Pulmonary renal syndrome in a child with coexistence of anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane disease: case report and literature review

BMC Nephrology

Milan Rodić²  Nataša Savić²  Nataša Stajić²  Jasmina Marković-Lipkovski¹  Predrag Minić²  Radovan Bogdanović² 

[1] Faculty of Medicine, University of Belgrade, Belgrade, Serbia;Institute of Mother and Child Healthcare of Serbia “Dr Vukan Čupić”, 8 R Dakica Str, Belgrade, 11070, Serbia

关键词: Anti-glomerular basement membrane disease;    Anti-myeloperoxidase anti-neutrophil cytoplasmic antibodies;    Children;    Pulmonary renal syndrome;   

Others  :  1082973
DOI  :  10.1186/1471-2369-14-66

 received in 2012-11-27, accepted in 2013-03-15,  发布年份 2013

【 摘 要 】

Background

Pulmonary renal syndrome (PRS), denoting the presence of diffuse alveolar hemorrhage and glomerulonephritis as manifestations of systemic autoimmune disease, is very rare in childhood. The coexistence of circulating anti-neutrophil cytoplasmic antibody (ANCA) and anti-glomerular basement membrane (GBM) disease in children affected by this syndrome is exceptional, with unfavorable outcome in five out of seven patients reported to date. We describe a child with PRS associated with both circulating anti-myeloperoxidase (anti-MPO) ANCA and anti-GBM disease on renal biopsy who was successfully treated with immunosuppressive therapy.

Case presentation

A 10-year old girl presented with fever, fatigue, malaise, and pallor followed by hemoptysis and severe anemia. Diffuse alveolar hemorrhage was revealed on fiberoptic bronchoscopy. Renal findings consisted of microscopic hematuria, moderate proteinuria, and anti-GBM disease on renal biopsy. ANCA with anti-MPO specificity were present whereas anti-GBM antibodies were on borderline for positivity. Methyl-prednisolone pulses followed by prednisone led to cessation of hemoptysis, marked improvement of lung fuction, and normal finding on chest x-ray within 10 days. An immunosuppressive regimen was then given consisting of prednisone daily for 4 weeks with subsequent taper on alternate day, i.v. cyclophosphamide pulses monthly for 6 doses, followed by mycophenolate mofetil that resulted in normal lung function tests, hemoglobin concentration, and anti-MPO level within four subsequent weeks. During 10-months of follow-up she remained well, her blood pressure and renal function tests were normal, and proteinuria and hematuria gradually resolved.

Conclusion

We report a child with an exceptionally rare coexistence of circulating ANCA and anti-GBM disease manifesting as PRS in whom renal disease was not the prominent part of clinical presentation, contrary to other reported pediatric patients. A review of literature on disease with double positive antibodies is also presented. Evaluation of a patient with PRS should include testing for presence of different antibodies. An early diagnosis and rapid institution of aggressive immunosuppressive therapy can induce remission and preserve renal function. Renal prognosis depends on the extent of kidney injury at diagnosis and appropriate treatment.

【 授权许可】

   
2013 Bogdanović et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Gallagher H, Kwan JTC, Jayne DRW: Pulmonary renal syndrome: A 4-year, single-center experience. Am J Kidney Dis 2002, 39:42-47.
• [2]Lee RW, D’Cruz DP: Pulmonary renal vasculitis syndromes. Autoimmun Rev 2010, 9:657-660.
• [3]Von Vigier RO, Trummler SA, Laux-End R, Sauvain MJ, Truttmann AC, Bianchetti MG: Pulmonary renal syndrome in childhood: a report of twenty-one cases and a review of the literature. Pediatr Pulmonol 2000, 29:382-388.
• [4]Jennette JC, Falk RJ: Small-vessel vasculitis. N Engl J Med 1997, 337:1512-1523.
• [5]Kluth DC, Rees AJ: Anti-glomerular basement membrane disease. J Am Soc Nephrol 1999, 10:2446-2453.
• [6]Jayne DRW, Marshall PD, Jones SJ, Lockwood CM: Autoantibodies to GBM and neutrophil cytoplasm in rapidly progressive glomerulonephritis. Kidney Int 1990, 37:965-970.
• [7]Bosch X, Mirapeix E, Font J, Cervera R, Ingelmo M, Khamashta MA, Revert L, Hughes GR, Urbano-Marquez A: Anti-myeloperoxidase autoantibodies in patients with necrotizing glomerular and alveolar capillaritis. Am J Kidney Dis 1992, 20:231-239.
• [8]Weber MFA, Nadrossy K, Pullig O, Koderisch J, Netzer K: Antineutrophil-cytoplasmic antibodies and antiglomerular basement membrane antibodies in Goodpasture’s syndrome and in Wegener’s granulomatosis. J Am Soc Nephrol 1992, 2:1227-1234.
• [9]Short AK, Esnault VL, Lockwood CM: Anti-neutrophil cytoplasm antibodies and anti-glomerular basement membrane antibodies: two coexisting distinct autoreactivities detectable in patients with rapidly progressive glomerulonephritis. Am J Kidney Dis 1995, 26:439-445.
• [10]Levy JB, Hammad T, Coulthart A, Dougan T, Pusey CD: Clinical features and outcome of patients with both ANCA and anti-GBM antibodies. Kidney Int 2004, 66:2535-2540.
• [11]Rutgers A, Slot M, Passen PV, Vriesman PVB, Heeninga P, Tervaert JWC: Coexistence of anti-glomerular basement membrane antibodies and myeloperoxidase-ANCAs in crescentis gomerulonephritis. Am J Kidney Dis 2005, 46:253-262.
• [12]Lindič J, Vizjak A, Ferluga D, Kovač D, Aleš A, Kveder R, Ponikvar R, Bren A: Clinical outcome of patients with coexistent antineutrophil cytoplasmic antibodies and antibodies against glomerular basement membrane. Ther Apher Dial 2009, 13:278-281.
• [13]Zoysa J, Taylor D, Thein H, Yehia M: Incidence and features of dual anti-GBM-positive and ANCA-positive patients. Nephrology 2011, 16:725-729.
• [14]Fanburg BL, Niles JL, Mark EJ: Case 52–1993: A 17-year-old girl with massive hemoptysis and acute oliguric renal failure. N Engl J Med 1993, 329:2019-2026.
• [15]Paueksakon P, Hynley TE, Lee SM, Fogo AB: A 12-year-old girl with pulmonary hemorrhage, skin lesions, and hematuria. Am J Kidney Dis 1999, 33:404-409.
• [16]Hijosa MM, Espinosa RL, Fernandez C, Picazo Garcia ML, Pascual Salcedo D, Navarro Torres M: Anti-GBM and anti-MPO antibodies coexist in a case of pulmonary renal syndrome. Pediatr Nephrol 2005, 20:807-810.
• [17]Naidoo S, Waller S: Anti-GBM antibodies co-exist with MPO-ANCA in a 4-year-old girl with acute renal failure. Pediatr Nephrol 2009, 24:215-216.
• [18]Williamson SR, Phillips CL, Andreoli SP, Nailescu C: A 25-year experience with pediatric anti-glomerular basement membrane disease. Pediatr Nephrol 2011, 26:85-91.
• [19]Lionaki S, Jennette JC, Falk RJ: Anti-neutrophil cytoplasmic (ANCA) and anti-glomerular basement membrane (GBM) autoantibodies in necrotizing and crescentic glomerulonephritis. Semin Immunopathol 2007, 29:459-474.
• [20]Kambham N: Crescentic glomerulonephritis: an update on pauci-immune and anti-GBM diseases. Adv Anat Pathol 2012, 19:111-124.
• [21]Rees L, Webb NJA, Brogan PA: Vasculitis. In Paediatric Nephrology. Edited by Rees L, Webb NJA, Brogan PA. Oxford: OUP; 2007:297-316.
• [22]Valentini RP: Pediatric anti-GBM disease (Good pasture Syndrome). http://emedicine.medscape.com/article/1001872-overview webcite
• [23]Pedchenko V, Vanacore R, Hudson B: Goodpasture’s disease: molecular architecture of the autoantigen provides clues to etiology and pathogenesis. Curr Opin Nephrol Hypertens 2011, 20:290-296.
• [24]Kallenberg CG: Pathogenesis of ANCA-associated vasculitides. Ann Rheum Dis 2011, 70:159-163.
• [25]Jennette JC, Falk RJ, Gasim AH: Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens 2011, 20:263-270.
• [26]Hellmark T, Niles JL, Collins B, Mccluskey RT, Brunmark C: Comparison of anti-GBM antibodies in sera with or without ANCA. J Am Soc Nephrol 1997, 8:376-385.
• [27]Yang R, Hellmark T, Zhao J, Cui Z, Segelmark M, Zhao M, Wang H: Antigen and epitope specificity of anti-glomerular basement membrane antibodies in patients with Goodpasture disease with or without anti-neutrophil cytoplasmic antibodies. J Am Soc Nephrol 2007, 18:1338-1343.
• [28]Hudson BG, Tryggvason K, Sudaramoorthy M, Neilson EG: Alport’s syndrome, Goodpasture’s syndrome, and type IV colagen. N Engl J Med 2003, 348:2543-2556.
• [29]Serratrice J, Chiche L, Dussol B, Granel B, Daniel L, Jego-Desplat S, Disdier P, Swiader L, Berland Y, Weiller PJ: Sequential development of perinuclear ANCA-associated vasculitis and anti-glomerular basement membrane glomerulonephritis. Am J Kidney Dis 2004, 43:e26-e30.
• [30]Olson SW, Arbogast CB, Baker TP, Owhalimpur D, Oliver DK, Abbott KC, Yuan CM: Asymptomatic autoantibodies associate with future anti-glomerular basement membrane disease. J Am Soc Nephrol 2011, 22:1946-1952.
• [31]Peces R, Rodrigues M, Pobes A, Seco M: Sequential development of pulmonary hemorrhage with MPO-ANCA complicating anti-glomerular basment membrane antibody-mediated glomerulonephritis. Am J Kidney Dis 2000, 35:954-957.
• [32]Desai A, Goldschmidt RA, Kim GC: Sequential development of pulmonary renal syndrome asociated with c-ANCA 3 years after development of anti-GBM glomerulonephritis. Nephrol Dial Transplant 2007, 22:926-929.
• [33]Vanhille PH, Noel LH, Reumaux D, Fleury D, Lemaitre V, Gobert P: Late emergence of systemic vasculitis with anti-neutrophil cytoplasmic antibodies in a dialyzed patient with anti-glomerular basement glomerulonephritis. Clin Nephrol 1990, 33:257-258.
• [34]Segelmark M, Hellmark T, Wieslander J: The prognostic significance in Goodpasture’s disease of specificity, titre and affinity of anti-glomerular-basement-membrane antibodies. Nephrol Clin Pract 2003, 94:c59-c68.
• [35]Mukhtvar C, Guillevin J, Cid MC, Dasgupta B, De Groot K, Gross W, Hauser T, Hellmich B, Jayne D, Kallenberg CG, Merkel PA, Raspe H, Salvarani C, Scot DG, Stegman C, Watts R, Westman K, Witter J, Yazici H, Luqmani R: European vasculitis study group: EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis 2009, 68:310-317.
• [36]Etter C, Gaspert A, Regenass S, Wuthrich R, Kistler T, Kain R, Cohen C: Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome. BMC Nephrol 2011, 12:1471-2369.
• [37]Kain R, Tadema H, McKinney EF, Benharkou A, Brandes R, Peschel A, Hubert V, Feenstra T, Sengolge G, Stegeman C, Heeringa P, Lyons PA, Smith KG, Kallenberg C, Rees AJ: High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibody-associated vasculitis. J Am Soc Nephrol 2012, 23:556-566.
• [38]KDIGO Clinical Practice Guidelines for Glomerulonephritis: Pauci-immune focal and segmental necrotizing glomerulonephritis. Kidney Int Suppl 2012, 2:233-239.
• [39]Jennette JC, Falk R: Renal and systemic vasculitis. In Comprehensive Clinical Nephrology. 4th edition. Edited by Floege J, Jonson RJ, Feehally J. St Louis: Elsevier; 2010:292-307.
• [40]Mandai S, Nagahama K, Tsuura Y, Hirai T, Yoshioka W, Takahashi D, Aki S, Aoyagi M, Tanaka H, Tamura T: Recovery of renal function in a dialysis-dependent patient with microscopic polyangiitis and both myeloperoxidase anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibodies. Intern Med 2011, 50:1599-1603.
• [41]Verburgh CA, Bruijn JA, Daha MR, vas Es LA: Sequential development of anti-GBM nephritis and ANCA-associated pauci-immune glomerulonephritis. Am J Kidney Dis 1999, 34:344-348.
• [42]Salama AD, Dougan T, Levy JB: Goodpasture’s disease in the absence of circulating anti-glomerular basement membrane antibodies as detected by standard techniques. Am J Kidney Dis 2002, 39:1162-1167.
• [43]Savige J, Davies D, Falk RJ, Jennette JC, Wiik A: Antineutrophil cytoplasmic antibodies and associated diseases: a review of the clinical and laboratory features. Kidney Int 2000, 57:846-862.
• [44]Cui Z, M-h Z, Wang H-y: Antiglomerular basement membrane disease with normal renal function. Kidney Int 2007, 12:1403-1408.