Clinical diagnosis
Case 37
【Discussion】
Anti-neutrophil cytoplasmic antibody (ANCA) which is a IgG type self-antibody was found from focus of renal necrotic angitis by Davies, DJ. et al in 1982 (1). Thereafter, ANCA was classified into cytoplasmic ANCA and perinuclear ANCA due to findings of microscopic stain pattern (2, 3). Based on clarification of the antigen in each, cytoplasmic ANCA is called myeloperoxidase (MPO) ANCA and perinuclear ANCA is called proteinase-3(PR-3)-ANCA. PR-3-ANCA is known to be specific for Wegener granulomatosis and MPO-ANCA is relatively specific for microscopic polyangitis and Churg-Strauss syndrome (2, 3).
In Chapel Hill conference 2012, ANCA associated vasculitis is divided into microscopic polyangitis (positive MPO-ANCA), granulomatous polyangitis (PR-3-ANCA) including Wegener granulomatosis, and eosinophilic granulomatous polyangitis (relatively positive MPO-ANCA) including Churg-Strauss syndrome or allergic granulomatous polyangitis (4). The incidence of microscopic polyangitis is greater than that of granulomatous polyangitis in Japan and vice versa in the U.S.A. and Europe (5).
According to diagnostic criteria of microscopic polyangitis (2), Main symptoms are: [1] rapidly progressive glomerular nephritis, [2] pulmonary hemorrhage or interstitial pneumonitis, [3] subcutaneous hemorrhage. Histological findings are: necrosis of arteriole・capillary with perivascular infiltration of inflammatory cells, Laboratory tests are : [1] positive MPO-ANCA, [2] positive CRP, [3] Hematuria, proteinuria or elevation of values of BUN or Creatinin. Chest radiographs shows pulmonary hemorrhage or interstitial pneumonitis. In our case, chest radiograph and chest CT showed ground glass opacification and honey comb pattern which meets meet main symptom. Although renal biopsy did not reveal necrotic change of renal capillaries, laboratory test revealed elevation of MPO-ANCA and CRP, hematuria and proteinuria. These data meets definite microscopic polyangitis.
Representative images of MPO-ANCA or microscopic polyangitis are intra-alveolar hemorrhage or interstitial pnumonitis (6-8). In short, first, the images differ such as wedge-like ground glass, consolidation or wedge-like mass depending on the volume of intrapulmonary hemorrhage. Second, the existence of interstitial pneumonitis preceding microscopic polyangitis is known (6-8). Chronic inflammatory status might trigger the production of MPO-ANCA. MPO-ANCA is reported to be positive with the incidence of approximately 10 % of idiopathic pulmonary fibrosis (2, 6-8). In terms of microscopic honey comb pattern and small airway disease, MPO-ANCA associated pneumonia is reported to be distinctive from idiopathic pulmonary fibrosis (6). In MPO-ANCA associated pneumonia, mortality was relatively high and life threatening acute exacerbation may occur (5). During the disease course of IPF, the presence of pulmonary eosinophilia and ground glass opacufication on CT might be predictive of MPO-ANCA positive conversion (2, 3). In our case, CT at present showed reappeared ground glass opacification, corresponding to pulmonary hemorrhage and eight days later, consolidation, micro-honey comb pattern and bronchiectatic change corresponding to pulmonary interstitial disorder.
As treatments for MPO-ANCA(microscopic polyangitis) associated pneumonia, glucocorticoid hormone or immunosuppressive agents such as cyclophsphamide or rituximab are used (9, 10). In our case, pulse therapy of steroid hormone was first used and then, pulse therapy of cyclophosphamide was done, inducing improvement. However, relapse of MPO-ANCA(microscopic polyangitis) associated pneumonia occurred at this time.
【Summary】
We present a seventy six-year-old male with MPO-ANCA (microscopic polyangitis) associated pneumonia. Chest radiograph and CT showed initially ground glass opacification corresponding to pulmonary hemorrhage and eight days later, consolidation, micro-honey comb pattern and broncheiectatic change corresponding to interstitial disorder. We should keep in mind that MPO-ANCA (microscopic polyangitis) associated pneumonia is present when pulmonary bleeding or worsening of interstitial pneumonia with eosinophilia is encountered.
【References】
1.Davies, DJ et al. (Aug 28 – Sep 4, 1982). Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? British medical journal (Clinical research ed.). 1982; 285 : 606. doi:10.1136/bmj.285.6342.606. PMC 1499415. PMID 6297657
2.Yamada H, et al. ANCA: associated lung fibrosis. Semin Respir Crit Care Med. 2011 Jun;32(3):322-7. doi: 10.1055/s-0031-1279828. Epub 2011 Jun 14.
3.ANCA associated vasculitis-Diagnostic and therapeutic guideline 2014 (in Japanese) minds4.jcqhc.or.jp/minds/ANCA/anca.pdf
4.Jennette JC, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013; 65:1–11.
5.Ando M, et al. Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis. Respir Med. 2013;107:608-615. doi: 10.1016/j.rmed.2013.01.006. Epub 2013 Feb 19.
6.Tanaka T, et al. Interstitial pneumonia associated with MPO-ANCA: clinicopathological features of nine patients. Respir Med. 2012;106:1765-1770. doi: 10.1016/j.rmed.2012.08.024. Epub 2012 Sep 17.
7.Gaudin PB , et al. The pathologic spectrum of pulmonary lesions in patients with anti-neutrophil cytoplasmic autoantibodies specific for anti-proteinase 3 and anti-myeloperoxidase. 1995 Am. J. Clin. Pathol. 104:7–16.
8.Ando Y , et al. Thoracic manifestation of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related disease. J. Comput. Assist. Tomogr. 2004; 28:710–716
9.Specks U et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis.N Engl J Med 2013 Aug 1;369:417. (http://dx.doi.org/10.1056/NEJMoa1213277)
10.Stone JH, et al. for the RAVE−ITN Research Group. Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis. N Engl J Med 2010; 363:221-232July 15, 2010DOI: 10.1056/NEJMoa0909905.
2016.12.21