Polyarteritis Nodosa: Clinical Manifestations and Frequency
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized vessels presenting most commonly with constitutional symptoms (71.5%), cutaneous involvement (70.5%), musculoskeletal findings (69.1%), and peripheral neuropathy (48%), with severe disease carrying a 40% mortality at 5 years if untreated 1.
Core Clinical Manifestations with Approximate Frequencies
Constitutional Symptoms (71.5%)
- Fever occurs in 52-87% of patients 2, 3
- Weight loss >4 kg in approximately 44% 4
- Profound asthenia and malaise are nearly universal
Cutaneous Manifestations (70.5-88%)
The skin is one of the most frequently affected organs 2, 3:
- Livedo reticularis
- Subcutaneous nodules (the "nodosa" in the name)
- Skin ulcerations
- Digital ischemia and gangrene
- Purpura
Critical diagnostic point: Deep skin biopsy reaching medium-sized vessels in the dermis is superior to superficial punch biopsy for establishing diagnosis 1.
Musculoskeletal Involvement (69-83%)
- Myalgia is present in 70-83% of patients 4, 5
- Muscle weakness and leg tenderness
- Arthralgia/arthritis in approximately 30% 4
- Frank myopathy requiring biopsy confirmation
Neurologic Manifestations (48-75%)
Peripheral nervous system (50-75% of patients) 6:
- Mononeuritis multiplex is the hallmark neurologic finding
- Peripheral neuropathy (both motor and sensory)
- Often one of the earliest symptoms
- More common in males than females 3
Central nervous system (2-10% of patients) 6:
- Occurs late in disease course
- Stroke
- Encephalopathy
- Seizures
- CNS involvement is an independent predictor of death 2
Diagnostic recommendation: Combined nerve and muscle biopsy yields higher diagnostic accuracy than nerve biopsy alone 1.
Gastrointestinal Involvement (33-52%)
Present in 52.2% of systemic PAN patients 2:
- Abdominal pain (33-52%)
- Mesenteric ischemia
- Gastrointestinal bleeding
- Bowel perforation
- Severe GI involvement predicts increased relapse risk and mortality 2, 5
Renal Manifestations (11-19%)
- Renovascular hypertension is common
- Proteinuria >400 mg/day in 11.2% of systemic PAN 2
- Serum creatinine >140 μmol/L at diagnosis is an independent predictor of death 2
- Critical distinction: Glomerulonephritis is ABSENT in PAN (this distinguishes it from microscopic polyangiitis)
Cardiac Involvement
- Coronary arteritis
- Myocardial infarction
- Heart failure
- Pericarditis
Genitourinary Manifestations
- Testicular pain/tenderness in 24% of males (higher than historically reported) 4
- Orchitis is a rare but specific manifestation 7
Respiratory Involvement
- More common in elderly patients 3
- Pulmonary hemorrhage is rare (helps distinguish from other vasculitides)
Disease Severity Classification
Severe disease (life- or organ-threatening) includes 1:
- Renal disease
- Mononeuritis multiplex
- Muscle disease
- Mesenteric ischemia
- Coronary involvement
- Limb/digit ischemia
- CNS involvement
Nonsevere disease includes 1:
- Mild systemic symptoms
- Uncomplicated cutaneous disease
- Mild inflammatory arthritis
Prognostic Factors
Five-Factor Score (FFS)
Approximately 33% of patients present with FFS ≥2 4. Higher FFS correlates with worse prognosis 4, 8.
Independent Predictors of Death 2:
- Age ≥65 years at diagnosis
- Serum creatinine >140 μmol/L at diagnosis
- Gastrointestinal manifestations
- Central nervous system involvement
Disease Course and Outcomes
Relapse Rates
- Relapse occurs in 40-48.5% of patients during follow-up 2, 8
- Median time to relapse: 82 months 8
- Severe GI involvement predicts higher relapse risk 5
- Smoking history independently predicts relapse (HR 6.28) 8
Survival Rates (Systemic PAN) 2:
- 1-year survival: 97.1%
- 5-year survival: 94.0%
- 10-year survival: 89.0%
Historical context: With modern immunosuppressive therapy, PAN has transformed from a uniformly fatal disease to one with >80% 5-year survival 9.
Diagnostic Imaging Findings
Abdominal vascular imaging (CT or MR angiography, or conventional angiography) shows 1:
- Saccular or fusiform aneurysms
- Stenotic lesions in mesenteric, hepatic, and renal arteries
- Positive findings in 96% when performed 5
Recommendation: Obtain abdominal vascular imaging in suspected PAN to establish diagnosis and determine disease extent, particularly when GI or renal symptoms are present 1.
Key Diagnostic Distinctions
PAN is characterized by the ABSENCE of:
- Anti-neutrophil cytoplasmic antibodies (ANCA)
- Glomerulonephritis
- Granulomas
- Giant cells
Special Populations
Pediatric PAN 5:
- Median age 8.5 years
- Fever (87%), myalgia (83%), skin (88%) most common
- Severe GI involvement (10%)
- Relapse rate 35%, mortality 4%
Secondary Causes to Exclude:
- Hepatitis B virus (now rare due to vaccination; only 11.5% in modern series) 4
- Deficiency of adenosine deaminase 2 (DADA2) - requires TNF inhibitor therapy 1
- Familial Mediterranean fever
- Malignancy-associated PAN 7
Common Pitfalls
- Superficial skin biopsy: Will miss medium-sized vessel involvement; always obtain deep biopsy 1
- Assuming all peripheral neuropathy is PAN: Combined nerve-muscle biopsy increases diagnostic yield 1
- Missing testicular involvement: Examine male patients for orchitis (24% prevalence) 4
- Confusing with ANCA-associated vasculitis: PAN is ANCA-negative and lacks glomerulonephritis
- Underestimating relapse risk: Nearly half of patients relapse, requiring long-term monitoring 2