Suspect Small Fiber Neuropathies for Unexplained Neuropathic Pain

LAS VEGAS—Recognizing the existence of small fiber neuropathies (SFNs) and their association with more conditions than previously identified may lead to improved treatment approaches, said Charles E. Argoff, MD, Professor of Neurology, Albany Medical College and Director, Comprehensive Pain Center, Albany Medical Center, Albany, New York.

Approximately 40 million people experience peripheral neuropathy, many with both large and small fiber involvement. Common neuropathic pain diagnoses range from postherpetic and trigeminal neuralgia, to spinal cord injury, poststroke pain, and HIV-related neuropathy.

Increasingly recognized is specific involvement of small myelinated or unmyelinated fibers resulting from damage to the peripheral nerves. Thermal perception, nociception, and enteric function are all subserved by small fibers.

Most SFNs occur in a length-dependent fashion, Dr. Argoff said, first with stocking distribution changes and later, glove distribution. “Rarely, non-length dependent SFN can result in symptoms involving the face, trunk, proximal limbs, or other more localized areas,” he said. The pathogenesis of injury to small fibers is not well understood, and SFN can progress to involve large fibers.

Symptoms vary widely in severity, with affected individuals often describing a gradual onset of vague distal sensory disturbances. Examples include feeling like there is sand in a person's shoe, a sock feeling as if it has pebbles in it, pins and needles or cold painful sensations, or tingling. Burning pain in the extremities, sometimes severe, may occur; socks or bed sheets may be painful; and symptoms are often worse at night. Autonomic and enteric dysfunction may include dry eyes, dry mouth, lightheadedness with changes in posture, syncope, abnormalities of sweating, erectile dysfunction, GI symptoms such as nausea and emesis, constipation, diarrhea, and changes in urinary frequency, including nocturia.

Dr. Argoff said a detailed diagnosis is vital to making a diagnosis of SFN, since patients will primarily have a normal basic physical and neurological examination. Possible findings included decreased pin prick, diminished thermal sensation, hyperalgesia, and dry skin. Diagnostic studies include blood tests, X-ray, CT, MRI, quantitative sensory testing, and epidermal skin biopsy. Although electromyography and nerve conduction velocity may also be used, he said limitations include that they are insensitive in acute injury, a normal result does not rule out neuropathic pain, and they cannot assess function of small-fiber nerves involved in most neuropathic pain.

Skin biopsy has become widely accepted as a technique to evaluate the structure of small nerve fibers, with the standard being a 3-mm skin punch biopsy that can be taken from anywhere over the body; however, due to the need to compare to normal values, the lower extremity is most commonly assessed (and because length-dependent SFN is more common). Results are expressed as the number of intraepidermal fibers per mm; the sensitivity (78%-92%) and specificity (65%-90%) is fairly high for this technique.

Dr. Argoff advised attendees to “treat the treatable,” and, if an underlying cause of SFN can be determined, optimal treatment of the causative condition may lessen SFN symptoms. Although few studies and no guidelines have examined pharmacologic treatment of the pain associated with SFN, gabapentin and tramadol have shown efficacy. One emerging treatment: intravenous immunoglobulin, study of which is warranted in larger studies.