Clinical diagnosis
Case 126
【Progress】He was treated with steroid hormone for 2 weeks, inducing marked improvement of edematous nasal and paranasal membrane and shrinkage of pulmonary nodules.
【Discussion】
Vasculitis is largely categorized into three types dependent upon the vascular sizes: large vessel vasculitis, aortitis (Takayasu disease), medium vessel vasculitis (Kawasaki disease), and small vessel vasculitis Burger disease. Antineutrophil cytoplasmic antibody (ANCA) related vasculitis occurs in medium and small vessels. As ANCA related vasculitis, microscopic polyangiitis, granulomatosis with polyangiitis (classically-called Wegener syndrome) and eosinophilic granulomatosis with polyangiitis (classically-called Churg–Strauss syndrome),are listed.(1, 2).
ANCA related vasculitis is caused by antigen-antibody complex of Type III hypersensitivity reaction (Type I, anaphylaxis by IgE, Type II, by antibody cytotoxic hypersensitivity by IgG, Type III, by complex of antigen & antibody, Type IV, delayed by T cell- and/or macrophage-mediated). Namely, the complex of ANCA-bound-neutrophils activates neutrophils adhering endothelial cells and attacking vascular wall. Further, from endothelial cells, various inflammatory substances effuse. It causes ANCA related vasculitis (3).
ANCA is categorized perinuclear-ANCA and cytoplasmic-ANCA with fluorescent stain pattern by indirect fluorescent antibody stain method. Myeroperoxidase (MPO) is an antigen compatible with perinuclear-ANCA and proteinase3 (PR3) is an antigen compatible with cytoplasmic-ANCA (1-3). Complex of MPO-ANCA causes microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis, while complex of PR3-ANCA causes granulomatosis with polyangiitis (3). The number of patients with granulomatosis with polyangiitis is approximately 2000 in Japan and that of patient with microscopic polyangiitis is three times or greater (4). Meanwhile, granulomatosis with polyangiitis occurs with more frequency than microscopic polyangiitis in Europe and USA (4). In our case, PR3-ANCA is positive, 89.2U/mL (<3.5) and MPO-ANCA is within normal limits, compatible with granulomatosis with polyangiitis.
Of the three ANCA related vasculitis, granulomatosis with polyangiitis causes the remarkable radiological findings: nodules and/or necrotizing nodules which implies cavity formation, plus ground glass opacity in the surrounding (5, 6). In our case, CT showed small to large nodules with no formation of cavity, and the larger nodules own the ground glass opacity in the surroundings. Radiologic configuration of eosinophilic granulomatosis with polyangiitis is similar as that of chronic eosinophilic pneumonia and acute eosinophilic pneumonia. Namely, it causes ground glass shadow in the peripheral zone along with pleural space like chronic eosinophilic pneumonia and/or consolidation with pleural effusion like acute eosinophilic pneumonia (5, 6). Radiologic configuration of microscopic polyangiitis is diffuse alveolar hemorrhage in acute phase and ground glass opacity of the peripheral zone in chronic phase. In short, radiologic configuration of chronic phase of eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis is the similar pattern as cryptogenic organizing pneumonia (COP) (5, 6).
【Summary】
We present a seventy one-year-old male in our hospital suffering from rhinitis for approximately one month and high fever of 38.7℃. Laboratory test revealed MPO-ANCA negative, PR3-ANCA 89.2U/mL (<3.5). Face CT and Chest CT showed sinusitis with diffuse thick edema of maxillary & ethmoid sinus and small to large nodules with ground glass opacity in the surrounding, respectively. These findings agree with granulomatosis with polyangiitis. It is borne in mind that ANCA related vasculitis is caused in medium and small vessels by antigen-antibody complex of Type III hypersensitivity reaction. In short, the complex of ANCA-bound-neutrophils activates neutrophils adhering endothelial cells and attacking vascular wall. Myeroperoxidase (MPO) is an antigen compatible with perinuclear-ANCA and proteinase3 (PR3) is an antigen compatible with cytoplasmic-ANCA. Complex of MPO-ANCA causes microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis, while complex of PR3-ANCA causes granulomatosis with polyangiitis. As the CT findings of granulomatosis with polyangiitis, nodules and/or necrotizing nodules which implies cavity formation, plus ground glass opacity in the surrounding. Meanwhile, eosinophilic granulomatosis looks like acute and chronic eosinophilic pneumonia on CT, and microscopic polyangiitis looks like diffuse alveolar hemorrhage in acute phase and COP in chronic phase.
【References】
1.Savige, J; Davies, D; Falk, RJ; Jennette, JC; Wiik, A (Mar 2000). "Antineutrophil cytoplasmic antibodies and associated diseases: a review of the clinical and laboratory features". Kidney International. 57 (3): 846–62.
2.Reumaux D, Duthilleul P, Roos D (2004). "Pathogenesis of diseases associated with antineutrophil cytoplasm autoantibodies". Hum Immunol. 65 (1): 1–12
3.Gross WL, et al.ANCA and associated diseases: immunodiagnostic and pathogenetic aspects. Clin Exp Immunol. 1993 Jan; 91(1): 1–12.
4.Harigai M, et al. 2017 Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis. Mod Rheumatol. 2018 Jul 13:1-29.
5.Feragalli B, et al. The lung in systemic vasculitis: radiological patterns and differential diagnosis. Br J Radiol. May 2016; 89(1061): 20150992..
6.Chung MP, et al. Imaging of Pulmonary Vasculitis. Radiology. 2010;255:322-341.
2018.10.24