What is the treatment for polyarteritis nodosa?

Treatment of Polyarteritis Nodosa

For patients with newly diagnosed active, severe polyarteritis nodosa (PAN), treatment with cyclophosphamide and high-dose glucocorticoids is strongly recommended over glucocorticoids alone to improve mortality and morbidity outcomes. 1, 2

Disease Classification and Initial Assessment

• PAN is a systemic necrotizing vasculitis primarily affecting medium-sized vessels, presenting with systemic symptoms like fever and weight loss 1
• Common manifestations include neurologic (mononeuritis multiplex, peripheral neuropathy), cutaneous (nodules, livedo reticularis), renal (hypertension), and gastrointestinal (abdominal pain) symptoms 1, 3
• Disease severity assessment is crucial for treatment decisions - severe disease is defined by life- or organ-threatening manifestations such as renal insufficiency and tissue ischemia 2
• Diagnosis is confirmed by tissue biopsy of affected organs or angiography, with typical findings including mixed-cell inflammatory infiltrates and fibrinoid necrosis in vessel walls 1

Treatment Algorithm Based on Disease Severity

Severe PAN Treatment

• Initial therapy: Cyclophosphamide plus high-dose glucocorticoids is the cornerstone of treatment for severe PAN 1, 2
• Consider intravenous pulse glucocorticoids over high-dose oral glucocorticoids for initial treatment of severe disease 2
• Cyclophosphamide therapy should be limited to 3-6 months per course due to toxicity concerns 1
• For patients unable to tolerate cyclophosphamide, use alternative immunosuppressive agents (azathioprine or methotrexate) with glucocorticoids rather than glucocorticoid monotherapy 1
• Plasmapheresis is not routinely recommended in combination with cyclophosphamide and glucocorticoids for non-HBV-associated PAN 1

Non-Severe PAN Treatment

• For newly diagnosed active, non-severe PAN, use non-glucocorticoid immunosuppressive agents (typically azathioprine or methotrexate) plus glucocorticoids rather than glucocorticoids alone 1, 2
• This approach helps minimize glucocorticoid use and subsequent toxicity, particularly important in pediatric populations 1

Maintenance Therapy and Treatment Duration

• After achieving remission with cyclophosphamide, transition to another less toxic immunosuppressive agent such as methotrexate or azathioprine for maintenance therapy 1, 2
• For patients in remission receiving non-glucocorticoid immunosuppressive therapy, discontinue these agents after 18 months rather than continuing indefinitely, provided sustained remission has been achieved 1, 2
• The optimal duration of glucocorticoid therapy is not well established and should be guided by the patient's clinical condition, with a preference for longer tapers to prevent disease flares 1

Management of Refractory Disease

• For severe PAN refractory to initial treatment with glucocorticoids and non-cyclophosphamide immunosuppressive agents, switch to cyclophosphamide rather than increasing glucocorticoids alone 1
• For truly refractory cases, TNF inhibitors (infliximab or etanercept) have shown efficacy in case reports and small series 4, 5
• In patients with clinical manifestations of deficiency of adenosine deaminase 2 (DADA2), TNF inhibitors are strongly recommended over glucocorticoids alone 1, 6

Special Considerations

• For patients with PAN with nerve and/or muscle involvement, physical therapy is recommended for recovery and rehabilitation 1
• For patients with abdominal involvement who become clinically asymptomatic, follow-up abdominal vascular imaging is recommended to assess disease control and treatment response 1, 2
• Serial neurologic examinations are preferred over repeated electromyography/nerve conduction studies for monitoring disease activity in patients with peripheral motor neuropathy 1, 2

Pitfalls and Caveats

• Consider DADA2 in patients with PAN-like syndrome with strokes, as these patients respond better to TNF inhibitors than conventional therapy 1, 2
• Avoid indefinite routine vascular imaging if abdominal vascular disease is shown to be quiescent 2
• Untreated severe PAN has a mortality rate of approximately 40% at 5 years, highlighting the importance of prompt and appropriate treatment 1, 2
• HBV-associated PAN requires a different treatment approach, focusing on antiviral therapy and plasma exchange rather than immunosuppression alone 7, 6