IgG4-related disease (IgG4-RD) is an immune-mediated condition that can involve nearly any organ in the body. It causes inflammation and symptoms that can mimic other illnesses. IgG4-RD is usually an indolent (slow-moving) disease. These characteristics often lead to long diagnostic delays and extended periods of evaluation before effective treatment is administered.

The condition can cause enlargement and fibrosis (scarring) in different organs. It often mimics infections, cancers, or other autoimmune diseases. This broad overlap with other conditions often makes diagnosis challenging. Experts believe IgG4-RD stems from an overactive immune response involving specific immune cells and antibodies. With timely recognition and treatment, many people do well on glucocorticoids (steroids) or more targeted therapies that calm the immune system and protect affected tissues.

Arriving at an IgG4 diagnosis can be a long road. Patients describe it as a winding, foggy journey with detours and false starts. The reason is simple: there is no single yes-or-no test for IgG4-related disease (IgG4-RD). Not even an elevated level of IgG4 in the blood is diagnostic. Instead, doctors combine clues from a variety of different sources, including those from the history of your disease and findings on physical examination, blood work, imaging, sometimes a small tissue sample (biopsy), to arrive at a diagnosis.

Almost any organ in the body can be affected by IgG4-RD. It is also possible for the disease to impact multiple organs at the same time, or to seem to add organs as the disease goes on over time (if untreated). Some of the more common organs involved are the pancreas and bile ducts, lacrimal and major salivary glands (the submandibular and parotid), and the orbits (eyes). However, IgG4-RD has been detected in the lungs, kidneys, retroperitoneum (a space in the back of the abdomen), blood vessels, meninges, and the prostate and pituitary gland. And others…

IgG4-RD can impact more than the original organ in which it was diagnosed. This can be a multi-organ disease, so knowing the proper diagnosis guidelines is important. If more organs are affected, be prepared for several specialists to be involved in diagnosing, treating and helping you manage your journey.

The most common treatment for IgG4-RD is to start with steroids (e.g., prednisone). Prednisone is effective – almost all people with IgG4-RD respond to this treatment - but the disease typically becomes active again at lower doses of prednisone and steroid treatment is often accompanied by many side effects. Your doctors should be working to get you off steroids quickly and into a more viable long term treatment plan.

There are B cell depletion and B cell inhibition treatments to explore. In addition, in some cases traditional pills known as “DMARDs” (disease-modifying anti-rheumatic drugs) or the placement of stents into certain affected organs can be discussed. The best course of action is to educate yourself on what is available and discuss options with your doctor/s.

B cell depletion means giving a treatment to temporarily lower the levels of certain immune cells (B lymphocytes, or B cells) that appear to drive the inflammation in IgG4RD. After a B cell depleting medication is given, B cells are not measurable in the peripheral blood for several months.

Through removal of these B cells that are a linchpin of IgG4-RD, the immune system activation and the resulting inflammation quiets; swelling within specific organs improves, and tissues begin to heal. Over a period of weeks to months, the level of IgG4 in the blood declines steadily in the direction of normal. A steady decline in IgG4 blood concentrations generally means that inflammation is coming under control.

The best-known B cell depletion medications are rituximab and inebilizumab. You should read more about each medication in IgG4ward! Academy and schedule a time when you can discuss these options with your doctors.

Genetics do likely play at least a small role in IgG4-RD, but the study of the genetic of this condition remains in its infancy. We anticipate major advances in the coming years in the understanding of genes and other potential risk factors for IgG4-RD, but for now it is important to say that IgG4-RD is not typically “passed-down” within families. Reports of two cases occurring in the same family are very rare.

No. People acquire IgG4-RD after birth. Cases in children are rare but not unheard of. The typical person with IgG4-RD is a middle-aged-to-elderly adult who has acquired the disease over time through risk factors that appear to be multiple and complex.

IgG4-RD does not discriminate as this disease can affect all ages, sexes and backgrounds. For reasons that are not understood, a slight majority of patients (up to two thirds) are men, but the disease certainly occurs in women, too. IgG4-RD appears to be a universal condition, being described in human beings all over the world of every race, country, and locale.

If diagnosed promptly and treated astutely, IgG4-RD is associated with an excellent prognosis. People with IgG4-RD can anticipate leading full, active lives, with careful attention to certain facts about living well with this condition.