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IgG4-Related Disease

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Rare Rheumatic Diseases of Immunologic Dysregulation

Part of the book series: Rare Rheumatic Diseases ((RRD))

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Abstract

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disease that is characterized by elevation of the serum IgG4 level and organ swelling and can involve essentially any organ simultaneously or metachronously. Since IgG4-RD mimics several malignant or inflammatory diseases, it is critical to differentiate IgG4-RD from malignant tumors and similar inflammatory diseases of the affected organ in an accurate and timely manner to avoid misdiagnosis and apply appropriate therapy. Characteristic histopathological findings of IgG4-RD are abundant infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. The diagnosis of IgG4-RD is a significant clinical challenge. Since there is no simple diagnostic test for IgG4-RD, it is diagnosed by a combination of clinical, imaging, serological, and pathological findings; other organ involvement; and steroid responsiveness. IgG4-RD responds well to steroids, but it sometimes relapses. Rituximab has recently been reported to be useful for its treatment. Although the short-term outcome is usually good, the long-term prognosis is unknown.

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References

  1. Kamisawa T, Zen Y, Pillai S, et al. IgG4-related disease. Lancet. 2015;385(9976):1460–71.

    Article  CAS  Google Scholar 

  2. Kamisawa T, Funata N, Hayashi Y, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gastroenterol. 2003a;38:982–4.

    Article  CAS  Google Scholar 

  3. Kamisawa T, Funata N, Hayashi Y, et al. Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut. 2003b;52:683–7.

    Article  CAS  Google Scholar 

  4. Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease, 2011. Mod Rheumatol. 2012a;22:21–30.

    Article  CAS  Google Scholar 

  5. Okazaki K, Chari ST, Frulloni L, et al. International consensus for the treatment of autoimmune pancreatitis. Pancreatology. 2017;17:1–6.

    Article  CAS  Google Scholar 

  6. Umehara H, Okazaki K, Masaki Y, et al. A novel clinical entity, IgG4-related disease: general consept and details. Mod Rheumatol. 2012b;22:1–14.

    Article  CAS  Google Scholar 

  7. Kanno A, Masamune A, Okazaki K, et al. Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2011. Pancreas. 2015;44:535–9.

    Article  Google Scholar 

  8. Okazaki K, Uchida K. Autoimmune pancreatitis. The past, present, and future. Pancreas. 2015;44:1006–16.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  10. Kamisawa T, Anjiki H, Egawa N, et al. Allergic manifestations in autoimmune pancreatitis. Eur J Gastroenterol Hepatol. 2009a;21:1136–9.

    Article  Google Scholar 

  11. Kuruma S, Kamisawa T, Tabata T, et al. Allergen-specific IgE antibody serologic assays in patients with autoimmune pancreatitis. Intern Med. 2014;53:541–3.

    Article  Google Scholar 

  12. Kamisawa T, Okazaki K, Kasa S, et al. Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2013 III. Treatment and prognosis of autoimmune pancreatitis. J Gastroenterol. 2014a;49:961–70.

    Article  CAS  Google Scholar 

  13. Khosroshahi A, Wallace ZS, Crowe JL, et al. Second International Symposium on IgG4-Related Disease International consensus guidance statement on the management and treatment of IgG4-related disease. Arthritis Rheumatol. 2015;67:1688–99.

    Article  CAS  Google Scholar 

  14. Inoue D, Yoshida K, Yoneda N, et al. IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 2015;94:e680.

    Article  CAS  Google Scholar 

  15. Koizumi S, Kamisawa T, Kuruma S, et al. Organ correlation in IgG4-related diseases. J Korean Med Sci. 2015;30:743–8.

    Article  CAS  Google Scholar 

  16. Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40:352–8.

    Article  Google Scholar 

  17. Ohara H, Okazaki K, Tsubouchi H, et al. Clinical diagnostic criteria of IgG4-related sclerosing cholangitis 2012. J Hepatobiliary Pancreat Sci. 2012;19:536–42.

    Article  Google Scholar 

  18. Kawano M, Saeki T, Nakashima H, et al. Proposal for diagnostic criteria for IgG4-related kidney disease. Clin Exp Nephrol. 2011;15:615–26.

    Article  Google Scholar 

  19. Masaki Y, Sugai S, Umehara H. IgG4-related diseases including Mikulicz’s disease and sclerosing pancreatitis: diagnostic insights. J Rheumatol. 2010;37:1380–5.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Brito-Zerón P, Ramos-Casals M, Bosch X, et al. The clinical spectrum of IgG4-related disease. Autoimmun Rev. 2014;13:1203–10.

    Article  Google Scholar 

  22. Carruthers MN, Khosroshahi A, Augustin T, et al. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015a;74:14–8.

    Article  CAS  Google Scholar 

  23. Kawaguchi K, Koike M, Tsuruta K, et al. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol. 1991;22:387–95.

    Article  CAS  Google Scholar 

  24. Notohara K, Burgart LJ, Yadav D. Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Am J Surg Pathol. 2003;27:1119–27.

    Article  Google Scholar 

  25. Zamboni G, Lüttges J, Capelli P. Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch. 2004;445:552–63.

    Article  Google Scholar 

  26. Kamisawa T, Chari ST, Lerch MM, et al. Recent advances in autoimmune pancreatitis: type 1 and type 2. Gut. 2013;62:1373–80.

    Article  CAS  Google Scholar 

  27. Ngwa T, Law R, Hart P, et al. Serum IgG4 elevation in pancreatic cancer: diagnostic and prognostic significance and association with autoimmune pancreatitis. Pancreas. 2015;44:557–60.

    Article  CAS  Google Scholar 

  28. Kamisawa T, Imai M, Yui Chen P, et al. Strategy for differentiating autoimmune pancreatitis from pancreatic cancer. Pancreas. 2008;37:62–7.

    Article  Google Scholar 

  29. Kamisawa T, Ohara H, Kim MH, et al. Role of endoscopy in the diagnosis of autoimmune pancreatitis and immunoglobulin G4-related sclerosing cholangitis. Dig Endosc. 2014b;26:627–35.

    Article  Google Scholar 

  30. Watanabe T, Maruyama M, Ito T, et al. Mechanisms of lower bile duct stricture in autoimmune pancreatitis. Pancreas. 2014;43:255–60.

    Article  CAS  Google Scholar 

  31. Hirano K, Tada M, Isayama H, et al. Intrapancreatic biliary stricture in autoimmune pancreatitis should not be included in IgG4-related sclerosing cholangitis. Pancreas. 2014;43:1123.

    Article  Google Scholar 

  32. Hamano H, Kawa S, Uehara T, et al. Immunoglobulin G4-related lymphoplasmacytic sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma: part of a spectrum of autoimmune pancreatitis? Gastrointest Endosc. 2005;62:152–7.

    Article  Google Scholar 

  33. Koizumi S, Kamisawa T, Kuruma S, et al. Clinical features of IgG4-related dacryoadenitis. Graefes Arch Clin Exp Ophthalmol. 2014;252:491–7.

    Article  CAS  Google Scholar 

  34. Van Bommel EF, Jansen I, Hendriksz TR, et al. Idiopathic retroperitoneal fibrosis: prospective evaluation of incidence and clinicoradiologic presentation. Medicine (Baltimore). 2009;88:193–201.

    Article  Google Scholar 

  35. Khosroshahi A, Carruthers MN, Stone JH, et al. Rethinking Ormond’s disease: “idiopathic” retroperitoneal fibrosis in the era of IgG4-related disease. Medicine (Baltimore). 2013;92:82–91.

    Article  CAS  Google Scholar 

  36. Chiba K, Kamisawa T, Tabata T, et al. Clinical features of 10 patients with IgG4-related retroperitoneal fibrosis. Intern Med. 2013;52:1545–51.

    Article  Google Scholar 

  37. Niaz A, Ahmad AH, Khaleeq-ur-Rahman, et al. IgG4-related retroperitoneal fibrosis: a case report and review of literature. J Pak Med Assoc. 2016;66:220–2.

    PubMed  Google Scholar 

  38. Kottra JJ, Dunnick NR. Retroperitoneal fibrosis. Radiol Clin North Am. 1996;34:1259–75.

    CAS  PubMed  Google Scholar 

  39. Lian L, Wang C, Tian JL. IgG4-related retroperitoneal fibrosis: a newly characterized disease. Int J Rheum Dis. 2016;19:1049–55.

    Article  CAS  Google Scholar 

  40. Kawano M, Saeki T. IgG4-related kidney disease—an update. Curr Opin Nephrol Hypertens. 2015;24:193–201.

    Article  CAS  Google Scholar 

  41. Saeki T, Nishi S, Imai N, et al. Clinicopathological characteristics of patients with IgG4-related tubulointerstitial nephritis. Kidney Int. 2010;78:1016–23.

    Article  CAS  Google Scholar 

  42. Raissian Y, Nasr SH, Larsen CP, et al. Diagnosis of IgG4-related tubulointerstitial nephritis. J Am Soc Nephrol. 2011;22:1343–52.

    Article  Google Scholar 

  43. Takahashi N, Kawashima A, Fletcher JG, et al. Renal involvement in patients with autoimmune pancreatitis: CT and MR imaging findings. Radiology. 2007;242:791–801.

    Article  Google Scholar 

  44. Kim B, Kim JH, Byun JH, et al. IgG4-related kidney disease: MRI findings with emphasis on the usefulness of diffusion-weighted imaging. Eur J Radiol. 2014;83:1057–62.

    Article  Google Scholar 

  45. Yamaguchi Y, Kanetsuna Y, Honda K, et al. Characteristic tubulointerstitial nephritis in IgG4-related disease. Hum Pathol. 2012;43:536–49.

    Article  Google Scholar 

  46. Yamamoto M, Takahashi H, Suzuki C, et al. Analysis of serum IgG subclasses in Churg-Strauss syndrome—the meaning of elevated serum levels of IgG4. Intern Med. 2010;49:1365–70.

    Article  Google Scholar 

  47. Vaglio A, Strehl JD, Manger B, et al. IgG4 immune response in Churg-Strauss syndrome. Ann Rheum Dis. 2012;71:390–3.

    Article  CAS  Google Scholar 

  48. Kawano M, Mizushima I, Yamaguchi Y, et al. Immunohistochemical characteristics of IgG4-related tubulointerstitial nephritis: detailed analysis of 20 Japanese cases. Int J Rheumatol. 2012;2012:609795. https://doi.org/10.1155/2012/609795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chang SY, Keogh KA, Lewis JE, et al. IgG4-positive plasma cells in granulomatosis with polyangiitis (Wegener’s): a clinicopathologic and immunohistochemical study on 43 granulomatosis with polyangiitis and 20 control cases. Hum Pathol. 2013;44:2432–7.

    Article  CAS  Google Scholar 

  50. Zen Y, Kitagawa S, Minato H, et al. IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol. 2005;36:710–7.

    Article  CAS  Google Scholar 

  51. Umeda M, Fujioka K, Origuchi T, et al. A case of IgG4-related pulmonary disease with rapid improvement. Mod Rheumatol. 2012;22:919–23.

    Article  Google Scholar 

  52. Lighaam LC, Aalberse RC, Rispens T, et al. IgG4-related fibrotic diseases from an immunological perspective: regulators out of control? Int J Rheumatol. 2012;2012:789164.

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  55. Matsui S, Hebisawa A, Sakai F, et al. Immunoglobulin G4-related lung disease: clinicoradiological and pathological features. Respirology. 2013;18:480–7.

    Article  Google Scholar 

  56. Sun X, Liu H, Feng R, et al. Biopsy-proven IgG4-related lung disease. BMC Pulm Med. 2016;26:20.

    Article  Google Scholar 

  57. Kawashima ST, Tagami T, Nakao K, et al. Serum levels of IgG and IgG4 in Hashimoto thyroiditis. Endocrine. 2014;45:236–43.

    Article  CAS  Google Scholar 

  58. Mulholland GB, Jeffery CC, Satija P, et al. Immunoglobulin G4-related diseases in the head and neck: a systematic review. J Otolaryngol Head Neck Surg. 2015;44:24.

    Article  Google Scholar 

  59. Dutta D, Ahuja A, Selvan C. Immunoglobulin G4 related thyroid disorders: diagnostic challenges and clinical outcomes. Endokrynol Pol. 2016;67:520–4.

    Article  CAS  Google Scholar 

  60. Watanabe T, Maruyama M, Ito T, et al. Clinical features of a new disease group: IgG4-related thyroiditis. Scand J Rheumatol. 2013;42:325–30.

    Article  CAS  Google Scholar 

  61. Kubo K, Yamamoto K. IgG4-related disease. Int J Rheum Dis. 2016;19:747–62.

    Article  CAS  Google Scholar 

  62. Cheuk W, Yuen HK, Chu SY, et al. Lymphadenopathy of IgG4-related sclerosing disease. Am J Surg Pathol. 2008;32:671–81.

    Article  Google Scholar 

  63. Chew W, Chan JK. IgG4-related sclerosing disease: a critical appraisal of an evolving clinicopathologic entity. Adv Anat Pathol. 2010;17:303–32.

    Article  Google Scholar 

  64. Saito Y, Kojima M, Tahata K, et al. Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease. Mod Pathol. 2009;22:589–99.

    Article  Google Scholar 

  65. Koizumi S, Kamisawa T, Kuruma S, et al. Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4-related diseases? World J Gastroenterol. 2013;19:5769–74.

    Article  CAS  Google Scholar 

  66. Ghazale A, Chari ST, Zhang L, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–15.

    Article  Google Scholar 

  67. Sandanayake NS, Church NI, Chapman MH, et al. Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol. 2009;7:1089–96.

    Article  CAS  Google Scholar 

  68. Hart PA, Kamisawa T, Brugge WR, et al. Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. Gut. 2013b;62:1771–6.

    Article  Google Scholar 

  69. Hart PA, Topazian MD, Witzig TE, et al. Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience. Gut. 2013a;62:1607–15.

    Article  CAS  Google Scholar 

  70. Carruthers MN, Topazian MD, Khosroshahi A, et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis. 2015b;74:1171–7.

    Article  CAS  Google Scholar 

  71. Kamisawa T, Shimosegawa T, Okazaki K, et al. Standard steroid treatment for autoimmune pancreatitis. Gut. 2009b;58:1504–7.

    Article  CAS  Google Scholar 

  72. Peng T, Hu Z, Xie T, et al. IgG4-related disease: a case report with duration of more than 16 years and review of literature. Springerplus. 2016;5:804.

    Article  Google Scholar 

  73. Kamisawa T, Egawa N, Inokuma S, et al. Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy. Pancreas. 2003c;27:235–8.

    Article  CAS  Google Scholar 

  74. Kamisawa T, Takuma K, Kuruma S, et al. Lacrimal gland function in autoimmune pancreatitis. Intern Med. 2009c;48:939–43.

    Article  Google Scholar 

  75. Stone JH. IgG4-related disease: pathophysiologic insights drive emerging treatment approaches. Clin Exp Rheumatol. 2016;34:66–8.

    PubMed  Google Scholar 

  76. Makiishi T, Shirase T, Hieda N, et al. Immunoglobulin G4-related disease with scant tissue IgG4. BMJ Case Rep. 2013;2013:bcr2013009800. https://doi.org/10.1136/bcr-2013-009800.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Hara S, Kawano M, Mizushima I, et al. A condition closely mimicking IgG4-related disease despite the absence of serum IgG4 elevation and IgG4 positive plasma cell infiltration. Mod Rheumatol. 2014;26:784–9.

    Article  Google Scholar 

  78. Hart PA, Smyrk TC, Chari ST. Lymphoplasmacytic sclerosing pancreatitis without IgG4 tissue infiltration or serum IgG4 elevation: IgG4-related disease without IgG4. Mod Pathol. 2015;28:238–47.

    Article  CAS  Google Scholar 

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Acknowledgement

This chapter was supported in-part by Research of Intractable Diseases from the Ministry of Health, Labour and Welfare, Japan (Chairman: Tsutomu Chiba).

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Authors and Affiliations

  1. Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan

    Satomi Koizumi, Terumi Kamisawa, Sawako Kuruma, Kazuro Chiba & Masataka Kikuyama

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  1. Satomi Koizumi
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  2. Terumi Kamisawa
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  3. Sawako Kuruma
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Correspondence to Terumi Kamisawa .

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  1. Department of Medicine, Duke University School of Medicine, Durham, NC, USA

    Teresa Kathleen Tarrant

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Koizumi, S., Kamisawa, T., Kuruma, S., Chiba, K., Kikuyama, M. (2019). IgG4-Related Disease. In: Tarrant, T. (eds) Rare Rheumatic Diseases of Immunologic Dysregulation. Rare Rheumatic Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-99139-9_4

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