What are the diagnostic criteria and treatment options for Polyarteritis nodosa (PAN)?

Diagnosis and Treatment of Polyarteritis Nodosa (PAN)

For diagnosing Polyarteritis nodosa, a combination of clinical features, vascular imaging, and tissue biopsy is required, with treatment varying based on disease severity, ranging from glucocorticoids alone for mild cases to combination therapy with cyclophosphamide for severe disease. 1

Diagnostic Criteria for PAN

Clinical Definition

PAN is characterized by necrotizing inflammation of medium-sized vessels, with several key clinical features:

• Systemic symptoms: Fever, weight loss, fatigue
• Organ-specific manifestations:
  • Peripheral neuropathy (50-75% of patients, often earliest symptom) 2
  • Skin lesions (livedo reticularis, nodules, ulcers)
  • Hypertension
  • Abdominal pain (mesenteric ischemia)
  • Renal involvement
  • Myalgia and arthralgia

Diagnostic Approach

1. Clinical Assessment

   • Identify signs and symptoms consistent with PAN
   • Rule out other conditions with similar presentations

2. Laboratory Testing

   • Elevated inflammatory markers (ESR, CRP)
   • Absence of ANCA (distinguishes from microscopic polyangiitis)
   • Hepatitis B serology (HBV-associated PAN)

3. Imaging Studies

   • Abdominal vascular imaging is conditionally recommended to aid diagnosis 1
   • Options include:
     • Conventional catheter-based angiography (gold standard)
     • CT angiography
     • MR angiography
   • Characteristic findings: saccular or fusiform aneurysms, stenotic lesions in medium-sized vessels 3

4. Tissue Biopsy

   • For suspected skin involvement: Deep-skin biopsy (reaching medium-sized vessels) is recommended over superficial punch biopsy 1
   • For peripheral neuropathy: Combined nerve and muscle biopsy is recommended over nerve biopsy alone 1
   • Histopathology shows necrotizing inflammation of medium-sized arteries

Diagnostic Criteria

While no universally accepted criteria exist for adult PAN, diagnosis typically requires:

• Characteristic clinical features
• Supportive laboratory findings
• Positive imaging or histopathology
• Exclusion of other vasculitides

Treatment of PAN

Treatment approach depends on disease severity:

1. Severe Disease

(Life- or organ-threatening manifestations: renal disease, mononeuritis multiplex, mesenteric ischemia, coronary involvement, limb/digit ischemia)

• First-line therapy:

  • IV pulse glucocorticoids (methylprednisolone 500-1000 mg/day for 3-5 days) followed by high-dose oral glucocorticoids 1
  • PLUS cyclophosphamide (conditionally recommended over glucocorticoids alone) 1

• For patients unable to tolerate cyclophosphamide:

  • Other non-glucocorticoid immunosuppressive agents with glucocorticoids 1

• Not recommended:

  • Plasmapheresis combined with cyclophosphamide and glucocorticoids (no added benefit over cyclophosphamide and glucocorticoids alone) 1
  • Rituximab (cyclophosphamide preferred) 1

2. Non-Severe Disease

(Mild systemic symptoms, uncomplicated cutaneous disease, mild inflammatory arthritis)

• Recommended therapy:
  • Non-glucocorticoid immunosuppressive agents (e.g., methotrexate or azathioprine) with glucocorticoids 1

3. Maintenance Therapy

• After achieving remission:
  • Consider non-glucocorticoid immunosuppressive agent for approximately 18 months 1
  • Gradual glucocorticoid taper based on clinical condition 1

4. Special Considerations

• HBV-associated PAN: Requires antiviral therapy combined with plasma exchange 4
• Monitoring: Serial neurologic examinations are preferred over repeated electromyography/nerve conduction studies for monitoring peripheral neuropathy 1
• Follow-up imaging: For patients with history of severe PAN with abdominal involvement who become asymptomatic, follow-up abdominal vascular imaging is recommended 1

Prognosis

• Untreated severe PAN has a mortality rate of approximately 40% at 5 years 3
• Early recognition and prompt treatment significantly improve outcomes
• The incidence of PAN is decreasing due to prevention of hepatitis B virus infection 3

Common Pitfalls in PAN Management

• Delayed diagnosis due to nonspecific initial symptoms
• Misdiagnosis as other inflammatory or infectious conditions
• Inadequate follow-up of vascular lesions
• Inappropriate discontinuation of immunosuppressive therapy
• Failure to identify and treat underlying causes (e.g., HBV infection)

PAN remains a challenging diagnosis requiring a high index of suspicion, appropriate diagnostic testing, and prompt initiation of therapy based on disease severity to improve outcomes and reduce mortality.