Vasculitis

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

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

  • 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)

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

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
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.

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

Recommended Use 

Preferred reflex panel for the workup of suspected vasculitis; panel detects ANCA, MPO, and PR-3 antibodies

For patients with a history of vasculitis, refer to the ANCA reflex panel that includes a titer, and MPO and PR-3 antibodies

Individual antibody tests are available; refer to serine protease 3 antibody or MPO antibody tests

Reflex pattern – if the ANCA screen detects antibodies at a 1:20 dilution or greater, then a titer to end point will be added

Clinical sensitivity – ~85-90% for AMA

Limitations 

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

Follow-up 

Biopsy for histology

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

Recommended Use 

Screen for various metabolic and kidney disorders

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Recommended Use 

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Recommended Use 

May help in ruling out infectious process

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Recommended Use 

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

Recommended Use 

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

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Five Things Physicians and Patients Should Question. An initiative of the ABIM Foundation. [Last revision Feb 2015; Accessed: Jan 2016]

Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65(1): 1-11. PubMed

Ntatsaki E, Carruthers D, Chakravarty K, D'Cruz D, Harper L, Jayne D, Luqmani R, Mills J, Mooney J, Venning M, Watts RA, BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford). 2014; 53(12): 2306-9. PubMed

Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario MO, Silva CA, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella AI, Olivieri AN, Alpigiani MG, Rumba I, Sztajnbok F, Tambic-Bukovac L, Breda L, Al-Mayouf S, Mihaylova D, Chasnyk V, Sengler C, Klein-Gitelman M, Djeddi D, Nuno L, Pruunsild C, Brunner J, Kondi A, Pagava K, Pederzoli S, Martini A, Ruperto N, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010; 69(5): 798-806. PubMed

Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, Kawasaki T, Lindsley C, Petty RE, Prieur AM, Ravelli A, Woo P. EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis. 2006; 65(7): 936-41. PubMed

Ruperto N, Ozen S, Pistorio A, Dolezalova P, Brogan P, Cabral DA, Cuttica R, Khubchandani R, Lovell DJ, O'Neil KM, Quartier P, Ravelli A, Iusan SM, Filocamo G, Magalhães CS, Unsal E, Oliveira S, Bracaglia C, Bagga A, Stanevicha V, Manzoni SM, Pratsidou P, Lepore L, Espada G, Kone-Paut I, Paut IK, Zulian F, Barone P, Bircan Z, Maldonado Md, Russo R, Vilca I, Tullus K, Cimaz R, Horneff G, Anton J, Garay S, Nielsen S, Barbano G, Martini A, Paediatric Rheumatology International Trials Organisation (PRINTO). EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part I: Overall methodology and clinical characterisation. Ann Rheum Dis. 2010; 69(5): 790-7. PubMed

General References

Berden A, Göçeroglu A, Jayne D, Luqmani R, Rasmussen N, Bruijn JA, Bajema I. Diagnosis and management of ANCA associated vasculitis. BMJ. 2012; 344: e26. PubMed

Buggiani G, Krysenka A, Grazzini M, Vašků V, Hercogová J, Lotti T. Paraneoplastic vasculitis and paraneoplastic vascular syndromes. Dermatol Ther. 2010; 23(6): 597-605. PubMed

Caspary L. Vasculitides of large vessels. Vasa. 2011; 40(2): 89-98. PubMed

Chung SA, Seo P. Microscopic polyangiitis. Rheum Dis Clin North Am. 2010; 36(3): 545-58. PubMed

Covino JM, Hofmann-Ribowsky J. Vasculitis: diagnosis and treatment of blood vessel wall inflammation. JAAPA. 2012; 25(7): 46-50. PubMed

Damoiseaux J. The diagnosis and classification of the cryoglobulinemic syndrome. Autoimmun Rev. 2014; 13(4-5): 359-62. PubMed

de Souza AW, de Carvalho JF. Diagnostic and classification criteria of Takayasu arteritis. J Autoimmun. 2014; 48-49: 79-83. PubMed

Frankel SK, Jayne D. The pulmonary vasculitides. Clin Chest Med. 2010; 31(3): 519-36. PubMed

Gedalia A, Cuchacovich R. Systemic vasculitis in childhood. Curr Rheumatol Rep. 2009; 11(6): 402-9. PubMed

Greco A, Rizzo MI, De Virgilio A, Gallo A, Fusconi M, Ruoppolo G, Altissimi G, De Vincentiis M. Churg-Strauss syndrome. Autoimmun Rev. 2015; 14(4): 341-8. PubMed

Harder N. Temporal arteritis: an approach to suspected vasculitides. Prim Care. 2010; 37(4): 757-66, vi-ii. PubMed

Harnden A, Tulloh R, Burgner D. Kawasaki disease. BMJ. 2014; 349: g5336. PubMed

Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture's disease (anti-GBM). J Autoimmun. 2014; 48-49: 108-12. PubMed

Hernández-Rodríguez J, Alba MA, Prieto-González S, Cid MC. Diagnosis and classification of polyarteritis nodosa. J Autoimmun. 2014; 48-49: 84-9. PubMed

Kallenberg CG. The diagnosis and classification of microscopic polyangiitis. J Autoimmun. 2014; 48-49: 90-3. PubMed

Kessel A, Vadasz Z, Toubi E. Cogan syndrome--pathogenesis, clinical variants and treatment approaches. Autoimmun Rev. 2014; 13(4-5): 351-4. PubMed

Langford CA. Vasculitis. J Allergy Clin Immunol. 2010; 125(2 Suppl 2): S216-25. PubMed

Lutalo PM, D'Cruz DP. Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener's granulomatosis). J Autoimmun. 2014; 48-49: 94-8. PubMed

Mouthon L, Dunogue B, Guillevin L. Diagnosis and classification of eosinophilic granulomatosis with polyangiitis (formerly named Churg-Strauss syndrome). J Autoimmun. 2014; 48-49: 99-103. PubMed

Nesher G. The diagnosis and classification of giant cell arteritis. J Autoimmun. 2014; 48-49: 73-5. PubMed

Saguil A, Fargo M, Grogan S. Diagnosis and management of kawasaki disease. Am Fam Physician. 2015; 91(6): 365-71. PubMed

Saulsbury FT. Henoch-Schönlein purpura. Curr Opin Rheumatol. 2010; 22(5): 598-602. PubMed

Sharma P, Sharma S, Baltaro R, Hurley J. Systemic vasculitis. Am Fam Physician. 2011; 83(5): 556-65. PubMed

Sinico RA, Radice A. Antineutrophil cytoplasmic antibodies (ANCA) testing: detection methods and clinical application. Clin Exp Rheumatol. 2014; 32(3 Suppl 82): S112-7. PubMed

Sánchez-Manubens J, Bou R, Anton J. Diagnosis and classification of Kawasaki disease. J Autoimmun. 2014; 48-49: 113-7. PubMed

Ting TV. Diagnosis and management of cutaneous vasculitis in children. Pediatr Clin North Am. 2014; 61(2): 321-46. PubMed

Weyand CM, Goronzy JJ. Clinical practice. Giant-cell arteritis and polymyalgia rheumatica. N Engl J Med. 2014; 371(1): 50-7. PubMed

Xiao X, Chang C. Diagnosis and classification of drug-induced autoimmunity (DIA). J Autoimmun. 2014; 48-49: 66-72. PubMed

Yang Y, Yu H, Chiang B. The diagnosis and classification of Henoch-Schönlein purpura: an updated review. Autoimmun Rev. 2014; 13(4-5): 355-8. PubMed

Yazici Y, Yurdakul S, Yazici H. Behçet's syndrome. Curr Rheumatol Rep. 2010; 12(6): 429-35. PubMed

Medical Reviewers

Tebo, Anne E., PhD, D(ABMLI), Medical Director, Immunology at ARUP Laboratories; Associate Professor of Clinical Pathology, University of Utah

Antiglomerular Basement Membrane Disease - Goodpasture Syndrome
Central Nervous System Tumors - Brain Tumors
Connective Tissue Diseases
Cryoglobulinemia
Giant Cell Arteritis - Temporal Arteritis
Granulomatosis with Polyangiitis - GPA
IgA Vasculitis - Henoch Schönlein Purpura
Microscopic Polyangiitis - MPA
Polyarteritis Nodosa - PAN
Sarcoidosis
Sjögren Syndrome
Systemic Lupus Erythematosus - SLE
Takayasu Arteritis

Last Update: September 2016

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