Polyarteritis Nodosa - PAN

Dx
Background
Peds
Lab Tests
Algorithm

Diagnosis

Indications for testing

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

Laboratory testing

Nonspecific testing
- CBC – rule out infection
- Electrolytes – determine imbalances
- Urinalysis (UA) – hematuria common, proteinuria, red cell casts
- Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) – initial vasculitis screening; usually elevated
Tests to consider to rule out other diagnoses
- Hepatitis B surface antigen – rule out concomitant chronic hepatitis
- ANA – rule out connective tissue diseases
- Antiglomerular basement membrane antibodies – rule out Goodpasture syndrome
ANCA – rarely positive

Histology

Small- and medium-size artery necrotizing vasculitis without 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

Alport syndrome
Connective tissue diseases
Goodpasture syndrome – anti-GBM disease
Vasculitis
- Microscopic polyangiitis
Infection
- M. tuberculosis
- Endocarditis
- Hepatitis B/hepatitis C
- T. pallidum – syphilis
- Cytomegalovirus
- Epstein-Barr virus
- HIV
- Plasmodium spp – malaria
Cryoglobulinemia
Malignancy
- Lymphoma
- Plasma cell dyscrasias

Clinical Background

Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium-sized arteries resulting in aneurysmal formation and organ infarction.

Epidemiology

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

Risk Factors

Chronic hepatitis B

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) or 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 without 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

Alport syndrome
Connective tissue diseases
Vasculitis
- Microscopic polyangiitis
- Kawasaki disease
- Henoch-Schönlein syndrome
Infection
- M. tuberculosis
- Endocarditis
- Hepatitis B/hepatitis C
- T. pallidum – syphilis
- Cytomegalovirus
- Epstein-Barr virus
- HIV
- Plasmodium spp – malaria

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
CBC with Platelet Count and Automated Differential 0040003 Method: Automated Cell Count/Differential	Identify anemia, leukocytosis, thrombocytoses
Electrolyte Panel 0020410 Method: Quantitative Ion-Selective Electrode/Enzymatic	Determine electrolyte imbalances
Sedimentation Rate, Westergren (ESR) 0040325 Method: Visual Identification	Initial screen in vasculitis
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
Urinalysis, Complete 0020350 Method: Reflectance Spectrophotometry/Microscopy	Useful in assessing renal involvement	Not specific for diagnosis of PAN
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	Most effective test to aid in differential diagnosis of PAN 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 Goodpasture syndrome	False positive results may occur due to reactivity against other chains of type IV collagen