Vasculitis

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

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

Vasculitis in Adults Testing Algorithm

Vasculitis in Children Testing Algorithm

  • 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

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

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

Limitations

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

Follow Up

Biopsy for histology

Urinalysis, Complete 0020350
Method: Reflectance Spectrophotometry/Microscopy

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

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

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

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

Additional Tests Available

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

Comments

Evaluate for suspected vasculitis

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

Comments

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

Comments

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

Comments

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

Comments

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

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 J, Falk R, Bacon P, Basu N, Cid M, Ferrario F, Flores-Suarez L, Gross W, Guillevin L, Hagen E, Hoffman G, Jayne D, Kallenberg C, Lamprecht P, Langford C, Luqmani R, Mahr A, Matteson E, Merkel P, Ozen S, Pusey C, Rasmussen N, Rees A, Scott D, Specks U, Stone J, Takahashi K, Watts R. 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 R, 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 S, Bakkaloglu A, Herlin T, Brik R, Buoncompagni A, Lazar C, Bilge I, Uziel Y, Rigante D, Cantarini L, Hilario M, Silva C, Alegria M, Norambuena X, Belot A, Berkun Y, Estrella A, Olivieri A, Alpigiani M, 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 M, Bagga A, Barron K, Davin J, Kawasaki T, Lindsley C, Petty R, Prieur A, 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 D, Cuttica R, Khubchandani R, Lovell D, O'Neil K, Quartier P, Ravelli A, Iusan S, Filocamo G, Magalhães C, Unsal E, Oliveira S, Bracaglia C, Bagga A, Stanevicha V, Manzoni S, Pratsidou P, Lepore L, Espada G, Kone-Paut I, Paut I, Zulian F, Barone P, Bircan Z, Maldonado M, 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 J, 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 S, Seo P. Microscopic polyangiitis. Rheum Dis Clin North Am. 2010; 36(3): 545-58. PubMed

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

Frankel S, 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 M, 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 M, Prieto-González S, Cid M. Diagnosis and classification of polyarteritis nodosa. J Autoimmun. 2014; 48-49: 84-9. PubMed

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

Lutalo P, D'Cruz D. 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 F. 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 R, 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 T. Diagnosis and management of cutaneous vasculitis in children. Pediatr Clin North Am. 2014; 61(2): 321-46. PubMed

Weyand C, Goronzy J. 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

Last Update: January 2016