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Corneal confocal microscopy in small fiber neuropathy: A, normal corneal nerve fibers and branching; B, marked reduction of corneal nerve fibers.
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Neuropathic pain: burning, numbness, tingling, itching, “frostbite-like” sensations Commonly “stocking-glove” pattern, but may be random, migratory, and intermittent Symptoms of dysautonomia (eg, skin changes, sweating abnormalities, dry eyes, dry mouth, gastrointestinal dysmotility, orthostasis, palpitations, bowel or bladder changes, sexual dysfunction) Normal neurologic examination, nerve conduction studies, needle electromyography First-tier studies Associated conditions 2-hour oral glucose tolerance test, hemoglobin A1c Diabetes, impaired glucose tolerance Extractable nuclear antigen testing for Sjögren syndrome A and B antibodies Sjögren syndrome Thyroid-stimulating hormone, free T4, T3 levels Hypothyroidism Vitamin B12, methylmalonic acid, homocysteine levels Vitamin B12 deficiency Serum and urine monoclonal protein analysis Paraproteinemia Tissue transglutaminase, antigliadin antibodies Celiac disease Complete metabolic panel Renal, hepatic impairment Complete blood cell count Hematologic abnormalities Human immunodeficiency virus (HIV) and hepatitis C virus antibodies (may be second-tier tests if no risk factors) HIV, hepatitis C Fasting lipid panel Hyperlipidemia Erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody Inflammatory disease Liver function tests, gamma-glutamyltransferase Alcohol abuse Second-tier studies Angiotensin-converting enzyme Sarcoidosis Thiamine (vitamin B1) Vitamin B1 deficiency Pyridoxine (vitamin B6) Vitamin B6 deficiency Copper Copper deficiency Serum and urine monoclonal protein analysis, fat pad analysis, nerve biopsy Systemic amyloidosis Paraneoplastic autoantibody panel Paraneoplastic disease Ganglionic acetylcholine receptor antibody Autoimmune autonomic ganglionopathy Genetic studies SCN9A and SCN10A genes Hereditary small fiber neuropathy GLA gene Fabry disease Transthyretin gene Familial amyloidosis ABCA1 gene Tangier disease Therapy Dosages (per day) Common adverse effects Anticonvulsants Gabapentin 300–3,600 mg Sedation, dizziness, peripheral edema, weight gain Pregabalin 150–600 mg Similar to gabapentin Topiramate 25–400 mg Weight loss, sedation, cognitive slowing, depression with suicidal ideation, renal stones, paresthesias, glaucoma Zonegran 100–400 mg Antidepressants Amitriptyline 20–100 mg Sedation, weight gain, anticholinergic effects, sexual dysfunction, arrhythmia (side effects most prominent with amitriptyline) Nortriptyline 20–100 mg Desipramine 20–200 mg Duloxetine 60–120 mg Topical anesthetics Lidocaine 5% patch 3 patches for 12 hours Local edema, burning, erythema Lidocaine 5% cream or gel 5 g to affected areas up to 20 g total Local edema, burning, erythema Capsaicin 0.75% Apply up to 4 times daily Burning Capsaicin 8% patch 60–90 minutes (applied by the clinician) Burning Other Tramadol 50–400 mg Sedation, dizziness, seizures, nausea, constipation Mexiletine 200–600 mg Nausea, vomiting, abdominal pain, dry mouth (not helpful for diabetic neuropathy) Treatments Dosage Comments Oral supplements Acetyl-l-carnitine 1,000 mg 3 times a day Some benefit seen in diabetic and human immunodeficiency virus neuropathy,45,47 but may worsen chemotherapy-induced neuropathy48 Alpha lipoic acid 600 mg/day Early studies found benefit with intravenous dosing but no data on optimal oral dose46 Glutamine 15 g twice a day Possible neuroprotective effect in chemotherapy-induced neuropathy with oral dose,49 pain reduction with intravenous dosing50 Curcumin Dose varies Some benefit in pain reduction for diabetic and chemotherapy-induced neuropathy51,52 Omega-3 fatty acids 1,000–3,000 g/day Possible pain reduction seen in mouse models; increased nerve growth in patients with diabetic small fiber neuropathy53,54 Topical products Vicks VapoRub Apply as needed May cause increased pain on initial contact Horse liniment cream Apply as needed May cause increased pain on initial contact Frankincense oil Apply as needed Reduces neuropathic pain in mice55 Hemp cream or oil Apply as needed Noncannabidiol form legal in all states
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