Symptoms depend on which organs are affected.
Most people with IgG4-RD are middle-aged to older men, but the disorder can affect people of any age and sex.
The exact cause of IgG4-RD is unknown, but it likely involves a problem with the immune system Overview of the Immune System The immune system is designed to defend the body against foreign or dangerous invaders. Such invaders include Microorganisms (commonly called germs, such as bacteria, viruses, and fungi) Parasites... read more .
IgG4-RD can damage organs before people notice symptoms and seek medical care.
Organ enlargement may cause concern about a cancer until the diagnosis is made.
Diagnosis typically requires biopsy.
Treatment is with corticosteroids and rituximab, drugs that modify the immune system's activity, and sometimes surgery.
Immunoglobulins are antibodies Antibodies One of the body's lines of defense (immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more , which are proteins that are part of the body's immune system Overview of the Immune System The immune system is designed to defend the body against foreign or dangerous invaders. Such invaders include Microorganisms (commonly called germs, such as bacteria, viruses, and fungi) Parasites... read more defenses. Immunoglobulins help protect against foreign or dangerous invaders, such as bacteria, viruses and cancer cells. The body produces thousands of different immunoglobulins, which are grouped into 5 classes (IgM, IgG, IgA, IgE, and IgD), some of which (eg, IgA and IgG) have subclasses.
IgG4 is the least common of the 4 subclasses of IgG. It has various normal functions in the body, but in IgG4-related disease, immune cells that produce IgG4, along with other related cells, accumulate abnormally in certain organs and damage them. The affected organs can enlarge and may eventually fill with scar tissue (fibrosis) and the damage can be permanent.
One or more organs are affected; the 11 organs considered typical of IgG4-RD include
Pancreas (organ that secretes digestive juices and hormones such as insulin)
Bile ducts (small tubes that carry bile, a fluid that aids in digestion)
Lacrimal (tear) glands
Parotid glands (salivary glands that lie just behind the angle of the jaw, below and in front of the ears)
Submandibular glands (salivary glands that lie under the side of the jaw)
Retroperitoneal tissues (at the back of the abdomen)
Aorta (the main blood vessel bringing blood from the heart to the body)
Meninges (layers of tissue that cover the brain and spinal cord)
Thyroid gland (gland in the front of the neck that controls many body activities)
Common symptoms of IgG4-RD include swollen lymph nodes Swollen Lymph Nodes Lymph nodes are tiny, bean-shaped organs that filter lymph fluid. They are located throughout the body, but particular collections are found just under the skin in the neck, under the arms,... read more and weight loss. Weight loss is particularly common when multiple organs are involved and/or when the pancreas does not make enough of the enzymes needed for digestion. IgG4-RD does not cause a fever.
Other symptoms are specific to the affected organs:
Pancreas and bile ducts: IgG4-RD that affects the pancreas may cause jaundice (yellowing of the skin) if swelling of the pancreas blocks the flow of bile. People may also develop acute pancreatitis Acute Pancreatitis Acute pancreatitis is sudden inflammation of the pancreas that may be mild or life threatening but usually subsides. Gallstones and alcohol abuse are the main causes of acute pancreatitis. Severe... read more , which causes abdominal pain and nausea. Some people develop chronic pancreatitis Chronic Pancreatitis Chronic pancreatitis is long-standing inflammation of the pancreas that results in irreversible deterioration of the structure and function of the pancreas. Alcohol use and cigarette smoking... read more and have symptoms of pancreatic insufficiency (for example, gas, feeling full, diarrhea, undernutrition, weight loss, diabetes).
Retroperitoneal (abdominal) tissues: People with retroperitoneal tissues affected by IgG4-RD may not have symptoms, or they may have flank or back pain. Retroperitoneal fibrosis can compress the ureters (tubes that carry urine from the kidneys to the bladder) which blocks urine flow and increases pressure in the kidneys, which can damage them. Sometimes the walls of the aorta are affected, which can lead to an aortic aneurysm Abdominal Aortic Aneurysms Abdominal aortic aneurysms are bulges (dilations) in the wall of the aorta in the part that passes through the abdomen (abdominal aorta). Abdominal aortic aneurysms typically slowly expand and... read more .
Salivary and lacrimal glands: These glands, if affected, usually cause painless, noticeable swelling on both sides of the face, below the chin, or over the outer portion of the upper eyelids. Dry mouth and/or eyes are uncommon.
Orbit: People with IgG4-RD affecting the orbits, particularly the muscles controlling the eyeballs, may develop bulging of the eyes (proptosis Eyes, Bulging Bulging or protruding of one or both eyes is called proptosis or exophthalmos. Exophthalmos is usually used when describing bulging eyes caused by Graves disease, a disorder causing overactivity... read more ), swelling and pain around the eyes, or pain when moving the eyes.
Lungs: If IgG4-RD affects the lungs, people may not have symptoms or may have a cough, shortness of breath, or sharp pain when inhaling, often due to inflammation of the pleura (the two thin layers of tissue that separate the lungs from the chest wall).
A biopsy is usually needed for doctors to distinguish IgG4-RD from other causes of enlarged organs and/or swollen lymph nodes.
Doctors usually do blood tests to measure levels of IgG4 and other immunoglobulins, but even though the disease involves IgG4 producing cells, IgG4 levels are not always elevated. And other diseases can cause elevated IgG4 levels. Other blood tests are done to see what organs may be affected.
Doctors will usually do a CT or MRI of areas where people have symptoms (for example, of orbits, chest, abdomen, and pelvis). They may also do imaging tests of other areas to look for organs that could be affected but are not causing symptoms.
Sometimes, urine and stool tests are helpful.
Treatment of IgG4-RD aims to reduce inflammation and stop the effects of the disorder.
Initial treatment is often with an oral corticosteroid (for example, prednisone), which is given for 2 to 4 weeks then tapered over the course of 2 to 3 months. Rituximab, a drug that modifies the immune system's activity, is often used when corticosteroids are not appropriate (for example, in people with uncontrolled diabetes). Rituximab is nearly universally effective in treating active IgG4-RD.
Typically, organ function returns to normal after treatment. However, if a lot of scar tissue had already formed in an organ, function may not fully return to normal.
Some people require surgical procedures, such as stenting, to relieve blockages of the ureters (the tubes that carry urine from the kidneys to the bladder) or bile ducts.
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