What is the treatment approach for a patient diagnosed with polyarteritis nodosa?

Treatment of Polyarteritis Nodosa

For newly diagnosed severe PAN, initiate combination therapy with cyclophosphamide and high-dose glucocorticoids immediately, preferably using IV pulse glucocorticoids rather than oral formulations. 1

Disease Severity Assessment

First, classify disease severity to guide treatment intensity:

• Severe disease includes life- or organ-threatening manifestations: renal disease, mononeuritis multiplex, muscle disease, mesenteric ischemia, coronary involvement, or limb/digit ischemia 1
• Non-severe disease includes mild systemic symptoms, uncomplicated cutaneous disease, or mild inflammatory arthritis without organ-threatening features 1

Initial Treatment by Disease Severity

Severe PAN

Initiate cyclophosphamide plus high-dose glucocorticoids over glucocorticoids alone to reduce mortality and preserve organ function 1

Glucocorticoid dosing:

• IV pulse glucocorticoids are preferred: methylprednisolone 500-1,000 mg/day for adults (or 30 mg/kg/day for children, maximum 1,000 mg/day) for 3-5 days 1
• Alternatively, high-dose oral prednisone 1 mg/kg/day (generally up to 80 mg/day in adults) can be used, though IV pulse is conditionally preferred 1

Cyclophosphamide is preferred over rituximab for initial treatment of severe PAN 1

Important caveat: Do NOT add plasmapheresis to cyclophosphamide and glucocorticoids in idiopathic (non-HBV) PAN, as there is no added benefit 1, 2

For patients unable to tolerate cyclophosphamide: Use alternative non-glucocorticoid immunosuppressive agents (azathioprine, methotrexate, or mycophenolate mofetil) combined with glucocorticoids rather than glucocorticoids alone 1

Non-Severe PAN

Use non-glucocorticoid immunosuppressive agents (typically methotrexate or azathioprine) plus glucocorticoids rather than glucocorticoids alone to minimize glucocorticoid toxicity while achieving disease control 1, 3

Maintenance Therapy and Duration

After achieving remission with cyclophosphamide, transition to a less toxic immunosuppressive agent (methotrexate or azathioprine) rather than continuing cyclophosphamide indefinitely 1, 3

Duration of non-glucocorticoid immunosuppression:

• Discontinue after 18 months of total therapy (including induction and maintenance) in patients who achieve sustained remission 1, 3
• This approach balances efficacy against cumulative toxicity 3

Glucocorticoid tapering:

• The optimal duration is not well-established and should be guided by clinical response and disease activity 1
• Taper gradually based on absence of active disease manifestations 3

Refractory Disease Management

For severe PAN refractory to glucocorticoids and non-cyclophosphamide immunosuppressive agents, switch to cyclophosphamide rather than simply increasing glucocorticoid doses 1, 3

Special Populations and Scenarios

Deficiency of Adenosine Deaminase 2 (DADA2)

For patients with clinical manifestations of DADA2 (a PAN-like syndrome often with strokes), strongly recommend tumor necrosis factor inhibitors over glucocorticoids alone 1, 3

This represents a critical diagnostic consideration, as DADA2 patients respond better to TNF inhibitors than conventional PAN therapy 3

Hepatitis B Virus-Associated PAN

Use a 2-week course of corticosteroids combined with plasma exchanges and antiviral agents rather than the standard immunosuppressive approach used for idiopathic PAN 4, 5

This distinct approach addresses the viral trigger while managing acute inflammation 4

Nerve and Muscle Involvement

Physical therapy is conditionally recommended for patients with nerve and/or muscle involvement to optimize functional recovery 1, 3

Monitoring and Follow-up

For patients with peripheral motor neuropathy, use serial neurologic examinations rather than repeated electromyography/nerve conduction studies every 6 months to monitor disease activity 1

For patients with abdominal involvement who become clinically asymptomatic, obtain follow-up abdominal vascular imaging to assess disease control and treatment response 1, 3

Critical Pitfalls to Avoid

• Do not use glucocorticoid monotherapy for severe disease – the combination with cyclophosphamide significantly improves outcomes, as untreated severe PAN has a 40% mortality rate at 5 years 3, 2
• Do not continue cyclophosphamide indefinitely – limit to 3-6 months per course due to cumulative toxicity, then transition to safer agents 3
• Do not add plasmapheresis routinely to cyclophosphamide and glucocorticoids in non-HBV PAN 1
• Consider DADA2 in atypical presentations (especially with strokes), as these patients require TNF inhibitors rather than conventional therapy 3