Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis
- Ronald J Falk, MD
Ronald J Falk, MD
- Nan and Hugh Cullman Eminent Professor of Nephrology
- Chair, Department of Medicine
- Director, UNC Kidney Center
- University of North Carolina-Chapel Hill
- Peter A Merkel, MD, MPH
Peter A Merkel, MD, MPH
- Section Editor — Vasculitis
- Chief, Division of Rheumatology
- University of Pennsylvania
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Gerald B Appel, MD
Gerald B Appel, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Columbia University College of Physicians and Surgeons
In January 2011, the Boards of Directors of the American College of Rheumatology (ACR), the American Society of Nephrology (ASN), and the European League Against Rheumatism (EULAR) recommended that the name "Wegener's granulomatosis" be changed to "granulomatosis with polyangiitis," abbreviated as GPA [1-3]. This change reflects a plan to gradually shift from honorific eponyms to a disease-descriptive or etiology-based nomenclature.
Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) include granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), including renal-limited vasculitis (RLV), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) [4-6]. All are associated with ANCA and have similar features on renal histology (eg, a focal necrotizing, often crescentic, pauci-immune glomerulonephritis).
The clinical manifestations and diagnosis of GPA, MPA, and RLV are reviewed here. EGPA has a different presentation and prognosis compared with the other forms of AAV. (See "Epidemiology, pathogenesis, and pathology of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)" and "Treatment and prognosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)".)
Issues related to ANCA, the pathogenesis of AAV, and the vasculitides in general are discussed separately. (See "Clinical spectrum of antineutrophil cytoplasmic autoantibodies" and "Pathogenesis of granulomatosis with polyangiitis and related vasculitides" and "Overview of and approach to the vasculitides in adults".)
CLASSIFICATION AND DIAGNOSTIC CRITERIA
There have been several attempts to standardize the classification and diagnostic criteria for small-vessel vasculitis [5,7,8]. The International Chapel Hill Consensus Conference (CHCC) criteria, which were revised in 2012, are the mostly commonly cited (table 1). However, as will be described, the classification algorithms have important limitations. (See 'Limitations of classification algorithms' below.)
- Falk RJ, Gross WL, Guillevin L, et al. Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis. Arthritis Rheum 2011; 63:863.
- Falk RJ, Gross WL, Guillevin L, et al. Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis. J Am Soc Nephrol 2011; 22:587.
- Falk RJ, Gross WL, Guillevin L, et al. Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis. Ann Rheum Dis 2011; 70:704.
- Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65:1.
- Jennette JC, Falk RJ, Andrassy K, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37:187.
- Hogan SL, Falk RJ, Chin H, et al. Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis. Ann Intern Med 2005; 143:621.
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- Hogan SL, Falk RJ, Nachman PH, Jennette JC. Various forms of life in antineutrophil cytoplasmic antibody-associated vasculitis. Ann Intern Med 2006; 144:377.
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- Craven A, Robson J, Ponte C, et al. ACR/EULAR-endorsed study to develop Diagnostic and Classification Criteria for Vasculitis (DCVAS). Clin Exp Nephrol 2013; 17:619.
- Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med 1997; 337:1512.
- Seo P, Stone JH. The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med 2004; 117:39.
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- Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116:488.
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- Haas M, Eustace JA. Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases. Kidney Int 2004; 65:2145.
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- Eisenberger U, Fakhouri F, Vanhille P, et al. ANCA-negative pauci-immune renal vasculitis: histology and outcome. Nephrol Dial Transplant 2005; 20:1392.
- Daoud MS, Gibson LE, DeRemee RA, et al. Cutaneous Wegener's granulomatosis: clinical, histopathologic, and immunopathologic features of thirty patients. J Am Acad Dermatol 1994; 31:605.
- Harper SL, Letko E, Samson CM, et al. Wegener's granulomatosis: the relationship between ocular and systemic disease. J Rheumatol 2001; 28:1025.
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- Ravanan R, Weale AR, Lear PA, et al. Hemoperitoneum in a patient with ANCA-associated polyangiitis syndrome. Am J Kidney Dis 2004; 44:908.
- Merkel PA, Lo GH, Holbrook JT, et al. Brief communication: high incidence of venous thrombotic events among patients with Wegener granulomatosis: the Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med 2005; 142:620.
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- Bautz DJ, Preston GA, Lionaki S, et al. Antibodies with dual reactivity to plasminogen and complementary PR3 in PR3-ANCA vasculitis. J Am Soc Nephrol 2008; 19:2421.
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- Finkielman JD, Lee AS, Hummel AM, et al. ANCA are detectable in nearly all patients with active severe Wegener's granulomatosis. Am J Med 2007; 120:643.e9.
- Falk RJ, Jennette JC. ANCA small-vessel vasculitis. J Am Soc Nephrol 1997; 8:314.
- Hagen EC, Daha MR, Hermans J, 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; 53:743.
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- Kitching AR, Hutchinson P, Atkins RC, Holdsworth SR. The role of flow cytometric ANCA detection in screening for acute pauci-immune crescentic glomerulonephritis. Nephrol Dial Transplant 2004; 19:365.
- Jennette JC, Falk RJ. The pathology of vasculitis involving the kidney. Am J Kidney Dis 1994; 24:130.
- Banerjee A, McKane W, Thiru S, Farrington K. Wegener's granulomatosis presenting as acute suppurative interstitial nephritis. J Clin Pathol 2001; 54:787.
- Wen YK, Chen ML. Transformation from tubulointerstitial nephritis to crescentic glomerulonephritis: an unusual presentation of ANCA-associated renal vasculitis. Ren Fail 2006; 28:189.
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- Hauer HA, Bajema IM, Van Houwelingen HC, et al. Determinants of outcome in ANCA-associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients. Kidney Int 2002; 62:1732.
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- NEW TERMINOLOGY
- CLASSIFICATION AND DIAGNOSTIC CRITERIA
- ACR criteria
- Chapel Hill Consensus Conference criteria
- European Medicines Agency algorithm
- Limitations of classification algorithms
- CLINICAL PRESENTATION
- Common clinical presentations
- Ear, nose, and throat
- Tracheal and pulmonary disease
- Renal manifestations
- - ANCA-negative pauci-immune crescentic glomerulonephritis
- Cutaneous manifestations
- Ophthalmic and orbital manifestations
- Other manifestations
- Nonsevere ANCA-associated vasculitis
- Establishing the diagnosis
- Physical examination
- Laboratory investigation
- Radiographic tests
- Bronchoalveolar lavage
- - Renal histology
- Pauci-immune glomerulonephritis
- Histologic variants
- Histopathologic classification
- - Renal-limited vasculitis
- DIFFERENTIAL DIAGNOSIS
- Concurrent glomerular disease
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS