Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

Table 5

Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011 [15].

[Concept]
IgG4-related disease (IgG4-RD) shows organ enlargement or nodular/hyperplastic lesions in various organs concurrently or metachronously, due to marked infiltration of lymphocytes and IgG4-positive plasma cells, as well as fibrosis of unknown etiology. IgG4-RD affects various organs, including the pancreas, bile duct, lacrimal gland, salivary gland, central nervous system, thyroid, lung, liver, gastrointestinal tract, kidney, prostate, retroperitoneum, arteries, lymph nodes, skin, and breast. Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, others show involvement of a single organ. Clinical symptoms vary depending on the affected organ, and some patients may experience serious complications, such as obstruction or compression symptoms due to organomegaly or hypertrophy and organ dysfunction caused by cellular infiltration or fibrosis. Steroid therapy is often effective.
[Comprehensive clinical diagnostic criteria for IgG4-RD,  2011]
(1) Clinical examination shows characteristic diffuse/localized swelling or masses in single or multiple organs.
(2) Hematological examination shows elevated serum IgG4 concentrations (≥135 mg/dL).
(3) Histopathologic examination shows;
(1) marked lymphocyte and plasmacyte infiltration and fibrosis
(2) infiltration of IgG4-positive plasma cells: ratio of IgG4/IgG positive cells > 40% and > 10 IgG4-positive plasma cells/HPF.
Definite: (1) + (2) + (3),   Probable: (1) + (3),   Possible: (1) + (2)
However, it is important to differentiate IgG4-RD from malignant tumors of each organ (e.g. cancer, lymphoma) and similar diseases (e.g. Sjögren’s syndrome, primary sclerosing cholangitis, Castleman’s disease, secondary retroperitoneal fibrosis, Wegener’s granulomatosis, sarcoidosis, and Churg-Strauss syndrome) by additional histopathological examination. Even when patients cannot be diagnosed using the CCD criteria, they may be diagnosed using organ-specific diagnostic criteria for IgG4RD.