Ternary Health
Hypermobility, Dysautonomia & Mast Cell · SFN

Small Fiber Neuropathy

When your symptoms don't fit large-fiber neuropathy testing — normal nerve conduction, normal EMG — that doesn't mean there's nothing wrong. It means the right test hasn't been done.

About SFN

What we mean when we say SFN.

Small Fiber Neuropathy (SFN) is a disorder of the small unmyelinated and thinly myelinated nerve fibers responsible for pain, temperature, and autonomic function. It produces a characteristic clinical picture of burning pain, allodynia, autonomic dysfunction, and sensory disturbance that is not detected on standard nerve conduction studies or EMG.

Diagnosis requires specific testing: skin punch biopsy with intraepidermal nerve fiber density quantification, autonomic reflex screen, and/or quantitative sensory testing. Many providers are unfamiliar with these tests and rely instead on the normal large-fiber studies to rule out neuropathy — which gives a false-negative answer for SFN.

Etiologies are diverse: diabetic, autoimmune (including Sjögren's, celiac, sarcoidosis), post-infectious (including Long COVID), genetic (sodium channel mutations), connective tissue (associated with hEDS), and idiopathic. The etiology determines the management.

Prevalence

True prevalence is unknown and likely substantially underestimated. Estimated at 50+ per 100,000 in some populations; significantly higher among patients with fibromyalgia, POTS, hEDS, and Long COVID.

The path to diagnosis

Why SFN gets missed.

Skin punch biopsy
Diagnostic gold standard
EFNS/PNS clinical guidelines
~40–50%
Of fibromyalgia patients have SFN on biopsy
Small fiber neuropathy in fibromyalgia literature

Small Fiber Neuropathy is missed for one reason: the tests that diagnose it are not the tests that get ordered. Standard EMG and nerve conduction studies evaluate large fibers and will be normal in SFN. Without skin biopsy or autonomic testing, the diagnosis is invisible. Patients are routinely told they have fibromyalgia, anxiety, or 'idiopathic' pain when the underlying SFN is the actual driver.

  1. 01
    Standard neurology workups evaluate large fibers. EMG and nerve conduction studies will be normal in pure SFN — and many patients are told 'your neurology workup was normal, so it's not neuropathy' when in fact the wrong test was performed.
  2. 02
    Skin punch biopsy with intraepidermal nerve fiber density quantification is the diagnostic gold standard, but the test is not part of routine neurology and requires specific labs to process. Autonomic reflex screen is the complementary test for autonomic small fiber involvement. Neither is widely ordered.
  3. 03
    Even when SFN is diagnosed, the etiologic workup — autoimmune, genetic, infectious, metabolic — is often incomplete. The cause of the SFN determines the treatment, and idiopathic SFN should be a diagnosis of exclusion rather than a default label.
  4. 04
    Autoimmune SFN responds to immunomodulatory treatment including IVIG in selected cases. Diabetic and metabolic SFN responds to underlying disease control. Genetic SFN — sodium channel mutations and others — has specific implications. Without etiologic characterization, the treatment is generic.
How we approach it

The Ternary Health approach to Small Fiber Neuropathy.

01

Confirm or rule out SFN through the appropriate testing — skin punch biopsy with IENFD quantification, autonomic reflex screen, and quantitative sensory testing where indicated. If these haven't been done, that's usually the highest-leverage next step.

02

Pursue the etiologic workup systematically — autoimmune panel including Sjögren's and celiac workups, sodium channel and other genetic testing where indicated, metabolic workup including B12 and glucose tolerance, and infectious considerations.

03

Characterize the autonomic component. Autonomic SFN frequently coexists with sensory SFN, drives the cardiovascular and GI symptoms, and responds to specific interventions.

04

Map comorbid conditions — POTS, hEDS, fibromyalgia, Long COVID — that frequently overlap with SFN and that may share the underlying mechanism. The integrated picture changes management.

Signals we look for

The Ternary Signal Library for SFN.

Our Signal Library for Small Fiber Neuropathy codifies the specific patterns that matter — biopsy and autonomic testing findings, etiologic workup, pain and sensory phenotype, and overlap with connective tissue and dysautonomia conditions. Your case is mapped against these signals; each present signal is identified and prioritized for your presentation.

Skin Biopsy & Autonomic Testing
  • Skin punch biopsy with intraepidermal nerve fiber density
  • Biopsy site selection — distal leg, thigh, where comparison performed
  • Autonomic reflex screen — sudomotor, cardiovagal, adrenergic
  • Quantitative sensory testing where performed
  • QSART for sweat-axon function assessment
Etiologic Workup (Autoimmune / Genetic / Metabolic)
  • Autoimmune panel — anti-nuclear, SSA/SSB for Sjögren's, celiac antibodies
  • Sodium channel and other genetic testing where indicated
  • B12, methylmalonic acid, glucose tolerance, HbA1c
  • Heavy metal screening where exposure suspected
  • Infectious workup — Lyme, hepatitis C, HIV, where appropriate
Pain & Sensory Phenotype
  • Distribution pattern — distal versus non-length-dependent
  • Burning, allodynia, and hyperalgesia mapping
  • Sensory threshold testing where performed
  • Pain qualitative descriptors and severity
  • Autonomic symptoms — orthostatic, GI, urinary, sudomotor
Comorbid Connective Tissue & Dysautonomia Patterns
  • POTS criteria and autonomic SFN overlap
  • Hypermobility — Beighton score, connective tissue findings
  • Fibromyalgia overlap and central sensitization markers
  • Long COVID and post-infectious patterns
  • Sarcoidosis and Sjögren's screening if not already pursued
The nine-stage workflow, applied

How a SFN case moves through our workflow.

Our nine-stage workflow is the same for every engagement. What changes per condition is the content at each stage — the records we pull, the signals we apply, the specialists we map, the pathways we evaluate. Below, how your case specifically would move through each stage.

Stage 01 · 0–2
Qualification
Fit screen confirms diagnosed or strongly suspected SFN, access to prior workup, and current symptom and treatment status. Etiologic workup completeness and prior immunomodulatory trials matter for case prioritization.
Stage 02 · 3–7
Intake & data aggregation
Records pull emphasizes skin biopsy report and IENFD data, autonomic testing if performed, prior etiologic workup, and complete medication trial history. Symptom distribution and timeline reconstructed.
Stage 03 · 7–10
Case structuring
Case schema populated. Sensory and autonomic phenotype mapped. Etiologic workup gaps identified. Comorbid POTS, hEDS, fibromyalgia, Long COVID screening initiated.
Stage 04 · 10–14
Signal analysis
The Ternary Signal Library for SFN is applied. Typical case activates 12–18 signals across biopsy, etiologic, phenotype, and comorbidity domains. Each signal evaluated for your specific presentation.
Stage 05 · 14–18
Evidence retrieval
Literature scan emphasizes the EFNS/PNS clinical guidelines, autoimmune SFN and IVIG evidence base, sodium channel SFN genetic research, autonomic SFN literature, and the SFN-in-fibromyalgia and Long COVID research. Condition-specific Evidence Matrix refreshed.
Stage 06 · 18–22
Pathway mapping
Pathway map built across SFN-experienced neurology, autonomic medicine, rheumatology for autoimmune workup, and where indicated genetics and pain medicine. Specialists mapped from our Specialist Graph.
Stage 07 · 22–26
Synthesis & plan construction
Every option weighed against the three questions (Evidence × Personalization × Action), then prioritized and sequenced. Dependencies encoded as a directed graph — etiologic identification informs treatment selection, autoimmune findings inform immunomodulatory consideration, autonomic findings inform comorbid management.
Stage 08 · 26–30
Delivery & calibration
Findings call with attention to etiologic workup completion, immunomodulatory candidacy where indicated, and pain and autonomic management priorities. Your priorities and constraints update the plan before finalization.
Stage 09 · 30–60
Execution support
30 days of asynchronous follow-up through the typical SFN consultation sequence — SFN-experienced neurology, autonomic medicine, rheumatology, and any indicated specialist consultations. Outcomes captured into the Ledger.
Deliverables

What you receive.

  • A written case synthesis covering biopsy findings, etiologic status, and phenotype characterization
  • Integration of biopsy, autonomic testing, etiologic workup, and comorbidity findings into a single view
  • Etiologic workup audit identifying gaps and recommended additional testing
  • Pain and autonomic management framework calibrated to your specific phenotype
  • Immunomodulatory candidacy assessment where autoimmune SFN is identified or suspected
  • Specialist identification for SFN-experienced neurology, autonomic medicine, and indicated etiologic workups
  • A written action plan and follow-up support as you implement it
What a Ternary report adds

What a Precision Deep Dive provides for SFN.

A Ternary Health Precision Deep Dive for small fiber neuropathy evaluates the testing strategy and biopsy approach, characterizes the autonomic component, pursues the etiologic workup (autoimmune, genetic, infectious, metabolic), and synthesizes the pharmacologic and immunomodulatory evidence including IVIG considerations in autoimmune SFN.

See the published sample reports · read the Ternary Method

Frequently coexisting conditions

What we look for alongside SFN.

Patients with Small Fiber Neuropathy frequently present with one or more of the following. Ternary reports evaluate the full picture rather than the condition in isolation.

Common questions — Small Fiber Neuropathy

What prospective Small Fiber Neuropathy clients ask most.

My EMG was normal. Could I still have neuropathy?
Yes — and this is exactly the diagnostic gap that defines SFN. EMG and nerve conduction studies evaluate large myelinated fibers; they will be normal in pure small fiber neuropathy. The test that would diagnose SFN is skin punch biopsy with intraepidermal nerve fiber density, which is a separate procedure entirely. Many patients told 'your nerve studies were normal' have SFN that was never tested for.
Can SFN be reversed?
It depends on the cause. Autoimmune SFN often responds to immunomodulatory treatment including IVIG in selected cases. Diabetic and metabolic SFN improves with underlying disease control. Some idiopathic SFN remains stable; some progresses. The etiologic identification is what determines the trajectory.
Should I be tested for sodium channel mutations?
If you have early-onset, family-history-positive, or distinctive distribution SFN — yes. SCN9A, SCN10A, and SCN11A mutations have been identified in subsets of SFN patients and the testing has become more accessible. The Ternary report evaluates whether genetic workup is appropriate for your case.
Do I need a confirmed diagnosis before applying?
A skin biopsy showing reduced IENFD, or a strongly consistent clinical picture with autonomic findings, is preferred. If you have suspected SFN but no biopsy, we can frame the diagnostic pathway. We do not order tests.
What about IVIG?
Evaluated in cases where autoimmune SFN is suspected or confirmed. The evidence base is uneven but real, the access barriers are substantial (insurance authorization, cost), and the response is highly individual. We assess candidacy and outline the pathway for cases where it's appropriate.
Working through this on your own?

Three ways to engage Ternary on SFN.

From a free starting point to a full personalized action plan — three tiers, one methodology, all tailored to SFN.

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Free Brief

$0

A 3–5 page personalized starting point on your condition. Most relevant labs, specialist categories, first decisions worth pursuing. No charge.

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Launchpad

$400

A research-based preparedness guide. Current literature, realistic prognosis, test and treatment categories worth exploring, and a checklist of what you might consider to better manage and understand your condition.

Delivered in 3–5 business days

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Precision Deep Dive

$6,500

A vigorously researched and highly personalized action plan: the specialists and centers of excellence worth considering, evidence-graded options, and a prioritized set of questions to raise — all curated for your specific condition and lifestyle, for you and your physicians to weigh together. The plan includes 30 days of follow-up support and tailored insights into how best to navigate your situation now and in the future.

September 2026 cohort

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What a Ternary report looks like

See exactly what you receive.

A composite sample illustrating the structure and depth of every Ternary Health Precision Deep Dive. Same universal 17-section format used for SFN — drawn from four research-validated patient profiles across four conditions.

Every Ternary engagement produces a report with the same architecture: client profile, applied methodology, signal analysis, lab and genetic findings, imaging synthesis, disease model, intervention prioritization, specialist pathway, staged medical therapy, 90-day roadmap, and monitoring cadence. The composite shows you exactly how that architecture renders.

Ready for clarity on your SFN?

Applications for the September 2026 cohort are open now and reviewed in the order received. Not ready? A free Ternary Brief on SFN is generated instantly, no charge.