What is the extended work-up for severe small fiber neuropathy?

From the Guidelines

For severe small fiber neuropathy, an extended work-up should include comprehensive blood tests, autonomic function testing, skin biopsy, and specialized nerve studies, as this comprehensive approach is crucial for identifying the underlying cause and providing targeted treatment. Begin with laboratory tests including complete blood count, comprehensive metabolic panel, hemoglobin A1c, vitamin B12, folate, thyroid function, immunological markers (ANA, RF, anti-SSA/SSB), and screening for hepatitis C, HIV, and monoclonal gammopathies 1. Genetic testing should be considered for hereditary causes like Fabry disease or familial amyloidosis, as early symptoms of Fabry disease often include episodic acroparesthesias and small-fiber involvement in the peripheral nervous system 1. A skin punch biopsy remains the gold standard diagnostic test, typically taken from the distal leg and proximal thigh to evaluate intraepidermal nerve fiber density. Autonomic testing including quantitative sudomotor axon reflex test (QSART), heart rate variability, and tilt table testing can assess autonomic involvement. Quantitative sensory testing helps evaluate thermal and pain thresholds. Consider specialized tests like corneal confocal microscopy or functional MRI in research settings.

Some key points to consider in the work-up and management of severe small fiber neuropathy include:

• The importance of a comprehensive neurological evaluation to assess disease extent and severity, particularly before the institution of any treatment 1
• The use of tools such as the Brief Pain Inventory or the McGill Pain Inventory to assess pain frequency and severity 1
• The potential benefits of a multidisciplinary pain rehabilitation program for patients with refractory small fiber neuropathy and chronic pain syndrome, as seen in the management of erythromelalgia 1
• The need for a tailored approach to management, taking into account the underlying cause of the small fiber neuropathy and the individual patient's symptoms and needs.

In terms of specific management options, a multidisciplinary approach including neurology, pain management, and rehabilitation is often necessary to address the complex needs of patients with severe small fiber neuropathy. This may involve the use of medications such as phenytoin, carbamazepine, or gabapentin to manage pain, as well as lifestyle modifications and behavioral therapies to improve functional and emotional functioning 1.

From the Research

Severe Small Fiber Neuropathy Extended Work-up

• Severe small fiber neuropathy is a condition that affects the sensory Aδ and C fibers, leading to chronic neuropathic pain and autonomic dysfunction 2.
• The diagnosis of small fiber neuropathy can be challenging, but it typically involves a combination of clinical presentation, diagnostic tests, and laboratory examinations 3, 4.
• Diagnostic tests for small fiber neuropathy may include:
  • Epidermal nerve fiber density in a skin biopsy 2, 5
  • Laser-evoked potentials 2
  • Heat- and cold-detection thresholds 2
  • Electrochemical skin conductance 2
  • Quantitative sensory testing 4
• The treatment of small fiber neuropathy depends on the underlying cause and may involve symptomatic, pathophysiologic, or causal measures 3.
• Common causes of small fiber neuropathy include:
  • Metabolic diseases (diabetes mellitus, glucose intolerance) 2
  • Dysimmunity syndromes (Sjögren's syndrome, sarcoidosis, monoclonal gammopathy) 2
  • Genetic abnormalities (familial amyloidosis due to a transthyretin mutation, Fabry disease, sodium channel diseases) 2, 3
  • Vitamin B12 deficiency 6
• A systematic approach to the etiology of small fiber neuropathy is essential for guiding treatment, and may involve a set of laboratory tests and genetic examinations 4.