Abstract
Introduction/objective
With widespread availability of anti-neutrophil cytoplasmic antibody (ANCA) testing, interpreting positive results has become increasingly challenging. Here, we conducted a retrospective study to evaluate indications for testing and diagnosis of patients with positive ANCA.
Methods
Positive ANCA tests (immunofluorescence or immunoassay) performed between April 2014 and March 2015 were identified using the Ottawa Hospital (TOH) laboratory information system. TOH electronic records of subjects with positive ANCA were reviewed.
Results
96 patients had first-time positive ANCA in the study year. The indications for testing were suspicion for: AAV in 22 patients (23%), unspecified vasculitis in 24(25%), an inflammatory condition in 46(48%), and unknown in 4(4%). Twenty-eight patients (29% of first-time positives) were diagnosed with AAV, corresponding to 16(72%), 8(33%), 4(9%), and 0 patients tested for these indications, respectively; 49(51%) of patients had other inflammatory or infectious etiologies, and non-inflammatory diagnoses accounted for the remaining 19(20%). One hundred and forty-four repeat ANCAs were performed with life-time mean of 4.4 re-tests per patient (range 0–44). Routine monitoring accounted for 86(72%) of all repeat tests. Management was changed following 34% of all re-tests performed for changed clinical status and 1% of re-tests conducted routinely.
Conclusion
Few patients who start with low clinical suspicion for AAV and have positive ANCA are subsequently diagnosed with AAV. Serial ANCA testing is common but is not supported by clear evidence, and rarely leads to change in management. Clarification of guidelines on effective ANCA ordering may reduce hospital laboratory costs.
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References
Csernok E, Moosig F (2014) Current and emerging techniques for ANCA detection in vasculitis. Nat Rev Rheum 10(8):494–501
Savige J, Gillis D, Benson E, Davies D, Esnault V, Falk RJ et al. (1999) International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol 111(4):507–513
Holle JU, Herrmann WL, Csernok E (2012) Comparative analysis of different commercial ELISA systems for the detection of anti-neutrophil cytoplasm antibodies in ANCA-associated vasculitides. Curr Exp Rheum 30(Suppl 70):S66–S69
Damoiseaux J, Csernok E, Rasmussen N, Moosig F, van Paassen P, Baslund B et al. (2016) Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays. Ann Rheum Dis 76(4):647–653
Rao JK, Weinberger M, Oddone EZ, Allen NB, Landsman P, Feussner JR (1995) The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener granulomatosis. A literature review and meta-analysis. Ann Intern Med 123(12):925–932
Vassilopoulos D, Hoffman GS (1999) Clinical utility of testing for antineutrophil cytoplasmic antibodies. Clin Diagn Lab Immunol 6(5):645–651
Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS et al (2013) Efficacy of remission-induction regimens for ANCA-associated vasculitis. NEJM 369(5):417–427
Terrier B, Pagnoux C, Geri G, Karras A, Khouatra C, Aumaitre O et al (2014) Factors predictive of ANCA-associated vasculitis relapse in patients given Rituximab-maintenance therapy. Arthritis Rheumatol 66(Suppl 10):779
Birck R, Schmitt WH, Kaelsch IA, van der Woude FJ (2006) ANCA determinations for monitoring disease activity in patients with ANCA-associated vasculitis: systematic review. Am J Kidney Dis 47(1):15–23
Schönermarck U, Lamprecht P, Csernok E, Gross WL (2001) Prevalence and spectrum of rheumatic diseases associated with proteinase 3-antineutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase-ANCA. Rheumatology 40(2):178–184
Robinson PC, Steele RH (2009) Appropriateness of antineutrophil cytoplasmic antibody testing in a tertiary hospital. J Clin Pathol 62(8):743–745
Takala JH, Kautiainen H, Malmberg H, Leirisalo-Repo M (2008) Incidence of Wegener’s granulomatosis in Finland 1981–2000. Clin Exp Rheumatol 26(Suppl.49):S82–S86
Bhagat M, Sehra ST, Shahane A, Kwan M (2014) Utility of immunologic testing in suspected rheumatologic disease. Curr Allergy Asthma Rep 14:405
Davies DJ, Moran JE, Niall JF, Ryan GB (1982) Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br Med J (Clin Res Ed) 285(6342):606
Edgar JDM, McMillan SA, Bruce IN, Conlan SK (1995) An audit of ANCA in routine clinical practice. Postgrad Med J 71(840):605–612
Debard A, Thibaudin L, Thibaudin D, Monard E, Alamartine E, Cathébras P (2013) Spectrum of ANCA-Associated Disorders according to serological phenotype in routine care: retrospective case series of 209 patients. J Autoimmune Dis Rheumatol 1:36–45
Tsiveriotis K, Tsirogianni A, Pipi E, Soufleros K, Papasteriades C (2011) antineutrophil cytoplasmic antibodies testing in a large cohort of unselected greek patients. Autoimmune Dis 2011:626495
Roozendaal C, Kallenberg CGM (1999) Are anti-neutrophil cytoplasmic antibodies (ANCA) clinically useful in inflammatory bowel disease (IBD)? Clin Exp Immunol 116(2):206–213
Draibe J, Salama AD (2015) Association of ANCA associated vasculitis and rheumatoid arthritis: a lesser recognized overlap syndrome. Springerplus 4:50
Sprong PE, Bootsma H, Horst G, Huitema MG, Limburg PC, Cohen JW et al (1996) Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus. Br J Rheum 35(7):625 – 31
Sinclair D, Saas M, Stevens JM (2004) The effect of a symptom related “gating policy” on ANCA requests in routine clinical practice. J Clin Pathol 57(2):131–134
Mandl LA, Solomon DH, Smith EL, Lew RA, Katz JN, Shmerling RH (2002) Using antineutrophil cytoplasmic antibody testing to diagnose vasculitis: can test-ordering guidelines improve diagnostic accuracy? Arch Intern Med 162(13):1509–1514
Specks U (2012) Controversies in ANCA testing. Clev Clin J Med 79(Suppl 3):7–11
Finkelman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, St Clair EW et al (2007) Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med 147(9):611–619
Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T et al (2016) EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 75(9):1583–1594
Kemna MJ, Damoiseaux J, Austen J, Winkens B, Peters J, van Paassen P et al. (2015) ANCA as a predictor of relapse: useful in patients with renal involvement but not in patients with nonrenal disease. J Am Soc Nephrol 26(3):537–542
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CC, RAB, and NM wrote the manuscript. CC and RAB extracted the data. CC and NM performed the data analysis. All authors approved the final manuscript prior to submission.
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Cyrus Chehroudi, Ronald Booth, and Nataliya Milman declare that they have no conflicts of interest related to this study. This study was approved by the Ottawa Hospital’s Research Ethics Board on April 8, 2015 (Ethics Approval Protocol no. 20150233-01H) with waive of informed consent as this was a retrospective chart review. Data collection was in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Chehroudi, C., Booth, R.A. & Milman, N. Diagnostic outcome and indications for testing in patients with positive ANCA at a Canadian tertiary care centre. Rheumatol Int 38, 641–647 (2018). https://doi.org/10.1007/s00296-017-3905-0
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DOI: https://doi.org/10.1007/s00296-017-3905-0