What is the treatment for Polyarteritis Nodosa (PAN)?

Treatment for Polyarteritis Nodosa (PAN)

For patients with polyarteritis nodosa (PAN), treatment should be based on disease severity, with cyclophosphamide plus glucocorticoids recommended as first-line therapy for severe disease, while less severe disease may be managed with other immunosuppressive agents plus glucocorticoids.

Disease Classification and Initial Assessment

• PAN is a systemic necrotizing vasculitis that primarily affects medium-sized vessels, presenting with manifestations such as peripheral neuropathy, cutaneous lesions, renal involvement, and gastrointestinal symptoms 1
• Disease severity should be assessed to guide treatment decisions, with severe disease defined by life- or organ-threatening manifestations such as renal insufficiency and tissue ischemia 2

Treatment Recommendations Based on Disease Severity

Severe PAN

• For newly diagnosed active, severe PAN, initiate treatment with cyclophosphamide and high-dose glucocorticoids rather than glucocorticoids alone 2
• Consider intravenous pulse glucocorticoids over high-dose oral glucocorticoids for initial treatment of severe disease 2
• Cyclophosphamide therapy should generally be limited to 3-6 months per course due to toxicity concerns 2
• After achieving remission with cyclophosphamide, transition to another less toxic immunosuppressive agent such as methotrexate or azathioprine for maintenance therapy 2
• For patients unable to tolerate cyclophosphamide, use alternative immunosuppressive agents with glucocorticoids rather than glucocorticoid monotherapy 2

Non-Severe PAN

• For newly diagnosed active, non-severe PAN, use non-glucocorticoid immunosuppressive agents (typically azathioprine or methotrexate) plus glucocorticoids rather than glucocorticoids alone 2
• This approach may help minimize glucocorticoid use and subsequent toxicity 2

Special Considerations

Duration of Therapy

• 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 2
• The optimal duration of glucocorticoid therapy is not well established and should be guided by the patient's clinical condition, values, and preferences 2

Refractory Disease

• For severe PAN refractory to initial treatment with glucocorticoids and non-cyclophosphamide immunosuppressive agents, switch to cyclophosphamide rather than increasing glucocorticoids alone 2
• Plasmapheresis is not routinely recommended in combination with cyclophosphamide and glucocorticoids for non-HBV-associated PAN 2

Specific Clinical Scenarios

• For patients with PAN with nerve and/or muscle involvement, physical therapy is recommended 2
• For patients with clinical manifestations of deficiency of adenosine deaminase 2 (DADA2), tumor necrosis factor inhibitors are strongly recommended over glucocorticoids alone 2
• For patients with abdominal involvement who become clinically asymptomatic, follow-up abdominal vascular imaging is recommended to assess disease control and treatment response 2

Treatment Outcomes and Monitoring

• Untreated PAN carries a poor prognosis, with severe PAN having a mortality rate of 40% at 5 years 2
• Treatment with steroids alone increases 5-year survival to 48%, while addition of cytotoxic immunosuppressive treatment improves outcomes dramatically 3
• Serial neurologic examinations are preferred over repeated electromyography/nerve conduction studies for monitoring disease activity in patients with peripheral motor neuropathy 2

Pitfalls and Caveats

• Distinguish between idiopathic PAN and hepatitis B-related PAN, as treatment approaches differ significantly 4
• HBV-associated PAN primarily requires antiviral therapy combined with plasma exchange, while idiopathic PAN requires immunosuppressive therapy 5
• Avoid indefinite routine vascular imaging if abdominal vascular disease is shown to be quiescent 2
• Be aware that PAN can present with isolated symptoms (such as abdominal pain) that may lead to life-threatening situations if aneurysms rupture 6
• Consider DADA2 in patients with PAN-like syndrome with strokes, as these patients respond better to TNF inhibitors than conventional therapy 2