What is an example of mononeuritis multiplex in an adult patient with a history of systemic diseases such as diabetes or vasculitis?

Examples of Mononeuritis Multiplex

Mononeuritis multiplex is a peripheral neuropathy pattern characterized by asymmetric involvement of multiple individual nerves, with classic examples including polyarteritis nodosa (PAN), eosinophilic granulomatosis with polyangiitis (EGPA), diabetes mellitus, systemic lupus erythematosus (SLE), and hepatitis E virus (HEV) infection. 1

Vasculitis-Associated Examples

Polyarteritis Nodosa (PAN)

• PAN is a prototypical cause of mononeuritis multiplex, classified as a severe, life-threatening manifestation requiring aggressive immunosuppressive therapy. 1
• Presents with asymmetric sensory and motor deficits affecting multiple peripheral nerves in a stepwise, sequential pattern rather than simultaneously 2
• Pain is a prominent feature, particularly in inflammatory or vasculitic causes 2
• The 2021 American College of Rheumatology/Vasculitis Foundation guidelines specifically define mononeuritis multiplex as a severe disease manifestation in PAN, alongside renal disease, muscle disease, mesenteric ischemia, coronary involvement, and limb/digit ischemia 1

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• EGPA is a common underlying cause of mononeuritis multiplex, often presenting with eosinophilia and asthma 3
• The presence of eosinophilia, asthma, or systemic vasculitis features suggests EGPA as the underlying cause 4
• ANCA testing is recommended when vasculitis is suspected 3

Hepatitis E Virus (HEV) Infection

• HEV genotype 3 infection has been documented as causing mononeuritis multiplex, primarily in European cohorts 1
• Approximately 150 cases of HEV-associated neurological injury have been described, with mononeuritis multiplex being one of the recognized patterns 1
• Most cases (>90%) occur in immunocompetent patients, though it also occurs in chronic HEV infection 1

Autoimmune and Systemic Disease Examples

Systemic Lupus Erythematosus (SLE)

• SLE can present with isolated mononeuropathy multiplex as the initial manifestation, characterized by asymmetric weakness, loss of sensation, and diminished reflexes 5
• Laboratory findings typically include positive ANA, anti-dsDNA, low complement levels, and elevated inflammatory markers 5
• Peripheral neuropathy has been reported as a significant predictor of damage in SLE 3

Diabetes Mellitus

• Diabetic mononeuritis multiplex can present as a particularly aggressive form with rapid progression 6
• One documented case involved severe postural hypotension with at least 6 cranial nerves and 4 somatic nerves involved within 4 months 6
• Some aggressive forms may have an immune mechanism and respond to immunosuppressive therapy including corticosteroids, intravenous immunoglobulins, and cyclosporin 6, 7
• A critical pitfall: vasculitic mononeuritis multiplex may initially mimic carpal tunnel syndrome, leading to misdiagnosis and delayed treatment. 8 Patients presenting with median nerve symptoms who fail to respond to carpal tunnel surgery and subsequently develop additional nerve involvement (such as foot drop) should raise suspicion for vasculitic mononeuritis multiplex 8

Emerging and Rare Causes

Immune Checkpoint Inhibitor Therapy

• Mononeuritis multiplex is a rare but severe neurological complication of immune checkpoint inhibitors (ipilimumab, nivolumab) used in cancer treatment 9
• Presents with progressive leg weakness, back pain, and difficulty ambulating 9
• Can be resistant to standard treatments including steroid pulses, chronic steroids, intravenous immunoglobulin, and rituximab 9
• Only two cases had been reported in the literature as of 2022, emphasizing the rarity but severity of this complication 9

Key Diagnostic Features Across All Examples

• Asymmetric sensory and/or motor deficits affecting multiple individual nerves in a non-contiguous distribution 2, 4
• Stepwise pattern where individual nerves become involved sequentially over time 4
• Pain as a prominent feature, particularly in inflammatory or vasculitic causes 2
• Nerve conduction studies show focal abnormalities in multiple individual nerves with asymmetric involvement 4
• Electromyography identifies discrete mononeuropathies affecting specific nerve distributions 4

Critical Clinical Distinction

The distinction between mononeuritis multiplex and symmetric polyneuropathy is crucial because they require fundamentally different treatment approaches. 2 Mononeuritis multiplex often requires immunosuppressive therapy when caused by inflammatory processes 2, while symmetric polyneuropathy management typically focuses on treating the underlying cause and symptom management 2