Small Fiber Neuropathy

Small fiber neuropathy affect the small, unmyelinated nerve fibers in the sensory nerves. These fibers convey pain and temperature sensations from the skin, as well as maintain autonomic function. The diagnosis can easily be missed, as the neurological examination may real only minor sensory abnormalities, and EMG and nerve conduction studies, that measure the large fibers, are frequently normal. Consequently, the diagnosis may be missed, or patients may be misdiagnosed as having a psychosomatic disorder, RSD, fibromyalgia, or restless leg syndrome .

Symptoms of Small Fiber Neuropathy

Symptoms of small fiber neuropathy include numbness, and annoying or painful sensations, called paresthesias, that are variably described as tingling, stinging, burning, freezing, itching, aching, pulling, squeezing, or electric shock-like. . Innocuous stimuli can provoke unpleasant sensations, called dysesthesias; Clothes can feel like sandpaper against the skin, the hands may become hypersensitive to touch, or pressure from shoes or socks can causes severe pain in the feet. Symptoms of small fiber neuropathy can occur anywhere in the body, including the arms, legs, torso, face, or even the mouth.

Causes of Small Fiber Neuropathy

Small fiber neuropathy be caused by many different conditions, and in some cases, the neuropathy is n the first manifestation of an underlying systemic disease. The most common cause is diabetes mellitus or glucose intolerance . Other causes include Sjogren's syndrome , lupus , sarcoid , vasculitis , inflammatory bowel disease , a variant of the Guillain-Barre syndrome , nutritional deficiencies, celiac disease , Lyme disease, HIV-1 infection, hereditary conditions including Fabry disease , amyloid, alcohol abuse or toxins . In cases where no cause can be found, the neuropathy is called idiopathic. In some cases, progressive neuropathies that affect both the small and large nerve fibers can present as small fiber neuropathies before they can be detected by electrodiagnostic studies. A listing of the known causes of small fiber neuropathy, and the corresponding diagnostic tests, is provided in Table I.

How is Small Fiber Neuropathy diagnosed?

The diagnosis of small fiber neuropathy can be made with certainty, by demonstrating a reduction in the density of small nerve fibers in the skin. EMG and nerve conduction studies are usually normal in this condition, as they mostly measure the large nerve fibers in the motor or sensory nerves. The epidermal nerve fiber density is normal in patients with central nervous system disease.

A skin specimen is obtained for analysis, using a 3 mm punch biopsy. The small nerve fibers in the epidermis are visualized by immunocytochemistry, using an antibody to an axonal protein. The number and structural integrity of the small fibers is then evaluated by a pathologist. Patients with small fiber neuropathy exhibit a reduction is the epidermal nerve fiber density, or structural abnormalities that are indicative of neuropathy. All procedures are done according to international standards and guidelines .

Skin specimens are routinely obtained by punch biopsy at the calf and thigh, under local anaesthesia. In length dependent neuropathies the epidermal nerve fiber density is more severely reduced distally at the calf, but in ganglioneuritis or multifocal neuropathies, the nerve fiber density may be preferentially reduced at the thigh. The procedure is easy to perform, takes no more than 5 to 10 minutes, and causes little discomfort. The biopsy site is routinely covered by a band aid for several days until the skin heals.

Treatment of Small Fiber Neuropathy

Therapy in patients with small fiber neuropathy is directed at both the underlying cause, once it is identified, and at ameliorating the symptoms. Some acute onset, idiopathic small fiber neuropathies respond to prednisone . Painful paresthesias are routinely treated using oral medications such as Lyrica or Cymbalta, or by topical applications such as the Lidoderm patch.

Causes of Small Fiber Neuropathy Evaluation
Diabetes Mellitus and glucose intolerance Blood glucose, glycosylated hemoglobin, glucose tolerance test
Sjogren's syndrome SSA-Ro and SSB-La antibodies, lacrymal duct biopsy
Lupus erythematosus ANA, dsDNA antibodies
Vasculitis Skin, nerve, or muscle biopsy
Sarcoid Chest radiogram, biopsy
Inflammatory bowel disease History, small or large bowel biopsy
Nutritional deficiency Serum B12, B6, or B1 vitamins
Celiac disease Gliadin and transglutaminase antibodies, duodenal biopsy
Lyme disease Serological tests for Lyme antibodies
HIV-1 infection Serological tests for HIV-1 antibodies
Fabry disease Alpha-galactosidase A activity
Amyloidosis Biopsy
Alcohol abuse Alcohol abuse
Toxins History, toxin levels