What diagnostic tests are recommended to confirm small fibre neuropathy in an outpatient setting?

Diagnostic Tests for Small Fiber Neuropathy in Outpatient Setting

Skin biopsy with intraepidermal nerve fiber (IENF) density assessment using PGP 9.5 immunohistochemistry is the recommended first-line diagnostic test to confirm small fiber neuropathy in an outpatient setting. 1

Primary Diagnostic Tests

1. Skin Biopsy with IENF Density Assessment

• Gold standard test for small fiber neuropathy diagnosis
• Provides direct visualization of small nerve fiber damage
• Sensitivity: 80-90%, Specificity: 72-90% 1
• Typically taken from distal leg (10 cm above lateral malleolus)
• Requires specialized processing with PGP 9.5 immunohistochemistry
• Particularly valuable when clinical symptoms suggest small fiber involvement but conventional tests are normal

2. Quantitative Sensory Testing (QST)

• Assesses thermal and pain thresholds which reflect small fiber function
• Tests include:
  • Warm and cold detection thresholds
  • Heat and cold pain thresholds
  • Mechanical pain sensitivity
• Less specific than skin biopsy but non-invasive
• Should be interpreted alongside clinical findings due to subjective nature

3. Autonomic Function Tests

• Quantitative Sudomotor Axon Reflex Test (QSART)
  • Evaluates postganglionic sympathetic sudomotor function
  • Sensitivity: 73-80%, Specificity: 93-94% 1
  • Particularly useful when autonomic symptoms are present
• Other autonomic tests:
  • Heart rate variability
  • Orthostatic blood pressure measurements
  • Cardiovascular reflex tests

Clinical Assessment

Before specialized testing, perform targeted clinical evaluation:

• Small fiber sensory assessment:
  • Pinprick sensation
  • Temperature perception (warm/cold)
  • Pain quality (burning, shooting, lancinating)
• Distribution pattern: Typically "glove and stocking" distribution
• Autonomic symptoms: Postural hypotension, abnormal sweating, gastrointestinal disturbances, bladder dysfunction
• Rule out large fiber involvement: Normal strength, reflexes, proprioception, and vibration sense suggest isolated small fiber neuropathy

Diagnostic Algorithm

1. Initial clinical suspicion based on symptoms (burning pain, paresthesias, autonomic symptoms)
2. Exclude large fiber neuropathy with normal nerve conduction studies
3. Perform skin biopsy with IENF density assessment as primary diagnostic test
4. Consider QST and autonomic testing as complementary tests
5. Rule out underlying causes with targeted laboratory testing based on clinical suspicion

Important Considerations

• Normal nerve conduction studies with abnormal small fiber tests are characteristic of isolated small fiber neuropathy 2
• Up to 50% of small fiber neuropathies may be idiopathic 2
• Small fiber neuropathy can be an early manifestation of conditions that later affect large fibers
• Patients with suspected neuropathic pruritus should have skin biopsy if small fiber neuropathy is suspected 1
• In diabetic patients, screening for small fiber neuropathy should begin at diagnosis of type 2 diabetes or 5 years after diagnosis of type 1 diabetes 1

Common Pitfalls to Avoid

• Relying solely on clinical symptoms without objective confirmation
• Misdiagnosing as fibromyalgia (which can coexist but requires different management) 3
• Overlooking potentially treatable underlying causes
• Delaying diagnosis due to normal conventional nerve conduction studies
• Failing to recognize autonomic symptoms as part of the small fiber neuropathy spectrum

Early diagnosis with appropriate testing is crucial for identifying potentially treatable causes and preventing progression of small fiber neuropathy, which can significantly impact quality of life through pain and autonomic dysfunction 4, 5, 6.