Polyarteritis Nodosa - PAN

Diagnosis

Indications for testing

  • Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory testing

  • Nonspecific testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • CBC – rule out infection
    • Urinalysis (UA) – hematuria, proteinuria, red blood cell casts
    • Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) –  usually elevated
  •  Testing to consider to rule out other diagnoses
    • ANCA – rarely positive, to rule out ANCA-associated vasculitis
    • Hepatitis B surface antigen – rule out concomitant chronic hepatitis
    • ANA – rule out connective tissue diseases
    • Antiglomerular basement membrane antibodies – rule out an antiglomerular basement membrane disease (anti-GBM)

Histology

  • Small- and medium-size artery necrotizing vasculitis with absence of glomerulonephritis
  • Arterioles, capillaries and/or venules – most affected
  • Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls

Imaging studies

  • Angiography – microaneurysms and stenoses of medium vessels

Differential Diagnosis

Clinical Background

Polyarteritis nodosa (PAN) is a necrotizing vasculitis resulting in aneurysmal formation and organ infarction. It is categorized as a medium vessel vasculitis (Chapel Hill 2012).

Epidemiology

  • Incidence –16-25/1,000,000 for systemic vasculitis as a group (includes eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, polyarteritis nodosa and granulomatosis with polyangiitis)
  • Age – peak onset in 50s
  • Sex – M:F, equal

Risk Factors

Clinical Presentation

  • Constitutional – fever, malaise, weight loss, arthralgias
  • Cardiovascular – coronary artery disease
  • Dermatological – vascular purpura, livedo reticularis, lower extremity ulcers, subcutaneous ulcers
  • Gastrointestinal – nonspecific abdominal pain, gastrointestinal bleeding, bowel perforation
  • Neurological – mononeuropathy multiplex
  • Renal – renovascular hypertension, vascular nephropathy

Pediatrics

Clinical Background

Epidemiology

  • Age – peak is 9-11 years
  • Sex – M<F, slight

Clinical Presentation

  • Tends to be a more limited disorder than in adults
  • Constitutional – fever, malaise, weight loss
  • Musculoskeletal – arthritis/arthralgia, myositis, myalgia
  • Renal – vascular hypertension, hematuria, proteinuria
  • Neurological – peripheral neuropathy
  • Gastrointestinal – nonspecific abdominal pain
  • Dermatological – livedo reticularis, skin nodules, skin infections

Diagnosis

Indications for testing

  • Unexplained systemic illness with multiple system involvement (renal, neurologic, dermatologic)

Laboratory testing

  • Nonspecific testing
    • CBC – anemia, leukocytosis, thrombocytoses
    • Erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) – frequently elevated
    • Urinalysis (UA) – proteinuria, hematuria, red cell casts
    • Electrolytes – increases in BUN/Cr not uncommon
  • ANCA – rarely positive

Histology

  • Small- and medium-size artery necrotizing vasculitis in the absence of glomerulonephritis
  • Vasculitis in arterioles, capillaries or venules
  • Immunofluorescence fails to demonstrate complement or immunoglobulin in vessel walls

Imaging studies

  • Angiography – microaneurysms and stenoses of medium vessels

Differential Diagnosis

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Identify anemia, leukocytosis, thrombocytoses

   
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Initial evaluation of suspected vasculitis

   
Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Assess renal involvement

Not specific for diagnosis of PAN

 
Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflex to ANA, IgG by IFA 0050080
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Initial screen for connective tissue diseases

All ELISA results reported as Detected are further tested by IFA

ANA ELISA screen is designed to detect antibodies against dsDNA, histone, SS-A (Ro), SS-B (La), Smith, snRNP/Sm, Scl-70, Jo-1, centromere, and an extract of lysed HEp-2 cells

Results are not disease specific

ANA ELISA assays have been reported to have lower sensitivities for antibodies associated with nucleolar and specked ANA-IFA patterns

 
Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Initial evaluation of suspected ANCA-associated vasculitis

If screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination

Not specific for diagnosis of PAN

 
Hepatitis B Virus Surface Antigen with Reflex to Confirmation 0020089
Method: Qualitative Chemiluminescent Immunoassay 

Rule out concomitant chronic hepatitis B infection

   
Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody

Rule out antiglomerular basement membrane disease

False positive results may occur due to reactivity against other chains of type IV collagen

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Hepatitis B Virus Surface Antigen, Confirmation 0020128
Method: Chemiluminescent Immunoassay

Rule out concomitant chronic hepatitis B infection