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IgG4-Related Disease



Cory Perugino

, DO, Harvard Medical School

Reviewed/Revised Aug 2023

Immunoglobulin G4-related disease (IgG4-RD) is an uncommon immune disorder that usually affects multiple tissues and organs with tumor-like masses and/or painless enlargement.

Immunoglobulins are antibodies Antibodies One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more Antibodies , which are proteins that are part of the body's immune system Overview of the Immune System The immune system is designed to defend the body against foreign or dangerous invaders. Such invaders include Microorganisms (commonly called germs, such as bacteria, viruses, and fungi) Parasites... read more defenses. Immunoglobulins help protect against foreign or dangerous invaders, such as bacteria, viruses and cancer cells. The body produces thousands of different immunoglobulins, which are grouped into 5 classes (IgM, IgG, IgA, IgE, and IgD), some of which (eg, IgA and IgG) have subclasses.

IgG4 is the least common of the 4 subclasses of IgG. It has various normal functions in the body, but in IgG4-related disease, immune cells that produce IgG4, along with other related cells, accumulate abnormally in certain organs and damage them. The affected organs can enlarge and may eventually fill with scar tissue (fibrosis) and the damage can be permanent.

One or more organs are affected. Other organs and tissues can be affected, but the 11 organs considered typical of IgG4-RD include

  • Pancreas (organ that secretes digestive juices and hormones such as insulin)

  • Bile ducts (small tubes that carry bile, a fluid that aids in digestion)

  • Lacrimal (tear) glands

  • Orbital tissues (tissues surrounding the eye)

  • Salivary glands (glands that lie under the side of the jaw and behind the angle of the jaw)

  • Lungs

  • Kidneys

  • Retroperitoneal tissues (at the back of the abdomen)

  • Aorta (the main blood vessel bringing blood from the heart to the body)

  • Meninges (layers of tissue that cover the brain and spinal cord)

  • Thyroid gland (gland in the front of the neck that controls many body activities)

Symptoms of IgG4-Related Disease

Common symptoms of IgG4-RD include swollen lymph nodes Swollen Lymph Nodes Lymph nodes are tiny, bean-shaped organs that filter lymph fluid. They are located throughout the body, but particular collections are found just under the skin in the neck, under the arms,... read more Swollen Lymph Nodes and weight loss. Weight loss is particularly common when multiple organs are involved and/or when the pancreas does not make enough of the enzymes needed for digestion. IgG4-RD almost never causes a fever.

Other symptoms are specific to the affected organs:

Diagnosis of IgG4-Related Disease

  • Biopsy

  • Blood tests

  • Imaging

A biopsy is usually needed for doctors to distinguish IgG4-RD from other causes of enlarged organs and/or swollen lymph nodes.

Doctors usually do blood tests to measure levels of IgG4 and other immunoglobulins, but even though the disease involves IgG4 producing cells, IgG4 levels are not always elevated. And other diseases can cause elevated IgG4 levels. Other blood tests are done to see what organs may be affected and to help exclude other diseases.

Doctors will usually do a CT or MRI of areas where people have symptoms (for example, of orbits, chest, abdomen, and pelvis). They may also do imaging tests of other areas to look for organs that could be affected but are not causing symptoms.

Sometimes, urine and stool tests are helpful.

Treatment of IgG4-Related Disease

  • Corticosteroids

  • Rituximab

  • Sometimes, surgery

Treatment of IgG4-RD aims to reduce inflammation and stop the effects of the disorder.

Initial treatment is often with an oral corticosteroid (for example, prednisone), which is given for 2 to 4 weeks then tapered over the course of 2 to 3 months. Rituximab, a medication that modifies the immune system's activity, is often used when corticosteroids are not appropriate (for example, in people with uncontrolled diabetes) or if the disease recurs when tapering or stopping corticosteroids. Rituximab is nearly universally effective in treating active IgG4-RD.

Typically, organ function returns to normal after treatment. However, if a lot of scar tissue had already formed in an organ, function may not fully return to normal.

Some people require surgical procedures, such as stenting, to relieve blockages of the ureters (the tubes that carry urine from the kidneys to the bladder) or bile ducts.

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