Small Fibre Neuropathy

Small fibre neuropathy is a nerve condition that causes severe pain attacks, typically starting in the feet or hands, and can significantly affect your quality of life despite not being life-threatening.

Table of contents

• What is Small Fibre Neuropathy?
• Symptoms and How They Present
• Causes and Risk Factors
• How the Condition is Diagnosed
• Treatment and Management
• Outlook and Complications
• Living with the Condition

What is Small Fibre Neuropathy?

Small fibre neuropathy is a form of peripheral neuropathy, which means it affects the nerves outside your brain and spinal cord. The condition happens when something damages the small nerve fibres in your skin and other parts of your body^[1]. These small nerve fibres include lightly myelinated A-delta fibres and unmyelinated C fibres, which are present throughout human skin, peripheral nerves, and organs^[6].

The damaged nerve fibres have two main jobs. The first is sensing pain, temperature, and itching in your skin. The second is controlling automatic body functions, such as your heart rate, blood pressure, sweating, digestion, and bladder control^[1]. When these fibres are damaged, both types of signals can be affected, leading to various symptoms.

Based on research, an estimated 53 out of 100,000 people worldwide have small fibre neuropathy, though this number may be low because many people with the condition never receive a proper diagnosis^[1]. In the United States, peripheral neuropathy in general affects about 15 to 20 million people over age 40^[3].

Symptoms and How They Present

The most common early symptoms are “pins-and-needles” pain or a burning sensation in your hands and feet. These symptoms may come and go at first, but they often become constant and typically worsen over time^[1]. The pain is often described as stabbing or burning, and many people also experience abnormal skin sensations such as tingling or itchiness^[2].

The pain and other sensory symptoms are usually more severe at night or during times of rest^[2]. Simple triggers that normally wouldn’t cause pain can set off intense symptoms. For example, cool air blowing on your skin or a bedsheet brushing against your feet can cause painful, intense tingling^[1].

One unusual feature of this condition is that while you may not be able to feel concentrated pain in a very small area (like a pinprick), you become more sensitive to pain in general. This is called hyperalgesia. You may also experience pain from things that normally don’t cause pain at all, which is called allodynia^[2]. People affected by this condition may also have a reduced ability to tell the difference between hot and cold^[1].

When the condition affects the small nerve fibres that control automatic body functions, you may experience additional symptoms including:

• Feeling lightheaded or fainting
• Heart palpitations or rapid heartbeat
• Numbness
• Stomach cramps, nausea, or vomiting
• Abnormal sweating (sweating more than usual or not sweating enough)
• Dry eyes or mouth
• Constipation or diarrhoea
• Bladder problems^[1][4]

The symptoms typically begin in the feet and may spread upward over time in what doctors call a “stocking” pattern. Eventually, the hands may become affected in a “glove-like” pattern^[7]. This is called length-dependent small fibre neuropathy because it affects the longest nerves first. However, in some people the symptoms appear in a patchy, non-length-dependent pattern that can affect the trunk, face, and other areas in a more random fashion^[7].

Causes and Risk Factors

About half of small fibre neuropathy cases happen for no known reason. Healthcare providers call this idiopathic small fibre neuropathy^[1]. For the other half, research shows several medical conditions, inherited disorders, or exposure to certain substances may cause the condition.

Diabetes is the most common condition causing small fibre neuropathy. It is believed that almost half of people with diabetes suffer from some form of the condition^[2][10]. High blood sugar levels are thought to damage the tiny nerve fibres over time. Even people with impaired glucose tolerance (pre-diabetes) can develop small fibre neuropathy^[1].

Other medical conditions that may lead to small fibre neuropathy include:

• Alcohol use disorder
• Immune system disorders such as coeliac disease, sarcoidosis, and Sjögren’s syndrome
• Infectious diseases like hepatitis C, human immunodeficiency virus (HIV), and Lyme disease
• Metabolic syndrome
• Thyroid disease
• Vitamin B12 deficiency
• Sepsis^[1][3]

Some people develop small fibre neuropathy because they inherit certain genetic changes. Mutations in the SCN9A or SCN10A genes can cause the condition. These genes provide instructions for making parts of sodium channels, which are essential for nerve cells to generate and transmit electrical signals. The changes in these genes cause nerve cells that transmit pain signals to become overactive, making people more sensitive to pain^[2]. About 30 percent of people with small fibre neuropathy have SCN9A gene mutations, while about 5 percent have SCN10A gene mutations^[2].

Other inherited disorders that may cause small fibre neuropathy include Ehlers-Danlos syndrome, Fabry disease, familial amyloidosis, Pompe disease, porphyria, and Wilson disease^[1].

Certain medications may increase your risk of developing the condition. These include specific antibiotics (metronidazole, nitrofurantoin, and linezolid), chemotherapy drugs (bortezomib, thalidomide, and vincristine), and tumour necrosis factor inhibitors like etanercept^[1].

How the Condition is Diagnosed

Healthcare providers diagnose small fibre neuropathy primarily through your medical history and a physical examination. However, routine neurological exams and standard nerve tests cannot always distinguish between large fibre and small fibre neuropathy^[7].

The gold standard for diagnosing small fibre neuropathy is a skin biopsy. During this test, a small sample of skin is removed and examined under a microscope to measure the density of small nerve fibres. A reduced number of nerve fibres confirms the diagnosis^[7][9].

When autonomic symptoms are present, doctors may perform autonomic testing. These tests assess how well your body controls functions like heart rate, blood pressure, breathing, and digestion in response to activities such as standing up or deep breathing^[10].

Another diagnostic tool is quantitative sensory testing, which assesses damage to small nerve endings by measuring your ability to detect thermal sensation, pain, and vibration^[10].

Your doctor will also perform blood tests to look for underlying conditions that might be causing your symptoms. These tests may check for diabetes, vitamin deficiencies, thyroid problems, immune system disorders, and other potential causes^[1].

If your doctor suspects a genetic cause, genetic testing can determine if you have mutations in the SCN9A or SCN10A genes^[17].

Treatment and Management

Healthcare providers treat small fibre neuropathy by focusing on two main goals: treating the underlying cause when possible, and managing the painful symptoms^[1].

When an underlying condition is identified, treating it is the first priority. For example, if diabetes is the cause, controlling blood sugar levels through diet, exercise, and medication may help improve the neuropathy or at least prevent it from getting worse^[11]. If vitamin B12 deficiency is the problem, B12 injections or tablets can help^[11].

For pain management, common painkillers like paracetamol and ibuprofen usually don’t work well for nerve pain. Instead, doctors typically prescribe medications that were originally developed for other conditions but have been found effective for nerve pain^[11]:

• Antidepressants such as amitriptyline and duloxetine
• Anticonvulsants (medications used to treat epilepsy) such as pregabalin and gabapentin
• In some cases, stronger painkillers like tramadol may be prescribed for short periods^[11]

These medications are usually started at a low dose, which is gradually increased until symptoms improve. They may cause side effects such as tiredness, dizziness, or feeling “drunk,” but these often improve after a week or two as your body adjusts^[11].

Topical treatments can also help. Capsaicin cream or patches, which contain the substance that makes chilli peppers hot, can be applied to the skin to help relieve localised pain^[11].

For severe cases that don’t respond to other treatments, spinal cord stimulation may be an option. This involves implanting a small device that sends electrical signals to disrupt pain messages traveling to the brain^[21].

Research shows that intravenous immunoglobulin (IVIG) is not effective for treating idiopathic painful small fibre neuropathy^[7].

Outlook and Complications

Small fibre neuropathy is not a life-threatening condition, but it may be a sign of other conditions that could be more serious^[1]. The condition has a generally benign course, meaning it progresses slowly. Most people affected by small fibre neuropathy do not develop large nerve fibre involvement over time^[7].

However, the condition can cause several complications. One significant risk is that small fibre neuropathy affects your ability to sense pain properly. You may not notice injuries, such as if you put your hand on a hot stovetop or develop a cut or blister on your foot^[1][6].

The condition can also make you feel dizzy or affect the way you walk, which increases your risk of falling and getting hurt^[1].

Perhaps most importantly, the symptoms of small fibre neuropathy can be severe and significantly affect your overall quality of life. The chronic pain, sleep problems, and limitations on daily activities can lead to anxiety and depression^[1][18].

Living with the Condition

Living with small fibre neuropathy requires adapting your daily life to manage symptoms and maintain the best possible quality of life. Several lifestyle changes and strategies can help.

Regular exercise may reduce pain, help improve blood sugar levels, and assist with weight loss. A comprehensive exercise routine should include aerobic exercise (such as brisk walking, swimming, or stationary cycling), flexibility exercises, strength training, and balance exercises. However, you should always talk to your healthcare provider before starting any exercise program^[14].

Getting enough sleep is crucial because sleep deprivation can make you more sensitive to pain. To improve sleep, stick to a regular bedtime and wake-up schedule, establish pre-bedtime relaxation rituals, avoid caffeine and alcohol before bed, and stay away from screens for at least 30 minutes before sleep. If symptoms worsen in bed, consider changing your sleep position or sleeping in a recliner^[14].

Eating a healthy diet that nourishes your nerves is important. Include plenty of vegetables and whole fruits, and eat foods rich in vitamin B12, such as meat, fish, dairy, eggs, and fortified cereals. Limit or avoid gluten-containing foods and alcohol, as alcohol is toxic to nerves and can worsen the condition^[14].

Managing stress is also important for coping with the condition. Many people find that staying involved in activities they enjoy and maintaining connections with family and friends helps combat feelings of isolation and depression^[10][18].

It’s essential to check your feet and hands regularly for any injuries you might not have felt, especially if you have reduced sensation. This is particularly important for people with diabetes^[6].

If you find yourself feeling depressed or isolated as a result of your symptoms, consider reaching out to a support group. Support groups can provide valuable emotional support and practical advice from others who understand what you’re going through^[10].