What is the laboratory workup for small fiber neuropathy?

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Last updated: March 21, 2025View editorial policy

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From the Guidelines

The laboratory workup for small fiber neuropathy should include a comprehensive assessment of clinical tests such as pinprick and temperature sensation to assess small-fiber function, as well as lower-extremity reflexes, vibration perception, and 10-g monofilament to assess large-fiber function and protective sensation. This approach is supported by the most recent guidelines from the Diabetes Care journal, which emphasize the importance of annual assessments for diabetic peripheral neuropathy using medical history and simple clinical tests 1.

The assessment of small fiber neuropathy is crucial for identifying potential underlying causes and guiding treatment. According to the guidelines, individuals with type 1 diabetes duration ≥ 5 years and all individuals with type 2 diabetes should be assessed annually for DPN using the medical history and simple clinical tests 1.

In addition to clinical tests, laboratory workup may include comprehensive blood tests to identify potential underlying causes, such as:

  • Complete blood count
  • Comprehensive metabolic panel
  • Hemoglobin A1C
  • Fasting glucose
  • Vitamin B12 levels
  • Thyroid function tests
  • Serum protein electrophoresis with immunofixation
  • Erythrocyte sedimentation rate
  • C-reactive protein
  • Antinuclear antibody
  • Rheumatoid factor
  • Hepatitis B and C serologies
  • HIV testing
  • Lyme disease antibodies

Specific tests for less common causes may also be considered, such as anti-SSA/SSB antibodies for Sjögren's syndrome, angiotensin-converting enzyme for sarcoidosis, and genetic testing for familial amyloidosis or Fabry disease when family history suggests these conditions 1.

It is essential to note that electrophysiological testing or referral to a neurologist is rarely needed, except in situations where the clinical features are atypical or the diagnosis is unclear 1.

By following this approach, healthcare providers can ensure that patients with small fiber neuropathy receive a comprehensive assessment and appropriate treatment, ultimately improving their quality of life and reducing the risk of complications.

From the Research

Laboratory Workup for Small Fiber Neuropathy

The laboratory workup for small fiber neuropathy (SFN) involves several tests to confirm the diagnosis and rule out other conditions. Some of the key tests include:

  • Skin biopsy with intraepidermal nerve fiber density evaluation, which is considered the gold standard diagnostic test for SFN 2, 3, 4
  • Autonomic function testing, which is useful when autonomic symptoms are present 3
  • Quantitative sensory testing, which can be used as a secondary or adjunctive test for SFN 2, 5
  • Corneal confocal imaging, which can be used as a secondary or adjunctive test for SFN 2
  • Screening for associated conditions, such as metabolic, toxic, immune-mediated, or genetic factors, which can help identify the underlying cause of SFN 3, 4

Diagnostic Criteria

The diagnosis of SFN is often based on the Besta Criteria, which include skin biopsy and quantitative sensory testing 5. The ACTTION criteria are also recommended for clinical trials 5.

Laboratory Tests

Laboratory tests, such as serum studies, genetic studies, and immunological markers, may be ordered to rule out other conditions and identify the underlying cause of SFN 6. Fat pad biopsy and nerve biopsy may also be useful in select cases 6. Magnetic resonance imaging and neuromuscular ultrasound have also shown promise in the evaluation of peripheral neuropathy, including SFN 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Small Fiber Neuropathy.

Seminars in neurology, 2019

Research

Small-fiber neuropathy definition, diagnosis, and treatment.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2019

Research

Small fiber neuropathy.

International review of neurobiology, 2024

Research

A Clinician's Approach to Peripheral Neuropathy.

Seminars in neurology, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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