Retrospective Investigation of Case Studies to Determine the Concurrent Malignancy Rate Associated with Microscopic Polyangiitis

Introduction: This retrospective study investigated the concurrence rate and clinical characteristics of recently developed malignancies with microscopic polyangiitis (MPA). Materials and Methods: The subjects included 42 Japanese MPA cases (16 males and 26 females) that had been newly admitted to t...

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Published inJournal of St. Marianna University Vol. 6; no. 1; pp. 23 - 29
Main Authors Yamada, Hidehiro, Ozaki, Shoichi, Yamasaki, Yoshioki, Mizushima, Machiko, Shibata, Tomohiko, Shibata, Toshiko, Nagafuchi, Hiroko
Format Journal Article
LanguageEnglish
Published St. Marianna University Society of Medical Science 2015
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Online AccessGet full text
ISSN2185-1336
2189-0277
2189-0277
DOI10.17264/stmarieng.6.23

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Abstract Introduction: This retrospective study investigated the concurrence rate and clinical characteristics of recently developed malignancies with microscopic polyangiitis (MPA). Materials and Methods: The subjects included 42 Japanese MPA cases (16 males and 26 females) that had been newly admitted to the hospital. Recent occurrences of malignancy (defined as malignancies diagnosed upon admission and up to two years prior to admission) and the presence of organ lesions were evaluated. As a control, recent occurrences of malignancy in 126 patients with rheumatoid arthritis (RA) were evaluated in a similar manner. Results: Recently developed malignancies occurred significantly more often in the MPA group (19.0%) than in the RA group (6.3%; odds ratio (OR), 3.47 [95% CI, 1.21–9.93]; Fisher’s exact test, p = 0.029). All MPA-associated malignancies were solid cancers, and none were from hematopoietic origin. With regard to characterization of organ lesions, MPA cases with malignancies exhibited peripheral neuropathy significantly more often (75% vs. 32.4%; OR, 6.27; 95% CI, 1.09–36.25; p = 0.045) and glomerulonephritis less often (37.5% vs. 82.4%; OR, 0.13; 95% CI, 0.02–0.69; p = 0.020) than MPA cases without malignancies. Skin lesions were observed in approximately 50% of cases, and there was no significant difference between MPA groups with and without malignancies (26.5%; OR, 2.78; 95% CI, 0.57–12.51; p value, 0.236). Conclusion: MPA coincided with malignancies at a higher ratio than did RA. Therefore, it is recommended that those admitted for MPA should be thoroughly screened for malignancies.
AbstractList Introduction: This retrospective study investigated the concurrence rate and clinical characteristics of recently developed malignancies with microscopic polyangiitis (MPA). Materials and Methods: The subjects included 42 Japanese MPA cases (16 males and 26 females) that had been newly admitted to the hospital. Recent occurrences of malignancy (defined as malignancies diagnosed upon admission and up to two years prior to admission) and the presence of organ lesions were evaluated. As a control, recent occurrences of malignancy in 126 patients with rheumatoid arthritis (RA) were evaluated in a similar manner. Results: Recently developed malignancies occurred significantly more often in the MPA group (19.0%) than in the RA group (6.3%; odds ratio (OR), 3.47 [95% CI, 1.21–9.93]; Fisher’s exact test, p = 0.029). All MPA-associated malignancies were solid cancers, and none were from hematopoietic origin. With regard to characterization of organ lesions, MPA cases with malignancies exhibited peripheral neuropathy significantly more often (75% vs. 32.4%; OR, 6.27; 95% CI, 1.09–36.25; p = 0.045) and glomerulonephritis less often (37.5% vs. 82.4%; OR, 0.13; 95% CI, 0.02–0.69; p = 0.020) than MPA cases without malignancies. Skin lesions were observed in approximately 50% of cases, and there was no significant difference between MPA groups with and without malignancies (26.5%; OR, 2.78; 95% CI, 0.57–12.51; p value, 0.236). Conclusion: MPA coincided with malignancies at a higher ratio than did RA. Therefore, it is recommended that those admitted for MPA should be thoroughly screened for malignancies.
Author Yamasaki, Yoshioki
Yamada, Hidehiro
Nagafuchi, Hiroko
Ozaki, Shoichi
Mizushima, Machiko
Shibata, Tomohiko
Shibata, Toshiko
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  organization: Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine
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References 29) Podjasek JO, Wetter DA, Pittelkow MR, Wada DA. Cutaneous small-vessel vasculitis associated with solid organ malignancies: the Mayo Clinic experience, 1996 to 2009. J Am Acad Dermatol 2012; 66: e55–e65.
30) Solans-Laqué R, Bosch-Gil JA, Pérez-Bocanegra C, Selva-O’Callaghan A, Simeón-Aznar CP, Vilardell-Tarres M. Paraneoplastic vasculitis in patients with solid tumors: report of 15 cases. J Rheumatol 2008; 35: 294–304.
13) Talar-Williams C, Hijazi YM, Walther MM, Linehan WM, Hallahan CW, Lubensky I, Kerr GS, Hoffman GS, Fauci AS, Sneller MC. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 1996; 124: 477–484.
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9) Knight A, Askling J, Ekbom A. Cancer incidence in a population-based cohort of patients with Wegener’s granulomatosis. Int J Cancer 2002; 100: 82–85.
27) Blanco R, Martínez-Taboada VM, Rodríguez-Valverde V, García-Fuentes M. Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients. Medicine (Baltimore) 1998; 77: 403–418.
1) Sigurgeirsson B, Lindelöf B, Edhag O, Allander E. Risk of cancer in patients with dermatomyositis or polymyositis. A population-based study. N Engl J Med 1992; 326: 363–367.
10) Westman KW, Bygren PG, Olsson H, Ranstam J, Wieslander J. Relapse rate, renal survival, and cancer morbidity in patients with Wegener’s granulomatosis or microscopic polyangiitis with renal involvement. J Am Soc Nephrol 1998; 9: 842–852.
23) Faurschou M, Mellemkjaer L, Sorensen IJ, Thomsen BS, Dreyer L, Baslund B. Cancer preceding Wegener’s granulomatosis: a case-control study. Rheumatology (Oxford) 2009; 48: 421–424.
25) García-Porrúa C, González-Gay MA. Cutaneous vasculitis as a paraneoplastic syndrome in adults. Arthritis Rheum 1998; 41: 1133–1135.
12) Robson J, Doll H, Suppiah R, Flossmann O, Harper L, Höglund P, Jayne D, Mahr A, Westman K, Luqmani R. Damage in the anca-associated vasculitides: long-term data from the European Vasculitis Study group (EUVAS) therapeutic trials. Ann Rheum Dis 2013; doi: 10.1136/annrheumdis-2013–203927. [Epub ahead of print]
16) Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger Jr TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT. Wilder RL, Hunder GG. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–324.
5) Tatsis E, Reinhold-Keller E, Steindorf K, Feller AC, Gross WL. Wegener’s granulomatosis associated with renal cell carcinoma. Arthritis Rheum 1999; 42: 751–756.
26) Hutson TE, Hoffman GS. Temporal concurrence of vasculitis and cancer: a report of 12 cases. Arthritis Care Res 2000; 13: 417–423.
28) Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1–11.
14) Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37: 187–192.
17) Azuma K, Yamada H, Ohkubo M, Yamasaki Y, Yamasaki M, Mizushima M, Ozaki S. Incidence and predictive factors for malignancies in 136 Japanese patients with dermatomyositis, polymyositis and clinically amyopathic dermatomyositis. Mod Rheumatol 2011; 21: 178–183.
20) Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RA, Pusey CD; European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007; 18: 2180–2188.
7) Faurschou M, Sorensen IJ, Mellemkjaer L, Loft AG, Thomsen BS, Tvede N, Baslund B. Malignancies in Wegener’s granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 2008; 35: 100–105.
24) Yamada T, Nakajima A, Inoue E, Tanaka E, Taniguchi A, Momohara S, Yamanaka H. Incidence of malignancy in Japanese patients with rheumatoid arthritis. Rheumatol Int. 2011; 31: 1487–1492.
11) Heijl C, Harper L, Flossmann O, Stücker I, Scott DG, Watts RA, Höglund P, Westman K, Mahr A; European Vasculitis Study Group (EUVAS). Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann Rheum Dis 2011; 70: 1415–1421.
22) Stillwell TJ, Benson RC Jr, DeRemee RA, McDonald TJ, Weiland LH. Cyclophosphamide-induced bladder toxicity in Wegener’s granulomatosis. Arthritis Rheum 1988; 31: 465–470.
8) Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116: 488–498.
19) De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, Gross WL, Luqmani R, Jayne DR. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005; 52: 2461–2469.
21) de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO; EUVAS (European Vasculitis Study Group). Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 2009; 150: 670–680.
32) Sánchez-Guerrero J, Gutiérrez-Ureña S, Vidaller A, Reyes E, Iglesias A, Alarcón-Segovia D. Vasculitis as a paraneoplastic syndrome. Report of 11 cases and review of the literature. J Rheumatol 1990; 17: 1458–1462.
18) Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniené J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C; European Vasculitis Study Group. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003; 349: 36–44.
3) Pankhurst T, Savage CO, Gordon C, Harper L. Malignancy is increased in ANCA-associated vasculitis. Rheumatology (Oxford) 2004; 43: 1532–1535.
31) Abe H, Momose S, Takeuchi T. Microscopic polyangitis complicating double carcinoma of the stomach and duodenum: improvement after the resection of these carcinomas. Rheumatol Int 2011; 31: 105–108.
6) Mahr A, Heijl C, Le Guenno G, Faurschou M. ANCA-associated vasculitis and malignancy: Current evidence for cause and consequence relationships. Best Pract Res Clin Rheumatol 2013; 27: 45–56.
4) Knight A, Askling J, Granath F, Sparen P, Ekbom A. Urinary bladder cancer in Wegener’s granulomatosis: risks and relation to cyclophosphamide. Ann Rheum Dis 2004; 63: 1307–1311.
15) Ozaki S. ANCA-associated vasculitis: diagnostic and therapeutic strategy. Allergol Int 2007; 56: 87–96.
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References_xml – reference: 10) Westman KW, Bygren PG, Olsson H, Ranstam J, Wieslander J. Relapse rate, renal survival, and cancer morbidity in patients with Wegener’s granulomatosis or microscopic polyangiitis with renal involvement. J Am Soc Nephrol 1998; 9: 842–852.
– reference: 1) Sigurgeirsson B, Lindelöf B, Edhag O, Allander E. Risk of cancer in patients with dermatomyositis or polymyositis. A population-based study. N Engl J Med 1992; 326: 363–367.
– reference: 30) Solans-Laqué R, Bosch-Gil JA, Pérez-Bocanegra C, Selva-O’Callaghan A, Simeón-Aznar CP, Vilardell-Tarres M. Paraneoplastic vasculitis in patients with solid tumors: report of 15 cases. J Rheumatol 2008; 35: 294–304.
– reference: 6) Mahr A, Heijl C, Le Guenno G, Faurschou M. ANCA-associated vasculitis and malignancy: Current evidence for cause and consequence relationships. Best Pract Res Clin Rheumatol 2013; 27: 45–56.
– reference: 14) Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994; 37: 187–192.
– reference: 16) Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger Jr TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT. Wilder RL, Hunder GG. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–324.
– reference: 27) Blanco R, Martínez-Taboada VM, Rodríguez-Valverde V, García-Fuentes M. Cutaneous vasculitis in children and adults. Associated diseases and etiologic factors in 303 patients. Medicine (Baltimore) 1998; 77: 403–418.
– reference: 15) Ozaki S. ANCA-associated vasculitis: diagnostic and therapeutic strategy. Allergol Int 2007; 56: 87–96.
– reference: 8) Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116: 488–498.
– reference: 9) Knight A, Askling J, Ekbom A. Cancer incidence in a population-based cohort of patients with Wegener’s granulomatosis. Int J Cancer 2002; 100: 82–85.
– reference: 28) Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CG, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1–11.
– reference: 31) Abe H, Momose S, Takeuchi T. Microscopic polyangitis complicating double carcinoma of the stomach and duodenum: improvement after the resection of these carcinomas. Rheumatol Int 2011; 31: 105–108.
– reference: 24) Yamada T, Nakajima A, Inoue E, Tanaka E, Taniguchi A, Momohara S, Yamanaka H. Incidence of malignancy in Japanese patients with rheumatoid arthritis. Rheumatol Int. 2011; 31: 1487–1492.
– reference: 12) Robson J, Doll H, Suppiah R, Flossmann O, Harper L, Höglund P, Jayne D, Mahr A, Westman K, Luqmani R. Damage in the anca-associated vasculitides: long-term data from the European Vasculitis Study group (EUVAS) therapeutic trials. Ann Rheum Dis 2013; doi: 10.1136/annrheumdis-2013–203927. [Epub ahead of print]
– reference: 25) García-Porrúa C, González-Gay MA. Cutaneous vasculitis as a paraneoplastic syndrome in adults. Arthritis Rheum 1998; 41: 1133–1135.
– reference: 5) Tatsis E, Reinhold-Keller E, Steindorf K, Feller AC, Gross WL. Wegener’s granulomatosis associated with renal cell carcinoma. Arthritis Rheum 1999; 42: 751–756.
– reference: 20) Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, Mirapeix E, Savage CO, Sinico RA, Stegeman CA, Westman KW, van der Woude FJ, de Lind van Wijngaarden RA, Pusey CD; European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007; 18: 2180–2188.
– reference: 3) Pankhurst T, Savage CO, Gordon C, Harper L. Malignancy is increased in ANCA-associated vasculitis. Rheumatology (Oxford) 2004; 43: 1532–1535.
– reference: 17) Azuma K, Yamada H, Ohkubo M, Yamasaki Y, Yamasaki M, Mizushima M, Ozaki S. Incidence and predictive factors for malignancies in 136 Japanese patients with dermatomyositis, polymyositis and clinically amyopathic dermatomyositis. Mod Rheumatol 2011; 21: 178–183.
– reference: 32) Sánchez-Guerrero J, Gutiérrez-Ureña S, Vidaller A, Reyes E, Iglesias A, Alarcón-Segovia D. Vasculitis as a paraneoplastic syndrome. Report of 11 cases and review of the literature. J Rheumatol 1990; 17: 1458–1462.
– reference: 21) de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO; EUVAS (European Vasculitis Study Group). Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med 2009; 150: 670–680.
– reference: 29) Podjasek JO, Wetter DA, Pittelkow MR, Wada DA. Cutaneous small-vessel vasculitis associated with solid organ malignancies: the Mayo Clinic experience, 1996 to 2009. J Am Acad Dermatol 2012; 66: e55–e65.
– reference: 4) Knight A, Askling J, Granath F, Sparen P, Ekbom A. Urinary bladder cancer in Wegener’s granulomatosis: risks and relation to cyclophosphamide. Ann Rheum Dis 2004; 63: 1307–1311.
– reference: 18) Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniené J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C; European Vasculitis Study Group. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 2003; 349: 36–44.
– reference: 19) De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, Gross WL, Luqmani R, Jayne DR. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 2005; 52: 2461–2469.
– reference: 11) Heijl C, Harper L, Flossmann O, Stücker I, Scott DG, Watts RA, Höglund P, Westman K, Mahr A; European Vasculitis Study Group (EUVAS). Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials. Ann Rheum Dis 2011; 70: 1415–1421.
– reference: 23) Faurschou M, Mellemkjaer L, Sorensen IJ, Thomsen BS, Dreyer L, Baslund B. Cancer preceding Wegener’s granulomatosis: a case-control study. Rheumatology (Oxford) 2009; 48: 421–424.
– reference: 7) Faurschou M, Sorensen IJ, Mellemkjaer L, Loft AG, Thomsen BS, Tvede N, Baslund B. Malignancies in Wegener’s granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 2008; 35: 100–105.
– reference: 22) Stillwell TJ, Benson RC Jr, DeRemee RA, McDonald TJ, Weiland LH. Cyclophosphamide-induced bladder toxicity in Wegener’s granulomatosis. Arthritis Rheum 1988; 31: 465–470.
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SubjectTerms ANCA-associated vasculitis
concurrent
malignancy
MPA
organ
Title Retrospective Investigation of Case Studies to Determine the Concurrent Malignancy Rate Associated with Microscopic Polyangiitis
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