Diagnosis of Classical Polyarteritis Nodosa
The diagnosis of classical (systemic) polyarteritis nodosa requires tissue biopsy from the most accessible symptomatic site combined with abdominal vascular imaging to confirm medium-vessel necrotizing vasculitis before initiating treatment. 1
Diagnostic Algorithm
Initial Clinical Assessment
Suspect PAN when patients present with:
- Constitutional symptoms: Fever and unexplained weight loss 1
- Cutaneous manifestations: Skin nodules and livedo reticularis 1
- Abdominal pain suggesting mesenteric ischemia 1
- Peripheral neuropathy: Mononeuritis multiplex or sensory/motor deficits 2
- Renal insufficiency from vascular involvement (not glomerulonephritis, which suggests microscopic polyangiitis instead) 1
Essential Diagnostic Testing
1. Tissue Biopsy (Preferred for Definitive Diagnosis)
Tissue confirmation is preferred over imaging alone. 1 The biopsy site should be selected based on clinical involvement:
For skin involvement: Obtain a deep-skin biopsy (reaching medium-sized vessels of the dermis) rather than superficial punch biopsy, as deeper tissue sampling is more likely to capture affected medium-sized vessels 2
For peripheral neuropathy: Obtain a combined nerve and muscle biopsy over nerve biopsy alone, as this increases diagnostic yield 2. Sample an affected purely sensory nerve (e.g., sural nerve) to avoid motor deficits 2
Histologic criteria: Look for mixed-cell inflammatory infiltrates, fibrinoid necrosis, and absence of granulomas (which would suggest granulomatosis with polyangiitis) 1
2. Vascular Imaging (Essential for Systemic Disease)
Abdominal vascular imaging is recommended to establish diagnosis and determine disease extent. 1 Options include:
- Conventional angiography (current gold standard with better resolution) 2
- CT angiography or MR angiography (noninvasive alternatives) 2
Angiographic findings: Saccular or fusiform aneurysms and stenotic lesions in mesenteric, hepatic, and renal arteries 1
3. Laboratory Testing
- ANCA testing: Should be negative (positive ANCA suggests microscopic polyangiitis, not PAN) 3
- Hepatitis B serology: Essential to identify HBV-associated PAN, which requires different treatment (antiviral therapy rather than immunosuppression alone) 4, 5
- Hepatitis C testing: Also associated with secondary PAN 3
Diagnostic Pitfalls to Avoid
- Do not rely on superficial skin biopsies when PAN is suspected—they miss medium-sized vessels 2
- Do not perform "blind" biopsies of clinically unaffected tissue 2
- Do not confuse PAN with microscopic polyangiitis: PAN does not affect the lungs and is ANCA-negative 5
- Do not miss HBV-associated PAN: This variant requires antiviral therapy, not standard immunosuppression 4, 5
Follow-Up Imaging
For patients with severe PAN and abdominal involvement who achieve clinical remission, follow-up abdominal vascular imaging is conditionally recommended, particularly when baseline imaging shows aneurysmal disease. 2 However, avoid indefinite routine imaging if vascular disease is quiescent. 2
Monitoring Disease Activity
For patients with peripheral motor neuropathy from PAN, use serial neurologic examinations rather than repeated electromyography/nerve conduction studies every 6 months, as repeated EMG is invasive and not warranted in stable patients. 2 Repeat EMG only if new or worsening neurologic symptoms develop. 2
Key Diagnostic Principle
The integration of clinical findings, tissue biopsy showing necrotizing vasculitis of medium-sized vessels, negative ANCA, and angiographic evidence of aneurysms or stenoses establishes the diagnosis. 6, 7 No single test reliably confirms or excludes PAN—diagnosis requires synthesizing multiple data sources. 7