How is IgG4-related disease diagnosed?
Immunoglobulin G4-related disease (IgG4-RD), also known as IgG4-related systemic disease, is an immune system condition that can affect almost any organ in the body.
It occurs when certain white blood cells in the immune system become overactive, causing overproduction of plasma cells that are positive for an antibody called immunoglobulin G4 (IgG4).
These plasma cells can enter various tissues, leading to organ inflammation, swelling, and scarring.
IgG4 itself is an anti-inflammatory antibody and is not the cause of symptoms in IgG4-RD. It is a measurable marker that helps doctors find out which specific immune pathway is active in a person’s body. Doctors will check a person’s IgG4 levels when diagnosing this disease, but other tests are also necessary.
This article explores how doctors identify IgG4-RD and which tests and features contribute to the diagnosis.
No single test can definitively diagnose IgG4-RD. It is a complex, systemic disease that can affect different organs in unique ways, and not everyone with an IgG4-RD diagnosis has elevated IgG4 levels in their blood.
While biopsy and histopathology (evaluation of atypical tissue under a microscope) are the gold standard in the diagnostic process, some organs may be difficult to reach or may not show classic features of the disease.
For these reasons, doctors use multiple methods to reach a diagnosis of IgG4-RD.
There are currently three sets of diagnostic criteria for IgG4-RD.
The Mayo Clinic introduced the
In 2011, a group of IgG4-RD experts in Japan created the Japanese Comprehensive Clinical Diagnostic (CCD) criteria to allow diagnosis in multiple organs, not just the pancreas. These criteria have since been updated for clinical practice.
And in 2019, another group of doctors
All three sets of diagnostic criteria are valid. Teams of experts created them for different purposes, and each has unique strengths and limitations.
Only the Japanese CCD criteria and the ACR/EULAR Criteria for IgG4-Related Disease are designed to assess IgG4-RD across multiple organ systems.
Doctors check for organ enlargement, tissue changes, and tumor-like lesions.
Healthcare professionals perform blood work to look for elevated IgG4 levels (135 milligrams per deciliter [mg/dL] or higher) in the blood.
Doctors measure the amount of IgG4 circulating in the blood.
Using diagnostic imaging tests such as CT scans, doctors check for enlarged organs, swelling, tissue thickening, or tumor-like masses.
The goal of imaging tests for IgG4-RD is to check organs for changes in size, shape, or structure. Healthcare professionals may take pictures of a person’s body using multiple types of technology, such as:
Imaging tests can reveal inflammation, scarring, and tumor-like growths or masses. They can also help doctors find out whether the disease is affecting multiple organs.
Laboratory tests typically involve using blood or other bodily fluids to check levels of substances in the body. They can provide clues about what is happening throughout a person’s body.
Diagnosing IgG4-RD may involve several laboratory tests. Doctors use these tests to look for disease markers such as IgG4 antibodies and to rule out other medical conditions.
During a biopsy, a healthcare professional takes a tissue sample from one or more affected organs. They will then send the sample for histopathology. A pathologist (a doctor trained to identify and diagnose disease processes at the microscopic level) will examine the sample.
Healthcare professionals consider biopsy and histopathology the gold standard for diagnosing IgG4-RD.
IgG4-RD is a complex immune system condition that can affect any organ in the body. It can cause inflammation, tumor-like masses, and scarring.
Because IgG4-RD can affect multiple organs in different ways, there is no single test to diagnose this condition. To confirm a diagnosis, doctors use a combination of methods, including clinical evaluations, laboratory tests, diagnostic imaging, and biopsies with histopathology.