Current concept and diagnosis of IgG4-related disease in the hepato-bilio-pancreatic system

Abstract

Recently, IgG4-related disease (IgG4-RD) has been recognized as a novel clinical entity with multiorgan involvement and unknown origin, associated with abundant infiltration of IgG4-positive cells. The Japanese research committee, supported by the Ministry of Health, Labor and Welfare of Japan, unified many synonyms for these conditions to the term “IgG4-RD” in 2009. The international symposium on IgG4-RD endorsed the comprehensive nomenclature as IgG4-RD, and proposed the individual nomenclatures for each organ system manifestations in 2011. Although the criteria for diagnosing IgG4-RD have not yet been established, proposals include the International Pathological Consensus (IPC) and the Comprehensive Diagnostic Criteria (CDC) for IgG4-RD for general use, and several organ-specific criteria for organ-specialized physicians, e.g., the International Consensus Diagnostic Criteria (ICDC) and the revised clinical diagnostic criteria in 2011 by the Japan Pancreas Society (JPS-2011) for type1 AIP; the Clinical Diagnostic Criteria 2012 for IgG4-sclerosing cholangitis (IgG4-SC-2012); the diagnostic criteria for IgG4-positive Mikulicz’s disease by the Japanese Society for Sjogren’s syndrome; and diagnostic criteria for IgG4-related kidney disease by the Japanese Society of Nephrology. In cases of probable or possible IgG4-RD diagnosed by the CDC, organ-specific diagnostic criteria should be concurrently used according to a diagnosis algorithm for IgG4-RD, with referral to a specialist.

Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 I. Concept and diagnosis of autoimmune pancreatitis

“…All of them show similar pathological findings with abundant infiltration of IgG4-positive cells as well as high serum IgG4, which support the possibility that AIP is a systemic disorder associated with pancreatic lesions. After several proposals of nomenclatures such as the IgG4-related systemic sclerosing disease [14], systemic IgG4-related plasmacytic syndrome (SIPS) [15] and IgG4-positive multi-organ lymphoproliferative syndrome (IgG4 MOLPS), [16] the consensus nomenclature of IgG4-related disease (IgG4-RD) [17][18][19][20] was proposed. Therefore, AIP related to IgG4 is now regarded as a pancreatic manifestation of IgG4-RD.…”

“…Type 1 AIP is considered to be a pancreatic manifestation of IgG4-RD [17][18][19][20][87][88][89]. Abundant infiltration of IgG4-positive plasmacytes is characteristic, but not specific for IgG4-RD.…”

“…Abundant infiltration of IgG4-positive plasmacytes is characteristic, but not specific for IgG4-RD. Because a few cases have been reported in which IgG4-positive plasmacytes appear in patients with pancreatic cancer or alcoholic pancreatitis, IgG4-positive plasmacytes cannot be used as the sole basis for the diagnosis of AIP [17][18][19][20][87][88][89]. Therefore, histopathological findings as well as infiltration of IgG4-positive plasmacytes are important in the diagnosis of IgG4-RD [17][18][19][20][87][88][89].…”

IgG4-related Disease Involving Multiple Organs with Elevated Serum Interleukin-6 Levels

“…IgG4-RD is a fibroinflammatory condition that is associated with abundant infiltration of IgG4-positive cells (1). To diagnose the disease, several organ-specific diagnostic criteria have been established, including the clinical diagnostic criteria for autoimmune pancreatitis (AIP) proposed by The Japan Pancreas Society (10), clinical diagnostic criteria of IgG4-related sclerosing cholangitis (11), diagnostic criteria for IgG4-related Mikulicz's disease (12), and IgG4-related kidney disease (13).…”

“…This disease has been found to involve a wide range of organs, including the pancreas, bile duct, lacrimal glands, salivary glands, central nervous system, thyroid, lungs, liver, gastrointestinal tract, kidneys, prostate, retroperitoneum, arteries, lymph nodes, skin, and breast (1)(2)(3). IgG4-RD is radiologically characterized by diffuse or focal organ enlargement and mass-forming or nodular/thickened lesions in the affected organs.…”