Can Fibromyalgia Be Diagnosed in Patients with Well-Documented Small Fiber Neuropathy?
Yes, fibromyalgia and small fiber neuropathy can coexist as distinct diagnoses, but when small fiber neuropathy is well-documented, it should be considered the primary diagnosis explaining the patient's symptoms, and the fibromyalgia diagnosis should be reconsidered or viewed as secondary.
The Diagnostic Relationship
The relationship between these two conditions is complex and evolving:
Small fiber neuropathy has been identified in approximately 30-50% of patients previously diagnosed with fibromyalgia, suggesting that what was labeled as fibromyalgia may actually represent undiagnosed small fiber neuropathy in a substantial subset of patients 1, 2.
When small fiber neuropathy is definitively diagnosed through skin biopsy showing reduced intraepidermal nerve fiber density (IENFD ≤8.8 fibers/mm at the ankle), this provides an objective pathological finding that fibromyalgia lacks 3, 4.
The most recent large study (2025) found that SFN was actually infrequent in FM patients when rigorously tested, with only 1 of 46 patients meeting diagnostic criteria for SFN 5. This suggests that while overlap exists, it is less common than earlier smaller studies suggested.
Clinical Approach When Small Fiber Neuropathy Is Documented
Prioritize the Objective Diagnosis
Small fiber neuropathy represents a definable pathological entity with structural nerve damage, whereas fibromyalgia remains a clinical syndrome without specific pathological findings 1.
Identifying small fiber neuropathy provides patients with a succinct diagnosis and increases treatment options by allowing investigation of underlying etiologies such as diabetes, autoimmune conditions, amyloidosis, or other metabolic causes 1, 3.
Investigate the Underlying Cause
When small fiber neuropathy is confirmed, pursue etiological workup:
- Metabolic screening including fasting glucose, HbA1c, and oral glucose tolerance test 4
- Autoimmune markers including anti-Sjögren antibodies (SSA/SSB) and serum protein electrophoresis 4
- Additional serologies including vitamin B12, thyroid function, hepatitis B/C, and HIV 4
- Consider amyloidosis screening (particularly ATTRwt) if the patient has upper extremity involvement, rapid progression, prominent autonomic symptoms, or prior carpal tunnel syndrome 4
Treatment Implications
- For diabetic small fiber neuropathy, optimize glycemic control immediately as the primary disease-modifying intervention 3
- First-line pharmacologic agents remain pregabalin, duloxetine, or gabapentin for neuropathic pain regardless of whether the label is fibromyalgia or small fiber neuropathy 3
- For sarcoidosis-related small fiber neuropathy, consider intravenous immunoglobulin (IVIg) alone or with anti-TNF therapy, with 75% of patients deriving symptomatic benefit 3
Important Caveats
Symptom Overlap Does Not Equal Disease Overlap
Recent rigorous testing shows that symptom questionnaires suggesting neuropathic pain (m-NPSI >58, PainDETECT >18) were positive in 32-43 of 46 FM patients, but only 1 actually had confirmed SFN 5. This demonstrates that neuropathic-type symptoms are common in fibromyalgia but do not indicate actual nerve pathology.
Neuropathic pain symptom scores were actually higher in fibromyalgia patients than in patients with confirmed neuropathy, suggesting these questionnaires lack specificity in this population 5.
Diagnostic Testing Pitfalls
Never rely solely on nerve conduction studies, as these only assess large fiber function and will be normal in small fiber neuropathy 3, 4.
Skin biopsy with IENFD assessment is the gold standard for diagnosing small fiber neuropathy, with sensitivity of 77.2-88% and specificity of 79.6-88.8% 3, 4.
Quantitative sudomotor axon reflex test (QSART) complements skin biopsy and documents small fiber dysfunction with high sensitivity 3, 4.
Practical Algorithm
When evaluating a patient with suspected fibromyalgia:
If clinical features suggest small fiber neuropathy (burning pain, temperature sensation abnormalities, autonomic dysfunction), perform skin biopsy with IENFD assessment and QSART 3, 4.
If IENFD is reduced (≤8.8 fibers/mm at ankle), diagnose small fiber neuropathy and pursue etiological workup 3, 4.
If small fiber neuropathy is confirmed, this becomes the primary diagnosis; the fibromyalgia label should be reconsidered as it may represent a misdiagnosis 1.
If testing is negative for small fiber neuropathy despite neuropathic symptoms, fibromyalgia remains the appropriate diagnosis 5.
Avoid using excessive cooling of extremities for pain relief, as this worsens tissue damage in small fiber neuropathy and can lead to ulcerations 3.