Utility of anti-neutrophil cytoplasmic antibody screening in idiopathic interstitial lung disease Vasculitis screening in ILD

Main Article Content

Lee Fidler
Sonja Kandel
Jolene Fisher
Shikha Mittoo
Shane Shapera

Keywords

interstitial lung disease, vasculitis, screening

Abstract

Background: Interstitial lung disease (ILD) is an established manifestation of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Autoimmune serologic screening is recommended by international consensus guidelines during the evaluation of idiopathic ILD, but ANCA testing only on a case-by-case basis. Objective: We aimed to evaluate the role of ANCA screening in patients with idiopathic ILD. Methods: We performed a retrospective review of patients seen between September 2015 and April 2017 in the ILD clinic at Toronto General Hospital. Patients referred with confirmed or suspected connective tissue disease were excluded. Patient demographics, symptoms, chest imaging, and pulmonary function testing was collected. We performed descriptive statistics based on the presence of ANCAs and estimated operating characteristics for ANCA screening. Results: In total, 360 patients with idiopathic ILD were reviewed, 159 met study inclusion criteria and 4 (2.5%) tested positive for ANCAs. Two patients (1.2%) had elevated myeloperoxidase-ANCAs (MPO-ANCA) and 2 (1.2%) had elevated proteinase-3-ANCAs (PR3-ANCA). There were no significant associations between patient demographics and ANCAs. One patient (0.6%) with PR3-ANCAs was diagnosed with vasculitis following rheumatologic evaluation. Despite negative ANCA testing, 1 patient (0.6%) was diagnosed with vasculitis following rheumatologic evaluation. The sensitivity and specificity of ANCA screening for vasculitis in patients with ILD was calculated as 50% (95% CI, 1.3%-98.7%) and 98% (95%CI, 4.4-155.5) respectively. Negative and positive likelihood ratios were 0.5 (95%CI 0.1-2.0) and 26.2 (95%CI 4.4-155.5) respectively. Conclusion: ANCA screening in patients with idiopathic ILD rarely yields positive results. These results support an individualized approach to ANCA testing as opposed to widespread screening.

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References

1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65:1–11.
2. Hoffman GS, Specks U. Antineutrophil cytoplasmic antibodies. Arthritis Rheum. 1998; 41(9): 1521-1537.
3. Guillevin L, Durand-Gasselin B, Cevallos R, Gayraud M, Lhote F, Callard P, et al. Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum. 1999; 42(3): 421.
4. Sinico RA, Di Toma L, Maggiore U, Tosoni C, Bottero P, Sabadini E, et al. Renal involvement in Churg-Strauss syndrome. Am J Kidney Dis. 2006; 47(5): 770.
5. Hagen EC, Daha MR, Hermans J, Andrassy K, Csernok E, Gaskin G, et al. Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR project for ANCA assay standardization. Kidney Int. 1998; 53(3): 743.
6. Fisher JH, Kolb M, Algamdi M, et al. Baseline characteristics and comorbidities in the CAnadian REgistry for Pulmonary Fibrosis. BMC Pulm Med. 2019; 19(1):223.
7. Arulkumaran N, Periselneris N, Gaskin G, Strickland N, Ind PW, Pusey CD, Salama AD. Intersitital lung disease and ANCA-associated vasculitis: a retrospective observational cohort study. Rheumatology. 2011; 50: 2035-43.
8. Alba MA, Flores-Suarez LF, Henderson AG, Xiao H, Hu P, Nachman PH, Falk RJ, Jennette JC. Interstitial lung disease in ANCA vasculitis. Autoimmun Rev. 2017; 16(7): 722-9.
9. Baqir M, Yi EE, Colby TV, Cox CW, Ryu JH, Specks U. Radiologic and pathologic characteristics of myeloperoxidase-antineutrophil cytoplasmic antibody-associated interstitial lung disease: a retrospective analysis. Sarcoidosis Vasc Diffuse Lung Dis 2019; 36(3): 195-201.
10. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT statement. Am J Respir Crit Care Med. 2018; 198(5):e44-68.
11. Mohammad AJ. An update on the epidemiology of ANCA-associated vasculitis. Rheumatology. 2020; 59(Supplement_3): iii42-iii50.
12. Ntatsaki E, Watts RA, Scott DG. Epidemiology of ANCA-associated vasculitis. Rheum Dis Clin North Am. 2010; 36(3):447-61.
13. Katsuyama T, Sada K, Makino H. Current concept and epidemiology of systemic vasculitides. Allergol Int. 2014l 63(4): 505-13.
14. Katsumata Y, Kawaguchi Y, Yamanaka H. Interstitial lung disease with ANCA-associated vasculitis. Clin Med Insights Circ Respir Pulm Med. 2015l 9(Suppl 1): 51-56.
15. Liu GY, Ventura IB, Achtar-Zadeh N, Elicker BM, Jones KD, Wolters PJ, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in North American patients with idiopathic pulmonary fibrosis. Chest. 2019; 156(4): 715-723.
16. Kishore N, Gupta N, Dhar A, Abrari A, Rath P. Interstitial lung disease with usual interstitial pneumonia pattern preceding the presentation of ANCA-associated vasculitis by 4 years: coincidence of correlation? Breathe. 2018; 14: e105-110.
17. T, Romagnoli M, Girelli F, Claussen M, Rabe KF. The use of auto-antibody testing in the evaluation of interstitial lung disease (ILD)—A practical approach for the pulmonologist. Respir Med. 2016; 113:80-92.
18. Wilson JMG, Jungner G. Principles and practice of screening for disease. World Health Organization. Geneva; 1968.
19. Mandl LA, Solomon DH, Smith EL, Lew RA, Katz JN, Shmerling RH. Using antineutrophil cytoplasmic antibody testing to diagnose vasculitis. Arch Intern Med. 2002; 162: 1509-1514.
20. Savige J, Gillis D, Benson E, et al. International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA). Am J Clin Pathol. 1999; 111: 507-513.
21. Kagiyama N, Takayanagi N, Kanauchi T, Ishiguro T, Yanagisawa T, Sugita Y. Antineutriphil cytoplasmic antibody-positive conversion in microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis. BMJ Open Resp Res. 2014;2:e000058.
22. Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015; 46: 976-987.
23. Chartrand S, Swigris JJ, Stanchev L, Lee JS, Brown KK, Fischer A. Clinical features and natural history of interstitial pneumonia with autoimmune features: a single center experience. Respir Med. 2016; 119:150-154.
24. Bossuyt X, Cohen Tervaert J, Arimura Y, et al. Revised 2017 international consensus on testing ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis. Nat Rev Rheumatol. 2017; 13(11):683-692.