IgG4-related disease

Last revised by Dr Michael P Hartung on 05 May 2022

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 multiorgan lymphoproliferative syndrome. Since 2012, however, IgG4-related disease has become the preferred term 9,10.

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:

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 (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.

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Cases and figures

  • Case 1: IgG4-related hypophysitis
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  • Case 2: IgG4-related AIP
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  • Case 3: IgG4-related AIP
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  • Case 4: sclerosing cholangitis
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  • Case 5: AIP
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  • Case 6
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  • Case 7: with porta-hepatis inflammtory mass
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  • Case 8: autoimmune cholangitis, pancreatitis, and pseudotumor
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