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IgG4-related Disease: 2013 Update

  • Vascular Disease (H Gornik and E Kim, Section Editors)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Opinion statement

Having diagnosed a patient as having IgG4-related disease, I would have a low threshold for recommending immune-suppressive treatment, and would make that recommendation for any patient with vascular involvement. My initial approach would be prednisone at 40–60 mg/day with a plan to reduce the dose every two weeks, e.g., 40, 30, 20, 15, 10, 7.5, 5, and 2.5 mg for 2 weeks each. In the event of relapse, I would double the current prednisone dose, slow the taper, and add azathioprine, anticipating using that drug for one year if the patient were to remain in remission. In the event or subsequent relapse, I would stop azathioprine and use rituximab. In a patient with large artery involvement, I would consult a vascular surgeon soon after diagnosis, anticipating a need for surgical repair.

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  1. Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R, et al. Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum. 2012;64:3061–7. Recent consensus statement to standardize nomenclature for a recently recognized family of diseases, with literature review.

    Google Scholar 

  2. Sakamoto A, Nagai R, Saito K, Imai Y, Takahashi M, Hosoya Y, et al. Idiopathic retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pericarditis–retrospective analysis of 11 case histories. J Cardiol. 2012;59:139–46.

    Article  PubMed  Google Scholar 

  3. Omura Y, Yoshioka K, Tsukamoto Y, Maeda I, Morikawa T, Konishi Y, et al. Multifocal fibrosclerosis combined with idiopathic retro-peritoneal and pericardial fibrosis. Intern Med. 2006;45:461–4.

    Article  PubMed  Google Scholar 

  4. Sugimoto T, Morita Y, Isshiki K, Yamamoto T, Uzu T, Kashiwagi A, et al. Constrictive pericarditis as an emerging manifestation of hyper-IgG4 disease. Int J Cardiol. 2008;130:e100–1.

    Article  PubMed  Google Scholar 

  5. Stone JR. Aortitis, periaortitis, and retroperitoneal fibrosis, as manifestations of IgG4-related systemic disease. Curr Opin Rheumatol. 2011;23:88–94.

    Article  PubMed  CAS  Google Scholar 

  6. Zen Y, Kasashima S, Inoue D. Retroperitoneal and aortic manifestations of immunoglobulin G4-related disease. Semin Diagn Pathol. 2012;29:212–8.

    Article  PubMed  Google Scholar 

  7. Kasashima S, Zen Y. IgG4-related inflammatory abdominal aortic aneurysm. Curr Opin Rheumatol. 2011;23:18–23.

    Article  PubMed  CAS  Google Scholar 

  8. Stone JH, Khosroshahi A, Deshpande V, Stone JR. IgG4-related systemic disease accounts for a significant proportion of thoracic lymphoplasmacytic aortitis cases. Arthritis Care Res (Hoboken). 2010;62:316–22. Identification of IgG4-related disease as the etiology of some cases of thoracic aortitis.

    Google Scholar 

  9. Ishizaka N, Sakamoto A, Imai Y, Terasaki F, Nagai R. Multifocal fibrosclerosis and IgG4-related disease involving the cardiovascular system. J Cardiol. 2012;59:132–8.

    Article  PubMed  Google Scholar 

  10. Zen Y, Nakanuma Y. IgG4-related disease: a cross-sectional study of 114 cases. Am J Surg Pathol. 2010;34:1812–9.

    Article  PubMed  Google Scholar 

  11. Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M, et al. Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis. 2009;68:1310–5.

    Article  PubMed  CAS  Google Scholar 

  12. Hamano H, Arakura N, Muraki T, Ozaki Y, Kiyosawa K, Kawa S. Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol. 2006;41:1197–205.

    Article  PubMed  Google Scholar 

  13. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539–51.

    Article  PubMed  CAS  Google Scholar 

  14. Uchida K, Masamune A, Shimosegawa T, Okazaki K. Prevalence of IgG4-Related Disease in Japan Based on Nationwide Survey in 2009. Int J Rheumatol. 2012;2012:358371.

    PubMed  Google Scholar 

  15. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol. 2012;22:1–14.

    Article  PubMed  CAS  Google Scholar 

  16. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–8.

    Article  PubMed  CAS  Google Scholar 

  17. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003;38:982–4.

    Article  PubMed  CAS  Google Scholar 

  18. Bjornsson E, Chari ST, Smyrk TC, Lindor K. Immunoglobulin G4 associated cholangitis: description of an emerging clinical entity based on review of the literature. Hepatology. 2007;45:1547–54.

    Article  PubMed  Google Scholar 

  19. Kasashima S, Zen Y, Kawashima A, Konishi K, Sasaki H, Endo M, et al. Inflammatory abdominal aortic aneurysm: close relationship to IgG4-related periaortitis. Am J Surg Pathol. 2008;32:197–204. Identification of IgG4-related disease as the etiology of some cases of inflammatory abdominal aortic aneurysm.

    Google Scholar 

  20. Sakata N, Tashiro T, Uesugi N, Kawara T, Furuya K, Hirata Y, et al. IgG4-positive plasma cells in inflammatory abdominal aortic aneurysm: the possibility of an aortic manifestation of IgG4-related sclerosing disease. Am J Surg Pathol. 2008;32:553–9.

    Article  PubMed  Google Scholar 

  21. Vaglio A, Buzio C. Chronic periaortitis: a spectrum of diseases. Curr Opin Rheumatol. 2005;17:34–40.

    Article  PubMed  Google Scholar 

  22. Inoue D, Zen Y, Abo H, Gabata T, Demachi H, Yoshikawa J, et al. Immunoglobulin G4-related periaortitis and periarteritis: CT findings in 17 patients. Radiology. 2011;261:625–33.

    Article  PubMed  Google Scholar 

  23. Matsumoto Y, Kasashima S, Kawashima A, Sasaki H, Endo M, Kawakami K, et al. A case of multiple immunoglobulin G4-related periarteritis: a tumorous lesion of the coronary artery and abdominal aortic aneurysm. Hum Pathol. 2008;39:975–80.

    Article  PubMed  CAS  Google Scholar 

  24. Tanigawa J, Daimon M, Murai M, Katsumata T, Tsuji M, Ishizaka N. Immunoglobulin G4-related coronary periarteritis in a patient presenting with myocardial ischemia. Hum Pathol. 2012;43:1131–4.

    Article  PubMed  Google Scholar 

  25. Wong DD, Pillai SR, Kumarasinghe MP, McGettigan B, Thin LW, Segarajasingam DS, et al. IgG4-related sclerosing disease of the small bowel presenting as necrotizing mesenteric arteritis and a solitary jejunal ulcer. Am J Surg Pathol. 2012;36:929–34.

    Article  PubMed  Google Scholar 

  26. Mitchinson MJ, Wight DG, Arno J, Milstein BB. Chronic coronary periarteritis in two patients with chronic periaortitis. J Clin Pathol. 1984;37:32–6.

    Article  PubMed  CAS  Google Scholar 

  27. Mitchinson MJ. Chronic periaortitis and periarteritis. Histopathology. 1984;8:589–600.

    Article  PubMed  CAS  Google Scholar 

  28. Yamashita K, Haga H, Kobashi Y, Miyagawa-Hayashino A, Yoshizawa A, Manabe T. Lung involvement in IgG4-related lymphoplasmacytic vasculitis and interstitial fibrosis: report of 3 cases and review of the literature. Am J Surg Pathol. 2008;32:1620–6.

    Article  PubMed  Google Scholar 

  29. Shrestha B, Sekiguchi H, Colby TV, Graziano P, Aubry MC, Smyrk TC, et al. Distinctive pulmonary histopathology with increased IgG4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology. Am J Surg Pathol. 2009;33:1450–62.

    Article  PubMed  Google Scholar 

  30. Zen Y, Inoue D, Kitao A, Onodera M, Abo H, Miyayama S, et al. IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol. 2009;33:1886–93.

    Article  PubMed  Google Scholar 

  31. Inoue D, Zen Y, Abo H, Gabata T, Demachi H, Kobayashi T, et al. Immunoglobulin G4-related lung disease: CT findings with pathologic correlations. Radiology. 2009;251:260–70.

    Article  PubMed  Google Scholar 

  32. Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92.

    Article  PubMed  Google Scholar 

  33. Ryu JH, Horie R, Sekiguchi H, Peikert T, Yi ES. Spectrum of Disorders Associated with Elevated Serum IgG4 Levels Encountered in Clinical Practice. Int J Rheumatol. 2012;2012:232960.

    PubMed  Google Scholar 

  34. Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, et al. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology. 2002;122:1264–9.

    Article  PubMed  Google Scholar 

  35. Kamisawa T, Shimosegawa T, Okazaki K, Nishino T, Watanabe H, Kanno A, et al. Standard steroid treatment for autoimmune pancreatitis. Gut. 2009;58:1504–7.

    Article  PubMed  CAS  Google Scholar 

  36. Khosroshahi A, Stone JH. Treatment approaches to IgG4-related systemic disease. Curr Opin Rheumatol. 2011;23:67–71.

    Article  PubMed  CAS  Google Scholar 

  37. Carruthers MN, Stone JH, Deshpande V, Khosroshahi A. Development of an IgG4-RD Responder Index. Int J Rheumatol. 2012;2012:259408.

    PubMed  Google Scholar 

  38. Ito T, Nishimori I, Inoue N, Kawabe K, Gibo J, Arita Y, et al. Treatment for autoimmune pancreatitis: consensus on the treatment for patients with autoimmune pancreatitis in Japan. J Gastroenterol. 2007;42 Suppl 18:50–8.

    Article  PubMed  Google Scholar 

  39. Hirano K, Tada M, Isayama H, Yagioka H, Sasaki T, Kogure H, et al. Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment. Gut. 2007;56:1719–24.

    Article  PubMed  CAS  Google Scholar 

  40. Kamisawa T, Okazaki K, Kawa S, Shimosegawa T, Tanaka M. Japanese consensus guidelines for management of autoimmune pancreatitis: III. Treatment and prognosis of AIP. J Gastroenterol. 2010;45:471–7.

    Article  PubMed  CAS  Google Scholar 

  41. Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–15.

    Article  PubMed  Google Scholar 

  42. Pannala R, Chari ST. Corticosteroid treatment for autoimmune pancreatitis. Gut. 2009;58:1438–9.

    Article  PubMed  CAS  Google Scholar 

  43. Vaglio A, Palmisano A, Alberici F, Maggiore U, Ferretti S, Cobelli R, et al. Prednisone versus tamoxifen in patients with idiopathic retroperitoneal fibrosis: an open-label randomised controlled trial. Lancet. 2011;378:338–46.

    Article  PubMed  CAS  Google Scholar 

  44. Ferry JA, Deshpande V. IgG4-related disease in the head and neck. Semin Diagn Pathol. 2012;29:235–44.

    Article  PubMed  Google Scholar 

  45. Pemberton JD, Fay A. Idiopathic sclerosing orbital inflammation: a review of demographics, clinical presentation, imaging, pathology, treatment, and outcome. Ophthal Plast Reconstr Surg. 2012;28:79–83.

    Article  PubMed  Google Scholar 

  46. Lacaille D, Guh DP, Abrahamowicz M, Anis AH, Esdaile JM. Use of nonbiologic disease-modifying antirheumatic drugs and risk of infection in patients with rheumatoid arthritis. Arthritis Rheum. 2008;59:1074–81.

    Article  PubMed  Google Scholar 

  47. Topazian M, Witzig TE, Smyrk TC, Pulido JS, Levy MJ, Kamath PS, et al. Rituximab therapy for refractory biliary strictures in immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol. 2008;6:364–6.

    Article  PubMed  CAS  Google Scholar 

  48. Khosroshahi A, Carruthers MN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore). 2012;91:57–66. Case series showing effectiveness of rituximab in treating IgG4-related disease.

    Google Scholar 

  49. Buch MH, Smolen JS, Betteridge N, Breedveld FC, Burmester G, Dorner T, et al. Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2011;70:909–20.

    Article  PubMed  CAS  Google Scholar 

  50. Molloy ES, Calabrese LH. Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies. Arthritis Rheum. 2012;64:3043–51.

    Article  PubMed  CAS  Google Scholar 

  51. Khan ML, Colby TV, Viggiano RW, Fonseca R. Treatment with bortezomib of a patient having hyper IgG4 disease. Clin Lymphoma Myeloma Leuk. 2010;10:217–9.

    Article  PubMed  CAS  Google Scholar 

  52. Kim S, Marigowda G, Oren E, Israel E, Wechsler ME. Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome. J Allergy Clin Immunol. 2010;125:1336–43.

    Article  PubMed  CAS  Google Scholar 

  53. Moosig F, Gross WL, Herrmann K, Bremer JP, Hellmich B. Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome. Ann Intern Med. 2011;155:341–3.

    PubMed  Google Scholar 

  54. Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007;56:1000–9.

    Article  PubMed  Google Scholar 

  55. Rao SA, Mandalam KR, Rao VR, Gupta AK, Joseph S, Unni MN, et al. Takayasu arteritis: initial and long-term follow-up in 16 patients after percutaneous transluminal angioplasty of the descending thoracic and abdominal aorta. Radiology. 1993;189:173–9.

    PubMed  CAS  Google Scholar 

  56. Liang P, Hoffman GS. Advances in the medical and surgical treatment of Takayasu arteritis. Curr Opin Rheumatol. 2005;17:16–24.

    Article  PubMed  CAS  Google Scholar 

  57. Park MC, Lee SW, Park YB, Lee SK, Choi D, Shim WH. Post-interventional immunosuppressive treatment and vascular restenosis in Takayasu's arteritis. Rheumatology (Oxford). 2006;45:600–5.

    Article  CAS  Google Scholar 

  58. Matthiesen C, Bogardus Jr C, Thompson JS, Farris B, Hildebrand L, Wilkes B, et al. The efficacy of radiotherapy in the treatment of orbital pseudotumor. Int J Radiat Oncol Biol Phys. 2011;79:1496–502.

    Article  PubMed  Google Scholar 

  59. Lee JH, Kim YS, Yang SW, Cho WK, Lee SN, Lee KJ, et al. Radiotherapy with or without surgery for patients with idiopathic sclerosing orbital inflammation refractory or intolerant to steroid therapy. Int J Radiat Oncol Biol Phys. 2012;84:52–8.

    Article  PubMed  Google Scholar 

  60. Prabhu RS, Kandula S, Liebman L, Wojno TH, Hayek B, Hall WA, Shu HK, Crocker I. Association of Clinical Response and Long-term Outcome Among Patients With Biopsied Orbital Pseudotumor Receiving Modern Radiation Therapy. Int J Radiat Oncol Biol Phys 2012.

  61. Stone WM, Fankhauser GT, Bower TC, Oderich GS, Oldenburg WA, Kalra M, et al. Comparison of open and endovascular repair of inflammatory aortic aneurysms. J Vasc Surg. 2012;56:951–6. Observational study of surgical approaches to treatment of inflammatory aortic aneurysm.

    Google Scholar 

  62. Paravastu SC, Ghosh J, Murray D, Farquharson FG, Serracino-Inglott F, Walker MG. A systematic review of open versus endovascular repair of inflammatory abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2009;38:291–7.

    Article  PubMed  CAS  Google Scholar 

  63. Pagni S, Ganzel BL, Williams M, Slater AD, Trivedi JR. Inflammatory aneurysms of the ascending aorta: diagnosis and surgical treatment. J Card Surg. 2011;27:70–4.

    Article  PubMed  Google Scholar 

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Disclosure

Dr. Paul Monach received a grant from Genentech for clinical studies involving the use of rituximab (not in IgG4-related disease).

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  1. Vasculitis Center and Section of Rheumatology, Boston University School of Medicine, 72 East Concord Street, E-533, Boston, MA, 02118, USA

    Paul A. Monach MD, PhD

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Monach, P.A. IgG4-related Disease: 2013 Update. Curr Treat Options Cardio Med 15, 214–223 (2013). https://doi.org/10.1007/s11936-013-0232-y

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