Key takeaways

  • IgG4-related disease (IgG4-RD) is a chronic autoimmune condition that may affect multiple organs in your body, causing tissue swelling and organ damage.
  • Because no single test can definitively diagnose IgG4-RD, doctors may order blood tests, imaging, and biopsies. Treatment may involve corticosteroids and immune-modifying medications to manage inflammation and prevent flares.
  • The outlook for IgG4-RD depends on the extent of organ damage and the timing of treatment. Early treatment can help limit organ damage and other complications, although relapses are possible.

Immunoglobulin G4-related disease (IgG4-RD) causes chronic (long-term) inflammation and the buildup of various immune cells in tissues in your body. Those immune cells include plasma cells that produce the antibody IgG4, a protein your immune system uses to help fight disease.

IgG4-RD may cause:

  • tissue swelling
  • fibrosis (fibrous tissue scarring)
  • pseudotumors (tumor-like growths or masses)
  • phlebitis (inflammation of veins)
  • arteritis (inflammation of arteries)

The disease can affect almost any organ, including your:

  • pancreas
  • bile ducts
  • kidneys
  • eye sockets
  • tear glands
  • salivary glands
  • thyroid gland
  • meninges (the thin layers of tissue that protect your brain and spinal cord)
  • lungs
  • aorta

In 60% to 90% of people who have IgG4-RD, the condition affects multiple organs.

IgG4-RD may damage affected organs and stop them from working as they should. In some cases, it can cause serious complications, including organ failure.

Read on to learn more about the cause, treatments, and outlook for IgG4-RD.

Experts believe that IgG4-RD is an autoimmune condition that involves changes in the immune system, but they don’t know exactly what causes those changes. Genetic, environmental, and lifestyle factors may all play a role.

The signs and symptoms of IgG4-RD depend on which organs are affected and how much organ damage has happened.

Possible signs and symptoms of IgG4-RD include:

  • pseudotumors
  • swelling in your abdomen, face, or neck or other parts of your body
  • pain in your abdomen, your back, or other parts of your body
  • bulging of one or both eyes
  • a yellow tint to your eyes or skin
  • skin itching or other skin changes
  • headache
  • mild fever
  • fatigue
  • weight loss
  • shortness of breath
  • difficulty urinating

It sometimes takes months or years for noticeable symptoms to develop.

No single test is available to diagnose IgG4-RD.

Your doctor will order multiple tests to check for signs of this condition, including:

  • blood tests to measure the level of IgG4 in your blood
  • imaging tests to check for tissue swelling, pseudotumors, or other changes
  • a biopsy (a procedure in which a healthcare professional collects a tissue sample for examination under a microscope)

Your doctor might also order tests to check for other health conditions that can cause signs and symptoms similar to those of IgG4-RD.

Corticosteroid therapy has historically been the main treatment for IgG4-RD.

Corticosteroids reduce inflammation and decrease IgG4 levels. They can bring IgG4-RD into remission, which means that disease activity is reduced (partial remission) or that there is no disease activity at all (complete remission).

Because long-term corticosteroid therapy comes with a high risk of side effects, doctors try to prescribe the lowest dose of corticosteroids necessary to treat IgG4-RD.

Your doctor may prescribe a higher dose of corticosteroids to treat a disease flare and then gradually reduce the dose over time. They might eventually stop your corticosteroid treatment, or they may advise you to continue taking a low dose of corticosteroids to prevent flares.

Your doctor might also prescribe a monoclonal antibody or other immune-modifying medication to help prevent disease flares. These treatments may reduce your need for long-term corticosteroid therapy.

Monoclonal antibody therapy

Inebilizumab-cdon (Uplizna) is the first monoclonal antibody that the Food and Drug Administration (FDA) has approved to treat IgG4-RD. It works by reducing the number of B cells in your immune system. B cells are immune cells that produce IgG4 and play a role in inflammation.

Scientists are also studying other monoclonal antibodies to treat IgG4-RD. For example, according to a 2023 research review, rituximab has shown potential for treating this condition.

Other immune-modifying medication

Doctors may prescribe other drugs that modify your immune system, such as:

  • azathioprine
  • cyclophosphamide
  • iguratimod
  • leflunomide
  • methotrexate
  • mycophenolate mofetil

Combining these medications with corticosteroid therapy may improve remission rates and reduce disease flares more than corticosteroid therapy alone.

Treatment for complications

If you’ve developed complications from IgG4-RD, your doctor might prescribe additional treatments.

Your treatment will depend on the specific complication you’re experiencing but may involve medication, surgery, or other therapies.

For example, if your bile ducts become blocked as a result of IgG4-related inflammation in your bile ducts or pancreas, your doctor might recommend biliary stenting. During this procedure, a surgeon will place small tubes in your bile ducts to keep them open.

Diet changes or other lifestyle changes may also help you manage certain complications.

Your outlook with IgG4-RD will depend on:

  • how early you get treatment
  • which organs the disease is affecting
  • how much organ damage you have

Early treatment helps limit fibrosis and prevent complications. It’s not always possible to reverse fibrosis or other complications once they’ve developed, but treatment may be available to manage certain complications.

Treatment can help bring IgG4-RD into remission, but a combination of treatments may be necessary to do so. Your doctor can help you understand your treatment options.

You might experience a relapse or disease flare, which is a period when disease activity returns or increases. Your doctor can help you find a treatment that may lower your risk of relapse. They can also help you learn how to recognize and manage a relapse if one occurs.

You can talk with your doctor to learn more about your treatment options and outlook. Let them know about any changes in your health, as well as any questions you have.

It’s important to attend regular checkups so your doctor can monitor your condition for signs of change. Your doctor may adjust your treatment if you experience a relapse or develop treatment side effects that are difficult to manage.

IgG4-RD is an autoimmune condition that may affect multiple organs and can cause swelling, scarring, and other tissue damage.

Early treatment is important for preventing complications. Your doctor may prescribe B-cell targeted therapy, corticosteroids, or other medications to help reduce inflammation and lower your IgG4 levels.

If you’ve developed complications, your doctor may recommend lifestyle changes, medication, surgery, or other treatments to manage them.

Regular checkups are important to allow your doctor to monitor for changes in your condition. Your doctor may recommend changes to your treatment if disease activity increases or if you develop bothersome side effects.

You can talk with your doctor to learn more about your condition, treatment options, and outlook.