin but less sedating. It can be started at 75 mg twice a day and gradually increased to 300 mg twice a day as needed. Weight gain and, rarely, swelling of the lower extremities may limit the use of both of these drugs.

Tricyclic antidepressants, such as amitriptyline, nortriptyline, and desipramine (Norpramin), are proven effective in controlling neuropathic pain, although no response with amitriptyline was seen in patients with painful HIV distal sensory neuropathy.34


Lidocaine patch is preferred if the painful area is small. Patients should be instructed to use the patch to cover the painful area 12 hours on and 12 hours off. If it does not provide relief within 1 week, it should be discontinued.

Tramadol is also helpful in treating neuropathic pain. It can be started at 50 mg two to four times a day as needed.

Nonsteroidal anti-inflammatory drugs and selective serotonin reuptake inhibitors are typically less effective than the other drugs mentioned.

Opioids should be reserved for refractory cases, given the potential for addiction, but they are sometimes necessary in patients with disabling pain that does not respond to other drugs.

TENS may be of benefit. The patient controls a pocket-size device that sends electrical signals to leads placed on affected areas.

Alternative therapies for small fiber neuropathy, such as meditation, yoga, and acupuncture, have yet to be studied.

It is also important to explain to patients that the typical course of small fiber neuropathy is relatively benign, as many patients worry about developing weakness and eventually not being able to walk. These concerns and fears can aggravate pain and depression, which can make treatment difficult.

WHAT IS THE PROGNOSIS OF SMALL FIBER NEUROPATHY?

Most patients with small fiber neuropathy experience a slowly progressive course, with symptoms and signs spreading proximally over time.

In one study, only 13% of 124 patients with small fiber neuropathy showed evidence of large-fiber involvement over a 2-year period. 21 None went on to develop Charcot joints, foot ulcers, weakness, or sensory ataxia, as is often seen in patients with long-standing or severe large fiber neuropathy. Neuropathic pain worsened in 30% and resolved spontaneously in 11%.21

Most patients with small fiber neuropathy require chronic pain management. Again, treatment of the underlying cause is important and can improve the prognosis.

We believe that the overall progression of small fiber neuropathy is slow. A longitudinal study with a follow-up longer than 2 years would be useful to confirm this.

TAKE-HOME POINTS

As the population continues to age and as more patients develop diabetes and the metabolic syndrome, the prevalence of small fiber neuropathy will rise. Patients who present to their primary care physicians with painful, burning feet require a thorough diagnostic evaluation, which may include referral for specialized neurodiagnostic testing. Aggressive cause-specific treatment, lifestyle modification, and pain control are key elements of a team approach to managing small fiber neuropathy.


References


https://www.mdedge.com/ccjm/article/95083/diabetes/small-fiber-neuropathy-burning-problem

Neuropathy, HIV And Foot Care

Today's post from journals.lww.com (see link below) is a very thorough examination of the relationship between HIV and neuropathy and how as a result, foot care is often overlooked in neuropathy patients. It provides relatively easy explanations for the damage process caused by either the virus itself or the medication used to treat it but misses out on the fact that HIV patients can also have other problems which may bring on neuropathy (cancer, diabetes for instance). The article goes on to provide some helpful advice as to how people should look after their feet, especially when there's a loss of feeling involved and all in all, is well worth reading, for all people living with neuropathy.

 

HIV Peripheral Neuropathy and Foot Care Management: A Review of Assessment and Relevant Guidelines
AJN, American Journal of Nursing:
December 2013 - Volume 113 - Issue 12 - p 34–40
Feature Articles
Anastasi, Joyce K. PhD, DrNP; Capili, Bernadette PhD, NP-C; Chang, Michelle MS

Author Information

Joyce K. Anastasi is an Independence Foundation endowed professor and founding director of the Division of Special Studies in Symptom Management (DS3M) at the New York University College of Nursing in New York City, where Bernadette Capili is an assistant professor and associate director of the DS3M, and Michelle Chang is a research associate at the DS3M. Contact author: Joyce K. Anastasi, ja2188@nyu.edu. The authors and planners have disclosed no potential conflicts of interest, financial or otherwise.

Abstract

Overview: Despite the decline in the incidence of central nervous system disease associated with HIV, distal sensory peripheral (DSP) neuropathy continues to be prevalent in this population, causing debilitating symptoms and affecting quality of life. Patients typically present with numbness, tingling, burning pain, and loss of sensation in the toes and soles of their feet. Although this complication causes loss of protective function and puts patients at elevated risk for injury, infection, and falls, foot care for people with HIV is often overlooked. This article reviews what is known about DSP neuropathy in HIV and discusses relevant foot care guidelines, adopted from the literature on other conditions associated with neuropathic foot disorders.

Peripheral neuropathy, a condition characterized by damaged sensory or motor peripheral nerves, may cause pain, sensory loss, or muscle weakness. Peripheral neuropathy may develop as a result of diabetes, physical injury, tumors, certain medications, heavy alcohol use, certain inherited disorders, autoimmune disease, vitamin deficiencies, and such infectious diseases as HIV.1 The prevalence of distal sensory peripheral (DSP) neuropathy (often referred to as distal symmetric polyneuropathy or distal sensory polyneuropathy) in HIV patients is estimated to range from 38% to 44%.2, 3

Presenting symptoms of DSP neuropathy in HIV typically include bilateral and symmetric tingling, burning, or loss of feeling in the toes and soles of the feet. Symptoms tend to start at the toes and travel up the feet to the ankles and, eventually, to the lower legs, a pattern known as a “stocking” distribution. Common signs include decreased or absent ankle reflexes, impaired pain and temperature perception, reduced or absent vibration sensation in the toes, and occasional intrinsic muscle weakness.4, 5 Patients may experience loss of balance, leading to falls, or have difficulty walking, bathing, or dressing. The symptoms can cause extreme discomfort, affecting employment, emotional health, independence, and quality of life.2

Foot care for people living with HIV is often overlooked as a clinical issue. HIV interferes with the body's immune system, increasing the risk of acquiring infections. Decreased sensation in the feet may lead to injuries and infections that go unnoticed. Tinea pedis (athlete's foot, a fungal infection that causes itching, scaling, blistering, and fissuring of the skin of the feet), onychomycosis (a fungal infection of the nail), and paronychia (a fungal or bacterial infection of the skin at the edge of the nail) frequently affect people who are immunocompromised and thus more prone to developing secondary systemic infections.6-8 In one study, the prevalence of onychomycosis among 500 people with HIV was 23%.7 Both onychomycosis and tinea pedis may lead to lower-extremity bacterial cellulitis.

For patients with diabetes, foot care guidelines and educational materials are ubiquitous. Although there are no specific foot care recommendations for people living with HIV, many of the principles guiding the care of patients with diabetes or cancer apply to this population as well. In this article, we integrate what is currently known about DSP neuropathy in HIV patients with the relevant guidelines for the management of other conditions that similarly render patients susceptible to neuropathic foot disorders.

PATHOPHYSIOLOGY

DSP neuropathy may be associated with the HIV infection itself or with antiretroviral toxicity. The condition is believed to be linked to axonal injury resulting from the binding of the viral envelope glycoprotein 120 to chemokine receptors and to macrophage dysregulation, which prompts the local release of proinflammatory neurotoxic cytokines.9, 10 The drug-associated neuropathies may be mediated by disrupted DNA synthesis, which interferes with mitochondrial function.11 With antiretroviral toxicity, symptom onset tends to be sudden and associated with the start of antiretroviral therapy (ART), usually peaking within the first three months of treatment.12, 13
 
RISK FACTORS

Several factors increase the risk that people with HIV will develop DSP neuropathy and associated foot problems. These include past or current use of neurotoxic drugs, advanced age, metabolic disorders, alcohol use, nutritional deficiencies, and a low CD4+ count.

Neurotoxic drugs. Some nucleoside reverse transcriptase inhibitors (NRTIs) are associated with neuropathy.14, 15 Because they inhibit mitochondrial DNA polymerase gamma, a key enzyme in mitochondrial replication, NRTIs may cause mitochondrial dysfunction, oxidative stress, increased production of free radicals, and tissue injury and toxicity— although other mechanisms likely contribute to the development of DSP neuropathy as well.16, 17 For example, infiltrating activated macrophages, proinflammatory cytokines, and other mediators may play a role in damaging peripheral nerve axons and dorsal root ganglia fibers.18 Of the NRTIs, the dideoxynucleoside NRTIs (d-NRTIs)—didanosine (Videx), zalcitabine (Hivid; taken off the market in 2006), and stavudine (Zerit)—have demonstrated the most mitochondrial toxicity and greatest association with neuropathy. The newer NRTIs demonstrate less toxicity; their association with neuropathy remains unclear.

Although the use of d-NRTIs is being phased out in developed countries, the prevalence of neuropathy remains high.2, 3 These drugs are still widely used in resource-limited regions of the world—particularly stavudine, the component most commonly found in the fixed-dose generic drugs.2 The cumulative, long-term effects of exposure to d-NRTIs are not yet clear.19, 20 A small study of patients with current or prior use of d-NRTI treatment found that subjects who had previously tolerated the drugs without developing neurotoxicity were not at significant risk for developing incident DSP neuropathy.21 Another study found that past, but not current, d-NRTI use was associated with an increased risk of pain in HIV-associated neuropathy after adjusting for other factors.2 Recent research on the potential contribution of protease inhibitors to the risk of neuropathy is inconclusive.22, 23

People living with HIV commonly manage comorbid conditions with multiple drugs, increasing the risk of neurotoxic adverse effects and drug–drug interactions. Drugs with neurotoxic potential frequently used to treat HIV include dapsone (Aczone), hydroxyurea (Droxia, Hydrea), metronidazole (Flagyl and others), vincristine, thalidomide (Thalomid), isoniazid, linezolid (Zyvox), and ribavirin (Rebetol and others).24

Advanced age. The introduction of ART greatly increased the life span of people with HIV, and advanced age has consistently been associated with DSP neuropathy in the eras both preceding and following the introduction of combination ART regimens, most often referred to as highly active ART (HAART).2, 25 As people age, the peripheral nervous system undergoes the following changes26, 27:

* the density of small and large myelinated fibers decreases

* the amplitude of nerve action potentials declines

* nerve conduction slows

By 2015, half of the people living with HIV in the United States will be over age 50.28 With the aging of the HIV population and prolonged exposure to ART, the prevalence and severity of DSP neuropathy is a growing concern.

Metabolic disorders, such as diabetes or impaired glucose tolerance, may further increase the risk of DSP neuropathy. Population studies indicate that neuropathy affects 60% to 70% of patients with type 1 and type 2 diabetes, and risk rises with age and with the duration of diabetes.29 It's been suggested that small-fiber neuropathy may be associated with impaired glucose tolerance and may also occur in prediabetes.30, 31 In both diabetes and HIV, high triglyceride levels are associated with neuropathy,32 and many people with diabetes experience neurovascular damage, which impedes blood flow to the extremities, potentially contributing to or exacerbating symptoms in those who also have HIV and DSP neuropathy.

Data suggest that the increased prevalence of glucose disorders among patients living with HIV is associated with HAART use.33 Individuals using HAART often experience such metabolic complications as lipodystrophy, dyslipidemia, and insulin resistance, which in turn increase their risk of diabetes. New-onset diabetes occurs in an estimated 1% to 6% of HIV-infected people using protease inhibitors.34

Alcohol use and nutritional deficiencies. Some people with HIV try to self-manage their neuropathic symptoms with alcohol or illegal drug use.35, 36 Long-term, heavy alcohol use can damage nerves, while causing deficiencies in the vitamins (particularly B vitamins) and minerals essential to healthy nerve function.37 The effects of nutritional deficiencies may be compounded by weight loss and poor diet, which are common problems in HIV owing to nausea, loss of appetite, diarrhea, and the adverse effects of medications.38, 39 In addition, poor diet may exacerbate impaired immunity, contributing to the progression of HIV and reducing the therapeutic effect of ART.

CD4+ count. Prior to the widespread use of HAART, a higher plasma HIV-1 RNA load and lower CD4+ count were associated with an increased risk of DSP neuropathy.40 In the post-HAART era, however, an elevated viral load no longer seems to be associated with increased risk, although DSP neuropathy remains prevalent among those with advanced, untreated HIV or a lower nadir CD4+ cell count.2
 
ASSESSMENT AND MANAGEMENT

It is useful to determine whether the patient has any neurologic symptoms, such as muscle, bowel, or bladder abnormalities. Documentation should include any history of drug or alcohol abuse, detailing the amount of the substance used and the duration of use; current and past medications; and an assessment of dietary and nutritional deficiencies.

All patients with HIV should receive an annual, comprehensive foot exam in which the skin, hair, nails, musculoskeletal structure, circulation, and sensation of the feet are assessed. Those diagnosed with DSP neuropathy may need more frequent foot exams. Inquire about and document any reports of leg discomfort, providing details about the following factors:

* symptom onset

* location

* duration

* the character or quality of described sensations (for example, whether pain is burning, sharp, or dull)

* the severity (using a 0-to-10-point scale)

* diurnal variation

* progression

* exacerbating or relieving factors

Sensory testing. An assessment should also include sensory testing of the feet. Pressure sensation is assessed using a 5.07 (10-g) Semmes-Weinstein nylon monofilament on the plantar surface of the foot while the patient's eyes are closed (see How to Perform a Pressure Sensory Exam). Practice varies as to the number (one to 10) and location of sites tested for skin breakdown.41 One study found that exams that included the first toe, third metatarsal head, and two other toes or metatarsal heads per foot produced a sensitivity of 90% to 93% for abnormal pressure sensation and required less than one minute to complete.42

Patients are tested for light touch with a cotton swab and for temperature discrimination with warm and cold stimuli. Pinprick sensation is tested using the sharp end of a disposable safety pin. Patients with a loss of protective sensation are at risk for injury, incomplete healing, and infection. Another useful assessment tool is the Brief Peripheral Neuropathy Screen used in several AIDS Clinical Trials Group protocols.43 With this tool, clinicians capture both subjective and objective findings by asking patients to rate the severity of their symptoms on a scale from 1 (mild) to 10 (most severe) and evaluating their vibration perception and deep tendon reflexes.24 Testing for reduced or absent Achilles tendon reflexes has a sensitivity of 84% and a specificity of 98% for DSP neuropathy in HIV.43 After assessing the patient's risk and documenting all foot exam findings, consider whether the patient would benefit from referral to a foot care specialist and schedule follow-up care.

Management. The Food and Drug Administration has not approved any therapies specifically for the treatment of HIV-associated DSP neuropathy. Current pharmacologic treatment is based on primary symptoms, with acetaminophen, nonsteroidal antiinflammatory drugs, antidepressants, anticonvulsants, topical agents, and opioids used as tolerated. Unfortunately, several drugs that are useful for other types of neuropathic pain—including the tricyclic antidepressant amitriptyline, topical lidocaine anesthetics, and the anticonvulsant pregabalin (Lyrica)—have been found to be ineffective for HIV-associated DSP neuropathy.44, 45

Symptom management also involves general lifestyle modifications, such as reducing cigarette smoking, attaining optimal nutrition, practicing meticulous foot care, and improving circulation through appropriate exercise. In 2010, the American Diabetes Association and the American College of Sports Medicine modified their positions to suggest that people with peripheral neuropathy who have no acute ulceration may participate in modest weight-bearing exercise.46 Moderate walking is unlikely to increase the risk of foot ulcers in people with peripheral neuropathy.
 
FOOT CARE EDUCATION

Nurses play a critical role in disseminating self-care information to patients. Since HIV-associated DSP neuropathy has many of the same signs and symptoms as diabetic and chemotherapy-induced neuropathies, foot care educational materials from such organizations as the American Diabetes Association, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Cancer Institute, and the American Cancer Society may be helpful to people with HIV. In studies of people with diabetes, foot care education improved patients’ foot care knowledge and practice in the short term.47

Daily foot hygiene. It's important to emphasize to patients that their feet need to be cleaned daily, using warm—not hot—water and a mild soap, and then towel dried thoroughly, particularly between the toes.48 Dry skin is a common foot problem. Advise patients with dry skin to moisturize the tops and bottoms of their feet with a thin coat of lotion—not a heavy cream or oil—and to avoid getting lotion between the toes. Nurses should counsel patients to inspect their feet every day for any cuts, cracks, blisters, redness, calluses, swelling, or dryness. Corns and calluses should be gently filed with an emery board or pumice stone after a bath or shower. Toenails should be cut once a week or as needed after washing, when they are soft. They should be cut to the shape of the toes and not too short. Patients who are unable to cut their nails should be referred to a podiatrist.

Footwear and fall prevention. Shoes should fit well and allow the toes to move. They should be wide enough to exert no pressure on the joints and long enough to allow 1 cm of space between the longest toe and the edge of the shoe when the patient is standing.49 Shoe material should be permeable because a warm, moist environment may harbor fungal organisms. Patients should shop for new shoes at the end of the day when their feet are larger from standing and walking; until new shoes are fully broken in, they should be worn only an hour a day. Before putting shoes on, patients should always check the insides to make sure the lining is smooth and there are no sharp edges that could injure their feet. Patients should always wear socks or stockings with shoes to prevent skin irritation and blisters. Remind patients that open-toed or thong sandals do not adequately protect the feet from injury. Reinforce the importance of wearing shoes at the beach.

Many older patients wear slippers indoors. Since DSP neuropathy may cause gait and balance problems, putting patients at risk for falls, teach patients about the importance of wearing slippers that fit properly and have slip-resistant soles.50 If a patient frequently stumbles, a walker or cane may provide needed support. To further protect against falls, advise patients to51, 52

* use night lights or keep a flashlight near the bed.

* roll up area rugs.

* remove any electric cords that could impede walking.

* install no-slip bath mats in the shower and tub.

Foot exercises. To promote lower limb circulation and prevent swelling, nurses should advise patients to elevate their feet when sitting, avoid crossing their legs, and perform simple foot exercises, such as wiggling the toes and moving ankles up and down, several times a day.

CONSIDER ALL RESOURCES

Although people with compromised immune systems and reduced sensory perception are clearly at elevated risk for foot infection, foot exams are often conducted only after a patient has established foot injuries. Advanced age further escalates the risks of HIV-associated foot problems owing to reduced peripheral nerve function, gait complications, and reduced mobility.27, 53

Within the diabetes community, efforts to educate patients on peripheral neuropathy and foot care have been intensive and should serve as lessons for providers who care for patients with HIV. Studies have shown that the efficacy of foot care education may depend on the type of education employed.54, 55 Nurses should take advantage of all available resources, including smartphone applications, which can set daily foot check reminders as well as provide instructional videos. By encouraging simple, preventive foot care education, nurses can promote health and overall well-being in patients at risk for HIV-associated DSP neuropathy, while reducing the potential for complications and related health care costs.

http://journals.lww.com/ajnonline/Fulltext/2013/12000/HIV_Peripheral_Neuropathy_and_Foot_Care.20.aspx