What are the clinical manifestations and laboratory findings associated with polyarteritis nodosa?

Clinical Manifestations and Laboratory Findings of Polyarteritis Nodosa

Polyarteritis nodosa presents most commonly with fever, weight loss, peripheral neuropathy (particularly mononeuritis multiplex), cutaneous nodules with livedo reticularis, hypertension, and abdominal pain, while laboratory testing characteristically shows elevated inflammatory markers with negative ANCA serology. 1

Clinical Manifestations

Constitutional Symptoms

• Fever and weight loss are the hallmark systemic features present in the majority of patients 1, 2
• These constitutional symptoms often precede organ-specific manifestations

Neurologic Manifestations (Most Common)

• Mononeuritis multiplex is one of the earliest and most frequent presentations, affecting 50-75% of patients 3
• Peripheral neuropathy involving sensory and motor deficits
• Central nervous system involvement is rare (2-10% of cases) and typically occurs late in the disease course 3

Cutaneous Manifestations

• Subcutaneous nodules along arterial pathways
• Livedo reticularis (mottled skin discoloration)
• Skin involvement occurs in approximately 81% of patients 2
• Vasculitic rash may be present 4

Renal Manifestations

• Hypertension (often renovascular in origin) is a key feature 1
• Proteinuria without active urinary sediment (distinguishes from ANCA-associated vasculitis) 4, 5
• Notably: PAN does NOT cause glomerulonephritis - the absence of red blood cells or casts in urinalysis helps differentiate from microscopic polyangiitis 4, 5
• Renal involvement affects approximately 40% of patients 2

Gastrointestinal Manifestations

• Abdominal pain from mesenteric arteritis
• Occurs in approximately 24-32% of patients 2
• Can lead to bowel ischemia or perforation in severe cases

Cardiac Manifestations

• Cardiac involvement in 7.5% of patients 2
• Coronary arteritis is a consistent autopsy finding, particularly in children 6
• Can present as cardiac failure or arrhythmias

Musculoskeletal

• Myalgias and arthralgias are common 5
• Testicular pain may occur from testicular arteritis 4

Laboratory Findings

Inflammatory Markers

• Elevated ESR (median 58 mm/h in one series) 2
• Elevated CRP (median 5.22 mg/dL) 2
• Leukocytosis (median 10,400/mm³) 2

Critical Negative Findings

• ANCA negative - this is a defining characteristic that distinguishes PAN from microscopic polyangiitis 1, 2, 5
• All patients in major series were ANCA negative 2

Serologic Testing

• Hepatitis B serology must be checked, as HBV-associated PAN is a distinct entity requiring different treatment 1, 7
• Approximately 10% may have positive hepatitis serology 2
• Rheumatoid factor may be positive (can cause diagnostic confusion with cryoglobulinemic vasculitis) 4
• Type II cryoglobulins may be present but with normal complement levels (helps distinguish from true cryoglobulinemic vasculitis) 4

Urinalysis

• Isolated proteinuria without active sediment 4
• Absence of red blood cells, red cell casts, or significant hematuria - this is crucial for distinguishing PAN from ANCA-associated vasculitis 4, 5

Diagnostic Confirmation

Tissue Biopsy

• Mixed-cell inflammatory infiltrates in vessel walls with fibrinoid necrosis 1
• Absence of granulomas and giant cells (distinguishes from granulomatosis with polyangiitis) 1
• For cutaneous involvement, deep-skin biopsy reaching medium-sized vessels is preferred over superficial punch biopsy 1

Vascular Imaging

• Saccular or fusiform aneurysms on angiography 1
• Stenotic lesions in mesenteric, hepatic, and renal arteries 1
• Both conventional angiography and CT/MR angiography are acceptable 1

Important Clinical Pitfalls

Distinguish PAN from microscopic polyangiitis: MPA patients have active urinary sediment (RBCs, casts), are typically pANCA positive, and have worse renal outcomes 5. PAN patients have normal urinalysis or isolated proteinuria and are ANCA negative.

Distinguish from cryoglobulinemic vasculitis: While both may have positive rheumatoid factor and cryoglobulins, PAN maintains normal complement levels and lacks the typical glomerulonephritis of cryoglobulinemia 4.

Consider DADA2 (deficiency of adenosine deaminase 2): In patients with PAN-like features, especially children or those with early-onset disease, genetic testing for DADA2 should be considered as it requires different treatment (TNF inhibitors) 1.