SMALL FIBER NEUROPATHY; Q & A

When should one consider doing a skin biopsy for determination of epidermal nerve fiber density (ENFD)

A skin biopsy for determination of epidermal nerve fiber density (ENFD) should be considered in patients suspected of small fiber neuropathy (SFN) that present with otherwise unexplained sensory or autonomic symptoms..

Sensory symptoms often include spontaneous annoying or painful sensations called paresthesias, that are described as numbness, tingling, aching, burning, stinging, itching, freezing, buzzing, crawling, or electric shock like, that can occur in any part of the body including the legs, arms, torso or face. Other symptoms include hypersensitivity to pressure or touch, or unpleasant altered sensations, called dysesthesias, as when clothes feel like sandpaper against the skin.

Autonomic symptoms can include dizziness or headaches when standing up resulting from postural hypotension or tachycardia, heat or cold intolerance, abnormal sweating, Raynaud's syndrome with discoloration of the skin in the fingers or toes, gastrointestinal dysmotility syndromes, or bladder irregularities.

SFN can also occur in patients with fibromyalgia, contributing to the symptoms. In such cases, identification of SFN helps the physician treat the underlying cause in addition to the symptoms.

Why is the diagnosis of Small Fiber Neuropathy easy to miss

The diagnosis of SFN is often missed because the neurological examination is often normal or shows only minimal abnormalities. EMG and nerve conduction studies that measure the electrical properties of the large nerve fibers are usually normal in SFN.

Patients with SFN are sometimes diagnosed as having other pain syndromes such as fibromyalgia, reflex sympathetic dystrophy, regional pain syndrome, restless leg syndrome, or eczema, among others. Some patients are told that they have a psychosomatic disorder, especially if they are depressed or anxious. The latter is often a result of having to live with chronic pain, compounded by not knowing what's wrong or no one believing them.

Why is it important to diagnose SFN

Making the diagnosis of SFN provides a biological explanation for the symptoms, guides the physician in further testing for an underlying cause, helps decide treatment, and prevents unnecessary testing for other conditions that can cause similar symptoms.

How is small fiber neuropathy diagnosed

SFN is most reliably diagnosed by punch skin biopsy for determination of epidermal nerve fiber density (ENFD). The skin biopsy is usually done at standard sites, distally at the ankle or foot, and proximally at the thigh. A reduction in the ENFD at one of these sites is consistent with the diagnosis of SFN. In distal neuropathies, the ENFD is more severely affected distally at the ankle or foot, whereas in multifocal neuropathy and sensory neuronopathy or ganglioneuritis, it may be more severely affected proximally at the thigh. Biopsies are usually done at both sites to increase the chances of making the diagnosis. In patients with localized symptoms, side to side comparisons may reveal the presence of a focal neuropathy.

In early or mild cases of SFN, the biopsy may be normal or show only mild abnormalities. The presence of normal ENFD values does not rule out the presence of SFN, but makes the diagnosis less likely, so that other causes for the symptoms should be investigated. If the symptoms progress, then a repeat biopsy at a later date may reveal more significant abnormalities.

What does the physician do after making a diagnosis of small fiber neuropathy

The next step is to test for an underlying cause. The known causes of small fiber neuropathy, and their diagnostic tests are listed under Overview of Small Fiber Neuropathy, in table I. If no cause can be found, then the neuropathy is classified as "idiopathic", or of unknown cause. In some cases SFN is the first manifestation of the more severe sensorimotor neuropathy. If the neuropathy progresses, and no cause can be found, then the physician may recommend doing a nerve biopsy to look for certain causes such as vasculitis, sensory CIDP, or amyloidosis, that might be only identified by pathological examination of an affected nerve.

How is SFN treated

Therapy is directed at both the symptoms, and at the underlying cause, if one can be identified. Neuropathic pain can be treated using a number of medications, alone or in combination. Such medications include gabapentin (Neurontin), amitriptyline (Elavil), nortriptyline (Pamelor), oxacarbazine (Trileptal), topiramate (Topomax), Lamotrigine (Lamictal), venlafaxine (Effexor), or opiates. Duloxetine (Cymbalta) or pregabaline (Lyrica) are FDA approved for neuropathic pain associated with diabetes. Lidocaine patches (Lidoderm) can be used for localized pain.