IgG4-Related Disease (IgG4-RD)

This leaflet provides information about IgG4-Related Disease (IgG4-RD), particularly focusing on how it affects the salivary glands (IgG4-Related Sialadenitis). It explains its symptoms, how it is diagnosed, available treatments, and long-term management. Please do not hesitate to discuss any questions or concerns with your specialist or healthcare team.

What is IgG4-Related Disease?

IgG4-Related Disease (IgG4-RD) is a recently recognized, rare autoimmune condition. It was first clearly identified in 2003 and links a number of inflammatory conditions across different organs that were previously considered unrelated. For example, when it affects the salivary glands, it was previously known under historical names such as "Mikulicz's disease" or "Küttner's tumor".

In IgG4-RD, cells in your immune system mistakenly produce harmful substances and antibodies (specifically a type called Immunoglobulin G4, or IgG4). These cells infiltrate your body's own tissues, leading to inflammation, the formation of hard lumps (tumefactive lesions), and eventually tissue scarring (known as storiform fibrosis).

Who is Affected?

Unlike many other autoimmune diseases (such as Sjögren’s Syndrome) which predominantly affect women, IgG4-RD most commonly occurs in middle-aged and older men (typically over the age of 50).

However, when the disease primarily affects the tear and salivary glands, it is equally likely to affect men and women.

What are the Symptoms?

IgG4-RD can affect almost any organ system in the body, either simultaneously or developing in different organs over months or years. Many patients may have no general symptoms (such as fever) and may feel well for a long time, even while the disease is active.

Salivary and Lacrimal Gland Symptoms

• Painless Swelling: The most common symptom in the head and neck is a dramatic, firm, and usually painless swelling of the salivary glands (most often the submandibular glands under the jaw, but also the parotid glands) and the lacrimal (tear) glands.
• Enlarged Lymph Nodes: Up to 70% of patients with salivary gland involvement will also have swollen lymph nodes in the neck.
• Mild Dryness: Unlike Sjögren's Syndrome where severe dry mouth is a hallmark, patients with IgG4-RD only sometimes experience mild to moderate dry mouth (xerostomia) or dry eyes.

Systemic Symptoms (Whole Body)

Because IgG4-RD is a systemic disease, it can also cause:

• Fatigue and unintentional weight loss.
• Inflammation in the pancreas (Autoimmune Pancreatitis), which can cause abdominal pain or painless jaundice (yellowing of the skin).
• Involvement of the kidneys, lungs (causing breathlessness or cough), thyroid, and the retroperitoneum (tissue deep in the abdomen).

How is it Diagnosed?

Diagnosing IgG4-RD is challenging because the swollen glands can easily mimic other conditions, including Sjögren’s Syndrome or even cancer. Diagnosis relies on a combination of clinical examination, blood tests, imaging, and histology:

• Blood Tests: Blood tests often show elevated levels of the IgG4 antibody. However, about 30% of patients with the disease have normal IgG4 levels, so a blood test alone is not enough to confirm or rule out the disease.
• Imaging:
  • Ultrasound: High-resolution ultrasound with color Doppler is excellent for assessing the salivary glands and often shows characteristic patterns of inflammation.
  • CT, MRI, or PET Scans: These are frequently used to look for involvement of other organs inside the chest or abdomen that might be silently affected.
• Biopsy (The Gold Standard): A biopsy of the swollen gland or lymph node is usually mandatory to confirm the diagnosis and definitively rule out cancer. Under the microscope, specialists look for a dense infiltration of immune cells, high numbers of IgG4-positive plasma cells, and the characteristic "whorled" pattern of scarring (storiform fibrosis). Note: Unlike Sjögren's Syndrome, a minor lip biopsy is often not reliable enough for diagnosing IgG4-RD; a biopsy of the major salivary gland or lymph node is usually preferred.

What are the Potential Complications?

If left undiagnosed and untreated, chronic inflammation from IgG4-RD can lead to severe and irreversible scarring (fibrosis) in vital organs, potentially causing serious organ damage to the kidneys, pancreas, or liver. Early diagnosis is essential to prevent this progression.

How is it Treated?

If diagnosed before serious permanent scarring has occurred, IgG4-RD typically responds exceptionally well to medical treatment. The goal of treatment is to rapidly stop the inflammation and prevent long-term damage.

• Glucocorticoids (Steroids): A course of steroids (like Prednisolone) is the traditional first-line treatment. Most patients experience a rapid and dramatic reduction in gland swelling and improvement in organ function within just a few weeks. The dose is usually high initially and gradually tapered down over several months.
• Steroid-Sparing Immunosuppressants: Because long-term steroid use has side effects, medications like Methotrexate, Azathioprine, or Mycophenolate Mofetil are often added to help maintain control of the disease while allowing the steroids to be stopped.
• Rituximab: For patients who do not respond fully to standard treatments, or who experience flare-ups when steroids are reduced, a medication called Rituximab is highly effective. Given as an intravenous infusion, Rituximab specifically targets and temporarily removes the B-cells responsible for producing the harmful IgG4 antibodies.

Long-Term Outlook

For most patients, IgG4-RD is a chronic condition that requires ongoing, long-term monitoring by a specialist team (often involving both a Rheumatologist and an ENT/Head & Neck Specialist).

The disease can flare up from time to time, particularly after steroids are stopped, requiring a temporary adjustment in medication. However, with appropriate and timely treatment, inflammation can be kept under control, symptoms resolve, and patients can lead full, active lives without permanent organ damage.