How to differentiate polyarteritis nodosa (PAN) from Henoch-Schönlein purpura (HSP)?

Differentiating Polyarteritis Nodosa from Henoch-Schönlein Purpura

To rule out PAN in a case of HSP, obtain a deep-skin biopsy reaching medium-sized vessels of the dermis to look for necrotizing vasculitis without IgA deposition, perform abdominal vascular imaging to identify aneurysms or stenotic lesions in mesenteric/hepatic/renal arteries, and assess for mononeuritis multiplex with combined nerve and muscle biopsy if peripheral neuropathy is present. 1

Key Diagnostic Distinctions

Histopathologic Differentiation

Deep-skin biopsy is essential for distinguishing these conditions. 1, 2

• HSP shows: Leukocytoclastic vasculitis of small vessels with IgA deposition on immunofluorescence 3, 4
• PAN shows: Necrotizing vasculitis of medium-sized vessels with mixed inflammatory infiltrates and fibrinoid necrosis, without IgA deposition and without granulomas or giant cells 1
• A superficial punch biopsy will miss PAN because it cannot reach the medium-sized vessels in the deeper dermis 1, 2
• Request a "deep" or "double" punch biopsy that reaches the medium-sized vessels of the dermis 1

Vascular Imaging Findings

Abdominal vascular imaging is critical when systemic involvement is suspected. 1

• PAN demonstrates: Saccular or fusiform aneurysms and stenotic lesions in mesenteric, hepatic, and renal arteries on CT angiography, MR angiography, or conventional angiography 1
• HSP does not produce: These characteristic medium-vessel aneurysms or stenoses 3, 5
• Obtain imaging if the patient has gastrointestinal symptoms, genitourinary symptoms, or renovascular hypertension 1

Neurologic Assessment

Peripheral neuropathy patterns differ significantly between these conditions. 1

• PAN characteristically causes: Mononeuritis multiplex and peripheral motor/sensory neuropathy affecting medium-sized vessels supplying nerves 1
• Obtain combined nerve and muscle biopsy (not nerve alone) to increase diagnostic yield for PAN 1
• Biopsy a clinically affected sensory nerve (e.g., sural nerve) to avoid motor deficits 1
• HSP rarely causes: Significant peripheral neuropathy 3

Clinical Red Flags Suggesting PAN Rather Than HSP

Organ-Threatening Manifestations

Severe systemic involvement points toward PAN. 1

• Rapidly progressive renal failure (not just hematuria/proteinuria) suggests PAN 3, 5
• Mesenteric ischemia with bowel infarction indicates medium-vessel involvement of PAN 1
• Acute myocardial infarction from coronary artery involvement is characteristic of PAN 3
• Limb or digit ischemia from arterial occlusion 1

Laboratory Markers

• All rheumatologic tests negative (including ANCA) supports PAN over other vasculitides 5
• Absence of IgA deposition on biopsy rules out HSP 3, 4
• Check for hepatitis B virus, as HBV-associated PAN is managed differently 1

Overlap Syndromes: A Critical Pitfall

Recognize that HSP/PAN overlap syndromes exist and are often fatal if not identified early. 3, 6, 4

• Patients may present with leukocytoclastic vasculitis and IgA deposition (HSP features) plus medium-vessel necrotizing arteritis with aneurysms (PAN features) 3, 4
• Key warning sign: Progressive acute renal failure in a patient initially diagnosed with HSP should immediately raise suspicion for overlap syndrome 3
• These overlap cases require aggressive immunosuppression with cyclophosphamide and high-dose glucocorticoids, not the conservative management typical of uncomplicated HSP 3, 4
• Mortality is high (reported deaths within 1-2 months) if overlap syndrome is not recognized and treated appropriately 3, 4

Algorithmic Approach to Rule Out PAN

Step 1: Clinical Assessment

• Document presence of mononeuritis multiplex, severe abdominal pain with ischemia, renovascular hypertension, or cardiac involvement 1, 5

Step 2: Tissue Diagnosis

• Obtain deep-skin biopsy if cutaneous lesions present, specifically requesting medium-vessel evaluation 1, 2
• If peripheral neuropathy exists, obtain combined nerve and muscle biopsy 1

Step 3: Vascular Imaging

• Perform abdominal CT or MR angiography to identify aneurysms or stenoses in visceral arteries 1
• Skip imaging only if isolated mononeuritis multiplex or myopathy without gastrointestinal/genitourinary symptoms 1

Step 4: Immunofluorescence Analysis

• IgA deposition present: Supports HSP (but does not exclude overlap syndrome) 3, 4
• IgA deposition absent with medium-vessel necrotizing vasculitis: Confirms PAN 1

Step 5: Reassess if Clinical Deterioration Occurs

• Rapidly progressive renal failure in presumed HSP mandates immediate re-evaluation for PAN or overlap syndrome 3
• Consider repeat imaging and deeper tissue sampling if initial workup was negative but clinical suspicion remains high 1