IgG4-Related Disease (IgG4-RD)

How to pronounce it: Rheumatoid - roo·muh·toyd


What is IgG4-Related Disease (IgG4-RD)?

IgG4-related disease (IgG4-RD) is a rare condition where the immune system becomes overactive and attacks healthy tissues. This can cause swelling (inflammation), damage, and sometimes scarring (fibrosis) in one or more organs.

It is not currently classified as an autoimmune or autoinflammatory arthritis disease, but it does involve the immune system. Researchers are still studying how it works and where it fits among immune conditions.



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Symptoms & Characteristics of AiArthritis Diseases

Common in All AiArthritis Diseases

Flares: Periods of worsening symptoms are called flares. A flare can last for hours, days, weeks, or months.


Physical Activity: Condition improves with activity and exercise and worsens with rest.


Comorbidities: When inflammation is left uncontrolled due to lack of proper treatment, comorbidities can develop. 70% of patients with chronic, lifelong disease will develop comorbidities, including dual or triple diagnoses.


Family History: Autoimmune diseases often run in families, indicating a potential genetic predisposition where that gene can cause disease. Autoinflammatory diseases can occur multiple times in a family, but is based off of genetic mutation. It is not a gene that causes the disease— but a mutation on the gene that can cause the disease which can then be passed on to the next generation.

"Auto" Symptoms

Fatigue: Severe fatigue or exhaustion that may not be helped by caffeine/stimulants and can happen even after a long period of rest.


Cognitive Dysfunction: Brain fog or periods of time where thinking gets clouded and it becomes difficult to concentrate.


Flu-like symptoms: Without having the flu- nausea, muscle weakness, and general malaise.


Fever: Typically low grade in autoimmune (with exception of juvenile idiopathic arthritis) and higher grade in autoinflammatory (% strongly varies per disease).


Reference: Early Symptoms of AiArthritis Study, AiArthritis, 2019.


View Early Symptom Study

Inflammatory Arthritis Symptoms

Stiffness: Severe stiffness in one or more joints, especially in the morning or after sitting for long periods of time. 


Joint Pain: Episodes of joint pain that may last for hours, days, or even weeks, that can appear and disappear suddenly. Often described as “jumping pain” into different locations.


Typically the joint pain will coincide with one or more “Auto” symptoms and start and stop suddenly - for no apparent reason (which is called a "flare"). Some people will experience all of the above symptoms, others only a few.


 If you have any of the arthritis features, and at least one of the “Auto” features, please consult your physician about a referral to a specialist.


Symptoms Often Associated with IgG4-Related Disease (IgG4-RD)

Symptoms depend on which organs are affected. You may notice:

  • Swelling or lumps in the face, neck, or belly
  • Dry eyes or mouth
  • Digestive issues
  • Trouble seeing
  • Fatigue 
  • Joint pain or stiffness (in some people)
  • Problems with kidneys, lungs, or bile ducts

Because the disease can affect many different organs at the same time, it may look very different from person to person.

  • Diagnosing IgG4-RD

    IgG4-RD can be hard to diagnose. There isn’t one single test that confirms it. Doctors usually look at a combination of the following:


    1. Blood Tests


    • IgG4 level – This may be high in many people with IgG4-RD, but not always. A normal level does not rule it out.
    • IgG1, IgE, and complement levels (C3 and C4) – These can also show changes linked to inflammation.
    • Organ-specific tests – Doctors may check how the liver, kidneys, pancreas, or other organs are working.

    2. Imaging Scans


    • CT scan (Computed Tomography) – Shows organ enlargement or masses
    • MRI (Magnetic Resonance Imaging) – Helpful for looking at soft tissue or brain involvement
    • Ultrasound – Often used to check for swelling in organs like the salivary glands or kidneys
    • PET scan (Positron Emission Tomography) – Helps show active inflammation

    3. Biopsy


    A biopsy is when a small sample of tissue is taken from a swollen or affected area. Doctors look at the tissue under a microscope for signs of IgG4-RD, such as:

    • High numbers of IgG4-positive plasma cells
    • Storiform (whorled) fibrosis
    • Obliterative phlebitis (veins blocked by inflammation)

    Not all biopsies show all of these features, but together they help confirm the diagnosis.


    Misdiagnosis is Common


    Because symptoms can look like other diseases, IgG4-RD is often misdiagnosed as:


    • Cancer (most common)
    • Sjögren’s disease
    • Sarcoidosis
    • Infections
    • Other autoimmune conditions

  • How Is IgG4-RD Treated?

    The goal of treatment is to control the disease, reduce inflammation, and prevent long-term organ damage.


    Common Treatments:


    • Steroids (such as prednisone) – Often the first treatment to reduce inflammation quickly
    • Immunosuppressive medications (such as azathioprine or mycophenolate mofetil) – May be used to keep the disease under control
    • Biologics (like uplizna and rituximab) – Used for patients who don’t respond well to steroids or need longer-term treatment

  • What Fellow Rheumatoid Arthritis Patients Want You to Know

    • Sometimes you may feel a locking feeling in the joints, like if you grab a hair brush or a cabinet handle - suddenly your fingers may stop moving while the rest of your hand continues in motion. This doesn't feel good.

    • Joints like your jaw can be affected.  Also the vocal chords, called the cricoarytenoid joint (although this is not common)

    • You CAN HAVE RA without positive blood work! You may hear some patients say they have "seronegative RA" or "seropositive RA". This is referring to their blood work. If a patient has "seronegative", it means they were diagnosed with RA and had no positive markers (inflammation, RF +, etc.) in their blood (normal bloodwork). 

    • A lot of patients choose not to use the word "arthritis" because they feel that's the only word others hear and think it's the same as the most common type of arthritis, osteoarthritis - caused by aging, wear and tear, overuse. While there has been movements in the past to try and change the name, there are many reasons why this is not likely to happen.

    Submit YOUR Advice

  • Interesting Facts about Rheumatoid Arthritis

    • There used to be a diagnosis of Juvenile Rheumatoid Arthritis (JRA) decades ago, but after it was realized that juvenile arthritis onset is not exactly the same disease as RA, it was changed to Juvenile Idiopathic (no known cause) Arthritis, or JIA. You may still hear people refer to it as JRA, especially if this was their diagnosis as a child.

    • While some adults originally diagnosed with either JRA or JIA may refer to their current diagnosis as Rheumatoid Arthritis (RA), it's really a matter of choice. Some adults still say JRA/JIA OR will say JRA/JIA/RA.

    • Evidence of RA-like symptoms has been found in skeletal remains of Native Americans dating back to at least 4500 B.C. This suggests that RA has been affecting humans for thousands of years. However, RA was not widely recognized in Europe until the 19th century.

    • The term “rheumatoid arthritis” was coined in 1859 by British rheumatologist Alfred Baring Garrod. “Rheumatoid” comes from the Greek word “rheuma,” meaning “that which flows,” referring to the characteristic joint swelling.

  • Rheumatoid Arthritis Awareness Days/Months

    • World Autoimmune and Autoinflammatory Arthritis Day - May 20th
    • Rheumatoid Arthritis Awareness Day - February 2nd
    • Autoimmune Awareness Month - March
    • Arthritis Awareness Week (UK) - May
    • Arthritis Awareness Month (US) - May
    • Arthritis Awareness Month (Canada) - September
    • World Arthritis Day - October 12th
    • Rheumatic Disease Awareness Month - September
    • Pain Awareness Month - September
    • Chronic Disease Awareness Day - July 10th
    • Invisible Disabilities Week - 3rd full week of October

  • Other Rheumatoid Arthritis Resources

    AiArthritis Resources

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