IgG4-Related Disease (IgG4-RD): Symptoms, Causes, and Management

Medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026

Quick Answer

IgG4-related disease (IgG4-RD) is a rare, chronic, immune-mediated inflammatory disease that causes noncancerous, tumor-like masses and organ enlargement, often in several organs at once, such as the salivary glands and pancreas. Corticosteroids are the first treatment, followed by anti-B-cell therapy like rituximab when needed. Early treatment helps prevent permanent scarring, though relapse is possible. [1]

What the research says

• Steroids work for almost everyone, but relapse is common. A systematic review of 62 studies (3,034 patients) found that 97% of patients treated with glucocorticoid monotherapy responded, yet relapses were reported in 464 of 1,395 patients (33%) despite typically short follow-up. (Brito-Zerón et al., Medicine, 2016)

• Rituximab maintenance may lower relapse. A meta-analysis of 18 studies (374 patients) reported a pooled response rate of 97.3% with rituximab induction, and a pooled relapse rate of 2.8% in studies that used maintenance therapy versus 21.5% in studies without it. (Liu et al., Eur J Intern Med, 2024)

• Inebilizumab reduced flares in a phase 3 trial. In a randomized, placebo-controlled trial of 135 adults, 10% of those given inebilizumab had a flare over 52 weeks versus 60% on placebo (hazard ratio 0.13); serious adverse events occurred in 18% versus 9%. (Stone et al., N Engl J Med, 2025)

What is IgG4-related disease?

IgG4-related disease, or IgG4-RD, is a rare, chronic condition in which inflammation leads to tumor-like masses or enlarged organs. Although the masses may look concerning on imaging tests, they are not cancerous. However, the inflammation can cause serious tissue damage and organ failure if the condition is not managed. [1] Researchers first classified IgG4-RD in the early 2000s, so it can take time to get a proper diagnosis. [1]

One of the most challenging aspects of IgG4-RD is that it can affect almost any organ, and it usually affects more than one at a time. The most commonly affected tissues include the major salivary glands, the tear glands and the bony cavity around the eye (orbit), the pancreas and biliary tree, the lungs, kidneys, aorta, thyroid gland and the meninges (the lining around the brain). [1] Some people have disease in only one organ, while others have two to six organs involved at once, and the classic patient is middle-aged to elderly and more likely to be male. [2] Because it can involve several organs, care often involves different specialists depending on which organs are affected.

Recognizing the symptoms

IgG4-RD symptoms vary greatly depending on which organs are affected, and they typically develop gradually. [1] It is also possible to have no symptoms at all, discovering the condition only after imaging tests for an unrelated reason. Many patients have no symptoms for months or even years, and organ damage can still occur during that time. [2]

Common symptoms by body region

Symptoms depend on the organ involved. The most common ones are listed below. [1]

Region	Potential symptoms
Head and neck	Painless swelling of the tear or salivary glands, dry eyes and mouth, poor tear drainage, double vision, bulging eyes, chronic nasal symptoms such as sneezing and a runny nose, and nasal polyps
Chest and abdomen	Abdominal pain, flank or back pain, cough, difficulty breathing, or sharp chest pain
Whole body	Jaundice (a yellow tint to the skin), unexplained weight loss, or swollen lymph nodes

If the thyroid gland is involved, it may become firm and enlarged, which can cause trouble swallowing or breathing. [1] Painless jaundice can occur when inflammation in the biliary tree blocks the flow of bile. [2]

Causes and the role of the immune system

Researchers do not yet know what causes IgG4-related disease, but they are actively studying it. It is an immune-mediated condition, which means the immune system does not act as it should and causes tissue damage through excessive inflammation. [1]

The disease is named after IgG4, one of four subtypes of immunoglobulin G (IgG), a type of antibody your body makes to help fight infections. Normally, your immune system makes immunoglobulins to defend against viruses or bacteria. In IgG4-RD, the immunoglobulins harm your body instead of protecting it. [1]

How IgG4-RD is diagnosed

IgG4-RD can be tricky to diagnose because it can look like many other conditions, and a large part of the process is ruling those out. [1] There is no single specialist for IgG4-RD, so you will likely see healthcare providers based on your symptoms or test results. [1] The workup may include:

• Blood tests: To check IgG4 levels and other markers of inflammation.

• Urinalysis: To look for signs of kidney involvement.

• Imaging: CT or MRI scans help identify tumor-like masses and enlarged organs.

• Biopsy: A small tissue sample can help confirm IgG4-related inflammation and rule out cancer and other conditions.

Treatment and long-term outlook

IgG4-RD is often treatable. The main goal of therapy is to reduce inflammation quickly to prevent permanent organ damage such as fibrosis (scarring). Most people first take corticosteroid pills, and nearly everyone improves within four weeks. Once there is improvement, the dose is gradually lowered with the aim of stopping the medicine entirely. [1] Glucocorticoids are generally viewed as the initial treatment, but the disease often recurs after they are stopped. [2]

If you cannot tolerate or stop corticosteroids, your provider may prescribe rituximab or inebilizumab, monoclonal antibodies that deplete the B cells that make IgG4. You may also receive this medicine if IgG4-RD comes back within 12 months of stopping corticosteroids, and some people need surgery or other procedures. [1]

Typically, tumor-like masses or organ enlargement go back to normal after treatment. If they do not, it may be a sign of permanent organ fibrosis, which is why early diagnosis and treatment are key. After treatment stops, the condition can come back, so regular follow-up with your healthcare team is important. [1]

Learn more. For more evidence-based health guides, visit Rinnit.com.

Frequently Asked Questions

Is IgG4-related disease a type of cancer?

No. It can cause tumor-like masses, but they are inflammatory, not cancerous. The masses can look like cancer on imaging and can still damage organs if not treated, which is why tissue testing is sometimes needed to tell the difference.

Can IgG4-RD be cured?

There is no guaranteed cure. Treatment can bring the disease under control and the masses usually shrink, but it can come back after treatment stops, so long-term follow-up is needed.

Is the condition contagious?

No. IgG4-RD is an immune-mediated disease caused by a problem with your own immune system. It cannot be spread from person to person.

What organs are most commonly affected?

The salivary glands, tear glands and the area around the eye, the pancreas and biliary tree, the lungs, kidneys, aorta, thyroid and the meninges are among the most commonly affected tissues. It often involves more than one organ at a time.

Why is it called IgG4-related disease?

IgG4-related disease is named after IgG4, one of the four subtypes of immunoglobulin G (IgG) antibodies, which are involved in the disease process.

Can I have IgG4-RD without any symptoms?

Yes. Some people have no symptoms and only find out after imaging tests done for another reason.

What happens if IgG4-RD is left untreated?

Ongoing inflammation can cause permanent scarring (fibrosis), organ damage and, in some cases, organ failure.

Are there specific specialists for this disease?

There is no single specialist for IgG4-RD. Depending on which organs are affected, you may see a rheumatologist, gastroenterologist, pulmonologist, nephrologist or another specialist.

How common is IgG4-RD?

IgG4-RD is rare. It was only first classified in the early 2000s, so it can take time to get a proper diagnosis.

Can the disease come back after treatment?

Yes. Relapse is possible after treatment stops, especially after corticosteroids. The American College of Rheumatology notes that about 40% of patients treated with glucocorticoids either do not reach complete remission or relapse within a year, which is why regular follow-up matters.

Are there side effects to the treatments?

Long-term corticosteroid use can cause side effects, which is why the dose is lowered gradually with the aim of stopping. Your healthcare team will discuss the risks of any treatment with you.

Is a biopsy always necessary for diagnosis?

Not always, but biopsies are one of the tests that may be used. A tissue sample can help confirm IgG4-related inflammation and rule out cancer and other conditions.

Does having IgG4-RD increase my risk for other diseases?

The main concern is organ damage from the disease itself, such as scarring or organ failure when diagnosis or treatment is delayed. Your healthcare team will monitor you for complications.

Can children get IgG4-RD?

IgG4-RD is most often seen in middle-aged and older adults, and more often in men, but in rare cases it can affect children.

How long does it take for treatment to work?

According to Cleveland Clinic, nearly everyone who takes corticosteroids improves within four weeks.

References

1. Cleveland Clinic. IgG4-Related Disease (IgG4-RD). Cleveland Clinic. Last updated March 27, 2026. https://my.clevelandclinic.org/health/diseases/igg4-disease

2. American College of Rheumatology. IgG4-Related Disease (IgG4-RD). American College of Rheumatology. Updated February 2025. https://rheumatology.org/patients/igg4-related-disease-igg4-rd

3. Brito-Zerón P, et al. Therapeutic approach to IgG4-related disease: A systematic review. Medicine (Baltimore). 2016;95(26):e4002. PMID 27368010. https://doi.org/10.1097/MD.0000000000004002

4. Liu Y, et al. Efficacy and safety of rituximab induction therapy and effect of rituximab maintenance for IgG4-related disease: a systematic review and meta-analysis. Eur J Intern Med. 2024;127:63-73. PMID 38871563. https://doi.org/10.1016/j.ejim.2024.06.006

5. Stone JH, et al. Inebilizumab for Treatment of IgG4-Related Disease. N Engl J Med. 2025;392(12):1168-1177. PMID 39541094. https://doi.org/10.1056/NEJMoa2409712

Medical disclaimer

This article is for general educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.