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IgG4-Related Disease pp 1–17Cite as

Current Concept of IgG4-Related Disease

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 401))

Abstract

IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unknown etiology, which is characterized by a tendency to form tumefactive lesions, increased serum levels of IgG4, and massive infiltration of IgG4-positive plasma cells with storiform fibrosis and/or obliterative phlebitis. Patients with IgG4-RD have frequently multiorgan involvements such as the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, and retroperitoneum. IgG4-RD mainly affects middle-aged to elderly men except for involvement in lachrymal and salivary glands, so-called Mikulicz’s disease. The clinical manifestations of IgG4-RD depend on individually involved organs and respond well to steroid, but the prognosis still remains unclear. Some patients develop serious complications such as obstructive jaundice due to hepatic, gallbladder, or pancreatic lesions; hydronephrosis due to retroperitoneal fibrosis; or respiratory symptoms due to pulmonary lesions. Nomenclatures of individual organ manifestation of IgG4-RD have been internationally consented.

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Abbreviations

AIP:

Autoimmune pancreatitis

CDC:

Comprehensive diagnostic criteria

GEL:

Granulocytic epithelial lesion

ICDC:

International consensus diagnostic criteria

IDCP:

Idiopathic duct-centric pancreatitis

IgG4-RD:

IgG4-related disease

IgG4-SC:

IgG4-related sclerosing cholangitis

IPC:

The international pathologic consensus criteria

JPS:

Japan Pancreas Society

LPSP:

Lymphoplasmacytic sclerosing pancreatitis

MD:

Mikulicz’s disease

MOLPS:

Multiorgan lymphoproliferative disease

OOI:

Other organ involvement

SjS:

SJÖGREN’S syndrome

PSC:

Primary sclerosing cholangitis

RF:

Rheumatoid factor

SIPS:

Systemic IgG4-related plasmacytic syndrome

References

  • Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, Zhang L, et al. (2006) Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 4:1010–1016

    Google Scholar 

  • Chari ST, Kloeppel G, Zhang L, Notohara K, Lerch MM, Shimosegawa T et al (2010) Histopathologic and clinical subtypes of autoimmune pancreatitis: the Honolulu consensus document. Pancreas 39:549–554

    Article  CAS  PubMed  Google Scholar 

  • Cheuk W, Chan AC, Lam WL, Chow SM, Crowley P, Lloydd R et al (2009) IgG4-related sclerosing mastitis: description of a new member of the IgG4-related sclerosing diseases. Am J Surg Pathol 33:1058–1064

    Article  PubMed  Google Scholar 

  • Comings DE, Skubi KB, Van Eyes J, Motulsky AG (1967) Familial multifocal fibrosclerosis. Ann Intern Med 66:884–892

    Article  CAS  PubMed  Google Scholar 

  • Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T et al (2012) Consensus statement on the pathology of IgG4-related disease. Mod Pathol 25:1181–1192

    Article  PubMed  Google Scholar 

  • Ghazale A, Chari ST, Zhang L, Smyrk TC, Takahashi N, Levy MJ et al (2008) Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology 134:706–715

    Article  PubMed  Google Scholar 

  • Goto H, Takahira M, Azumi A (2015) Japanese study group for IgG4-related ophtalmic disease. Diagnostic criteria for IgG4-related ophthalmic disease. Jpn J Ophthalmol 59:1–7, 2015

    Google Scholar 

  • Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T et al (2001) High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med 344:732–738

    Article  CAS  PubMed  Google Scholar 

  • Hamano H, Kawa S, Ochi Y, Unno H, Shiba N, Wajiki M et al (2002) Hydronephrosis associated with retroperitoneal fibrosis and sclerosing pancreatitis. Lancet 359:1403–1404

    Article  PubMed  Google Scholar 

  • Hamano H, Kawa S, Uehara T, Ochi Y, Takayama M, Komatsu K et al (2005) Immunoglobulin G4-related lymphoplasmacytic sclerosing cholangitis that mimics infiltrating hilar cholangiocarcinoma: part of a spectrum of autoimmune pancreatitis? Gastrointest Endosc 62:152–157

    Article  PubMed  Google Scholar 

  • Hamano H, Arakura N, Muraki T, Ozaki Y, Kiyosawa K, Kawa S (2006) Prevalence and distribution of extrapancreatic lesions complicating autoimmune pancreatitis. J Gastroenterol 41:1197–1205

    Article  PubMed  Google Scholar 

  • Inoue D, Zen Y, Abo H, Gabata T, Demachi H, Kobayashi T et al (2009) Immunoglobulin G4-related lung disease: CT findings with pathologic correlations. Radiology 251:260–270

    Article  PubMed  Google Scholar 

  • Japan Pancreas Society (2002) Clinical diagnostic criteria for autoimmune pancreatitis. Suizou 17:585–587

    Google Scholar 

  • Kakudo K, Li Y, Hirokawa M, Ozaki T (2011) Diagnosis of Hashimoto’s thyroiditis and IgG4-related sclerosing disease. Pathol Int 61:175–183

    Article  CAS  PubMed  Google Scholar 

  • Kamisawa T, Okamoto A (2006) Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease. J Gastroenterol 41:613–625

    Google Scholar 

  • Kamisawa T, Okamoto A (2008) IgG4-related sclerosing disease. World J Gastroenterol 14:3948–3955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamisawa T, Funata N, Hayashi Y, Tsuruta K, Okamoto A, Amemiya K et al (2003) Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis. Gut 52:683–687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kasashima S, Zen Y, Kawashima A, Konishi K, Sasaki H, Endo M et al (2008) Inflammatory abdominal aortic aneurysm: lose relationship to IgG4-related periaortitis. Am J Surg Pathol 32:197–204

    Article  PubMed  Google Scholar 

  • Kawaguchi K, Koike M, Tsuruta K, Okamoto A, Tabata I (1991) Fujita N. Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas. Hum Pathol 22:387–395

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto M, Okimura Y, Kimura K et al (2000) Multifocal fibrosclerosis as a possible cause of panhypopituitarism with central diabetes insipidus. Endocr J 47:335–342

    Article  CAS  PubMed  Google Scholar 

  • Klöppel G, Detlefsen S, Chari ST, Longnecker DS, Zamboni G (2010) Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions. J Gastroenterol 45:787–793

    Article  PubMed  Google Scholar 

  • Komatsu K, Hamano H, Ochi Y, Takayama M, Muraki T, Yoshizawa K et al (2005) High prevalence of hypothyroidism in patients with autoimmune pancreatitis. Dig Dis Sci 50:1052–1057

    Article  PubMed  Google Scholar 

  • Küttner H (1896) U¨ ber entzündiche Tumoren der submaaxilla¨ren Speicheldrüse. Beitr Klin Chir 15:815–834

    Google Scholar 

  • Küttner K. (1972) Light microscopic determination of nuclear inclusion bodies in juvenile nasopharyngeal fibroma. Z Laryngol Rhinol Otol 51:57–60

    Google Scholar 

  • Li Y, Bai Y, Liu Z, Ozaki T, Taniguchi E, Mori I et al (2009) Immunohistochemistry of IgG4 can help subclassify Hashimoto’s autoimmune thyroiditis. Pathol Int 59:636–641

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Nishihara E, Hirokawa M, Taniguchi E, Miyauchi A, Kakudo K (2010) Distinct clinical, serological, and sonographic characteristics of hashimoto’s thyroiditis based with and without IgG4-positive plasma cells. J Clin Endocrinol Metab 95:1309–1317

    Article  CAS  PubMed  Google Scholar 

  • Lopes J et al (2010) Autoimmune esophagitis: IgG4-related tumors of the esophagus. J Gastrointest Surg 14:1031–1034

    Article  PubMed  Google Scholar 

  • Masaki Y, Dong L, Kurose N, Kitagawa K, Morikawa Y, Yamamoto M et al (2009) Proposal for a new clinical entity, IgG4-positive multi-organ lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders. Ann Rheum Dis 68:1310–1315

    Article  CAS  PubMed  Google Scholar 

  • Matsui S, Taki H, Shinoda K, Suzuki K, Hayashi R, Tobe K et al (2012) Respiratory involvement in IgG4-related Mikulicz’s disease. Mod Rheumatol 22:31–39

    Article  CAS  PubMed  Google Scholar 

  • Mikulicz J (1892) Über eine eigenartige symmetrishe Erkrankung der Tränen und Mundspeicheldrüsen. Beitr z Chir Fesrschr f Theodor Billroth, Stuttgart, pp 610–630

    Google Scholar 

  • Nakazawa T, Ohara H, Yamada T, Ando H, Sano H, Kajino S et al (2001) Atypical primary sclerosing cholangitis cases associated with unusual pancreatitis. Hepatogastroenterology 48:625–630

    CAS  PubMed  Google Scholar 

  • Neild GH, Rodriguez-Justo M, Wall C, Connolly JO (2006) Hyper-IgG4 disease: report and characterisation of a new disease. BMC Med 4:23

    Article  PubMed  PubMed Central  Google Scholar 

  • Nishimori I, Kohsaki T, Onishi S, Shuin T, Kohsaki S, Ogawa Y et al (2007) IgG4-related autoimmune prostatitis: two cases with or without autoimmune pancreatitis. Intern Med 46:1983–1989

    Article  PubMed  Google Scholar 

  • Notohara K, Burgart LJ, Yadav D, Chari S, Smyrk TC (2003) Idiopathic chronic pancreatitis with periductal lymphoplasmacytic infiltration: clinicopathologic features of 35 cases. Am J Surg Pathol 27:1119–1127

    Article  PubMed  Google Scholar 

  • Okazaki K, Kawa S, Kamisawa T, Naruse S, Tanaka S, Nishimori I, et al. (2006) Research Committee of Intractable Diseases of the Pancreas. Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal. J Gastroenterol. 41:626–631

    Google Scholar 

  • Okazaki K, Kawa S, Kamisawa T, Ito T, Inui K, Irie H et al (2009) Japanese clinical guidelines for autoimmune pancreatitis. Pancreas 38:849–866

    Article  PubMed  Google Scholar 

  • Okazaki K, Uchida K, Koyabu M, Miyoshi H, Takaoka M (2011) Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease. J Gastroenterol 46:277–288

    Article  CAS  PubMed  Google Scholar 

  • Ravi K, Chari ST, Vege SS, Sandborn WJ, Smyrk TC, Loftus EV Jr (2009) Inflammatory bowel disease in the setting of autoimmune pancreatitis. Inflamm Bowel Dis 15:1326–1330

    Article  PubMed  Google Scholar 

  • Riedel BMCL (1896) Die chronische, zur Bildung eisenharter Tumoren fuhrende Entzundung der Schilddruse. Verhandlung der deutsche Gesellschaft furChirurgie 25:101–105

    Google Scholar 

  • Saegusa H, Momose M, Kawa S, Hamano H, Ochi Y, Takayama M et al (2003) Hilar and pancreatic gallium-67 accumulation is characteristic feature of autoimmune pancreatitis. Pancreas 27:20–25

    Article  PubMed  Google Scholar 

  • Sarles H, Sarles JC, Muratore R (1961) Guien C. Chronic inflammatory sclerosis of the pancreas—an autonomous pancreatic disease? Am J Dig Dis 6:688–698

    Article  CAS  PubMed  Google Scholar 

  • Sato Y, Kojima M, Takata K, Morito T, Asaoku H, Takeuchi T et al (2009) Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman’s disease. Mod Pathol 22:589–599

    Article  CAS  PubMed  Google Scholar 

  • Sato Y, Notohara K, Kojima M, Takata K, Masaki Y, Yoshino T (2010) IgG4-related disease: historical overview and pathology of hematological disorders. Pathol Int 60:247–258

    Article  CAS  PubMed  Google Scholar 

  • Sato Y, Takeuchi M, Takata K, Ohno K, Iwaki N, Orita Y, Goto N et al (2012) Clinicopathologic analysis of IgG4-related skin disease. Mod Pathol. doi:10.1038/modpathol.2012

  • Shimatsu A, Oki Y, Fujiswa I, Sano T (2009) Pituitary and stalk lesions (Infundibulo-hypophysitis) associated with immunoglobulin G4-related systemic disease: an emerging clinical entity. Endocr J 56:1033–1041

    Article  PubMed  Google Scholar 

  • Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M et al (2011) International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the international association of pancreatology. Pancreas 40:352–358

    Article  PubMed  Google Scholar 

  • Stone JH, Khosroshahi A, Hilgenberg A, Spooner A (2009) IsselbacherEM, Stone JR. IgG4-related systemic disease and lymphoplasmacytic aortitis. Arthritis Rheum 60(10):3139–3145

    Article  PubMed  Google Scholar 

  • Stone JH, Khosroshahi A, Deshpande V, Chan JK, Heathcote JG, Aalberse R et al (2012) Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations. Arthritis Rheum 64:3061–3067

    Article  CAS  PubMed  Google Scholar 

  • Takeda S, Haratake J, Kasai T, Takaeda C, Takazakura E (2004) IgG4-associated idiopathic tubulointerstitial nephritis complicating autoimmune pancreatitis. Nephrol Dial Transplant 19:474–476

    Article  PubMed  Google Scholar 

  • Uchiyama-Tanaka Y, Mori Y, Kimura T, Watanabe S, Nozaki Y, Fujita K et al (2004) Acute tubulointerstitial nephritis associated with autoimmune-related pancreatitis. Am J Kidney Dis 43:e18–e25

    Article  PubMed  Google Scholar 

  • Uehara T, Hamano H, Kawa S, Sano K, Oki K, Kobayashi Y et al (2010) Chronic gastritis in the setting of autoimmune pancreatitis. Am J Surg Pathol 34:1241–1249

    Article  PubMed  Google Scholar 

  • Ueno K, Watanabe T, Kawata Y, Gotoh T, Tsuji Y, Ida H et al (2008) IgG4-related autoimmune pancreatitis involving the colonic mucosa. Eur J Gastroenterol Hepatol 20:1118–1121

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T et al (2012b) Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol 22:21–30

    Article  CAS  PubMed  Google Scholar 

  • Umemura T, Zen Y, Hamano H, Kawa S, Nakanuma Y, Kiyosawa K (2007) Immunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology 46:463–471

    Article  CAS  PubMed  Google Scholar 

  • Umemura T, Zen Y, Hamano H, Joshita S, Ichijo T, Yoshizawa K et al (2011) Clinical significance of immunoglobulin G4-associated autoimmune hepatitis. J Gastroenterol 46(Suppl 1):48–55

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto M, Takahashi H, Ohara M, Suzuki C, Naishiro Y, Yamamoto H, Shinomura Y, Imai K (2006) A new conceptualization for Mikulicz’s disease as an IgG4-related plasmacytic disease. Mod Rheumatol 16:335–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamamoto M, Yajima H, Takahashi H, Yokoyama Y, Ishigami K, Shimizu Y et al (2015) Everyday clinical practice in IgG4-related dacryoadenitis and/or sialadenitis: results from the SMART database. Mod Rheumatol 25:199–204

    Article  CAS  PubMed  Google Scholar 

  • Yoshida K, Toki F, Takeuchi T, Watanabe S, Shiratori K (1995) Hayashi N. Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis. Dig Dis Sci 40:1561–1568

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura Y, Takeda S, Ieki Y, Takazakura E, Koizumi H, Takagawa K (2006) IgG4-associated prostatitis complicating autoimmune pancreatitis. Intern Med 45:897–901

    Article  PubMed  Google Scholar 

  • Zamboni G, Luttges J, Capelli P, Frulloni L, Cavallini G, Pederzoli P et al (2004) Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch 445:552–563

    Google Scholar 

  • Zen Y, Harada K, Sasaki M, Sato Y, Tsuneyama K, Haratake J et al (2004) IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis: do they belong to a spectrum of sclerosing pancreatitis? Am J Surg Pathol 28:1193–1203

    Article  PubMed  Google Scholar 

  • Zen Y, Kitagawa S, Minato H, Kuramaya H, Katayanagi K, Masuda S et al (2005) IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung. Hum Pathol 36:710–717

    Article  CAS  PubMed  Google Scholar 

  • Zen Y, Inoue D, Kitao A, Onodera M, Abo H, Miyayama S et al (2009) IgG4-related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol 33:1886–1893

    Article  PubMed  Google Scholar 

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Acknowledgment

This study was partially supported by (1) Grant-in-Aid for Scientific Research (C) of the Ministry of Culture and Science of Japan (20590810, 24591020, 12008507), (2) the Research Program on Intractable Diseases, from the Ministry of Labor and Welfare of Japan, and (3) grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, from CREST Japan Science, and Technology Agency.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan

    Kazuichi Okazaki

  2. The Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Shinmachi, Hirakata, Osaka, 573-1197, Japan

    Kazuichi Okazaki

  3. Northern County Center for RA and Autoimmune Disease, Hayashi Hospital, Fukui, Japan

    Hisanori Umehara

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  1. Kazuichi Okazaki
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  2. Hisanori Umehara
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Correspondence to Kazuichi Okazaki .

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  1. Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Osaka, Japan

    Kazuichi Okazaki

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Okazaki, K., Umehara, H. (2016). Current Concept of IgG4-Related Disease. In: Okazaki, K. (eds) IgG4-Related Disease. Current Topics in Microbiology and Immunology, vol 401. Springer, Cham. https://doi.org/10.1007/82_2016_47

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