IgG4-RD
About IgG4-RD
Last Updated on October 7, 2025
IgG4-Related Disease (IgG4-RD) is a rare condition where the immune system attacks the body, leading to inflammation (swelling and irritation) and fibrosis (excessive scarring) in various organs and tissues. The exact cause of IgG4-RD is unknown. Signs and symptoms vary widely depending on which organs are involved, but may include fatigue, unintentional weight loss, swollen glands, tumor-like masses, or dysfunction of involved organs.
Diagnosing IgG4-RD can be tricky because many of the symptoms may be quite subtle and go unrecognized early in the disease course. In addition, its symptoms are often similar to other conditions, and it can even be mistaken for cancer. Doctors rely on a combination of medical history, lab tests, tissue biopsies, and imaging scans to confirm the diagnosis. Treatment typically involves glucocorticoids (steroids) and/or other medications that suppress the immune system. Living with IgG4-RD involves ongoing management and monitoring, but with proper care, most people with IgG4-RD achieve remission and have a normal life expectancy.
Quick Facts
Estimated number of cases worldwide is unknown
Estimated 5 cases per 100,000 in United States
Any age, but most frequently ages 50-70
Rare in children
More common in males
More common in people of Japanese descent, but can affect all ethnic groups
IgG4-Related Disease (IgG4-RD) is a rare condition where your immune system doesn’t work correctly. Your immune system normally protects you from infections, but in IgG4-RD, it becomes too active and attacks your own body. This causes inflammation (swelling and irritation) and fibrosis (excessive scarring) in different organs and tissues.
Many people with this disease have high levels of immunoglobulin G4 (IgG4) in their blood, though not everyone does. Immunoglobulins are proteins that help your body fight infection. IgG4 is normally present in everyone’s blood as part of the immune system, but it’s often much higher in people with IgG4-RD. However, IgG4 can also be elevated for many other reasons, and in fact, most people with elevated IgG4 levels in the blood do not have IgG4-RD.
The causes of IgG4-RD are not fully understood. Research into autoimmune diseases has shown that some people have a genetic predisposition to developing an autoimmune disease. People with this genetic predisposition have a higher chance than average of developing an autoimmune disease such as IgG4-RD, but many people with this genetic predisposition will never develop an autoimmune disease. A combination of factors such as genetic predisposition and environmental factors seem to be involved in triggering autoimmune related conditions such as IgG4-RD. Smoking and tobacco use have been identified as risk factors for developing certain manifestations of IgG4-RD.
It is estimated that IgG4-RD affects around 5 in 100,000 people in the United States. Autoimmune diseases are typically more common in women than men, but IgG4-RD is more common in men. IgG4-RD can affect people of any age, including children, but it typically affects people who are in their 50’s or 60’s.
The signs and symptoms of IgG4-RD vary depending on what organ system or site of the body is affected. General signs and symptoms may include:
- Fatigue
- Unintended weight loss
- Swelling and tumor-like masses/lumps in affected areas such as the pancreas or kidneys
- Swelling and enlargement of affected organs such as salivary glands or lymph nodes
- Dysfunction of affected organs such as the pancreas or kidneys
- Tumor-like inflammatory masses in affected areas of the body
Organ and site specific signs & symptoms may include:
Eyes Sockets
- Double vision
- Bulging eyes
- Eye pain
- Rarely, vision loss
Salivary and Tear Glands
- Glands are swollen and firm to touch
- Dry eyes
- Dry mouth
Thyroid & Pituitary Glands
- Hormonal imbalances
- Fatigue
Central Nervous System
- Seizures
- Headaches
Heart & Aorta
- Swelling and weakening of blood vessels
- Heart disease
Retroperitoneum (region surrounding the aorta in the abdomen)
- Abdominal pain
- Narrowing of the tubes connecting kidneys to the bladder leading to kidney swelling
Biliary Tract & Liver
- Narrowing and inflammation of ducts
- Jaundice (yellowing of skin and eyes)
Kidneys
- Chronic kidney disease
- Swelling of legs and feet
Pancreas
- Rapid weight loss
- New-onset diabetes, often progressing quickly
- Abdominal pain
- Digestive issues
Lungs
- Masses in the lungs
- Lung disease
- Shortness of breath
Prostate
- Weak urinary stream
- Incomplete bladder emptying
Elevated concentrations of IgG4 in the blood are common in IgG4-RD but are not always present. It is estimated that IgG4 levels are elevated in about 70% of people with IgG4-RD but approximately 30% of people who have IgG4-RD will have normal levels of IgG4 in their blood.
Elevated levels of IgG4 do not necessarily mean you have IgG4-RD as IgG4 levels may be high for other reasons including infection, asthma or allergic diseases, lymphoma, or other autoimmune and inflammatory diseases such as other types of vasculitis, lupus and Sjögren’s disease.
Among the most serious potential complications of IgG4-RD is irreversible damage to major organs such as the kidneys and pancreas. With appropriate treatment, worsening damage such as irreversible scarring (fibrosis) in organs can be prevented. The risk of pancreas and kidney problems decreases significantly once the disease is in remission. Most people with IgG4-RD have multiple episodes of disease flare over time, so long-term follow-up to monitor for disease flares is important.
During the treatment phase of IgG4-RD, the most serious potential complication is infection. Many of the treatments for IgG4-RD suppress your immune system. It is important to take precautions to protect yourself from infection while on immunosuppressive treatments. Learn more about preventing infection on our Immunity and Infection webpage.
Diagnosing IgG4-RD can take time. IgG4-RD is a relatively new discovery, so many healthcare providers may not be familiar with it. Symptoms can vary widely from person to person and can look similar to other inflammatory conditions. Part of the process of diagnosing IgG4-RD involves ruling out other potential diagnoses. Because IgG4-RD can cause mass-like growths in organs which may look like tumors on imaging studies, swollen lymph nodes, and elevated levels of certain serum markers that may be associated with cancer, it is sometimes mistaken for cancer.
There is no single test for diagnosing IgG4-RD. Your doctor will consider a number of factors when making a diagnosis, including a detailed medical history and physical examination, as well as:
- Lab tests: Your doctor may order tests to measure the level of IgG4 and other immunoglobulins such IgG1 and IgE in your blood (serum levels). Your doctor may also test the serum levels of complements C3 and C4. Some lab tests can help your doctor determine whether or not IgG4-RD is impacting your organs. High levels of lipase may indicate inflammation in the pancreas, whereas low levels of lipase or stool elastase or an elevated hemoglobin A1c (test for diabetes) may indicate damage to your pancreas. Creatinine levels may be measured to look for possible kidney damage. Your doctor may order additional lab tests, such as ANCA tests, to help rule out other possible conditions. Lab tests are not conclusive on their own. A tissue biopsy is often needed.
- Tissue biopsy: Doctors often need to take a small piece of tissue to look at under a microscope to help diagnose IgG4-RD and rule out conditions that can present similarly. A biopsy allows a pathologist to identify findings characteristic of IgG4-RD such as IgG4-positive plasma cell infiltration (accumulation of abnormally high levels of a type of white blood cell within an organ), storiform fibrosis (scarring of a tissue or organ in a distinct pattern), and obliterative phlebitis (buildup of inflammation and scar tissue that blocks a vein). A tissue biopsy helps confirm diagnosis and avoid misdiagnosis.
- Imaging studies: These may include magnetic resonance imaging (MRI), computed tomography (CT) scan, ultrasound, and positron emission tomography (PET) scan. These imaging studies help identify organ enlargement, thickening, fibrosis, and the extent of organ involvement.
Clinical Guidelines for Making the Diagnosis
In 2025, a task force of experts, patient representatives, and primary care physicians identified potential red flags for IgG4-RD to provide guidance to primary care providers as to when to suspect IgG4-RD. Red flags identified by the task force included:
- Swelling in one or more organ systems
- Swelling of the pancreas
- Thickening of the biliary tree
- Tumor-like inflammatory masses
- Increased serum IgG4 concentration
- IgG4+ plasma cell tissue infiltration
- Obliterative phlebitis
- Mass forming lesions in organs such as the submandibular glands, parotid glands, orbital and periocular region, pancreas, biliary tract, retroperitoneum, kidneys
Effective treatment of IgG4-RD aims to induce remission, prevent relapse, and avoid long-term organ damage. Most patients require treatment to prevent long-term, irreversible damage to organ systems. In some limited cases, such as when the disease activity is limited to head and neck involvement (e.g., submandibular glands), you and your doctor may choose to monitor closely rather than treat.
Glucocorticoids (such as prednisone) are a common initial treatment for IgG4-RD. Glucocorticoids, also called steroids, work quickly and reliably in IgG4-RD. While steroids are effective at quickly inducing remission and preventing organ damage, long-term treatment with steroids can have serious side effects. Targeted treatments that are steroid sparing are a focus of current research and are recommended for most people with IgG4-RD.
In 2025, the US FDA approved inebilizumab for the treatment of IgG4-RD. Inebilizumab is a biologic medication. Biologic medications are complex proteins derived from living organisms. They target certain parts of the immune system to control inflammation. Inebilizumab works by targeting and depleting a type of B-cell (a cell in your immune system) that is not working properly. Rituximab is another biologic medication that may be used in the treatment of IgG4-RD and works in a similar way. Other immunosuppressive medications such as azathioprine or mycophenolate mofetil are sometimes used in the treatment of this disease to suppress the immune system and prevent disease progression.
Once the disease is in remission, patients may need to continue taking maintenance medications such as inebilizumab or rituximab, to keep the disease under control. The dose of glucocorticoids (steroids) is usually tapered once steroid-sparing agents are started.
There is ongoing research into treatments for IgG4-RD. Other biologics such as obexelimab have shown potential as treatments for IgG4-RD, but larger randomized trials are ongoing. Rilzabrutinib, a Bruton’s tyrosine kinase inhibitor, is currently being studied as a possible treatment for IgG4-RD. Bruton’s tyrosine kinase inhibitors prevent B-cell division by interfering with B-cell receptor signaling pathways. Other potential treatments under investigation include zanubrutinib, another Bruton’s tyrosine kinase inhibitor, and a class of medications called JAK inhibitors which work by blocking a specific enzyme called Janus kinase-1 (JAK1), which is involved in the process that causes inflammation.
The medications used to treat IgG4-RD have potentially serious side effects such as lessening your body’s ability to fight infection. Side effects of treatment with high doses of glucocorticoids (steroids) include potential bone loss (osteoporosis), diabetes, loss of muscle mass, weight gain, and glaucoma. Patients receiving B-cell depleting therapies (like rituximab and inebilizumab) should be aware of potential risks such as infections (especially early post-infusion), low immunoglobulin levels (hypogammaglobulinemia), and poor vaccine response (vaccine timing is critical).
It is important to see your doctor for regular checkups. Medications may be prescribed to offset side effects. Infection prevention is also very important. Talk to your doctor about getting vaccines for the flu, pneumonia, COVID-19, RSV and/or shingles, which can reduce your risk of these infections. It is important to discuss the timing of vaccines if you are being treated with a B-cell depleting therapy as these therapies reduce the ability of your immune system to respond to vaccines.
Even with effective treatment, relapse of IgG4-RD may occur. Once your disease is in remission, your medical team may have you continue on maintenance treatments with the goal of preventing relapse, or in some cases you may just be closely monitored. Each person with IgG4-RD is unique, and your treatment plan will be greatly influenced by how IgG4-RD manifests in your body. Learn as much as you can about IgG4-RD. Your input will be important as you and your treatment team make decisions together about how best to treat and monitor your disease.
Regular doctor visits and ongoing monitoring of laboratory and imaging tests are important in detecting relapses early. General guidelines recommend monitoring every 3-4 months with labs and physical exams with imaging tests (if needed) repeated every 6-12 months, though these specifics are highly individualized to each patient. Serum IgG4 levels (IgG4 levels in the blood) can help assess disease activity, but they do not tell the whole story and are just one tool your doctor will use. Which labs and imaging tests are used for monitoring depend on what body systems were involved during active disease.
Effective treatment of IgG4-RD may require the coordinated efforts and ongoing care of a team of medical providers and specialists. In addition to a primary care provider, IgG4-RD patients may need to see the following specialists depending on which organ systems and sites of the body are impacted by the disease:
- Rheumatologist (joints, muscles, immune system)
- Nephrologist (kidneys)
- Gastroenterologist (digestive system), pancreatologist (pancreas), and/or hepatologist (liver, biliary tree)
- Pulmonologist (lungs)
- Cardiologist (heart)
- Endocrinologist (hormones and endocrine glands-pituitary, thyroid, pancreas, etc.)
- Other specialists as needed
The best way to manage your disease is to actively partner with your health care providers. Get to know the members of the health care team. It may be helpful to keep a health care journal or use an app to track your medications, symptoms, test results and notes from doctor appointments in one place. The IgG4ward Foundation has developed an app that can help you track your medical history. Find out more at https://igg4ward.org/igg4-me-app/.
To get the most out of your doctor visits, make a list of questions beforehand and bring along a supportive friend or family member to provide a second set of ears and take notes.
Remember, it’s up to you to be your own advocate. If you have concerns with your treatment plan, speak up. Your doctor may be able to adjust your dosage or offer different treatment options. It is always your right to seek a second opinion.
While IgG4-RD can be successfully treated, the disease is not curable at this time. With proper treatment, people with IgG4-RD can have long periods of remission during which their disease is not active, and in some people, the disease never returns. However, you may experience periods when your disease flares (becomes active again). It is important to see your doctor regularly to monitor for potential flares and treat them before they cause lasting damage.
Living with a chronic disease such as IgG4-RD can be challenging at times. Fatigue, pain, emotional stress, and medication side effects can take a toll on your sense of well-being, affecting relationships, work, and other aspects of your daily life. Sharing your experience with family and friends, connecting with others through a support group, or talking with a mental health professional can help.
There is no cure at this time for IgG4-RD, but with treatment and careful monitoring, the vast majority of people with IgG4-RD will achieve remission. Remission refers to a state where the disease is quiet and is not doing additional damage to organs or tissues.
Though there are exceptions, in the majority of cases, IgG4-RD progresses slowly, giving your medical team time to get the disease under control before severe damage occurs. Most people with IgG4-RD will see a swift improvement in symptoms with treatment and can expect to have a similar life expectancy as someone without IgG4-RD.
There is ongoing research into targeted treatments for IgG4-RD with the goal of helping people to maintain remission with fewer side effects than those associated with current treatments. Research into IgG4-RD is accelerating as researchers seek to better understand the causes and pathophysiology (how the disease impacts your body on a functional and cellular level) of IgG4-RD.
