What is the treatment for Polyarteritis Nodosa (PAN)?

Treatment of Polyarteritis Nodosa

For newly diagnosed severe PAN, initiate cyclophosphamide plus high-dose glucocorticoids immediately, as this combination is the standard of care that has been shown to prolong survival in patients with adverse prognostic factors. 1, 2

Initial Disease Severity Assessment

Treatment decisions hinge on whether PAN is classified as severe or non-severe:

• Severe disease includes life- or organ-threatening manifestations such as renal insufficiency, tissue ischemia, cardiac involvement, gastrointestinal ischemia, or central nervous system involvement 2
• Assess for hepatitis B virus (HBV) association, as this fundamentally changes treatment approach 3, 4
• Consider testing for adenosine deaminase 2 (ADA2) deficiency (DADA2) in patients with early-onset disease, recurrent strokes, or PAN-like vasculitis, particularly in pediatric cases 1, 2

Treatment by Disease Severity

Severe PAN (Idiopathic)

Induction therapy:

• Cyclophosphamide plus high-dose glucocorticoids is the cornerstone of treatment 1, 2
• Consider intravenous pulse glucocorticoids over high-dose oral glucocorticoids for initial treatment 2
• Limit cyclophosphamide to 3-6 months per course due to cumulative toxicity 1, 2

Maintenance therapy:

• After achieving remission with cyclophosphamide, transition to methotrexate or azathioprine rather than continuing cyclophosphamide indefinitely 1, 2
• This transition is based on experience from ANCA-associated vasculitis and minimizes long-term cyclophosphamide toxicity 1

Alternative for cyclophosphamide-intolerant patients:

• Use azathioprine or methotrexate plus glucocorticoids rather than glucocorticoid monotherapy 1
• This provides glucocorticoid-sparing effects and is particularly important in pediatric populations 1

Non-Severe PAN

Combination therapy is preferred:

• Use non-glucocorticoid immunosuppressive agents (azathioprine or methotrexate) plus glucocorticoids rather than glucocorticoids alone 1, 2
• This contradicts older Five-Factor Score recommendations that suggested glucocorticoid monotherapy for non-severe disease 1
• The rationale is to minimize glucocorticoid toxicity and improve long-term outcomes 1, 2

Special Clinical Scenarios

HBV-Associated PAN

• Primary treatment is antiviral therapy combined with plasma exchange and short-term corticosteroids, not immunosuppression 3, 4
• This represents a fundamentally different treatment paradigm from idiopathic PAN 3

DADA2 (Adenosine Deaminase 2 Deficiency)

• Strongly recommend TNF inhibitors over glucocorticoids alone for patients with confirmed DADA2 1, 2
• TNF inhibitors prevent recurrent strokes, which are the major cause of morbidity and mortality in DADA2 1
• Consider DADA2 testing in any patient with PAN-like syndrome presenting with strokes, particularly in childhood-onset cases 1, 2

Refractory Disease

• For severe PAN refractory to glucocorticoids and non-cyclophosphamide immunosuppressives, switch to cyclophosphamide rather than escalating glucocorticoid doses 1, 2
• Infliximab (TNF inhibitor) may be considered for refractory cases, with one case series showing 89% significant improvement after 4 months 5

Nerve/Muscle Involvement

• Physical therapy is recommended for patients with peripheral neuropathy or myopathy 1, 2
• This provides rehabilitation benefits with minimal risk 1

Duration of Treatment

Immunosuppressive Therapy

• Discontinue non-glucocorticoid immunosuppressive agents after 18 months of sustained remission rather than continuing indefinitely 1, 2
• The majority of PAN cases are monophasic, though relapses occur in approximately 28% of patients (average 26 months from diagnosis) 4

Glucocorticoid Therapy

• Duration should be individualized based on clinical response, disease activity, and patient preferences 1
• Longer tapers are generally preferred over rapid tapers, as faster tapers in other vasculitides led to more flares 1
• No specific evidence exists to mandate tapering off by 6 months versus longer durations 1

What NOT to Do

Plasmapheresis in Non-HBV PAN

• Do not routinely use plasmapheresis combined with cyclophosphamide and glucocorticoids for non-HBV-associated PAN 1, 2
• Evidence is insufficient, with wide confidence intervals from a single 1995 trial that did not distinguish HBV from non-HBV PAN 1
• May be considered only in catastrophic cases unresponsive to aggressive immunosuppression 1

Glucocorticoid Monotherapy

• Avoid glucocorticoid monotherapy even in non-severe disease, as substantial numbers ultimately require additional immunosuppression 1

Clinical Pitfalls and Monitoring

Key considerations:

• Untreated severe PAN has 40% mortality at 5 years, emphasizing the need for aggressive treatment 2
• Serial neurologic examinations are preferred over repeated EMG/nerve conduction studies for monitoring peripheral neuropathy 2
• For abdominal involvement, obtain follow-up vascular imaging to assess treatment response once clinically asymptomatic, but avoid indefinite routine imaging if disease is quiescent 2
• Current 5-year and 10-year survival rates are 83% and 74% respectively with appropriate treatment 4