Expert Clinical Perspectives: Management of Small Fiber Neuropathy: A Clinical Perspective-Article

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Small fiber neuropathy (SFN) is a prevalent neurological condition characterized by sensory disturbances such as burning pain and tingling, as well as autonomic symptoms like orthostatic dizziness. SFN primarily affects small peripheral nerve fibers—unmyelinated C-fibers and thinly myelinated A-delta fibers—that transmit pain, temperature, and autonomic signals. The etiology of SFN is diverse, including metabolic (e.g., diabetes, vitamin deficiencies), autoimmune, infectious (e.g., HIV, Lyme disease, hepatitis C), toxic (e.g., chemotherapy, vaccinations), hereditary genetic variants (notably sodium channel gene mutations), or idiopathic causes.<br /><br />Diagnostically, SFN is best confirmed by reduced intraepidermal nerve fiber density on a 3-mm skin biopsy, with nerve conduction studies (NCS) and electromyography (EMG) used to exclude large fiber neuropathies. Quantitative sudomotor axon reflex testing (QSART) measures autonomic small fiber function and can support diagnosis, though less definitively. Dysautonomia evaluations like tilt-table testing assist when autonomic symptoms predominate.<br /><br />Treatment depends on underlying causes; for instance, diabetes requires glycemic control. In idiopathic SFN, management focuses on symptom relief, primarily neuropathic pain. First-line pharmacotherapies include tricyclic antidepressants (amitriptyline, nortriptyline) and antiepileptic drugs (gabapentin, pregabalin). Both drug classes have efficacy but carry side effects that must be managed. Topical therapies like lidocaine and capsaicin patches may provide adjunctive pain relief with fewer systemic effects. Second-line options involve serotonin-norepinephrine reuptake inhibitors (duloxetine, venlafaxine), with opioids and tramadol reserved for refractory or breakthrough pain due to dependency risks. Emerging therapies such as alpha-lipoic acid and non-pharmacologic approaches including biofeedback, rehabilitation, and transcutaneous electrical nerve stimulation (TENS) show promise.<br /><br />Autonomic symptoms are addressed with targeted pharmacologic agents (e.g., beta blockers for postural orthostatic tachycardia syndrome, fludrocortisone for orthostatic hypotension) and supportive measures like increased fluid and salt intake. Intravenous immunoglobulin (IVIG) therapy may benefit selected autoimmune-mediated SFN cases but lacks evidence for widespread use in idiopathic SFN.<br /><br />Given its complexity, SFN requires a multidisciplinary approach with thorough clinical evaluation, diagnostic testing, etiologic investigation, and tailored symptomatic management to improve patient quality of life.

Keywords

Small fiber neuropathy

Sensory disturbances

Autonomic symptoms

Peripheral nerve fibers

Skin biopsy

Nerve conduction studies

ncs

Neuropathic pain

Pharmacotherapy

Autonomic dysfunction

Multidisciplinary management