Online publication June 24, 2009 ANCA MPA WG ANCA CRP PSL CY / AZ MPA/WG 2 7 QOL PSL CY/AZ 3 CMV J Jpn Coll Angiol, 2009, 49: 93 99 compromized host, immunosuppressive therapy, ANCA associated vasculitis, infection control antineutrophil cytoplasmic antibodies: ANCA renal limited vasculitis: RLV Wegener s granulomatosis: WG microscopic polyangiitis: MPA allergic granulomatous angiitis: AGA ANCA ANCA-associated vasculitis: AAV 1 CS IS 2 1998 AAV 3 2008 MPO-ANCA JMAAV 4 1998 AAV AAV 266 1:1.7 56 C PR-3 AAV P MPO AAV 1:3 MPA WG AGA 121 RLV 104 RA PSS SSc 33 [ rapidly progressive glomerulonephritis: RPGN ] [ WG ] ANCA CRP 2008 9 8 THE JOURNAL of JAPANESE COLLEGE of ANGIOLOGY Vol. 49, 2009 93
Table 1 Clinical findings in dead AAV cases (n = 41) I: Infection death (n = 19) II: Vasculitis death (n = 22) Fisher s test Age > 65 y.o. 12/19 (63%) 16/22 (73%) Male/Female 18/19 (95%) 14/22 (64%) RPGN 17/19 (89%) 19/22 (86%) Dyspnea 14/19 (74%) 17/22 (77%) Lung bleeding 3/18 (16%) 14/22 (64%) *p < 0.01 GI. bleeding 0/19 (0%) 6/22 (27%) *p < 0.02 CNS sym 1/18 (5.6%) 8/22 (36.4%) *p < 0.02 Anemia 4/19 (21%) 16/22 (73%) Leukocytosis 14/19 (74%) 19/22 (86%) Thrombocytosis 4/19 (21%) 6/22 (27%) High CRP 19/19 (100%) 22/22 (100%) High LDH 10/19 (53%) 16/22 (73%) PSL < 60mg/day 8/16 (50%) 13/15 (87%) *p < 0.05 Pulse steroid therapy 12/17 (71%) 19/20 (95%) Immunosuppressant 11/19 (58%) 10/22 (46%) Plasmapheresis 5/18 (28%) 7/21 (33%) γ 1, 2 AAV ANCA CRP ANCA CRP 1, 2 AAV CS CY IS RLV AAV 60 70 10 30 41 19 37 4 MRSA 3 Table 1 1998 AAV 41 3 I 19 II 22 RPGN I II p < 0.01 CS PSL 60mg/ I II p < 0.05 AAV CS PSL 60mg/ Keller 5 WG 155 CY WG 3 6 PSL 5 10mg/ Fig. 1 2008 JMAAV MPO-ANCA 50 19 29 CY 27 14 51.5 17 CY 3.877 6 β AAV β CSBG ELISA 7 CSBG β β-6 β Fig. 2 CSBG 22 2,677 ± 1,686U 94 Vol. 49, 2009
Figure 1 Infection events periods in MAAV (n = 50)(2008). 6 Figure 2 Comparison of Anti-CSBG titer in AAV patients. 9 AAV 14 691 ± 522U AAV 24 547 ± 416U CSBG CSBG Fig. 3 MPO-ANCA 68U AAV RPGN β 300U CSBG 100U AAV CS 2 MPO-ANCA CSBG 800U 2 CS [1,200 500 /mm 3 ] 0.2 10 4 /mm 3 CSBG 1,400U 700U AAV CSBG β AAV 7, 8, 13, 14 Fig. 4 AAV 2 IS CS Vol. 49, 2009 95
Figure 3 A 67-year-old woman with AAV + Aspergillus pneumonia. 9 Figure 4 Hypothesis of opportunistic infections in compromised AAV. compromised host Fig. 3 T 1 2 AZ CY 9 10 Fig. 3 CD4 200 /µl IgG 600mg/dl 600 /µl 96 Vol. 49, 2009
Figure 5 Strategy of prevention of infections in AAV. AAV 2002 9 Fig. 5 8 AAV ANCA CRP LDH 1 AAV AAV 37 3 CRP [ 2,000 600 /mm 3 ] [CD4 200 /µl] IgG 600mg/dl WG AAV ST 13, 14 4 6 / / 2,400mg/ 500ml ITCZ 100 200mg/ AAV 15 16 1 50 CS PSL 1.2mg/kg/ PSL 0.8mg/kg/ IS PSL 0.4mg/kg IS PSL 0.8mg/kg/ 500 /µl PSL 0.4mg/kg/ 500 /µl 2 ST TMP/SMX 1 1g 1g/ 4g/ 2g/ 8g 4g/ 1A 300mg 300mg/ 300mg/2 3 1,000/µl 500 /µl Fig. 5 Vol. 49, 2009 97
AAV AAV ANCA ANCA JMAAV JMAAV 1 ANCA 2001 90 1702 1707 2 ANCA 2003 29 249 254 3 ANCA 10 1999 213 229 4 Axel A, Brakhage, Bernhard J, Axel S eds. Aspergillus fumigatus. Biology, Clinical Aspects and Molecular Approaches to Pathogenesity (Contributions to Microbiology, Vol. 2). Tokyo: Karger, 1999, 62 86. 5 Reinhold-Keller E, Beuge N, Latza U et al: An interdisciplinary approach to the care of patients with Wegener s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum, 2000, 43: 1021 1032. 6 ANCA 20 2009 29 31. 7 Masuzawa S, Yoshida M, Ishibashi K et al: Solubilized Candida Cell Wall β-glucan, CSBG, Is an epitope of Natural Human Antibody. Drug Devel Res, 2003, 58: 1 11. 8 Ishibashi K, Yoshida M, Nakabayashi I et al: Role of anti-β-glucan antibody in host defense against fungi. FEMS Immunol Med Microbiol, 2005, 44: 99 109. 9 Yoshida M, Ishibashi K, Hida S et al: Rapid decrease of anti-β-glucan antibody as an indicator for early diagnosis of carinii pneumonitis and deep mycotic infections following immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis. Clin Rheumatol, 2008, 28: 565 571. 102003 29 417 422 11 ANCA β- 2004 31 17 22. 12 2002 50 52 13 Stegeman CA, Tervaert JW, de Jong PE et al: Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener s granulomatosis. N Engl J Med, 1996, 335: 16 20. 14 Hida S, Yoshida M, Nakabayashi I et al: Anti-fungal activity of sulfamethoxazole toward Aspergillus species. Biol Pharm Bull, 2005, 28: 773 778. 15 2009 51 114 120 16, 2005 3 14 19 98 Vol. 49, 2009
Strategy of Infection Control in Immunosuppressive Therapy for ANCA-Associated Vasculitis Masaharu Yoshida Renal Unit of Internal Medicine, Hachioji Medical Center of Tokyo Medical University, Tokyo, Japan compromized host, immunosuppressive therapy, ANCA associated vasculitis, infection control Antineutrophil cytoplasmic antibodies (ANCA) are well known to be associated with small vessel vasculitic diseases such as microscopic polyangiitis (MPA), allergic granulomatous angiitis (AGA), and Wegener s granulomatosis (WG). Disease assessment by 1) vasculitic activity, 2) damage resulting from vasculitis, and 3) patient function, were the required endpoints for the therapeutic trials in ANCA-associated vasculitis (AAV). Harmonized steroids and cyclophosphamide or azathiopurine are effective for active AAV. In evaluating tools for monitoring disease, titers of ANCA and the levels of CRP were found useful in AAV. However, it will be important for clinicians to observe AAV patients more closely and reduce immunosuppressive drug doses more cautiously, especially to prevent several infections (i.e., deep mycosis, pneumocystis jirovecii pneumonia and cytomegalovirus). We indicated that strategy of infection control in immunosuppressive therapy for AAV. (J Jpn Coll Angiol, 2009, 49: 93 99) Vol. 49, 2009 Online publication June 24, 2009 99