Vasculitis

Diagnosis

Indications for Testing

  • Multisystem disease presentation – including upper airway disease, renal disease, pulmonary disease, palpable purpura, urticaria, or mononeuritis multiplex

Laboratory Testing

  • Initial testing – helpful in excluding other diagnoses or identifying organ dysfunction
    • CBC –  evaluate for anemia, leukocytosis, thrombocytopenia
    • C-reactive protein (CRP)
    • Urinalysis – evaluate for presence of hematuria, proteinuria, or and/or red blood cell casts
    • Renal function tests (BUN/creatinine) – assess for renal involvement
    • Liver function tests – provide clues for hepatic involvement (most common in polyarteritis nodosa)
    • ANCA – most useful for differentiating ANCA(+) vasculitis from other vasculitis
      • Indirect immunofluorescence assay (IFA) – sensitive marker for ANCA-associated vasculitis
      • To confirm positive results, PR3 or MPO specific assays (ELISA, Western blot or multianalyte fluorescence detection [MAFD]) required (European League Against Rheumatism [EULAR], 2010 grade A recommendation)
      • Pattern of ANCA frequently helpful – pANCA vs. cANCA
      • Absence of a positive test result does not rule out vasculitis
      • ANCA(+) vasculitides – granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis
  • Other possible secondary testing – antinuclear antibody, rheumatoid arthritis, hepatitis B and C viruses

Histology

  • Determines size of artery involvement (EULAR, 2009 grade C recommendation; Chapel Hill, 2012)
  • In conjunction with clinical presentation, combination of ANCA, urinalysis
  • Usually identifies specific vasculitis (see the Vasculitis in Adults Testing Algorithm and Vasculitis in Children Testing Algorithm)

Imaging Studies

  • Chest X-ray – nonspecific pulmonary nodules, cavitation, consolidation or pleural effusion suggest pulmonary involvement
  • Angiogram of affected area – demonstrates aneurysms and vascular occlusion
    • Magnetic resonance angiography or computed tomography angiography may be preferred
  • Echocardiography
    • 40% detection rate for Kawasaki
    • Also used in Takayasu arteritis
  • Ultrasound – for giant cell arteritis diagnosis and monitoring
  • CT sinus – useful in granulomatosis with polyangiitis (GPA)

Other Testing

  • Nerve conduction testing if neurologic manifestations present

Differential Diagnosis

Monitoring

  • 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 should be performed every visit to monitor for renal involvement (EULAR, 2010)
    • CBC, inflammatory markers, renal and liver function testing should be performed every 1-3 months (EULAR, 2010 grade C recommendation)

Clinical Background

The systemic vasculitides are a group of uncommon conditions characterized by inflammation and necrosis of blood vessel walls. Some of these syndromes are also categorized by the presence of antineutrophil cytoplasmic antibodies (ANCA) – so called ANCA-associated vasculitides (Chapel Hill 2012).

Epidemiology

  • Incidence – 100/1,000,000
  • Age – peak onset is 65-74 years; unusual in children
  • Sex – M>F (minimal)

Nomenclature

  • Based on affected blood vessel size – small, medium, or large
  • Chapel Hill Consensus Conference Nomenclature of Systemic Vasculitis (Revised 2012)

    Revised Systemic Vasculitis Nomenclature

    – International Chapel Hill Consensus Conference 2012

    Large vessel vasculitis (LVV)

    Takayasu arteritis (TAK)

    Giant cell arteritis (GCA)

    Medium vessel vasculitis (MVV)

    Polyarteritis nodosa (PAN)

    Kawasaki disease (KD)

    Small vessel vasculitis (SVV)

    ANCA-associated vasculitis (AAV)

    • Microscopic polyangiitis (MPA)
    • Granulomatosis with polyangiitis (GPA)
    • Eosinophilic granulomatosis with polyangiitis

    Immune complex

    • Cryoglobulinemia vasculitis (CV)
    • IgA vasculitis (Henoch-Schönlein) (IgAV)
    • Anti-glomerular membrane disease
    • Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)

    Variable vessel vasculitis (VVV)

    Behçet’s disease (BD) vasculitis

    Cogan’s syndrome (CS)

    Single organ vasculitis (SOV)

    Cutaneous leukocytoclastic angiitis

    Cutaneous arteritis

    Primary CNS vasculitis

    Isolated aortitis

    Vasculitis associated with systemic disease

    Lupus vasculitis

    Rheumatoid vasculitis

    Sarcoid vasculitis

    Vasculitis associated with probable etiology

    Hepatitis C virus-associated cryoglobulinemic vasculitis

    Hepatitis B virus-associated vasculitis

    Syphilis-associated aortitis

    Drug-associated ANCA-associated vasculitis

    Cancer-associated vasculitis

Clinical Presentation

  • Nonspecific signs/symptoms early in disease – fever, arthralgias, fatigue, weight loss, myalgias
  • Multisystem involvement later in disease – dermatologic, ophthalmologic, renal, pulmonary, hepatic, gastrointestinal tract, vascular, central nervous system
  • Patients present with diverse organ involvement in most cases

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
ANCA-Associated Vasculitis Profile (ANCA/MPO/PR-3) with Reflex to ANCA Titer 2006480
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Initial testing for suspected ANCA-associated vasculitis

Monitor treatment of granulomatosis with polyangiitis

Reflex pattern – if screen is positive, titer will be added

Clinical sensitivity – ~85-90% for AMA

Negative antibody testing does not rule out ALD; no single test shows absolute specificity

All interpretation of antibody patterns must be done in conjunction with clinical presentation

There may be overlap between diseases and antibodies detected

Crossreaction may occur with cationic protein 57 (CAP 57), cathepsin G, elastase, lactoferrin, and other lysosomal proteins

Biopsy for histology

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Screen for hematuria, proteinuria, and RBC casts

   
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry
Preferred test to detect inflammatory processes in suspected vasculitis    
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential
May help in ruling out infectious process    
Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Initial screening for hepatobiliary inflammation

Monitor treatment of vasculitis

Panel includes bilirubin direct; bilirubin total (serum or plasma), alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, protein total (serum or plasma), albumin (serum or plasma)

   
Renal Function Panel 0020144
Method: Quantitative Chemiluminescent Immunoassay/Quantitative Enzyme-Linked Immunosorbent Assay

Evaluate for kidney dysfunction in patients with known risk factors (eg, hypertension, diabetes, obesity, family history of kidney disease)

Monitor treatment of vasculitis

Panel includes albumin, calcium, carbon dioxide, creatinine, chloride, glucose, phosphorous, potassium, sodium, and BUN and a calculated anion gap value

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Evaluate for suspected vasculitis

MPO/PR-3 (ANCA) Antibodies 0050707
Method: Semi-Quantitative Multiplex Bead Assay

Use to monitor previously established MPO/PR-3 antibodies or confirm an IFA c-ANCA or p-ANCA positive test result

Test does not include pANCA or cANCA testing; refer to ANCA reflex to titer and MPO/PR-3 antibodies or ANCA-associated vasculites profile (ANCA/MPO/PR-3) reflex to ANCA titer for  pANCA or cANCA testing

Myeloperoxidase Antibody 0050526
Method: Semi-Quantitative Multiplex Bead Assay
Serine Protease 3 Antibody 0050527
Method: Semi-Quantitative Multiplex Bead Assay
Anti-Neutrophil Cytoplasmic Antibody, IgG 0050811
Method: Semi-Quantitative Indirect Fluorescent Antibody

Use as an adjunct diagnostic tool to differentiate ulcerative colitic from Crohn disease

Assess for ANCA-associated vasculitis

Reflex pattern – if ANCA screen detects antibodies ≥1:20 dilution, then titer to end point will be added

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

Preferred panel for evaluating and managing individuals with a  known diagnosis of vasculitis

Reflex pattern – if screen is positive, then titer and MPO/PR-3 antibodies will be added to aid in antibody determination

Cryoglobulin, Qualitative with Reflex to IFE Typing and Quantitative IgA, IgG, and IgM 2002403
Method: Qualitative Cold Precipitation/Qualitative Immunofixation Electrophoresis/Quantitative Nephelometry

Reflex pattern – if qualitative is positive, Immunofixation Electrophoresis Typing and Quantitative IgA, IgG and IgM will be added

Glomerular Basement Membrane Antibody, IgG by Multiplex Bead Assay and IFA 2008403
Method: Semi-Quantitative Multiplex Bead Assay/Qualitative Indirect Fluorescent Antibody
Cryoglobulin, Qualitative 0050185
Method: Qualitative Cold Precipitation