Small Fiber Neuropathy: Symptoms, Types, Causes and Treatment

Small fiber neuropathy (SFN) is a disorder that affects the small nerve fibers responsible for pain, temperature sensation, and autonomic functions. Though it is common, SFN is often underdiagnosed due to its subtle symptoms and the limitations of routine nerve tests. Understanding the symptoms, types, causes, and treatments of SFN is crucial for both patients and clinicians, as early identification and management can greatly improve quality of life.

Symptoms of Small Fiber Neuropathy

Recognizing the symptoms of small fiber neuropathy is the first step towards diagnosis and effective management. SFN primarily affects the small myelinated Aδ and unmyelinated C fibers, resulting in a range of sensory and autonomic symptoms that can be both distressing and disabling.

Symptom	Description	Frequency/Pattern	Source(s)
Pain	Burning, shooting, or stabbing pain	Often starts in feet/hands	1 3 4 5 7 8 9
Pruritus	Itching, often severe and distressing	Limb/back, evening	3 8
Dysesthesia	Abnormal or unpleasant sensations	Burning, tingling, numbness	3 5 7 9
Autonomic	Cardiovascular, GI, sweating dysfunction	Orthostasis, GI upset	1 4 5 6 9 14

Table 1: Key Symptoms

Sensory Symptoms

The hallmark of SFN is neuropathic pain, often described as burning, stabbing, or shooting. Many patients also report dysesthesia—strange sensations like tingling or numbness. Pruritus, or itching, is a less recognized but common symptom, affecting over two-thirds of patients in some studies, and often occurs along with burning and pain, especially in the evening or at night. These symptoms usually begin in the feet or hands and can progress up the limbs in a "length-dependent" fashion, but non-length-dependent (patchy or focal) patterns also occur 1 3 4 5 7 8 9 10.

Autonomic Symptoms

SFN doesn't just cause pain or sensory issues—it can also disrupt the autonomic nervous system, which controls functions like blood pressure, heart rate, digestion, and sweating. Patients may experience:

• Orthostatic intolerance (feeling faint on standing)
• Palpitations
• Gastrointestinal disturbances (nausea, diarrhea, constipation)
• Urinary problems
• Abnormal sweating (either increased or decreased) 1 4 5 6 9 14

These symptoms can significantly reduce quality of life and may sometimes be more disabling than the pain itself.

Symptom Patterns

SFN can present in several patterns:

• Length-dependent: Most common; symptoms start in the feet and progress upwards.
• Non-length-dependent: Patchy, multifocal, or proximal onset; more common in autoimmune or sarcoidosis-associated SFN.
• Acute or chronic onset: Some cases develop suddenly, while others progress slowly over years 10 14.

Types of Small Fiber Neuropathy

SFN is not a single disease but a spectrum of disorders with varied presentations and underlying mechanisms. Understanding the types helps tailor diagnosis and management.

Type	Clinical Pattern	Key Feature	Source(s)
Sensory SFN	Sensory symptoms only	Pain, burning, dysesthesia	1 4 5 9
Autonomic SFN	Autonomic symptoms predominate	Dysautonomia (CV, GI, sweat)	4 5 6 9 14
Mixed SFN	Both sensory & autonomic	Combination of above	1 4 5 6 9
Acute/Chronic	Time course	Sudden or slow onset	10 14

Table 2: Types of Small Fiber Neuropathy

Sensory Small Fiber Neuropathy

This is the most common type, dominated by sensory symptoms—primarily pain, burning, tingling, or numbness. Patients may have minimal or no autonomic complaints. Sensory SFN often follows a length-dependent pattern, starting in the feet and progressing upwards ("stocking-glove" distribution) 1 4 5 9.

Autonomic Small Fiber Neuropathy

Some cases present mainly with autonomic dysfunction—problems with blood pressure control, heart rate, gastrointestinal motility, or sweating. These cases may have little or no pain, making diagnosis more challenging. Autonomic involvement can be subclinical or significant, sometimes leading to dangerous complications (e.g., severe orthostatic hypotension) 4 5 6 9 14.

Mixed Sensory and Autonomic SFN

Many patients have both sensory and autonomic symptoms. The balance between these varies by individual and underlying cause 1 4 5 6 9.

Acute vs. Chronic and Focal vs. Diffuse

• Acute SFN may develop rapidly, sometimes following infections or autoimmune triggers.
• Chronic SFN progresses slowly over months to years, often without an obvious cause.
• Focal or Multifocal SFN refers to patchy or asymmetric involvement, which may suggest specific causes like sarcoidosis or vasculitis 10 14.

Causes of Small Fiber Neuropathy

There are many potential causes of SFN, but in about half of cases, the cause remains unidentified (idiopathic). Identifying an underlying etiology can guide specific treatment.

Cause Category	Examples/Details	Frequency	Source(s)
Metabolic	Diabetes, pre-diabetes, impaired glucose tolerance	Most common	1 5 6 7 8 9
Immune-mediated	Sarcoidosis, Sjögren’s, lupus, celiac, vasculitis	Common, often overlooked	1 8 9 10 14
Genetic	Sodium channelopathies, Fabry, amyloidosis	Rare but important	8 9 10
Toxic	Chemotherapy, alcohol, HIV, drugs	Variable	6 7 8 13
Idiopathic	No identifiable cause	Up to 50%	1 5 9 10

Table 3: SFN Causes

Metabolic and Endocrine Causes

Diabetes mellitus is the leading known cause of SFN worldwide, including both type 1 and type 2 diabetes, as well as prediabetes. Impaired glucose metabolism can damage small nerve fibers before large fibers are affected, making SFN an early manifestation of diabetic neuropathy 1 5 6 7 8 9.

Immune-Mediated and Inflammatory

Autoimmune mechanisms are increasingly recognized. Diseases like sarcoidosis, Sjögren’s syndrome, systemic lupus erythematosus, celiac disease, and vasculitis can all cause SFN. In sarcoidosis, SFN is common and can be severe, often appearing within a few years of the systemic disease 1 8 9 10 14.

Genetic and Familial

Genetic forms of SFN, though rare, are important to recognize. Sodium channel gene mutations (Nav1.7, Nav1.8, Nav1.9) are increasingly identified, and other hereditary neuropathies (e.g., Fabry disease, amyloidosis) can also present as SFN, especially in young patients or those with a family history 8 9 10.

Toxic and Infectious

Exposure to toxins (chemotherapy, alcohol, certain medications) or infections (HIV, hepatitis) can injure small fibers. These causes are sometimes reversible if identified early 6 7 8 13.

Idiopathic

Despite extensive testing, no cause is found in up to half of patients—these are termed idiopathic SFN. Ongoing research continues to uncover new etiologies 1 5 9 10.

Treatment of Small Fiber Neuropathy

Managing SFN requires a multi-faceted approach, tailored to the individual and the underlying cause when possible. Because there is no universal cure, symptom control—especially of pain—and improving quality of life are central goals.

Treatment Type	Main Strategies/Medications	Notes/Effectiveness	Source(s)
Treat Underlying	Manage diabetes, autoimmune, etc.	Essential if possible	5 7 8 16
Neuropathic Pain	Antidepressants, anticonvulsants, topical agents	First-line for pain	5 12 16
Immunotherapy	IVIG, steroids, anti-TNF	For immune-mediated SFN	8 14 15
Novel Therapies	ARA 290, GDNF receptor agonists	Clinical trials, experimental	2 13 16
Non-Pharmacologic	Physical therapy, psychological	Adjuncts, improve function	12 16

Table 4: SFN Treatments

Treating the Underlying Cause

The first step is identifying and treating any reversible cause:

• Diabetes: Tight glycemic control can slow progression and sometimes improve symptoms.
• Autoimmune SFN: Immunosuppressive drugs (steroids, IVIG, anti-TNF) may be considered, especially in sarcoidosis or other clear autoimmune cases 5 7 8 14 16.
• Toxic/infectious: Removing the offending agent (e.g., stopping a drug, treating HIV) can help recovery 6 7 8 13.

Neuropathic Pain Management

For most patients, especially those with idiopathic SFN, controlling pain is key.

• First-line drugs:
  • Antidepressants (e.g., duloxetine, amitriptyline)
  • Anticonvulsants (e.g., gabapentin, pregabalin)
  • Topical therapies (e.g., capsaicin cream, lidocaine patches)
• Second-line: Tramadol, tapentadol, and in select cases, opioids—though these have risks 5 12 16.

No single medication works for all, and combinations are often tried to balance efficacy and side effects.

Immunotherapy

In select immune-mediated cases, IVIG, corticosteroids, or anti-TNF agents have shown benefit, particularly in sarcoidosis-associated SFN. However, results are mixed, and not all patients respond 8 14 15.

• For idiopathic SFN, IVIG has not consistently shown benefit for pain in clinical trials 15.

Emerging and Experimental Therapies

• ARA 290: A peptide shown to reduce neuropathic pain in sarcoidosis-SFN in small trials 2.
• Neurotrophic factors: Topical agents that modulate GDNF receptor signaling are in early research stages 13.
• Other immunomodulators: Under investigation for autoimmune SFN 8 16.

Non-Pharmacologic Approaches

• Physical therapy: Maintains mobility, reduces falls.
• Psychological support: Addresses chronic pain’s mental health impact.
• Lifestyle adjustments: Skin care, fall prevention, regular mild exercise 12 16.

Multimodal and Individualized Care

Successful management often requires a blend of therapies, personalized to the patient’s symptoms, comorbidities, and preferences. Ongoing follow-up is important to adjust treatment as needed.

Conclusion

Small fiber neuropathy is a complex, multifaceted disorder that can significantly impair quality of life. While it most often presents with burning pain and sensory disturbances, it can also involve the autonomic nervous system, leading to a wide range of symptoms.

Key takeaways:

• Symptoms: Include pain, burning, itching, dysesthesia, and autonomic dysfunction (e.g., orthostasis, GI issues) 1 3 4 5 7 8 9 14.
• Types: Sensory, autonomic, and mixed forms exist, with varying clinical patterns 1 4 5 6 9.
• Causes: Diabetes is the most common; others include autoimmune, genetic, toxic, and idiopathic origins 1 5 6 7 8 9 10 14.
• Treatment: Focuses on treating any underlying condition, managing neuropathic pain with medications, considering immunotherapy in select cases, and combining with non-pharmacologic strategies 2 5 8 12 13 14 15 16.

Ongoing research is expanding our understanding of SFN, promising more targeted and effective therapies in the future. Early recognition and a personalized, compassionate approach remain the cornerstones of care.