Office approach to small fiber neuropathy
ABSTRACT
Small fiber neuropathy is often characterized by neuropathic pain in the feet with normal nerve conduction studies and neurologic examination. Diagnosis requires specialized nerve tests, including autonomic studies and a skin biopsy study showing reduced intraepidermal nerve fiber density. Small fiber neuropathy has numerous causes but is often idiopathic. A practical approach to identifying an underlying cause is to first screen for common ones and then proceed with further testing as needed. Treatment consists of correcting the underlying cause, managing pain, and modifying lifestyle.
KEY POINTS
- Patients typically develop a symmetric “stocking-glove” pattern of sensory loss in the feet and hands.
- The diagnosis may be confirmed with skin biopsy for nerve fiber density, which can easily be done in a clinic setting with commercially available kits.
- Diabetes is the most common identifiable cause of small fiber neuropathy.
- Serologic testing can help uncover a vitamin deficiency or other potentially treatable condition.
- Antiepileptics, antidepressants, and topical agents are first-line drugs for managing pain.
TREATING SPECIFIC DISORDERS
For patients with an identified cause of neuropathy, targeted treatment offers the best chance of halting progression and possibly improving symptoms. Below are recommendations for addressing neuropathy associated with the common diagnoses.
Diabetes, impaired glucose tolerance, and metabolic syndrome. In addition to glycemic- and lipid-lowering therapies, lifestyle modifications with a specific focus on exercise and nutrition are integral to treating diabetes and related disorders.
In the Look AHEAD (Action for Health in Diabetes) study,37 which evaluated the effects of intensive lifestyle intervention on neuropathy in 5,145 overweight patients with type 2 diabetes, patients in the intervention group had lower pain scores and better touch sensation in the toes compared with controls at 1 year. Differences correlated with the degree of weight loss and reduction of hemoglobin A1c and lipid levels.
As running and walking may not be feasible for many patients owing to pain, stationary cycling, aqua therapy, and swimming are other options. A stationary recumbent bike may be useful for older patients with balance issues.
Vitamin B12 deficiency. As reduced absorption rather than low dietary intake is the primary cause of vitamin B12 deficiency for many patients, parenteral rather than oral supplementation may be best. A suggested regimen is subcutaneous or intramuscular methylcobalamin injection of 1,000 µg given daily for 1 week, then once weekly for 1 month, followed by a maintenance dose once a month for at least 6 to 12 months. Alternatively, a daily dose of vitamin B12 1,000 µg can be taken sublingually.
Sjögren syndrome. According to anecdotal case reports, intravenous immune globulin, corticosteroids, and other immunosuppressants help painful small fiber neuropathy and dysautonomia associated with Sjögren syndrome.10
Sarcoidosis. Sarcoidosis-associated small fiber neuropathy may also respond to intravenous immune globulin, as well as infliximab and combination therapy.9 Culver et al38 found that cibinetide, an experimental erythropoetin agonist, resulted in improved corneal nerve fiber measures in patients with small fiber neuropathy associated with sarcoidosis.
Celiac disease. A gluten-free diet is the treatment for celiac disease and can help some patients.
GENERAL MANAGEMENT
For all patients, regardless of whether the cause of small fiber neuropathy has been identified, managing symptoms remains key, as pain and autonomic dysfunction can markedly impair quality of life. A multidisciplinary approach that incorporates pain medications, physical therapy, and lifestyle modifications is ideal. Integrative holistic treatments such as natural supplements, yoga, and other mind-body therapies may also help.
Pain control
Mexiletine, a voltage-gated sodium channel blocker used as an antiarrhythmic, may help refractory pain or hereditary small fiber neuropathy related to sodium channel dysfunction. However, it is not recommended for diabetic neuropathy.39
Combination regimens that use drugs with different mechanisms of action can be effective. In one study, combined gabapentin and nortriptyline were more effective than either drug alone for neuropathic pain.40
Inhaled cannabis reduced pain in patients with HIV and diabetic neuropathy in a number of studies. Side effects included euphoria, somnolence, and cognitive impairment.41,42 The use of medical marijuana is not yet legal nationwide and may affect employability even in states in which it has been legalized.
Owing to the opioid epidemic and high addiction potential, opioids are no longer a preferred recommendation for chronic treatment of noncancer-related neuropathy. A population-based study of 2,892 patients with neuropathy found that those on chronic opioid therapy (≥ 90 days) had worse functional outcomes and higher rates of addiction and overdose than those on short-term therapy.43 However, the opioid agonist tramadol was found to be effective in reducing neuropathic pain and may be a safer option for patients with chronic small fiber neuropathy.44
Integrative, holistic therapies
PROGNOSIS
For many patients, small fiber neuropathy is a slowly progressive disorder that reaches a clinical plateau lasting for years, with progression to large fiber involvement reported in 13% to 36% of cases; over half of patients in one series either improved or remained stable over a period of 2 years.5,57 Long-term studies are needed to fully understand the natural disease course. In the meantime, treating underlying disease and managing symptoms are imperative to patient care.
