IgG4-related disease

Author: Dr Anthony Yung, Dermatologist, Hamilton, New Zealand; Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, March 2014.

What is IgG4?

IgG4 is a subclass of IgG, which is the most common form of immunoglobulin (antibody proteins found throughout the body). IgG accounts for 75% of antibodies circulating in the blood. Antibodies are an important part of the body's secondary response to infection and toxins. They are made by plasma cells, a specialised type of B lymphocyte (an immune cell).

There are 4 subclasses of IgG. Subclass IgG4 is the least common of these, accounting for about 4% of IgG in serum (the non-cellular portion of blood). IgG4 has unique structure. Its specific biological role is uncertain.

What is IgG4-related disease?

IgG4-related disease is a newly-described rare syndrome consisting of many disease entities that were previously thought to be unrelated. These conditions have the common pathological features of:

Elevated serum IgG4 is present in 60–70% patients.

What are the symptoms of IgG4-related disease?

IgG4-related disease presents in various ways.

Organ-specific IgG4-related disease
OrganDisease
Gastrointestinal disease
  • Pancreatitis (type 1 autoimmune pancreatitis)
  • Idiopathic retroperitoneal fibrosis (Ormond disease)
  • Sclerosing cholangiitis
  • Gastritis
  • Hepatitis
Lymph node involvement
  • Generalised lymphadenopathy
Salivary and lacrimal disease
  • Mikulicz disease of the lacrimal glands (dacroadenitis) and salivary glands (sialoadenitis)
  • Sclerosing sialoadenitis (Küttner tumour of the submandibular salivary gland)
  • Chronic sclerosing dacroadenitis of the lacrimal glands
Eye disease
  • Inflammatory pseudotumour of the orbit
Heart disease
  • Chronic sclerosing aortitis and periaortitis
  • Constrictive periaortitis
Thyroid disease
  • Riedel thryroiditis
  • Fibrosing Hashimoto thyroiditis
Lung disease
  • Inflammatory pseudotumour
  • Interstitial pneumonitis
Kidney disease
  • Tubulointerstitial nephritis
  • Membranous glomerulonephritis
  • Inflammatory pseudotumour
Skin disease
  • Inflammatory pseudotumour
Other
  • Prostatitis
  • Hypophysitis (inflammation of pituitary gland)
  • Pachymeningitis (thickening of dura mater around the brain or spinal cord)

What is the cause of IgG4-related disease?

The cause of IgG4-related disease is unknown.

How is IgG4-related disease diagnosed?

Diagnosis of IgG4-related disease can be difficult, as multiple organs may be involved simultaneously. Diagnostic criteria have not been fully developed.

Investigation in suspected IgG4-related disease requires a combination of clinical, endoscopic, radiological and serological tests looking for organ involvement and end organ damage (eg hormonal abnormalities).

Tissue diagnosis requires biopsy of affected organ tissues, including skin biopsy, demonstrating:

Blood tests are not diagnostic but may show:

There are specific criteria for the diagnosis of some tissue-specific disorders, eg autoimmune pancreatitis.

How is IgG4-related disease treated?

IgG4-related disease is usually treated with systemic steroids, ie prednisone 40mg per day for 2–4 weeks followed by a gradual tapering of the dose.

In patients that cannot be taken off prednisone, a steroid-sparing agent like azathioprine or mycophenolate may be used. Rituximab, a B cell-depleting monoclonal antibody, has been used with some success.

Organ-specific replacement therapy may be required:

What is the prognosis of IgG4-related disease?

Prognosis of IgG4-related disease is variable. It may spontaneously resolve or persist, with remitting and relapsing symptoms.

Major causes for morbidity and mortality are major organ involvement such as:

IgG4-related disease may be associated with a possible increased risk of non-Hodgkin lymphoma. It is not known if IgG4-related disease leads to an increased risk of other forms of cancer.

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