What is the differential diagnosis and initial management for acute onset peripheral mononeuropathy of the right upper limb?

Acute Onset Peripheral Mononeuropathy of Right Upper Limb: Differential Diagnosis

Primary Differential Diagnosis

The differential diagnosis for acute onset mononeuropathy of the right upper limb includes compressive/entrapment neuropathies (median, ulnar, or radial nerve), inflammatory/vasculitic causes, infectious etiologies, and systemic autoimmune disorders. 1

Compressive/Entrapment Neuropathies

• Median nerve compression (carpal tunnel syndrome or pronator syndrome) presents with numbness and paresthesias in the thumb, index, middle, and radial half of ring finger, with potential thenar weakness 1, 2
• Ulnar nerve compression (cubital tunnel or Guyon's canal) causes numbness in the ulnar 1.5 fingers and hypothenar/interosseous weakness 1
• Radial nerve compression (spiral groove or posterior interosseous syndrome) results in wrist drop and/or finger extension weakness with variable sensory loss over the dorsal first web space 1

Inflammatory/Vasculitic Causes

• Mononeuritis multiplex from vasculitis presents with asymmetric sensory and motor deficits affecting individual nerves, with pain as a prominent feature 3, 4
• Systemic lupus erythematosus can present as isolated mononeuropathy multiplex with asymmetric weakness, sensory loss, and diminished reflexes, requiring evaluation for positive ANA, anti-dsDNA, and low complement levels 4
• Hypersensitivity vasculitis secondary to infectious agents may cause progressive sensory disorder starting in the hands 5

Infectious Etiologies

• Parvovirus B19 infection can cause mononeuropathy multiplex beginning with sensory symptoms in a hand, potentially preceded by purpuric eruption 5
• Hepatitis B virus may cause confluent multiple mononeuropathy through direct viral action on nerves or vasculitis of vasa nervorum 6
• COVID-19 infection has been associated with axonal mononeuropathies as a sequela, even in patients without intensive care stay 7

Other Systemic Causes

• Diabetes mellitus is associated with both mononeuropathies and polyneuropathies, requiring assessment of glycemic control 2
• Sarcoidosis can cause mononeuropathy through granulomatous inflammation 3
• Paraneoplastic syndromes should be considered, particularly in older patients 3

Initial Diagnostic Approach

Clinical Assessment

• Document the specific nerve distribution by identifying the exact pattern of sensory loss and motor weakness (median nerve: thenar weakness and sensory loss in radial 3.5 digits; ulnar nerve: hypothenar and interosseous weakness with ulnar 1.5 digit sensory loss; radial nerve: wrist/finger extension weakness) 1
• Assess for asymmetry and pain characteristics, as inflammatory/vasculitic causes typically present with prominent pain and asymmetric deficits 3
• Evaluate for systemic symptoms including fever, rash, weight loss, or other organ involvement that would suggest vasculitis or autoimmune disease 4, 5

Electrodiagnostic Testing

• Nerve conduction studies and EMG are essential to confirm mononeuropathy, localize the lesion, and differentiate axonal from demyelinating pathology 1, 3
• EMG findings showing asymmetric involvement of multiple individual peripheral nerves suggest mononeuritis multiplex rather than isolated compression 4
• Electrodiagnostic testing helps distinguish between focal compression (localized conduction block) and inflammatory/axonal injury (reduced amplitudes with denervation) 7

Laboratory Evaluation

• Screen for systemic causes with complete blood count, erythrocyte sedimentation rate, C-reactive protein, fasting glucose or HbA1c, thyroid function tests, and vitamin B12 3
• Autoimmune workup should include ANA, anti-dsDNA, complement levels (C3, C4), rheumatoid factor, and ANCA if vasculitis is suspected 4
• Infectious serologies including hepatitis B surface antigen, hepatitis C antibody, HIV, and parvovirus B19 IgM/IgG if clinical context suggests recent infection 5, 6

Imaging

• MRI of the affected limb may show nerve root enhancement or thickening in inflammatory cases, though this is more commonly used for plexopathies or radiculopathies 3
• Plain radiographs or ultrasound can identify structural causes of nerve compression (e.g., fractures, masses, ganglion cysts) 1

Critical Clinical Pitfalls

• Do not assume diabetic neuropathy in patients with diabetes who present with acute, asymmetric mononeuropathy—this pattern warrants investigation for alternative causes including vasculitis 2
• Distinguish acute mononeuropathy from chronic polyneuropathy by recognizing that polyneuropathy presents with distal, symmetric, length-dependent deficits, while mononeuropathy affects individual nerve territories asymmetrically 3, 2
• Consider recent viral illness (COVID-19, parvovirus B19, hepatitis B) as a potential trigger for inflammatory mononeuropathy, even in patients without severe systemic illness 5, 7, 6
• Recognize that sensory symptoms preceding motor deficits is characteristic of inflammatory mononeuropathy multiplex, particularly when starting in the hand 5

Initial Management Considerations

Symptomatic Treatment

• First-line neuropathic pain management includes gabapentin (100-300 mg at bedtime, titrated to 1800-3600 mg/day), pregabalin (150-600 mg/day), or duloxetine (30-60 mg daily) 3, 8
• Tricyclic antidepressants (nortriptyline 10-25 mg at bedtime, titrated to 75-150 mg/day) are alternative options for neuropathic pain 3, 8

Disease-Specific Treatment

• Intravenous immunoglobulin may be effective for inflammatory mononeuropathy multiplex secondary to viral infections or autoimmune causes 5
• Corticosteroids and immunosuppressants are indicated for vasculitic or autoimmune-mediated mononeuropathy multiplex, such as SLE-associated cases 4
• Compressive neuropathies may require conservative management (splinting, activity modification) or surgical decompression depending on severity and electrodiagnostic findings 1