IgG4-Related Disease

What IgG4-related disease is

IgG4 is one of four subclasses of the IgG antibody. In IgG4-RD, the immune system drives a characteristic pattern in affected tissues:

• dense infiltrates of lymphocytes and IgG4-producing plasma cells
• a "storiform" (cartwheel-like) pattern of fibrosis
• inflammation of small veins (obliterative phlebitis)

The cause is not fully understood. It is thought to involve specific T cells and B cells that drive inflammation and fibrosis. It is not an infection and is not contagious. Many conditions once considered separate, such as type 1 autoimmune pancreatitis, Mikulicz disease and Riedel thyroiditis, are now recognized as IgG4-RD.

Organs commonly affected

Many people have more than one organ involved, either at the same time or over years.

Symptoms

IgG4-RD typically develops over months and often causes no fever. Symptoms depend on the organs involved:

• painless swelling of glands in the neck, face or around the eyes
• yellow skin and eyes, itching, dark urine (bile duct or pancreas involvement)
• upper belly or back pain
• weight loss
• new or worsening diabetes
• dry mouth and dry eyes
• bulging eyes or double vision
• leg swelling or reduced urine from ureter blockage
• asthma or allergies, which are common in people with IgG4-RD

Diagnosis

Diagnosis can be difficult because IgG4-RD mimics cancer, lymphoma, infection, sarcoidosis, Sjogren's syndrome and vasculitis. Doctors use:

1. Biopsy: the most important test, showing the characteristic tissue pattern and many IgG4-positive plasma cells.
2. Blood tests: serum IgG4 is raised in many, but not all, patients, and a raised level alone is not diagnostic. Other findings include high eosinophils, IgE and low complement.
3. Imaging: CT, MRI and PET-CT to map organ involvement and guide biopsy.
4. Excluding mimics: especially cancer and lymphoma.
5. Classification criteria: the 2019 ACR/EULAR criteria are used to confirm the diagnosis consistently.

Treatment

Treatment is recommended for symptomatic or active disease, and urgently when vital organs (pancreas, bile ducts, kidneys, aorta, retroperitoneum) are threatened, because inflammation can progress to irreversible fibrosis.

• Glucocorticoids: prednisone is the first-line treatment. Most patients respond within 2 to 4 weeks, with shrinking swelling and improving lab tests. Doses are tapered over months.
• Rituximab: an antibody that depletes B cells, highly effective for relapse or to spare steroids.
• Inebilizumab: a B-cell depleting antibody shown to reduce flares, approved by the FDA in 2025 for adults with IgG4-RD.
• Other steroid-sparing medicines: azathioprine, mycophenolate, methotrexate.
• Procedures: bile duct or ureteral stents when there is a blockage.

Outlook

Most people respond well to treatment, but relapses are common, occurring in about half of patients within a few years after steroids are stopped. Long-term monitoring with blood tests and imaging is important. Advanced fibrosis may not reverse, so early diagnosis and treatment protect organ function.

Frequently asked questions

What is IgG4-related disease?

It is a chronic immune-mediated condition in which immune cells infiltrate organs, causing swelling, masses and scarring. It commonly affects the pancreas, bile ducts, salivary and tear glands, kidneys and tissues around the aorta. It often mimics cancer.

What are the symptoms of IgG4-related disease?

Symptoms depend on the organs involved. Common ones include painless swelling of glands near the jaw or eyes, jaundice, belly or back pain, weight loss, new diabetes, dry mouth and leg swelling from blocked ureters. Fever is usually absent.

Does a high IgG4 level mean I have IgG4-related disease?

Not necessarily. Raised IgG4 levels can occur in other conditions, including allergies, some infections and cancers, and some people with IgG4-RD have normal levels. Diagnosis relies mainly on biopsy, imaging and clinical features.

Is IgG4-related disease cancer?

No. It is an immune condition, not cancer, although it often forms masses that look like tumors on scans. A biopsy is usually needed to tell them apart. There may be a slightly increased risk of some cancers, so follow-up is recommended.

How is IgG4-related disease treated?

Steroids such as prednisone are the first treatment and work well for most people. Rituximab, inebilizumab or other immune-suppressing medicines are used to prevent relapses and reduce steroid exposure. Stents may be needed for blocked bile ducts or ureters.