What is the treatment for Mononeuritis multiplex?

Treatment of Mononeuritis Multiplex

Glucocorticoids combined with immunosuppressive therapy are the first-line treatment for mononeuritis multiplex, with cyclophosphamide recommended for severe cases and methotrexate or azathioprine for non-severe presentations.

Underlying Causes and Diagnosis

• Mononeuritis multiplex is a peripheral neuropathy characterized by asymmetric involvement of multiple peripheral nerves, presenting with altered sensation, pain, muscle weakness or atrophy 1

• Common underlying causes include:

  • Systemic vasculitis (ANCA-associated vasculitis, polyarteritis nodosa) 2
  • Systemic lupus erythematosus 3
  • Eosinophilic granulomatosis with polyangiitis (EGPA) 1
  • Non-vasculitic inflammatory processes 4
  • Paraneoplastic syndromes, infections, or as a complication of immunotherapy 5

• Diagnosis should include:

  • Nerve conduction studies (NCS) and electromyography to identify mononeuropathies and differentiate multiple mononeuropathy from polyneuropathy 1
  • CSF analysis when inflammatory demyelinating polyradiculoneuropathy is suspected 1
  • Deep skin biopsy reaching medium-sized vessels when PAN is suspected 1
  • Testing for ANCA when vasculitis is suspected 1, 2

Treatment Approach Based on Severity and Etiology

For Vasculitis-Associated Mononeuritis Multiplex

1. Severe Disease:

   • First-line: High-dose glucocorticoids combined with cyclophosphamide for remission induction 1
   • After achieving remission with cyclophosphamide, transition to maintenance therapy with methotrexate, azathioprine, or mycophenolate mofetil 1
   • Duration of maintenance therapy: approximately 18 months 1

2. Non-Severe Disease:

   • First-line: Glucocorticoids combined with non-cyclophosphamide immunosuppressants (methotrexate, azathioprine, or mycophenolate mofetil) 1
   • For EGPA-associated cases, mepolizumab with glucocorticoids may be considered over other immunosuppressants 1

3. Refractory Cases:

   • Consider switching to cyclophosphamide if not previously used 1
   • Rituximab may be considered, particularly in ANCA-positive cases 1
   • Intravenous immunoglobulin or plasma exchange in severe or treatment-resistant cases 1

For SLE-Associated Mononeuritis Multiplex

• Glucocorticoids alone or with immunosuppressive therapy (60-75% response rate) 1
• Consider intravenous immunoglobulin, plasma exchange, or rituximab in severe cases 1
• Anticoagulation may be considered in antiphospholipid-positive patients not responding to immunosuppressive therapy 1

Adjunctive Therapies

• Physical therapy is recommended for patients with nerve and/or muscle involvement 1
• For patients with deficiency of adenosine deaminase 2 (DADA2), tumor necrosis factor inhibitors are strongly recommended over glucocorticoids alone 1

Treatment Response and Monitoring

• Monitor for clinical improvement in neurological symptoms and function 1
• Follow nerve conduction studies to assess improvement, though parameters may remain unchanged in most (67%) patients over time 1
• Be aware that peripheral neuropathy has been reported to be a significant predictor of damage in SLE 1

Treatment Challenges and Considerations

• Early initiation of therapy is crucial, as delay (>2 weeks) is associated with severe neurological deficits 1
• Non-vasculitic forms of mononeuritis multiplex may be steroid-responsive without requiring additional immunosuppression 4
• Some cases may be resistant to standard therapies, requiring aggressive and prompt treatment 5
• Consider potential complications of COVID-19 vaccination as a rare trigger for mononeuritis multiplex in diagnostic workup 6