原著・高平先刷り用

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1 MPO-ANCA 5 Comparison of Treatment with Corticosteroid Alone vs Corticosteroid and Cyclophosphamide in Combination in Patients with MPO-ANCA Positive Necrotizing Crescentic Glomerulonephritis During 5 Years Follow-up Syuji Takahira (Department of Nephrology, Saitama Medical School, Moroyama, Iruma-gun, Saitama , Japan) To evaluate the long-term outcome of patients with anti-myeloperioxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, the impact of addition of an intravenous pulse cyclophosphamide therapy to a daily oral corticoid therapy was assessed in 20 patients for 5 years. No patient diagnosed with Wegener's granulomatosis was included in this study. Ten patients received corticosteroid treatment alone (OCS group) and 10 patients were treated with corticosteroid and cyclophosphamide in combination (CYC group). Four patients in CYC group, survived their renal function without dialysis. Three of 6 patients that required dialysis therapy, died of gastric ulcer, thrombocytopenia probably due to cyclophosphamide, and cardiac failure. Two of 10 patients in OCS group did not need dialysis therapy. Five (50%) of these patients died and 3 (30%) received dialysis therapy. Three patients died of pulmonary hemorrhage, one died of colon cancer, and one died of cardiac failure. At the diagnosis, no significant differences in the levels of serum creatinine and MPO-ANCA titer, sex ratio and ages were observed between two groups. However, the retrospective analysis revealed that 1) the patients who survived for 5 years without dialysis therapy irrespectively of two types of therapy were all women, 2) the levels of MPO-ANCA at 3 months after the initiation of treatment were significantly higher (p 0.05) in patients treated with corticosteroids alone than those with combination therapy, and that 3) the scores of renal histopathology (glomerular sclerosis and interstitial fibrosis) were significantly higher in patients who failed to survive than those who succeeded to survive without dialysis therapy. From these results, it is suggested that the combination therapy with corticosteroids and cyclophosphamide might be effective for improvement of life and renal survival of patients with MPO- ANCAassociated vasculitis. Moreover, the values of MPO-ANCA should be evaluated after the start of the therapy. Keywords: Wegener s granulomatosis, cyclophosphamide, corticosteroid, crescentic formation J Saitama Med School 2002;29: (Received September 10, 2002) ANCA 1994 Chapel Hill Wegener Churg Strauss ANCA Wegener 60 1) Wegener MPO-ANCA 2) ANCA 3 3)

2 MPO-ANCA Wegener 4) 5) 2) MPO-ANCA methyl prednisolone OCS CYC mg / 4 30 ml/min 500 mg/ PSL OCS MPO-ANCA MPO-ANCA MPO- ANCA enzyme-linked immunosorbent assay (ELISA) 6) 2 pauci-immune PR3-ANCA Wegener 7) C 5.0 mg/dl 2 3 methyl prednisolone 7 mg/kg 4) OCS OCS 1 PSL 0.7 mg/kg 1 PSL 1.8 mg/kg/ mg/ CYC CYC ) (0 to 4) (0 to 4) (0 to 4) (0 to 4) (0 to 4) 4,8) 2 t Mann-Whitney U test

3 MPO-ANCA 3 Kruskal Wallis Kaplan-Meier log-rank test p Table 1 OCS 5 5 CYC 4 6 OCS CYC OCS mg/dl CYC mg/dl MPO- ANCA OCS IU/ml CYC IU/ml MPO-ANCA OCS 3 1 CYC 1 2 (Fig. 1) 3 OCS Fig. 2A Fig. 2B CYC MPO-ANCA Fig. 3A OCS MPO-ANCA 5 1 MPO- ANCA 10 IU/ml 1 1 MPO-ANCA CYC 1 MPO-ANCA 10 IU/ml Fig. 3B Fig. 3 MPO-ANCA Fig. 4 OCS CYS Table 1 OCS IU/ml CYC IU/ml CYC IU/ml 5 OCS IU/ml CYC p IU/ml 3 5 CYC 10 IU/ml 5 CYC 4 500/mm 3 1 CYC OCS 2 Table 1. Clinical and histopathological characteristics of subjects at biopsy OCS: corticosteroid treatment alone, CYC: corticosteroid and cyclophosphamide in combination Fig. 1. Life sur vival cur ve of 2 groups of the patients w i t h M P O - A N C A p o s i t i v e n e c r o t i z i n g c r e s c e n t i c glomerulonephritis. Kaplan Meier-survival curve showed the time courses of patients who were treated with intravenous pulse cyclophosphamide (CYC) and with oral corticosteroids (OCS) administration. Open circle represented a survival curve of OCS group, and closed circle represented CYC group, respectively. There is no significant difference in life survival rate on both groups. Abbreviations are the same as the following figure legends.

4 Fig. 2. A)Course of individual serum creatinine values over time in OCS group. B) Course of individual serum creatinine values over time in CYC group. - - indicates patients who were not introduced into dialysis therapy. - - indicates needed dialysis therapy. - - indicates patients who were dead during the study. Fig. 3. A) Course of individual MPO-ANCA titers over time in OCS group. B) Course of individual MPO-ANCA titers over time in CYC group. - - indicates patients who were not introduced into dialysis therapy. - - indicates patients who needed dialysis therapy. - - indicates patients who were dead during the study. Fig. 4. Changes in mean values of MPO-ANCA in patients with CYC (open column) and OCS (closed column) groups during 5 years. Values are mean SD. *p 0.05 CYC vs. OCS Table Fig. 5 MPO ANCA 3 (Fig. 6)

MPO-ANCA MPO-ANCA Table 2. Characteristics of patients without dialysis, on dialysis and dead at 5 years Fig. 5. Mean values of the scores of renal histopathology in three groups; death, survival and dialysis.

5 MPO-ANCA MPO-ANCA Table 2. Characteristics of patients without dialysis, on dialysis and dead at 5 years Fig. 5. Mean values of the scores of renal histopathology in three groups; death, survival and dialysis. Survival (open column), dialysis (hatched column) and non survival (closed column). Values are mean SE. *p 0.05 Survival vs dialysis or non sur vival. GS:glomer ular sclerosis. CF:crescent formation. IF;interstitial fibrosis.ta:tubular atrophy. AS:arteriolosclerosis. Fig. 6. Changes in mean values of MPO-ANCA in three groups; death, survival and dialysis. Survival (open column), dialysis (hatched column) and non survival (closed column). Values are mean SE. *p 0.05 Survival vs dialysis or non survival. 5 MPO-ANCA Nachman 4) ANCA ANCA vs 56 ANCA ) 5) Wegener MPO-ANCA Franssen 9) 3 MPO- ANCA MPO-ANCA 1 1 g MPO-ANCA Franssen 9) MPO-ANCA 10-12) 13) 14) MPO-ANCA 9) CYC OCS 5 mg/dl 12)

6 Ara 15) MPO- ANCA 16-18) MPO-ANCA OCS 3 MPO-ANCA OCS MPO-ANCA ANCA 12) 3 MPO-ANCA OCS CYC MPO- ANCA 19) ) OCS 3 30 MPO-ANCA MPO-ANCA Gayaud 20) ) mg/dl 5 mg/dl Cohen Clark 22) 94 1 CYC 4 MPO ANCA 1 MPO ANCA ANCA Chapel Hill microscopic polyangiitis microscopic polyangiitis rapidly progressive glomerulonephritis necrotizing crescentic glomerulonephritis 21) microscopic polyangiitis microscopic polyangiitis MPO-ANCA MPO-ANCA

7 MPO-ANCA MPO ANCA 1 CYC OCS MPO-ANCA CYC 10 OCS 3 5 CYC OCS OCS 3 5 MPO ANCA 3 OCS CYC MPO ANCA 3 MPO ANCA 3 MPO-ANCA 3 MPO ANCA 7 3 MPO ANCA CYC MPO-ANCA CYC ) Savage COS. ANCA-associated renal vasculitis. Kidney Int 2001;60: ) Yamagata K, Koyama A. Recent advances of clinical and basic research in rapidly progressive glomerulonephritis. Nippon Rinsho 2001;59: ) de Groot K, Adu D, Savage CO. The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis and critical review. Nephrol Dial Transplant 2001;16: ) Nachman PH, Hogan SL, Jennette C, Falk RJ. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996;7: ) Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, T ravis WD, et al. Wegener's granulomatosis: An analysis of 158 patients. Ann Intern Med 1992;116: ) ELISA MPO-ANCA 1995;19: ) Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rhum 1994;37: ) Okada H, Suzuki H, Konishi K, Sakaguchi H, Saruta T. Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy. Clin Nephrol 1992;37: ) Franssen CF, Stegeman CA, Oost-Kor t WW, Kallenberg CG, Limburg PC, T iebosch A, et al. Determinants of renal outcome in antim y e l o p e r o x i d a s e - a s s o c i a t e d n e c r o t i z i n g crescentic glomerulonephritis. J Am Soc Nephrol 1998;9: )Wilkowski MJ, Velosa JA, Holley KE, Offord KP,

8 Chu CP, Torres VE, et al. Risk factors in idiopathic renal vasculitis and glomerulonephritis. Kidney Int 1989;36: )Hogan SL, Nachman PH, Wilkman AS, Jennette JC, Falk RJ. Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996;7: )Falk RJ, Nachman PH, Hogan SL, Jennette C. ANCA glomerulonephritis and vasculitis: A Chapel Hill perspective. Am J Kidney Dis 2000;20: )Grans ROB, Kuizinga MC, Goldschmeding R, Assmann K, Huysmans FT, Gerlag PG, et al. Clinical features and outcome in patients with glomerulonephritis and antineutrophil cytoplasmic autoantibodies. Nephron 1993;64: )Andrassy K, Erb A, Koderisch J, Waldherr R, Ritz E. Wegener's granulomatousis with renal involvement: Patient sur vival and correlations between initial renal function, renal histology, therapy and renal outcome. Clin Nephrol 1991;35: )Ara J, Mirapeix E, Rodriguez R, Saurina A, Darnell A. Relationship between ANCA and disease activity in small vessel vasculitis patients with anti-mpo ANCA. Nephrol Dial Transplant 1999;14: )Gaskin G, Savage CO, Ryan JJ, Jones S, Rees AJ, Lockwood CM, et al. Anti-neutrophil cytoplasmic antibodies and disease activity during long term follow up of 70 patients with systemic vascultis. Nephrol Dial Transplant 1991;5: )Petterson E, Heigl Z. Antineutrophil cytoplasmic antibody (canca and panca) titers in relation to disease activity in patients with necrotizing vasculitis: a longitudinal study. Clin Nephrol 1992;37: )De Oliviera J, Gaskin G, Dash A, Rees AJ, Pusey CD. Relationship between disease activity and ANCA concentration in long term management of systemic vasculitis. Am J Kidney Dis 1995;25: )Pusey CD, Rees AJ, Evans DJ, Peters DK, Lockwood CM. Plasma exhange in focal necrotizing glomerulonephritis without anti-gbm anti-bodies. Kidney Int 1991;40: )Gayraud M, Guillevin L, le Toumelin P, Cohen P, Lhote F, Casassus P, et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome. Ar thritis Rhum 2001;44: ) 2002;44: )Cohen BA, Clark WF. Pauci-immune renal vasculitis: natural history, prognostic factors, and impact of therapy. Am J Kidney Dis 2000;36: The Medical Society of Saitama Medical School

顔面神経麻痺を来したMPO―ANCA 陽性の中耳炎２症例

顔面神経麻痺を来したMPO―ANCA 陽性の中耳炎２症例 11367 : MPOANCA MPO ANCA MPOANCA 134EU MPO ANCA 67EU MPOANCA ANCA : MPOANCAANCA antineutrophil cytoplasmic antibody ; ANCA Davies IgG ANCA PR3proteinase3ANCA MPOmyeloperoxidaseANCA Wegener PR3ANCA MPO