What are the signs, symptoms, diagnosis, and management of polyarteritis nodosa (PAN)?

Polyarteritis Nodosa: Signs/Symptoms, Diagnosis, and Management

Clinical Manifestations

Polyarteritis nodosa presents with constitutional symptoms and multisystem involvement reflecting necrotizing inflammation of medium-sized arteries, most critically affecting the gastrointestinal tract, peripheral nerves, kidneys, and skin. 1

Constitutional and Systemic Features

• Fever and weight loss are common presenting symptoms 1
• Myalgias and generalized weakness frequently occur 2
• The disease spares the lungs, which helps distinguish PAN from other vasculitides 2

Organ-Specific Manifestations

Severe disease includes life- or organ-threatening manifestations 3:

• Mononeuritis multiplex affecting peripheral motor and sensory nerves 3, 1
• Mesenteric ischemia with abdominal pain, potentially leading to bowel infarction 1, 4
• Renal insufficiency from vascular involvement (not glomerulonephritis) 1
• Limb or digit ischemia, which can progress to critical limb ischemia requiring amputation 2
• Coronary artery involvement 3

Nonsevere disease includes 3:

• Skin nodules and livedo reticularis as cutaneous manifestations 1
• Mild systemic symptoms 3
• Uncomplicated cutaneous disease 3
• Mild inflammatory arthritis 3

Diagnostic Approach

Laboratory and Serologic Testing

• Negative ANCA (antineutrophil cytoplasmic antibodies) helps differentiate PAN from microscopic polyangiitis and other ANCA-associated vasculitides 2
• Test for hepatitis B virus, as HBV-associated PAN requires different management with antiviral therapy 4, 5
• Consider testing for adenosine deaminase 2 deficiency (DADA2) in childhood-onset or familial cases, as this requires TNF inhibitor therapy rather than standard immunosuppression 6, 7

Vascular Imaging

For suspected PAN, obtain abdominal vascular imaging (CT angiography, MR angiography, or conventional angiography) to establish diagnosis and determine disease extent. 3, 1

• Angiography reveals saccular or fusiform aneurysms and stenotic lesions in mesenteric, hepatic, and renal arteries 1, 4
• Microaneurysms at vessel bifurcations are characteristic 8
• Follow-up abdominal vascular imaging is recommended for patients with severe PAN and abdominal involvement who become clinically asymptomatic 3

Tissue Biopsy

When skin involvement is suspected, obtain a deep-skin biopsy reaching medium-sized vessels of the dermis rather than a superficial punch biopsy. 3, 1

• Look for necrotizing vasculitis of medium-sized vessels with mixed inflammatory infiltrates and fibrinoid necrosis 4
• Absence of IgA deposition distinguishes PAN from Henoch-Schönlein purpura 4
• Absence of granulomas or giant cells distinguishes PAN from granulomatous vasculitides 4

For suspected PAN with peripheral neuropathy, obtain a combined nerve and muscle biopsy rather than nerve biopsy alone to increase diagnostic yield. 3, 4

Management

Severe Disease (Life- or Organ-Threatening)

For newly diagnosed active, severe PAN, initiate treatment with cyclophosphamide and high-dose glucocorticoids rather than glucocorticoids alone. 3, 1

Initial glucocorticoid regimen:

• IV pulse methylprednisolone 500-1,000 mg/day for adults (or 30 mg/kg/day for children, maximum 1,000 mg/day) for 3-5 days is preferred over high-dose oral glucocorticoids 3, 1
• Follow with high-dose oral prednisone 1 mg/kg/day (adults, generally up to 80 mg/day) or 1-2 mg/kg/day (children, up to 60 mg/day) 3

Cyclophosphamide is preferred over rituximab for severe PAN 3

For patients unable to tolerate cyclophosphamide, use other non-glucocorticoid immunosuppressive agents (azathioprine, methotrexate, mycophenolate mofetil) with glucocorticoids rather than glucocorticoids alone 3

Plasmapheresis is NOT recommended in combination with cyclophosphamide and glucocorticoids 3

Nonsevere Disease

For newly diagnosed active, nonsevere PAN, treat with non-glucocorticoid immunosuppressive agents and glucocorticoids rather than glucocorticoids alone. 3

Remission Maintenance

After achieving remission with cyclophosphamide, transition to a less toxic immunosuppressive agent such as methotrexate or azathioprine for maintenance therapy. 1

Monitoring Disease Activity

For patients with peripheral motor neuropathy secondary to PAN, perform serial neurologic examinations rather than repeated electromyography/nerve conduction studies every 6 months to monitor disease activity. 3, 1

Critical Pitfalls

• Do not miss DADA2 in early-onset or familial cases, as TNF inhibitors are the treatment of choice rather than standard immunosuppression 6, 7
• Test for hepatitis B before initiating immunosuppression, as HBV-associated PAN requires concurrent antiviral therapy 4, 5
• Avoid superficial skin biopsies when PAN is suspected—they miss medium-sized vessel involvement 3, 4
• Recognize that untreated severe PAN has approximately 40% mortality at 5 years, but current treatment regimens achieve >80% 5-year survival 1, 6