What causes intense internal burning sensation and pain in hands and fingers, potentially related to underlying conditions such as neuropathy, diabetes, or nutritional deficiencies?

Intense Internal Burning Sensation and Pain in Hands and Fingers

The most likely cause of intense internal burning sensation and pain in the hands and fingers is peripheral neuropathy affecting small nerve fibers, most commonly from diabetic neuropathy, nutritional deficiencies (especially vitamin B12), or other metabolic disorders. 1, 2

Primary Differential Diagnoses to Consider

Diabetic Peripheral Neuropathy

• Burning pain and "electrical shock" sensations are hallmark descriptors of neuropathic pain affecting small nerve fibers, typically presenting in a symmetrical, bilateral pattern in the hands (though feet are usually affected first). 2
• Up to 50% of diabetic peripheral neuropathy may be asymptomatic initially, but when symptomatic, patients describe burning pain, uncomfortable tingling (paresthesias), and altered temperature perceptions. 1
• Pain characteristically worsens at night, often causing severe sleep disturbance and significantly impacting quality of life. 2, 3
• Screen all patients with these symptoms for diabetes mellitus using fasting glucose and HbA1c, as diabetic neuropathy is the most common cause of small fiber neuropathy. 2

Nutritional Deficiencies

• Vitamin B12 deficiency is a critical reversible cause that must be excluded in all patients presenting with burning hand pain. 1
• Thiamine deficiency (particularly in chronic alcohol users) can cause peripheral neuropathy with burning sensations. 4
• Vitamin E deficiency should be measured in patients with associated spinocerebellar symptoms. 4

Complex Regional Pain Syndrome (CRPS)

• CRPS should be considered if the burning pain is excruciating, disproportionate to any inciting injury, and worsens with touch or stimulation. 1, 5
• Unlike typical neuropathy, CRPS pain may start unilaterally but can spread to involve the contralateral limb. 1, 5
• Associated findings include hair loss, tissue changes, skin discoloration, temperature dysregulation, and abnormal sweating patterns. 1, 5
• Three-phase bone scintigraphy has 78% sensitivity and 88% specificity for CRPS diagnosis. 5

Erythromelalgia

• Consider erythromelalgia if burning pain is accompanied by redness and warmth of the hands, typically triggered by heat exposure or dependency. 1
• This rare condition presents with episodic burning pain and erythema, often relieved by cooling (though prolonged cold water immersion should be avoided due to risk of skin ulceration). 1

Other Important Causes

• HIV-associated neuropathy presents with "cold burning pain" in a glove-and-stocking distribution, with prevalence between 13-50% in people living with HIV. 1
• Medication-induced neuropathy from chemotherapy agents or certain antiretrovirals (stavudine, didanosine, zalcitabine). 1
• Chronic renal insufficiency causes metabolic neuropathy that improves with renal transplantation. 4
• Hypothyroidism, multiple myeloma, chronic inflammatory demyelinating neuropathy, and vasculitis must be excluded. 1

Rare but Critical: Burning Hands Syndrome

• If burning hand pain follows trauma (even minor) or is associated with neck pain, consider Burning Hands Syndrome—a variant of central cord syndrome requiring urgent cervical spine imaging. 6, 7
• This represents a spinal cord at risk for further injury and requires prompt recognition despite potentially normal CT findings. 6

Diagnostic Approach

Clinical Examination

• Assess small fiber function: pinprick and temperature sensation. 1
• Assess large fiber function: vibration perception using 128-Hz tuning fork, lower-extremity reflexes. 1
• Assess protective sensation: 10-g monofilament testing. 1
• Peripheral neuropathic pain is invariably symmetrical; asymmetrical symptoms should prompt investigation for alternative etiologies such as CRPS, nerve entrapment, or cervical spine pathology. 2, 3

Essential Laboratory Workup

• Fasting glucose and HbA1c (diabetes screening). 2
• Vitamin B12 level. 1
• Thyroid function tests (TSH). 1
• Renal function (creatinine, eGFR). 4
• Consider HIV testing if risk factors present. 1
• If clinically indicated: serum protein electrophoresis (multiple myeloma), inflammatory markers (vasculitis), vitamin E level. 1, 4

Imaging Considerations

• Standard nerve conduction studies may be completely normal in small fiber neuropathy, as these tests only evaluate large myelinated fibers. 2
• Cervical spine MRI if trauma history, neck pain, or atypical features suggesting Burning Hands Syndrome. 6, 7
• Three-phase bone scintigraphy if CRPS suspected. 5

Treatment Algorithm

Address Underlying Etiology First

• Aggressively optimize glycemic control in diabetic patients (target HbA1c individualized but generally <7%), as this can prevent progression though it does not reverse neuronal loss. 1
• Treat vitamin B12 deficiency with supplementation. 1
• Manage blood pressure and lipids, as treating these modifiable risk factors can aid in prevention of neuropathy progression. 1

First-Line Pharmacologic Treatment for Neuropathic Pain

For diabetic peripheral neuropathy and most other causes of neuropathic burning pain, initiate treatment with pregabalin, duloxetine, or gabapentin. 2, 8

Pregabalin Dosing (FDA-approved for diabetic neuropathy)

• Start at 50 mg three times daily (150 mg/day). 9
• May increase to 100 mg three times daily (300 mg/day) within 1 week based on efficacy and tolerability. 9
• Maximum recommended dose is 300 mg/day; doses above this are not recommended due to dose-dependent adverse reactions without additional benefit. 9
• 38% of patients achieve ≥50% pain reduction at optimal dosing. 2

Gabapentin Dosing

• Start at 300 mg at bedtime, titrate up to 2400 mg daily divided into 3 doses. 1
• Gabapentin and pregabalin have proven efficacy in reducing neuropathic pain. 2, 10

Duloxetine

• Specifically recommended for neuropathic pain, numbness, and tingling. 2
• First-line option particularly if comorbid depression or anxiety (present in over two-thirds of patients with painful neuropathy). 2, 3

Second-Line Pharmacologic Options

If first-line agents fail after 3-4 month trial: 1

• Tricyclic antidepressants: amitriptyline or nortriptyline. 1, 8
• SNRIs: venlafaxine up to 75 mg daily. 1
• Sodium channel blockers: carbamazepine or mexiletine. 1

Topical Therapies

• Compounded amitriptyline-ketamine cream (up to 5% combination) for localized hand involvement. 1
• Topical capsaicin 0.025-0.075% applied 3-4 times daily (though often not helpful in clinical experience and causes initial burning). 1
• Topical lidocaine or diclofenac 1% gel. 1

Special Considerations for Erythromelalgia

If erythromelalgia confirmed: 1

• Step 1: Aspirin 325 mg orally daily for 1-month trial. 1
• Step 2: Gabapentin or pregabalin (as above). 1
• Step 3: SSRI (sertraline preferred) or sodium channel blockers. 1
• Avoid prolonged cold water immersion despite symptomatic relief, as this risks immersion foot, skin ulceration, and infection. 2

CRPS-Specific Management

If CRPS diagnosed: 5

• Physical and occupational therapy are the cornerstone of treatment—all other interventions serve to facilitate participation in rehabilitation. 5
• Gentle stretching, active range of motion exercises, and sensorimotor integration training. 5
• NSAIDs and acetaminophen to enable physical therapy participation. 5
• Oral corticosteroids for inflammation and edema. 5
• Sympathetic nerve blocks (stellate ganglion blocks) for moderate to severe cases with sympathetic dysfunction. 5
• Critical pitfall: Delaying physical therapy while waiting for pain to resolve worsens outcomes through disuse and pain upregulation. 5

Non-Pharmacologic Approaches

• Physical activity and exercise are recommended as adjunctive therapy, with early evidence suggesting protective effects on neuropathy progression. 2
• Cognitive behavioral therapy for patients with refractory pain or chronic pain syndrome. 1, 5
• Transcutaneous electrical nerve stimulation (TENS) is well-tolerated and inexpensive, though benefits are modest. 8

Monitoring and Follow-Up

• Monitor for depression and anxiety, as over two-thirds of patients with painful neuropathy develop these comorbidities, and addressing psychological factors improves overall pain outcomes. 2, 3
• Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common (dizziness, somnolence, peripheral edema, weight gain), and serious adverse effects can occur. 9, 8
• When discontinuing pregabalin or gabapentin, taper gradually over minimum of 1 week to avoid withdrawal symptoms. 9
• Opioids should generally be avoided for chronic neuropathic pain. 8

Common Pitfalls to Avoid

• Failing to screen for reversible causes (vitamin B12 deficiency, hypothyroidism) before attributing symptoms to diabetic neuropathy. 1
• Missing cervical spine pathology in patients with hand burning after trauma. 6, 7
• Prescribing pregabalin doses above 300 mg/day for diabetic neuropathy, which increases adverse effects without additional benefit. 9
• Continuing ineffective medications without objective reassessment of pain scores and functional outcomes. 8
• In CRPS, using sympathetic blocks indefinitely without documented progressive improvement. 5