List of underlying causes
Much of the information regarding underlying causes of small fiber neuropathy is sourced from three pivotal scientific articles known as ‘reviews.’
- Current View of Diagnosing Small Fiber Neuropathy(2021), https://pubmed.ncbi.nlm.nih.gov/31773305/1
- Current Diagnosis and Treatment of Painful Small Fiber Neuropathy (2019), https://pubmed.ncbi.nlm.nih.gov/31773305/2
- Advances in the Management of Small Fiber Neuropathy (2021), https://pubmed.ncbi.nlm.nih.gov/33223078/3
These review articles offer comprehensive overviews of the subject, drawing from numerous primary studies. Ideally, from a rigorous scientific perspective, direct references to these primary sources would be made rather than relying on review articles. “Over time, the primary sources will be added step by step. Regardless, the origins of the information presented here are traceable and rooted in scientific literature.
Insights have also been obtained from OpenAI’s GPT-4 model, particularly when suggesting potential tests. It’s important to recognize that this model, a large language model, predicts word sequences based on patterns in vast datasets. Thus, information from it should be viewed as suggestions or ideas, not definitive truths.
Lastly, anecdotal accounts from individuals affected by small fiber neuropathy have been included. These narratives encompass personal experiences, diagnoses, or suspicions—either self-formed or shared by healthcare professionals. While these may not have a direct scientific basis, their inclusion offers valuable context and breadth to the understanding of the condition.
Metabolic:
Condition | Tests | References |
---|---|---|
Diabetes Mellitus | Fasting plasma glucose test | 1,4,5 |
Oral glucose tolerance test (OGTT) | 5 | |
Hemoglobin A1c (HbA1c) test | 5 | |
Random plasma glucose test | 5 | |
Impaired glucose intolerance | Oral glucose tolerance test (OGTT) | 1,6,5 |
Hyperlipidemia, Metabolic Syndrome | Lipid panel, cholesterol test | 3 |
Rapid Glycemic Lowering | Similar tests as diabetes, monitoring blood glucose levels | 3,5 |
Chronic Kidney Disease | Glomerular filtration rate (GFR), urine albumin | 3 |
Autoimmune/Inflammatory:
Condition | Tests | References |
---|---|---|
Sjögren’s syndrome | Anti-Ro (SSA) and anti-La (SSB) antibodies test | 1,7,5 |
Salivary gland biopsy | 5 | |
Lupus | Antinuclear antibody (ANA) test | 1,8,5 |
Anti-dsDNA test | 5 | |
Anti-Ro (SSA) and Anti-La (SSB) test | 5 | |
Complement levels test | 5 | |
Rheumatic diseases (undifferentiated connective tissue disorders, rheumatoid arthritis, psoriasic arthropathy) | Rheumatoid factor (RF) test | 1,9 |
Anti-cyclic citrullinated peptide (anti-CCP) test | ||
Erythrocyte sedimentation rate (ESR) test | ||
C-reactive protein (CRP) test | ||
Sarcoidosis | Angiotensin-converting enzyme (ACE) test | 3,10,5 |
Chest X-ray | 5 | |
Biopsy of affected tissue | 5 | |
Vasculitis | ANCA (antineutrophil cytoplasmic antibody) test | 1,3,5 |
C-reactive protein (CRP) test | 5 | |
Erythrocyte sedimentation rate (ESR) test | 5 | |
Biopsy of affected tissue | 5 | |
Hypothyroidism, Autoimmune Thyroiditis | TSH test | 3,5 |
Free T4 test | 5 | |
Thyroid antibodies test | 5 | |
Inflammatory bowel disease | Fecal calprotectin test | 1,3,5 |
Stool test for parasites and bacteria | 5 | |
Colonoscopy with biopsy | 5 | |
Celiac disease/gluten sensitivity | Tissue transglutaminase (tTG) antibody test | 1,2,3,5 |
Endomysial antibody (EMA) test | 5 | |
Duodenal biopsy | 5 | |
Mixed connective tissue disease | Antinuclear Antibody (ANA) Test | 3,5 |
Anti-U1-RNP Antibodies Test | 5 | |
Complete Blood Count (CBC) | 5 | |
Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) Tests | 5 | |
Chest X-Ray or CT Scan | 5 | |
Echocardiogram | 5 | |
Churg-Strauss Disease | Blood tests for eosinophilia | 3,5 |
Immunoglobulin E (IgE) test | 5 | |
Other Immune-mediated (TS-HDS, FGFR-3, Plexin D1, Anti-Voltage-Gated Potassium Channel (VGKC) Antibody) | Various specific antibody and immunological tests, depending on the suspected condition | 5 |
Vitamin/Micronutrient related:
Condition | Tests | References |
---|---|---|
Vitamin B12 deficiency | Vitamin B12 blood test | 1,2,5 |
Methylmalonic acid (MMA) test | 5 | |
Homocysteine test | 5 | |
Vitamin B6 deficiency | Vitamin B6 (pyridoxine) level test | 2,5 |
Vitamin B1 deficiency | Vitamin B1 (thiamine) level test | 2,5 |
Vitamin E deficiency | Vitamin E level test | 2,5 |
Vitamin B6 toxicity | Vitamin B6 level test | 2,5 |
Copper deficiency | 2 |
Toxic:
Condition | Tests | References |
---|---|---|
Chemotherapeutic agents (taxanes, platinum family, vinca alkaloids, thalidomide, bortezomib, epothilones, and arsenic trioxide) | Complete blood count (CBC) | 2 |
Kidney function tests, liver function tests | ||
Electrocardiogram (ECG) | ||
Nerve conduction studies | ||
Antibiotics (isoniazid, linezolid, oxazolidinones, nitrofurantoin, metronidazole, and fluoroquinolones) | Complete blood count (CBC) | 2,3 |
Kidney function tests | ||
Liver function tests | ||
Anti-retroviral medications | Complete blood count (CBC) | 3 |
Liver function tests | ||
Kidney function tests | ||
Gout medications (colchicine, allopurinol) | Complete blood count (CBC) | 2 |
Kidney function tests | ||
Liver function tests | ||
Heavy metal toxicity (lead, arsenic, mercury, thallium) | Heavy metal levels in blood and urine | 2,3 |
Blood lead level test | ||
Excessive alcohol use | Alcohol level test | 2,3 |
Liver function tests | ||
Complete blood count (CBC) | ||
Neurotoxic drugs | Complete blood count (CBC) | 3 |
Liver function tests | ||
Kidney function tests | ||
Nerve conduction studies | ||
Cholesterol-lowering medications (Statins) | 3 | |
Gadolinium toxicity | 11 |
Infectious:
Condition | Tests | References |
---|---|---|
Lyme | Enzyme-linked immunosorbent assay (ELISA) test | 2,5 |
Western blot test | 5 | |
Human immunodeficiency virus (HIV) | HIV antibody test | 2,5 |
Viral load test | 5 | |
Herpes simplex virus (HSV) | HSV antigen test | 2,5 |
HSV culture test | 5 | |
HSV DNA test | 5 | |
Varicella zoster virus (VZV) | VZV antibody test | 2 |
VZV antigen test | ||
Cytomegalovirus (CMV) | CMV antibody test | 2,5 |
CMV antigen test | 5 | |
Hepatitis-C virus (HCV) | HCV antibody test, HCV RNA test | 2 |
Hepatitis-B virus (HBV) | HBV antibody test | 2,5 |
HBV surface antigen test | 5 | |
Leprosy | Skin biopsy | 2,5 |
Nerve biopsy | 5 | |
Bacterial culture | 5 |
Hereditary:
Condition | Tests | References |
---|---|---|
Fabry’s disease | Enzyme assay test for alpha-galactosidase | 12,5 |
Genetic testing for GLA mutations | 5 | |
Mutation in sodium channels (SCN9A, SCN10A, SCN11A) | Genetic testing for specific mutations | 2,5 |
Wilson’s disease | (No specific tests listed under this condition) | 13 |
Ehlers-Danlos syndrome/joint hypermobility syndrome | (No specific tests listed under this condition) | 2,14 |
HSAN (Hereditary Sensory and Autonomic Neuropathy) | Genetic testing | 3 |
Clinical evaluation | ||
Tangier Disease | Blood tests for HDL cholesterol levels | 3 |
Genetic testing | ||
Pompe Disease | Enzyme assay test for acid alpha-glucosidase | 3 |
Genetic testing |
Other causes:
Condition | Tests | References |
---|---|---|
Monoclonal gammopathy | Serum protein electrophoresis (SPEP) | 15,2 |
Immunofixation electrophoresis (IFE) test | ||
Bone marrow biopsy | ||
Fibromyalgia | No specific blood test, diagnosis based on symptoms and medical history | 16 |
Paraneoplastic and cancer related | 2 | |
Amyloidosis (transthyretin or familial (TTR), light chain (AL), secondary/autoimmune (AA)) | Genetic testing for TTR mutations | 2 |
Biopsy to identify amyloid deposits | ||
Degenerative (associated with Parkinson’s disease or multisystem atrophy) | 2 | |
Idiopathic | 1,2 | |
Post viral illness | 11 | |
Vaccine injury | 11 |
Footnotes
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Raasing LRM, Vogels OJM, Veltkamp M, van Swol CFP, Grutters JC. Current View of Diagnosing Small Fiber Neuropathy. J Neuromuscul Dis. 2021;8(2):185-207. doi:10.3233/JND-200490 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11
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Farhad K. Current Diagnosis and Treatment of Painful Small Fiber Neuropathy. Curr Neurol Neurosci Rep. 2019;19(12):103. Published 2019 Nov 26. doi:10.1007/s11910-019-1020-1 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13 ↩14 ↩15 ↩16 ↩17 ↩18 ↩19 ↩20 ↩21 ↩22 ↩23 ↩24 ↩25 ↩26 ↩27 ↩28
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Zeidman LA. Advances in the Management of Small Fiber Neuropathy. Neurol Clin. 2021;39(1):113-131. doi:10.1016/j.ncl.2020.09.006 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13 ↩14 ↩15 ↩16 ↩17 ↩18 ↩19 ↩20
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Alam U, Jeziorska M, Petropoulos IN, et al. Diagnostic Utility of Corneal Confocal Microscopy and Intra-Epidermal Nerve Fibre Density in Diabetic Neuropathy. Vol 12.; 2017. doi:10.1371/journal.pone.0180175 ↩
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Generated by OpenAI’s GPT-4 LLM on [2023-09-17]. Readers should treat insights from this GPT-4 as a guide/suggestion, not a definitive answer. ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13 ↩14 ↩15 ↩16 ↩17 ↩18 ↩19 ↩20 ↩21 ↩22 ↩23 ↩24 ↩25 ↩26 ↩27 ↩28 ↩29 ↩30 ↩31 ↩32 ↩33 ↩34 ↩35 ↩36 ↩37 ↩38 ↩39 ↩40 ↩41 ↩42 ↩43 ↩44 ↩45 ↩46 ↩47 ↩48 ↩49 ↩50 ↩51 ↩52 ↩53 ↩54 ↩55 ↩56 ↩57 ↩58 ↩59 ↩60 ↩61
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Khoshnoodi MA, Truelove S, Burakgazi A, Hoke A, Mammen AL, Polydefkis M. Longitudinal Assessment of Small Fiber Neuropathy: Evidence of a Non-Length- Dependent Distal Axonopathy. Vol 73.; 2016. doi:10. 1001/jamaneurol.2016.0057 ↩
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Zouari HG, Wahab A, Ng Wing Tin S, S`ene D, Lefaucheur JP. The Clinical Features of Painful Small- Fiber Neuropathy Suggesting an Origin Linked to Primary Sjögren’s Syndrome. Pain Pract. 2019;19(4):426-34. doi:10.1111/papr.12763 ↩
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Gøransson LG, Tjensvoll AB, Herigstad A, Mellgren SI, Omdal R. Small-diameter nerve fiber neuropathy in systemic lupus erythematosus. Arch Neurol. 2006;63(3):401-4. doi:10.1001/archneur.63.3.401 ↩
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Devigili G, TugnoliV, Penza P, et al. The Diagnostic Criteria for Small Fibre Neuropathy: From Symptoms to Neuropathology. Vol 131.; 2008. doi:10.1093/brain/awn093 ↩
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Bakkers M, Faber CG, Drent M, et al. Pain and Autonomic Dysfunction in Patients with Sarcoidosis and Small Fibre Neuropathy. Vol 257.; 2010. doi:10.1007/s00415- 010-5664-7 ↩
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Potential causes that have been reported by individuals within a Small Fiber Neuropathy Facebook group . These are anecdotal experiences and have not been scientifically validated. ↩ ↩2 ↩3
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Biegstraaten M, Hollak CEM, Bakkers M, Faber CG, Aerts JMFG, van Schaik IN. Small fiber neuropathy in Fabry disease. Mol Genet Metab. 2012;106(2):135-41. doi:10.1016/j.ymgme.2012.03.010 ↩
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Sturniolo GC, Lazzarini D, Bartolo O, et al. Small fiber peripheral neuropathy in wilson disease: An in vivo documentation by corneal confocal microscopy. Investig Ophthalmol Vis Sci. 2015;56(2):1390-5. doi:10.1167/iovs.14- 15004 ↩
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Cazzato D, Castori M, Lombardi R, et al. Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes. Neurology. 2016;87(2):155-9. doi:10.1212/ WNL.0000000000002847
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Farhad K, Traub R, Ruzhansky KM, Brannagan TH. Causes of neuropathy in patients referred as “idiopathic neuropathy.” Muscle and Nerve. 2016;53(6):856-61. doi:10.1002/mus.24969 ↩
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Lawson VH, et al. Fibromyalgia syndrome and small fiber, early or mild sensory polyneuropathy. Muscle Nerve. 2018; This study confirms the presence of small fiber neuropathy in a subset of patients with fibromayalgia and also shows evidence of early large fiber neuropathy in these patietns. ↩