Subscribe to RSS
DOI: 10.1055/s-0031-1279824
Epidemiology and Etiology of Wegener Granulomatosis, Microscopic Polyangiitis, Churg-Strauss Syndrome and Goodpasture Syndrome: Vasculitides with Frequent Lung Involvement
Publication History
Publication Date:
14 June 2011 (online)
![](https://www.thieme-connect.de/media/srccm/201103/lookinside/thumbnails/10.1055-s-0031-1279824-1.jpg)
ABSTRACT
This review focuses on the epidemiological characteristics and etiologies of four primary systemic vasculitides with frequent lung involvement, namely Wegener granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS), and Goodpasture syndrome (GPS). Elucidation of the mechanisms underlying these vasculitides with frequent lung involvement is complicated by their rarity, which hampers the undertaking of large-scale studies; difficulties in classification; and their multifaceted clinical presentations, which infer the existence of several etiologic pathways. Notwithstanding, epidemiological research showed some evidence for international, interethnic, and temporal variations of the frequencies of these four vasculitides; led to the identification of several genetic and environmental risk factors; and provided insight on the extent to which genes and environment might contribute to their development. Available data support the concept that WG, MPA, CSS, and GPS have unique and shared risk determinants. Although the precise causes of these vasculitides are not yet fully understood and the development of prevention strategies is out of our reach at present, current knowledge enables the formulation of etiologic hypotheses to provide caregivers and their patients with valuable information on the nature of these rare entities.
KEYWORDS
Epidemiology - etiology - lung vasculitis - ANCA-associated vasculitis - Goodpasture syndrome
REFERENCES
- 1 Jennette J C, Falk R J. Small-vessel vasculitis. N Engl J Med. 1997; 337 (21) 1512-1523
- 2 Savage C O, Harper L, Adu D. Primary systemic vasculitis. Lancet. 1997; 349 (9051) 553-558
- 3 Carruthers D M, Watts R A, Symmons D P, Scott D G. Wegener's granulomatosis—increased incidence or increased recognition?. Br J Rheumatol. 1996; 35 (2) 142-145
- 4 Watts R A, Carruthers D M, Scott D G. Epidemiology of systemic vasculitis: changing incidence or definition?. Semin Arthritis Rheum. 1995; 25 (1) 28-34
- 5 Cotch M F, Hoffman G S, Yerg D E, Kaufman G I, Targonski P, Kaslow R A. The epidemiology of Wegener's granulomatosis: estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources. Arthritis Rheum. 1996; 39 (1) 87-92
- 6 Dadoniene J, Kirdaite G, Mackiewicz Z, Rimkevicius A, Haugeberg G. Incidence of primary systemic vasculitides in Vilnius: a university hospital population based study. Ann Rheum Dis. 2005; 64 (2) 335-336
- 7 González-Gay M A, García-Porrúa C. Systemic vasculitis in adults in northwestern Spain, 1988-1997: clinical and epidemiologic aspects. Medicine (Baltimore). 1999; 78 (5) 292-308
- 8 Gibson A, Stamp L K, Chapman P T, O'Donnell J L. The epidemiology of Wegener's granulomatosis and microscopic polyangiitis in a Southern Hemisphere region. Rheumatology (Oxford). 2006; 45 (5) 624-628
- 9 Gonzalez-Gay M A, Garcia-Porrua C, Guerrero J, Rodriguez-Ledo P, Llorca J. The epidemiology of the primary systemic vasculitides in northwest Spain: implications of the Chapel Hill Consensus Conference definitions. Arthritis Rheum. 2003; 49 (3) 388-393
- 10 Haugeberg G, Bie R, Bendvold A, Larsen A S, Johnsen V. Primary vasculitis in a Norwegian community hospital: a retrospective study. Clin Rheumatol. 1998; 17 (5) 364-368
- 11 Hissaria P, Cai F Z, Ahern M, Smith M, Gillis D, Roberts-Thomson P. Wegener's granulomatosis: epidemiological and clinical features in a South Australian study. Intern Med J. 2008; 38 (10) 776-780
- 12 Knight A, Ekbom A, Brandt L, Askling J. Increasing incidence of Wegener's granulomatosis in Sweden, 1975-2001. J Rheumatol. 2006; 33 (10) 2060-2063
- 13 Koldingsnes W, Nossent H. Epidemiology of Wegener's granulomatosis in northern Norway. Arthritis Rheum. 2000; 43 (11) 2481-2487
- 14 Mohammad A J, Jacobsson L T, Mahr A D, Sturfelt G, Segelmark M. Prevalence of Wegener's granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology (Oxford). 2007; 46 (8) 1329-1337
- 15 Mahr A, Guillevin L, Poissonnet M, Aymé S. Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener's granulomatosis, and Churg-Strauss syndrome in a French urban multiethnic population in 2000: a capture-recapture estimate. Arthritis Rheum. 2004; 51 (1) 92-99
- 16 Mohammad A J, Jacobsson L T, Westman K W, Sturfelt G, Segelmark M. Incidence and survival rates in Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and polyarteritis nodosa. Rheumatology (Oxford). 2009; 48 (12) 1560-1565
- 17 Ormerod A S, Cook M C. Epidemiology of primary systemic vasculitis in the Australian Capital Territory and south-eastern New South Wales. Intern Med J. 2008; 38 (11) 816-823
- 18 Reinhold-Keller E, Herlyn K, Wagner-Bastmeyer R, Gross W L. Stable incidence of primary systemic vasculitides over five years: results from the German vasculitis register. Arthritis Rheum. 2005; 53 (1) 93-99
- 19 Reinhold-Keller E, Herlyn K, Wagner-Bastmeyer R et al.. No difference in the incidences of vasculitides between north and south Germany: first results of the German vasculitis register. Rheumatology (Oxford). 2002; 41 (5) 540-549
- 20 Reinhold-Keller E, Zeidler A, Gutfleisch J, Peter H H, Raspe H H, Gross W L. Giant cell arteritis is more prevalent in urban than in rural populations: results of an epidemiological study of primary systemic vasculitides in Germany. Rheumatology (Oxford). 2000; 39 (12) 1396-1402
- 21 Takala J H, Kautiainen H, Malmberg H, Leirisalo-Repo M. Incidence of Wegener's granulomatosis in Finland 1981-2000. Clin Exp Rheumatol. 2008; 26 (3, suppl 49) S81-S85
- 22 Watts R A, Al-Taiar A, Scott D G, Macgregor A J. Prevalence and incidence of Wegener's granulomatosis in the UK general practice research database. Arthritis Rheum. 2009; 61 (10) 1412-1416
- 23 Watts R A, Lane S E, Bentham G, Scott D G. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom. Arthritis Rheum. 2000; 43 (2) 414-419
- 24 Salama A D, Levy J B, Lightstone L, Pusey C D. Goodpasture's disease. Lancet. 2001; 358 (9285) 917-920
- 25 Bolton W K. Goodpasture's syndrome. Kidney Int. 1996; 50 (5) 1753-1766
- 26 Brisson M, Edmunds W J, Law B et al.. Epidemiology of varicella zoster virus infection in Canada and the United Kingdom. Epidemiol Infect. 2001; 127 (2) 305-314
- 27 Lane S E, Watts R A, Bentham G, Innes N J, Scott D G. Are environmental factors important in primary systemic vasculitis? A case-control study. Arthritis Rheum. 2003; 48 (3) 814-823
- 28 Shah M K, Hugghins S Y. Characteristics and outcomes of patients with Goodpasture's syndrome. South Med J. 2002; 95 (12) 1411-1418
- 29 O'Donnell J L, Stevanovic V R, Frampton C, Stamp L K, Chapman P T. Wegener's granulomatosis in New Zealand: evidence for a latitude-dependent incidence gradient. Intern Med J. 2007; 37 (4) 242-246
- 30 Gatenby P A, Lucas R M, Engelsen O, Ponsonby A L, Clements M. Antineutrophil cytoplasmic antibody-associated vasculitides: could geographic patterns be explained by ambient ultraviolet radiation?. Arthritis Rheum. 2009; 61 (10) 1417-1424
- 31 Watts R A, Lane S E, Scott D G et al.. Epidemiology of vasculitis in Europe. Ann Rheum Dis. 2001; 60 (12) 1156-1157
- 32 Kamali S, Erer B, Artim-Esen B et al.. Predictors of damage and survival in patients with Wegener's granulomatosis: analysis of 50 patients. J Rheumatol. 2010; 37 (2) 374-378
- 33 Cisternas M, Soto L, Jacobelli S Grupo de estudio de las vasculitis, Sociedad Chilena de Reumatología et al. Clinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients [in Spanish]. Rev Med Chil. 2005; 133 (3) 273-278
- 34 Oh M J, Lee J Y, Kwon N H, Choi D C. Churg-Strauss syndrome: the clinical features and long-term follow-up of 17 patients. J Korean Med Sci. 2006; 21 (2) 265-271
- 35 de Souza F H, Radu Halpern A S, Valente Barbas C S, Shinjo S K. Wegener's granulomatosis: experience from a Brazilian tertiary center. Clin Rheumatol. 2010; 29 (8) 855-860
- 36 Flores-Suárez L F, Villa A R. Spectrum of Wegener granulomatosis in a Mexican population. Ann N Y Acad Sci. 2007; 1107 400-409
- 37 Fujimoto S, Uezono S, Hisanaga S et al.. Incidence of ANCA-associated primary renal vasculitis in the Miyazaki Prefecture: the first population-based, retrospective, epidemiologic survey in Japan. Clin J Am Soc Nephrol. 2006; 1 (5) 1016-1022
- 38 Teague C A, Doak P B, Simpson I J, Rainer S P, Herdson P B. Goodpasture's syndrome: an analysis of 29 cases. Kidney Int. 1978; 13 (6) 492-504
- 39 Watts R A, Scott D G, Jayne D R et al.. Renal vasculitis in Japan and the UK—are there differences in epidemiology and clinical phenotype?. Nephrol Dial Transplant. 2008; 23 (12) 3928-3931
- 40 Knight A, Sandin S, Askling J. Risks and relative risks of Wegener's granulomatosis among close relatives of patients with the disease. Arthritis Rheum. 2008; 58 (1) 302-307
- 41 Knight A, Sandin S, Askling J. Increased risk of autoimmune disease in families with Wegener's granulomatosis. J Rheumatol. 2010; 37 (12) 2553-2558
- 42 Phelps R G, Rees A J. The HLA complex in Goodpasture's disease: a model for analyzing susceptibility to autoimmunity. Kidney Int. 1999; 56 (5) 1638-1653
- 43 Heckmann M, Holle J U, Arning L et al.. The Wegener's granulomatosis quantitative trait locus on chromosome 6p21.3 as characterised by tagSNP genotyping. Ann Rheum Dis. 2008; 67 (7) 972-979
- 44 Jagiello P, Gencik M, Arning L et al.. New genomic region for Wegener's granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes. Hum Genet. 2004; 114 (5) 468-477
- 45 Vaglio A, Martorana D, Maggiore U Secondary and Primary Vasculitis Study Group et al. HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome. Arthritis Rheum. 2007; 56 (9) 3159-3166
- 46 Wieczorek S, Hellmich B, Gross W L, Epplen J T. Associations of Churg-Strauss syndrome with the HLA-DRB1 locus, and relationship to the genetics of antineutrophil cytoplasmic antibody-associated vasculitides: comment on the article by Vaglio et al. Arthritis Rheum. 2008; 58 (1) 329-330
- 47 Tsuchiya N, Kobayashi S, Hashimoto H, Ozaki S, Tokunaga K. Association of HLA-DRB1*0901-DQB1*0303 haplotype with microscopic polyangiitis in Japanese. Genes Immun. 2006; 7 (1) 81-84
- 48 Esnault V L, Testa A, Audrain M et al.. Alpha 1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis. Kidney Int. 1993; 43 (6) 1329-1332
- 49 Mahr A D, Neogi T, Merkel P A. Epidemiology of Wegener's granulomatosis: Lessons from descriptive studies and analyses of genetic and environmental risk determinants. Clin Exp Rheumatol. 2006; 24 (2, suppl 41) S82-S91
- 50 Mahr A D, Edberg J C, Stone J H et al.. Alpha1-antitrypsin deficiency-related alleles Z and S and the risk of Wegener's granulomatosis. Arthritis Rheum. 2010; 62 (12) 3760-3767
- 51 Carr E J, Niederer H A, Williams J et al.. Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis. BMC Med Genet. 2009; 10 121
- 52 Jagiello P, Aries P, Arning L et al.. The PTPN22 620W allele is a risk factor for Wegener's granulomatosis. Arthritis Rheum. 2005; 52 (12) 4039-4043
- 53 Holle J U, Wieczorek S, Gross W L. Genetic association studies in ANCA-associated vasculitides: what we have learnt so far and what needs to be done in the future. Clin Exp Rheumatol. 2010; 28 (1, suppl 57) 5-7
- 54 Wieczorek S, Hoffjan S, Chan A et al.. Novel association of the CD226 (DNAM-1) Gly307Ser polymorphism in Wegener's granulomatosis and confirmation for multiple sclerosis in German patients. Genes Immun. 2009; 10 (6) 591-595
- 55 Giscombe R, Wang X, Huang D, Lefvert A K. Coding sequence 1 and promoter single nucleotide polymorphisms in the CTLA-4 gene in Wegener's granulomatosis. J Rheumatol. 2002; 29 (5) 950-953
- 56 Slot M C, Sokolowska M G, Savelkouls K G, Janssen R G, Damoiseaux J G, Tervaert J W. Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis. Clin Immunol. 2008; 128 (1) 39-45
- 57 Spriewald B M, Witzke O, Wassmuth R et al.. Distinct tumour necrosis factor alpha, interferon gamma, interleukin 10, and cytotoxic T cell antigen 4 gene polymorphisms in disease occurrence and end stage renal disease in Wegener's granulomatosis. Ann Rheum Dis. 2005; 64 (3) 457-461
- 58 Zhou Y, Huang D, Paris P L, Sauter C S, Prock K A, Hoffman G S. An analysis of CTLA-4 and proinflammatory cytokine genes in Wegener's granulomatosis. Arthritis Rheum. 2004; 50 (8) 2645-2650
- 59 Hemminki K, Li X, Sundquist J, Sundquist K. Familial associations of rheumatoid arthritis with autoimmune diseases and related conditions. Arthritis Rheum. 2009; 60 (3) 661-668
- 60 Mahr A, Artigues N, Coste J, Aouba A, Pagnoux C, Guillevin L. French Vasculitis Study Group . Seasonal variations in onset of Wegener's granulomatosis: increased in summer?. J Rheumatol. 2006; 33 (8) 1615-1622
- 61 Kain R, Exner M, Brandes R et al.. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med. 2008; 14 (10) 1088-1096
- 62 Nuyts G D, Van Vlem E, De Vos A et al.. Wegener granulomatosis is associated to exposure to silicon compounds: a case-control study. Nephrol Dial Transplant. 1995; 10 (7) 1162-1165
- 63 Hogan S L, Cooper G S, Savitz D A et al.. Association of silica exposure with anti-neutrophil cytoplasmic autoantibody small-vessel vasculitis: a population-based, case-control study. Clin J Am Soc Nephrol. 2007; 2 (2) 290-299
- 64 Gregorini G, Ferioli A, Donato F et al.. Association between silica exposure and necrotizing crescentic glomerulonephritis with p-ANCA and anti-MPO antibodies: a hospital-based case-control study. Adv Exp Med Biol. 1993; 336 435-440
- 65 Beaudreuil S, Lasfargues G, Lauériere L et al.. Occupational exposure in ANCA-positive patients: a case-control study. Kidney Int. 2005; 67 (5) 1961-1966
- 66 Parks C G, Conrad K, Cooper G S. Occupational exposure to crystalline silica and autoimmune disease. Environ Health Perspect. 1999; 107 (suppl 5) 793-802
- 67 Duna G F, Cotch M F, Galperin C, Hoffman D B, Hoffman G S. Wegener's granulomatosis: role of environmental exposures. Clin Exp Rheumatol. 1998; 16 (6) 669-674
- 68 Albert D, Clarkin C, Komoroski J, Brensinger C M, Berlin J A. Wegener's granulomatosis: possible role of environmental agents in its pathogenesis. Arthritis Rheum. 2004; 51 (4) 656-664
- 69 Knight A, Sandin S, Askling J. Occupational risk factors for Wegener's granulomatosis: a case-control study. Ann Rheum Dis. 2010; 69 (4) 737-740
- 70 Cuadrado M J, D'Cruz D, Lloyd M, Mujic F, Khamashta M A, Hughes G R. Allergic disorders in systemic vasculitis: a case-controlled study. Br J Rheumatol. 1994; 33 (8) 749-753
- 71 Haubitz M, Woywodt A, de Groot K, Haller H, Goebel U. Smoking habits in patients diagnosed with ANCA associated small vessel vasculitis. Ann Rheum Dis. 2005; 64 (10) 1500-1502
- 72 Mohammad A J, Segelmark M. Association of cigarette smoking with organ damage in primary systemic vasculitis. Scand J Rheumatol. 2011; 40 (1) 51-56
- 73 Gao Y, Zhao M H, Guo X H, Xin G, Gao Y, Wang H Y. The prevalence and target antigens of antithyroid drugs induced antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with hyperthyroidism. Endocr Res. 2004; 30 (2) 205-213
- 74 Gunton J E, Stiel J, Clifton-Bligh P, Wilmshurst E, McElduff A. Prevalence of positive anti-neutrophil cytoplasmic antibody (ANCA) in patients receiving anti-thyroid medication. Eur J Endocrinol. 2000; 142 (6) 587
- 75 Harper L, Chin L, Daykin J et al.. Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves' disease. Clin Endocrinol (Oxf). 2004; 60 (6) 671-675
- 76 Sera N, Ashizawa K, Ando T et al.. Treatment with propylthiouracil is associated with appearance of antineutrophil cytoplasmic antibodies in some patients with Graves' disease. Thyroid. 2000; 10 (7) 595-599
- 77 Slot M C, Links T P, Stegeman C A, Tervaert J W. Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: a long-term follow-up study. Arthritis Rheum. 2005; 53 (1) 108-113
- 78 Wada N, Mukai M, Kohno M, Notoya A, Ito T, Yoshioka N. Prevalence of serum anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) in patients with Graves' disease treated with propylthiouracil and thiamazole. Endocr J. 2002; 49 (3) 329-334
- 79 Zhao M H, Chen M, Gao Y, Wang H Y. Propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Kidney Int. 2006; 69 (8) 1477-1481
- 80 Lionaki S, Hogan S L, Falk R J et al.. Association between thyroid disease and its treatment with ANCA small-vessel vasculitis: a case-control study. Nephrol Dial Transplant. 2007; 22 (12) 3508-3515
- 81 Hauser T, Mahr A, Metzler C et al.. The leucotriene receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study. Thorax. 2008; 63 (8) 677-682
- 82 Harrold L R, Patterson M K, Andrade S E et al.. Asthma drug use and the development of Churg-Strauss syndrome (CSS). Pharmacoepidemiol Drug Saf. 2007; 16 (6) 620-626
- 83 Jennette J C, Falk R J, Andrassy K et al.. Nomenclature of systemic vasculitides: proposal of an international consensus conference. Arthritis Rheum. 1994; 37 (2) 187-192
- 84 Watts R, Lane S, Hanslik T et al.. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis. 2007; 66 (2) 222-227
- 85 Hunder G G, Arend W P, Bloch D A et al.. The American College of Rheumatology 1990 criteria for the classification of vasculitis: introduction. Arthritis Rheum. 1990; 33 (8) 1065-1067
- 86 Zhou Y, Giscombe R, Huang D, Lefvert A K. Novel genetic association of Wegener's granulomatosis with the interleukin 10 gene. J Rheumatol. 2002; 29 (2) 317-320
- 87 Bártfai Z, Gaede K I, Russell K A, Muraközy G, Müller-Quernheim J, Specks U. Different gender-associated genotype risks of Wegener's granulomatosis and microscopic polyangiitis. Clin Immunol. 2003; 109 (3) 330-337
- 88 Wieczorek S, Hellmich B, Arning L et al.. Functionally relevant variations of the interleukin-10 gene associated with antineutrophil cytoplasmic antibody-negative Churg-Strauss syndrome, but not with Wegener's granulomatosis. Arthritis Rheum. 2008; 58 (6) 1839-1848
Alfred MahrM.D.
Department of Internal Medicine, Hospital Saint-Louis, University Paris 7–Paris Diderot, Assistance Publique–Hôpitaux de Paris, 1, avenue Claude-Vellefaux
75475 Paris Cedex 10, France
Email: alfred.mahr@sls.aphp.fr