IgG4-Related Disease (IgG4-RD)

How to pronounce it:  Eye-Gee-Gee-Four Related Disease

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.


Why Is AiArthritis Raising Awareness?

Even though IgG4-RD is not officially part of the AiArthritis disease umbrella, many people with may be misdiagnosed with an AiArthritis disease or still undiagnosed. IgG4-RD is currently considered immune-mediated, but may end up being classified as autoimmune or autoinflammatory in the future. If arthritis is also considered a major symptom, then it may eventually fall under our umbrella, but for now this is to be determined.

Download IgG4-RD Fact Sheet
  • Close-up of hands showing Rheumatoid Arthritis symptoms in hands and fingers, with red highlights indicating areas of joint pain and swelling in multiple finger joints against a white background

    Button

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)

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

  • 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

  • Who Treats IgG4-RD?

    IgG4-RD usually requires a team of doctors, depending on which parts of the body are affected. This may include:


    • Rheumatologist – Expert in immune and inflammatory diseases
    • Gastroenterologist – For pancreas, liver, or bile duct involvement
    • Nephrologist – For kidney involvement
    • Pulmonologist – If the lungs are affected
    • Ophthalmologist – For eye-related problems
    • Radiologist & Pathologist – Help interpret scans and biopsies
    • Primary care doctor – Helps coordinate care

    These doctors work together to create a treatment plan that fits your needs.


    Submit YOUR Advice

  • Treatments For IgG4-RD

    Common treatments include:


    • Steroids (like prednisone) to reduce inflammation
    • Immune-suppressing medicines (such as azathioprine or mycophenolate)
    • Biologics (like uplizna and rituximab) for long-term care

    Note: As of April 3, 2025, the FDA approved a treatment called Uplizna for IgG4-RD. Learn more at uplizna.com



  • Learn More

    Visit aiarthritis.org/Equation to download our Mystery Patient Guide and listen to Talk Show episodes


    Find more resources at:


    igg4ward.org – Education and patient stories

    igg4rdoutloud.com – Tools and care planning

    uplizna.com – Info on the FDA-approved treatment

    AiArthritis Resources

More IgG4-RD Content By AiArthritis

Go With Us! to EULAR 2025: What Is IgG4-Related Disease—and Why Are So Many Patients Misdiagnosed?

In this EULAR 2025 go with us debrief video, Health Education Manager Leila P.L. Valete discusses IgG4-related disease (IgG4-RD), a rare immune condition often confused with other autoimmune diseases.Topics include: diagnostic challenges , the significance of “SACQ” and gaps between lab results and symptoms, histology's role and potential pitfalls, treatments and

Ep 109: The Mystery Patient Experience and the Overlap with IgG4-RD

Managing AiArthritis diseases is tough without a clear diagnosis. In this episode, AiArthritis Health Education Manager Leila discusses the “mystery patient” experience of those with persistent symptoms.  She revisits earlier topics and introduces resources like the updated Mystery Patient Guide and the AUTO + Inflammatory Arthritis = X or YZ Project, exploring conditions such as IgG4-related disease. Leila also shares a touching story of a patient who struggled for years without a diagnosis.

Go With Us to EULAR 2023 - Ig-G4, UCTD, RMDs and the Brain - Tiffany, Deb, and Eileen do a deep-dive into the newest research and information presented throughout EULAR 2023 which includes an update on IgG4 from the European Congress of Rheumatology.

Physician showing woman xray of chest

Breaking the Silence: Celebrating IgG4-RD Awareness Day on April 4

March 27, 2025
Explore the complexities of IgG4-Related Disease (IgG4-RD), its symptoms, diagnosis, and treatment options. Learn about the importance of IgG4-RD Awareness Day in promoting early diagnosis and improving patient care through support and advocacy.

Get Involved!

Sometimes the best medicine is diving in to learn more, meeting those who have similar lived experiences, and doing activities that can help to improve your health and the AiArthritis community!

Where to Start:

  • Follow AiArthritis on Social Media:
Learn More