ANCA-Associated Lung Fibrosis

ABSTRACT

The possible link between pulmonary fibrosis, anti-neutrophil cytoplasmic autoantibody (ANCA) positivity, and vasculitis is poorly understood. During the past 6 years, five retrospective case-control studies have been published. These studies suggest that pulmonary fibrosis (PF) is an underestimated manifestation of ANCA-associated vasculitis. Common clinical characteristics include older age (around 70 years), constant positivity of myeloperoxidase (MPO)-ANCA and the poor prognosis of the pulmonary disease. The diagnosis of PF often predates the development of vasculitis. There are no significant differences of pulmonary function parameters, bronchoalveolar lavage analysis, or high-resolution computed tomographic (HRCT) findings between ANCA-associated PF and idiopathic pulmonary fibrosis (IPF). The high mortality rate of ANCA-associated PF indicates that a search for ANCAs should be performed at diagnosis in every patient with PF because the presence of ANCAs increases the risk of development of vasculitis and should promote specific monitoring of patients with positive MPO-ANCA.

MPO-ANCA - pulmonary fibrosis - interstitial lung disease - microscopic polyangiitis

REFERENCES

• 1 Nada A K, Torres V E, Ryu J H, Lie J T, Holley K E. Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients.  Mayo Clin Proc. 1990;  65 (6) 847-856
• 2 Gaudin P B, Askin F B, Falk R J, Jennette J C. The pathologic spectrum of pulmonary lesions in patients with anti-neutrophil cytoplasmic autoantibodies specific for anti-proteinase 3 and anti-myeloperoxidase.  Am J Clin Pathol. 1995;  104 (1) 7-16
• 3 Gal A A, Salinas F F, Staton Jr G W. The clinical and pathological spectrum of antineutrophil cytoplasmic autoantibody-related pulmonary disease: a comparison between perinuclear and cytoplasmic antineutrophil cytoplasmic autoantibodies.  Arch Pathol Lab Med. 1994;  118 (12) 1209-1214
• 4 Homma S, Matsushita H, Nakata K. Pulmonary fibrosis in myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitides.  Respirology. 2004;  9 (2) 190-196
• 5 Nozu T, Kondo M, Suzuki K, Tamaoki J, Nagai A. A comparison of the clinical features of ANCA-positive and ANCA-negative idiopathic pulmonary fibrosis patients.  Respiration. 2009;  77 (4) 407-415
• 6 Hervier B, Pagnoux C, Agard C French Vasculitis Study Group et al. Pulmonary fibrosis associated with ANCA-positive vasculitides: retrospective study of 12 cases and review of the literature.  Ann Rheum Dis. 2009;  68 (3) 404-407
• 7 Foulon G, Delaval P, Valeyre D et al.. ANCA-associated lung fibrosis: analysis of 17 patients.  Respir Med. 2008;  102 (10) 1392-1398
• 8 Tzelepis G E, Kokosi M, Tzioufas A et al.. Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis.  Eur Respir J. 2010;  36 (1) 116-121
• 9 American Thoracic Society . Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS).  Am J Respir Crit Care Med. 2000;  161 (2 Pt 1) 646-664
• 10 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
• 11 Birnbaum J, Danoff S, Askin F B, Stone J H. Microscopic polyangiitis presenting as a “pulmonary-muscle” syndrome: is subclinical alveolar hemorrhage the mechanism of pulmonary fibrosis?.  Arthritis Rheum. 2007;  56 (6) 2065-2071
• 12 Eschun G M, Mink S N, Sharma S. Pulmonary interstitial fibrosis as a presenting manifestation in perinuclear antineutrophilic cytoplasmic antibody microscopic polyangiitis.  Chest. 2003;  123 (1) 297-301
• 13 Al Riyami B M, Al Kaabi J K, Elagib E M, El Khatim H S, Woodhouse N J. Subclinical pulmonary haemorrhage causing a restrictive lung defect in three siblings with a unique urticarial vasculitis syndrome.  Clin Rheumatol. 2003;  22 (4–5) 309-313
• 14 Schnabel A, Reuter M, Csernok E, Richter C, Gross W L. Subclinical alveolar bleeding in pulmonary vasculitides: correlation with indices of disease activity.  Eur Respir J. 1999;  14 (1) 118-124
• 15 Buschman D L, Ballard R. Progressive massive fibrosis associated with idiopathic pulmonary hemosiderosis.  Chest. 1993;  104 (1) 293-295
• 16 Corrin B, Jagusch M, Dewar A et al.. Fine structural changes in idiopathic pulmonary haemosiderosis.  J Pathol. 1987;  153 (3) 249-256
• 17 Foucher P, Heeringa P, Petersen A H et al.. Antimyeloperoxidase-associated lung disease. An experimental model.  Am J Respir Crit Care Med. 1999;  160 (3) 987-994
• 18 Falk R J, Terrell R S, Charles L A, Jennette J C. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro.  Proc Natl Acad Sci U S A. 1990;  87 (11) 4115-4119
• 19 Collins C E, Quismorio Jr F P. Pulmonary involvement in microscopic polyangiitis.  Curr Opin Pulm Med. 2005;  11 (5) 447-451
• 20 Cambridge G, Williams M, Leaker B, Corbett M, Smith C R. Anti-myeloperoxidase antibodies in patients with rheumatoid arthritis: prevalence, clinical correlates, and IgG subclass.  Ann Rheum Dis. 1994;  53 (1) 24-29
• 21 Braun M G, Csernok E, Schmitt W H, Gross W L. Incidence, target antigens, and clinical implications of antineutrophil cytoplasmic antibodies in rheumatoid arthritis.  J Rheumatol. 1996;  23 (5) 826-830
• 22 Cottin V, Nunes H, Brillet P Y Groupe d'Etude et de Recherche sur les Maladies Orphelines Pulmonaires (GERM O P) et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity.  Eur Respir J. 2005;  26 (4) 586-593