IgG4-Related Sclerosing Disease Incorporating Sclerosing Pancreatitis, Cholangitis, Sialadenitis and Retroperitoneal Fibrosis with Lymphadenopathy

A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

“…Autoimmune pancreatitis (AIP) is also associated with a variety of extrapancreatic lesions, including sclerosing cholangitis, sclerosing sialadenitis, and dacryoadenitis, resulting in the concept of IgG4-related systemic disease [20], also called IgG4-related autoimmune disease [21] or IgG4-related sclerosing disease [15]. The finding of elevated serum IgG4 and IgG4-positive plasma cell infiltration in MD suggested that MD was a systemic disease, which was called systemic IgG4 plasmacytic syndrome (SIPS) [22].…”

“…Clinically, type 1 AIP seems to be the pancreatic manifestation of IgG4RD, characterized by: (1) mild abdominal symptoms, usually without acute attacks of pancreatitis; (2) occasional occurrence of obstructive jaundice; (3) increased serum gammaglobulin, IgG, and/or IgG4 concentrations; (4) presence of autoantibodies; (5) diffuse enlargement of the pancreas with a capsule-like low-density rim; (6) irregular narrowing of the pancreatic duct (sclerosing pancreatitis on endoscopic retrograde cholangiopancreatography [ERCP] images); (7) lymphocyte and IgG4-positive plasmacyte infiltration and fibrosis, and obliterative phlebitis; (8) occasional association with extrapancreatic lesions, such as sclerosing cholangitis similar to primary sclerosing cholangitis (PSC), sclerosing cholecystitis, sclerosing sialoadenitis, RPF, interstitial renal tubular disorders, enlarged celiac and hilar lymph nodes, chronic thyroiditis, and pseudotumor of the pancreas, liver, or lung; and (9) responsiveness to steroid therapy. Older males with IgG-related AIP often have obstructive jaundice, with both pancreatic and extrapancreatic manifestations responding to steroid therapy [12–15, 21, 33, 34]. …”

“…IgG4-positive plasma cell infiltration has also been observed in patients with other conditions, including retroperitoneal and mediastinal fibrosis [15, 16], inflammatory pseudotumor of the lung and liver [17], Küttner tumor [18], and interstitial nephritis [19], indicating that these diseases and conditions collectively constitute a new disease concept, IgG4-related disease (Fig. 1).…”

Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease

“…Such abnormalities include an elevated serum IgG4 level and numerous IgG4-positive plasma cells infiltrating the affected tissue, and these disorders are classified as IgG4-related diseases. [1][2][3][4][5][6][7][8][9][10][11] Castleman's disease is a rather rare atypical lymphoproliferative disorder 12 classified according to the histopathologic findings of the affected lymph nodes as plasma cell type, hyaline-vascular type or a mixed-type variant of the two. 13,14 Patients with the plasma cell or the mixed-type variant frequently have systemic manifestations (so-called multicentric Castleman's disease), such as low-grade fever, fatigue, loss of appetite, and weight loss.…”

“…17,18 Multicentric Castleman's disease exhibits an aggressive and usually fatal disease course associated with infectious complications and risk of malignant tumors; one-third of such patients develop Kaposi sarcoma or B-cell lymphoma. 17,18 IgG4-related disease sometimes involves regional and/or systemic lymph nodes, 3,4,11 and is often clinically and/or histologically suspected to be multicentric Castleman's disease and/or malignant lymphoma. 5,6,11 However, systemic IgG4-related lymphadenopathy is either not mentioned or only briefly alluded to in previous reports.…”