IgG4-related disease

Last revised by Yuranga Weerakkody on 3 Apr 2024

IgG4-related disease (IgG4-RD) is a systemic disease that is characterized by fibroinflammatory infiltration of various organs induced by plasma cells that express IgG4 (immunoglobulin G subclass 4).

Since 2012, IgG4-related disease has become the preferred term 9,10. However, it has been known by many other names in the past:

  • IgG4-related sclerosing disease

  • IgG4-related systemic disease

  • IgG4-related systemic sclerosing disease

  • IgG4-syndrome, IgG4-associated disease

  • IgG4-related multiorgan lymphoproliferative syndrome

IgG4-related diseases are more common in middle-aged 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:

Three major histopathologic characteristics of IgG4-related disease are 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 (hpf)) 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.

Supportive are also circulating plasmablasts 12.

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