Systemic Vasculitis

Diagnosis

Indications for Testing

• General presentation
  • Fever
  • Joint pain and inflammation
  • Malaise, weight loss
• Large vessel vasculitides
  • Aortic dilation
  • Asymmetric or absent pulses
  • Bruits
  • Pain due to claudication
  • Stroke-like symptoms
• Medium vessel vasculitides
  • Mononeuritis multiplex
  • Skin signs (eg, livedo reticularis, nodules)
  • Digital necrosis
  • Microaneurysms
  • Abdominal pain
  • Gastrointestinal ulcers
• Small vessel vasculitides
  • Alveolar hemorrhage
  • Glomerulonephritis
  • Skin signs (eg, purpura, splinter hemorrhages)
  • Uveitis
  • Episcleritis
  • Purpura
  • Urticaria 

Laboratory Testing

• Useful testing for the evaluation of vasculitis
  • Antineutrophil cytoplasmic antibody (ANCA): most useful for differentiating ANCA(+) vasculitis from other vasculitis
    • Indirect fluorescent antibody (IFA) test: preferred screening method for ANCA-associated vasculitis with 2 main patterns: C-ANCA and P-ANCA
    • Proteinase 3 (PR3) or myeloperoxidase (MPO) specific assays (by enzyme-linked immunosorbent assay [ELISA], Western blot, or multianalyte fluorescence detection [MAFD]) can confirm positive C-ANCA or P-ANCA result
      • C-ANCA is associated with PR3 antibodies
      • P-ANCA is associated with MPO antibodies
    • Absence of a positive test result does not rule out vasculitis
  • C-reactive protein (CRP)
    • Often elevated in active disease; nonspecific marker suggestive of systemic inflammation
    • If CRP not available, erythrocyte sedimentation rate (ESR) may be used
  • CBC may demonstrate
    • Normochromic normocytic anemia: chronic inflammation
    • Eosinophilia: eosinophilic granulomatosis with polyangiitis
    • Leukocytosis: inflammation
    • Reactive thrombocytosis: inflammation
  • Peripheral smear
  • Renal function tests: evaluate type and extent of kidney damage
    • Urinalysis: evaluate for hematuria, proteinuria, red blood cell casts, nitrates, and leukocytes
    • Serum kidney function tests (blood urea nitrogen [BUN]/creatinine)
    • Spot urine albumin/creatinine
    • Estimated glomerular filtration rate
• Evaluation for other vasculitis associations
  • Liver function tests
    • Evaluate hepatic involvement: most common in polyarteritis nodosa
  • Immunoglobulin levels/complement levels and functional assay/cryoglobulins
  • Antiglomerular basement membrane (anti-GBM) testing: detect GBM antibodies in suspected or established anti-GBM disease (Goodpasture Syndrome)
    • By IFA and/or multiplex bead assay
  • Coagulation and synthetic function testing
    • Prothrombin time
  • Infectious vasculitis testing
    • Rickettsia rickettsii
    • Hepatitis C and B: cryoglobulinemic vasculitis
    • Treponema pallidum
    • HIV
    • Varicella zoster virus (VZV)
  • Autoimmune rheumatic systemic disease testing: lupus, rheumatoid arthritis, antiphospholipid antibody syndrome (APS)
    • Antinuclear antibody (ANA)
    • Double-stranded DNA (dsDNA)
    • Extractable nuclear antigen (ENA) antibodies panel
    • Angiotensin converting enzyme (ACE)
    • Rheumatoid factor (RF)
    • Anticardiolipin antibodies, lupus anticoagulant

Other Testing

• Biopsy with histology required to confirm or rule out diagnosis
  • Assess damage and characterize disease
  • Determine sze of blood vessels involved (small, medium, large)
  • Identify IgA deposition for IgA vasculitis
  • Evaluate for eosinophils in eosinophilic granulomatosis with polyangiitis
• Imaging studies: may include chest X-rays, angiography, echocardiology, ultrasound, and/or computed tomography (CT)

Monitoring

• Antineutrophil cytoplasmic antibody (ANCA): if positive in initial evaluation
  • Titers may decrease after induction of remission and elevation may herald relapse
    • Rising titers do not reliably predict relapse
    • Titers cannot be used to guide treatment
• Urinalysis: perform every visit to monitor for infection or renal involvement (European League Against Rheumatism [EULAR]/European Renal Association-European Dialysis and Transplant Association [ERA-EDTA], 2016)
• Inflammatory markers and renal function testing: perform every 1-3 months (EULAR/ERA-EDTA, 2016)
• Malignancy evaluation: higher risk for cancer in Wegener’s granulomatosis and microscopic polyangiitis, specifically for bladder, skin, and hematologic malignancies (Kermani, 2011)
  • Consider careful monitoring

Pediatrics

Vasculitis in pediatrics is categorized by the predominant size of the blood vessels affected; most vasculitides can affect a range of sizes (overlap) (Foster, 2012). The most common pediatric vasculitides are immunoglobulin A (IgA) vasculitis and Kawasaki disease; eosinophilic granulomatosis with polyangiitis is extremely rare in children, and giant cell arteritis is not seen. Laboratory testing and other evaluation with confirmation by biopsy is similar to adult testing. See Diagnosis for adult testing recommendations.