IgG4-related disease (IgG4-RD) is a systemic disease that is characterized by fibroinflammatory infiltration of various organs, including by plasma cells that express IgG4 (immunoglobulin G subclass 4).
This condition has been known by many other names in the past, such as IgG4-related sclerosing disease, IgG4-related systemic disease, IgG4-related systemic sclerosing disease, IgG4-syndrome, IgG4-associated disease, and IgG4-related multi-organ lymphoproliferative syndrome. Since 2012, however, IgG4-related disease has become the preferred term 9,10.
IgG4-related diseases are more common in middle age or elderly males.
Clinical manifestations vary by the organ involved. These organ systems may be either synchronously or sequentially involved.
The disease spectrum is broad across organ systems:
- central nervous system
- head and neck
There are three major histopathologic characteristics of IgG4-related disease 9:
- dense lymphoplasmacytic infiltrate
- at least focally storiform fibrosis
- obliterative phlebitis
Two of these features are required for a confident pathologic diagnosis of IgG4-related disease, with a few organ-specific exceptions 9. Additional supporting features are non-obliterative phlebitis and eosinophilia 9.
Immunohistochemistry should demonstrate plasma cells that stain for IgG4. IgG4+ plasma cells must account for more than 40% of IgG+ plasma cells 9. The absolute density of IgG4+ plasma cells (number per high power field) suggestive of the diagnosis varies by organ. For example, the cutoff is >10/hpf for pancreatic biopsy specimens and >100/hpf for lacrimal and salivary glands 9.
Serology is often, but not always, abnormal in IgG4-related diseases. A serum IgG4 level >135 mg/dL is supportive of the diagnosis 9.
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