What is the treatment for polyarteritis nodosa?

Treatment for Polyarteritis Nodosa (PAN)

For patients with polyarteritis nodosa, treatment should be stratified based on disease severity, with severe PAN requiring high-dose glucocorticoids plus cyclophosphamide, while non-severe PAN should be treated with glucocorticoids plus non-cyclophosphamide immunosuppressive agents. 1

Disease Classification and Initial Assessment

Disease Severity Assessment

PAN should be classified as either:

• Severe PAN: Life- or organ-threatening manifestations including:

  • Renal disease
  • Mononeuritis multiplex
  • Muscle disease
  • Mesenteric ischemia
  • Coronary involvement
  • Limb/digit ischemia

• Non-severe PAN: Without life- or organ-threatening manifestations:

  • Mild systemic symptoms
  • Uncomplicated cutaneous disease
  • Mild inflammatory arthritis

Diagnostic Workup

• Abdominal vascular imaging: Recommended for suspected PAN to establish diagnosis and determine disease extent 1
• Tissue biopsy:
  • For skin involvement: Deep-skin biopsy (reaching medium-sized vessels of dermis) 1
  • For peripheral neuropathy: Combined nerve and muscle biopsy rather than nerve biopsy alone 1

Treatment Algorithm

1. Severe PAN Treatment

• Initial therapy (induction):

  • IV pulse glucocorticoids (methylprednisolone 500-1000 mg/day for 3-5 days) 1
  • PLUS cyclophosphamide (oral or IV) 1

• If cyclophosphamide cannot be tolerated:

  • Alternative non-glucocorticoid immunosuppressants (azathioprine or methotrexate) with glucocorticoids 1

• Plasmapheresis: Not recommended routinely for non-HBV-associated PAN 1

2. Non-severe PAN Treatment

• Initial therapy:
  • Oral glucocorticoids (prednisone 1 mg/kg/day, up to 80 mg/day)
  • PLUS non-glucocorticoid immunosuppressive agent (azathioprine or methotrexate) 1

3. Maintenance Therapy

• After achieving remission with cyclophosphamide:

  • Transition to another non-glucocorticoid immunosuppressive agent (azathioprine or methotrexate) 1
  • Continue maintenance therapy for approximately 18 months, then consider discontinuation 1

• Glucocorticoid tapering:

  • Optimal duration not well established
  • Taper guided by clinical condition, with longer tapers often preferred by patients 1

4. Treatment of Refractory Disease

• For severe PAN refractory to non-cyclophosphamide immunosuppressants:
  • Switch to cyclophosphamide rather than increasing glucocorticoid dose 1

5. Special Considerations

• DADA2 (Deficiency of Adenosine Deaminase 2):

  • Consider in PAN-like vasculitis with early onset and recurrent strokes
  • Strongly recommended to use TNF inhibitors rather than conventional therapy 1

• Peripheral nerve/muscle involvement:

  • Physical therapy is recommended 1
  • Monitor with serial neurologic examinations rather than repeated electromyography 1

Follow-up Monitoring

• For PAN with abdominal involvement:

  • Follow-up abdominal vascular imaging after clinical remission 1
  • Timing depends on severity of initial vascular abnormalities and response to therapy

• For peripheral neuropathy:

  • Serial neurologic examinations rather than repeated electromyography/nerve conduction studies 1

Important Caveats

1. Cyclophosphamide toxicity: Limit to 3-6 months per course due to toxicity concerns 1

2. Rituximab: Currently insufficient evidence to recommend over cyclophosphamide, despite some promising case reports 1

3. Disease course: While some patients experience relapse, the majority have monophasic disease, making indefinite treatment unnecessary 1

4. Glucocorticoid toxicity: Non-glucocorticoid immunosuppressive agents help minimize cumulative steroid dose and associated toxicity 1

5. Hepatitis B-associated PAN: May require different management approach (not fully addressed in these guidelines) 1