Recurring Uveitis and Autoimmune Disease: Is IgG4-Related Disease (IgG4-RD) Being Overlooked?

Blurry vision. Light sensitivity. Persistent floaters. Swollen glands near the eyes. Recurring uveitis (eye inflammation).

These symptoms can all point to eye inflammation, including uveitis, a condition that can return in repeated flares.

Even so, uveitis alone does not confirm a rare disease.

However, uveitis that keeps coming back and resists standard treatment deserves a closer look.

What to watch for:

• swelling around the eyes from inflamed tear-producing (lacrimal) glands
• recurring pain or pressure near the eyelids
• persistent uveitis flares that don’t improve with treatment

If you notice these symptoms, then it may be reasonable to ask your doctor about further evaluation, including IgG4-related disease.

In other words, recurring uveitis deserves a closer look when the cause isn’t clear.

And in some cases, IgG4-related disease (IgG4-RD) can be linked to eye inflammation — especially when more common causes have been ruled out.

How can gland swelling affect the eyes?

When the glands near your eyes — especially the tear (lacrimal) glands — become inflamed or swollen, the tissues around the eyes can puff up and feel tender. This “swelling around the eye” may make your eyes feel irritated or gritty, as if you have sand in them. You may experience increased sensitivity to light and sometimes blurry or double vision if the swelling presses on nearby muscles.

You might also notice redness or a heavy, aching sensation around your eyes. It’s important to see your eye doctor or a rheumatologist so they can identify the cause of the swelling and help protect your vision if these symptoms don’t improve or keep recurring.

What is Uveitis?

Uveitis refers to inflammation inside the eye. More specifically, it affects the uvea — the eye’s middle layer, which is rich in blood vessels and helps nourish the eye. When inflammation develops in this layer, it can damage important eye structures and, without treatment, may lead to permanent vision loss.

The good news is that proper treatment often controls uveitis well.

Even so, uveitis can return, and these recurring flares can happen for different reasons.

While swollen glands might be one cause, there are other possibilities too, such as:

• infections,
• an injury to the eye, or
• conditions where your body’s immune system causes inflammation, such as Sjögren’s disease.

Types of uveitis include:

Anterior uveitis (iritis): “Anterior” means front. So, anterior uveitis is inflammation in the front part of the eye.  Anterior uveitis can often start suddenly, and symptoms can last for weeks. Some cases are persistent or recur over time.

Intermediate uveitis: “Intermediate” means middle. So, intermediate uveitis is inflammation in the middle part of the eye.  Symptoms may last weeks to years and can cycle between better and worse.

Posterior uveitis: “Posterior” means back. So, posterior uveitis is inflammation in the back part of the eye.  Symptoms tend to develop gradually and may last for years.

Many autoimmune diseases — including rheumatoid arthritis, lupus, and psoriatic arthritis — can lead to uveitis.

However, not every case fits this pattern. For some individuals, the inflammation continues to flare despite treatment with biologics or steroid drops. Doctors don’t always know why this happens.

In rare situations, doctors may consider another condition called IgG4-related disease (IgG4-RD), which can also cause inflammation in the body, including around the eyes.

What Is IgG4-Related Disease?

With IgG4-related disease, the immune system does not work the way it should. Normally, your immune system protects you from germs. But in IgG4-related disease, the immune system becomes overactive or “misdirected.”

Instead of only fighting off infections, the immune system in IgG4-related disease mistakenly attacks healthy organs and tissues. As a result, people with IgG4-RD can develop problems in many parts of the body, including the pancreas, salivary glands, and lungs.

In addition, this chronic immune system condition causes inflammation and tissue damage throughout the body, including the eyes and orbital tissues. These orbital tissues support the eye’s structure, movement, protection, and function. Without prompt treatment, inflammation from IgG4-RD can lead to scarring, swelling, and lasting vision changes.

However, doctors sometimes miss the diagnosis because IgG4-RD can resemble other conditions such as uveitis, Sjögren’s disease, or sarcoidosis. To identify the disease, doctors typically use a combination of blood tests, imaging scans, and—when needed—a biopsy to look for IgG4-positive cells.

How are these different conditions diagnosed?

Doctors usually diagnose uveitis through an eye exam, your medical history, and symptoms such as redness, floaters, blurred vision, or light sensitivity.

In many cases, they begin treatment right away. Steroid eye drops or systemic medications are often used based on the pattern of inflammation and how the eye appears during the exam. Acting quickly helps control inflammation, prevent complications, and protect your vision.

If an underlying autoimmune disease is later identified, doctors can tailor the treatment plan more specifically to your needs.

In contrast, IgG4-related disease (IgG4-RD) is a systemic condition that can affect multiple organs and requires a more complex diagnostic workup.

To evaluate for IgG4-RD, doctors may use a combination of tests, including:

• blood tests to measure IgG4 levels (though levels are not always elevated)

• imaging such as MRI or CT scans to detect inflammation in orbital tissues

• a tissue biopsy to confirm IgG4-positive plasma cells

The key distinction is that diagnosing IgG4-RD requires tissue confirmation — examining a small sample under a microscope to look for IgG4-positive cells. For patients with recurring or unexplained uveitis or orbital inflammation, doctors may consider IgG4-RD as a possible diagnosis. When confirmed, this diagnosis can lead to more targeted and effective treatment.

How is IgG4-RD treated?

Treatment often includes corticosteroids and immunosuppressants. Doctors may prescribe medications such as inebilizumab, a monoclonal antibody that targets the CD19 protein to reduce B cells, which are immune cells that contribute to inflammation and tissue fibrosis in IgG4-RD. Doctors refer to this treatment as B-cell depletion therapy.

Not Always More than Meets the Eye

Having repeated uveitis flares doesn’t automatically mean you have another condition, such as IgG4-RD. Many cases of uveitis respond well to standard treatments. If uveitis persists or returns without a clear cause, talk with your ophthalmologist about other possible reasons and whether additional testing is appropriate. Learn more about other eye conditions here.

Blurry Days, Bright Lights, and a Clear Diagnosis

Mahsa Pazokifard, 34, from California, recalls the morning she realized her eyes were signaling something was seriously wrong. “I woke up… my eyes were puffed shut.” She learned her lacrimal (tear) glands were swollen, known as dacryoadenitis, which caused one eye to produce too many tears and barely any tears in the other eye. On bad days, her vision blurred.

Finding answers took persistence. “I went through five different ophthalmologists,” she says, until a PET-CT finally captured multiglandular inflammation, which led to gland biopsies and a clearer path toward reaching a diagnosis.

From there, her care team finally put the pieces together — confirming IgG4-related Mikulicz’s disease, a form of IgG4-RD, that inflames the tear and salivary glands and helps explain the eye swelling, pain, and dryness she’d been battling.

She emphasized the importance of seeing a neuro-ophthalmologist—an eye doctor who specializes in vision problems related to the brain, nerves, and eye muscles—or an immuno-ophthalmologist, who focuses on eye issues caused by the immune system.

What Is IgG4-Related Dacryoadenitis and Sialadenitis?

Mikulicz’s disease is now understood to be one manifestation of IgG4-RD — often called IgG4-related dacryoadenitis and sialadenitis.

Characteristics of IgG4-related dacryoadenitis and sialadenitis (Mikulicz’s disease):

• It usually causes long-lasting swelling of the tear glands (lacrimal) and the main salivary glands on both sides of the face.
• Blood tests often reveal higher IgG4 levels, and the glands contain immune cells known as IgG4-positive cells.
• Treatment with steroids often works very well to reduce swelling and symptoms.

How IgG4-RD Affects More Than the Eyes

Because IgG4-RD can involve multiple organs, people with Mikulicz’s may also develop related conditions like autoimmune pancreatitis or retroperitoneal fibrosis. Retroperitoneal fibrosis (RPF) is a condition where fibrous (scar-like) tissue grows in the space behind the abdominal organs, called the retroperitoneum. It can press on organs like the kidneys or ureters, causing pain, kidney problems, or urinary obstruction.

Like autoimmune pancreatitis, some cases of RPF are linked to IgG4-RD. In short, Mikulicz’s sits on the IgG4-RD spectrum, which explains both the eye/salivary gland symptoms and the potential for whole-body involvement.

Living with Ongoing Eye Inflammation

Frequent uveitis can affect much more than your eyesight. Flares can disrupt your work, hobbies, and relationships. For many people, this emotional burden is just as challenging as the physical symptoms — something Lilly and Abby describe in the stories below.

“I’m at more peace with myself now,” Lilly says. “There are more people than I thought going through this. Sharing my story has helped me connect.”

Lilly’s Story: Living With Intermediate Uveitis

At 25, Lilly from Connecticut recalls being diagnosed with intermediate uveitis as a teenager, after dealing with constant floaters and blurry vision.  She underwent steroid injections and a vitrectomy (a procedure to remove debris from the eye). Lilly’s doctor has told her that her condition may be linked to autoimmune diseases like psoriasis or psoriatic arthritis, both of which are in her personal and family medical history.

“Even some retina specialists might not know what to do because intermediate uveitis is so rare,” she says. Over the years, she’s learned how to advocate for herself and communicate her symptoms and side effects more effectively. “I tell my doctors how I feel, explain the side effects, and try not to be on too many medications.”

Though she often jokes about it, Lilly says the weight of living with chronic inflammation is real. “It’s a heavy weight I carry around,” she says, adding that support from her family and community has helped her find peace. “I’ve accepted that medications will be part of my life.”

Lilly’s recurring uveitis, with treatment-resistant symptoms, highlights the need to stay vigilant in monitoring symptoms and seek help from her care team when needed.

Abby’s Story: When Uveitis Starts Young

Abby, a 40-year-old from Texas, first experienced eye inflammation at age 12 and was later diagnosed with juvenile arthritis at 14. Over the years, she has tried treatments ranging from steroid drops to a disease-modifying antirheumatic drug (DMARD). She now takes a biologic medication, which mostly keeps her symptoms at bay.

Even with treatment, flares still appear right before her next infusion. During these times, her vision blurs, floaters increase, and she often needs to enlarge the text on her screen to read. “It can change daily,” she explains. “One day your vision is fine. The next day, it’s hard to see or drive.”

That uncertainty has been a source of frustration throughout her medical journey.

“Doctors in the early days didn’t want to do testing,” she recalls. “We had to go to another city just to get answers.” Her advice for others is simple but powerful: “If you don’t get the answers that sit well with you, find another provider who will listen.”

Lilly and Abby’s stories remind us that although ongoing eye inflammation can feel overwhelming, there is always a path forward. Clear answers may take time, persistence, and even switching doctors — but progress is possible. The key is not to give up.

Finding Support and Self-Advocacy for Recurring Uveitis

Advocating for yourself can help you get the care you need. Talk openly about your symptoms, ask questions, and seek a second opinion if something doesn’t feel right. Support from family, friends, and patient groups can also make the emotional load feel lighter.

Most importantly, if you’re living with recurring eye problems, know that your voice matters. You deserve answers, and with persistence and self-advocacy, you can move closer to relief, better treatment, and hope for the future

Why IgG4-RD Can Be Overlooked in Recurring Uveitis

The condition IgG4-RD can mimic frequent uveitis and other eye diseases but may not respond to typical treatments like steroids or TNF inhibitors.

Some key signs that may suggest IgG4-RD:

• Chronic or recurrent inflammation that doesn’t fully resolve
• Swelling in or around the eyes (including the lacrimal glands)
• Imaging showing inflammation near the optic nerve or orbit
• A history of other unexplained inflammatory symptoms
• A blood test for elevated IgG4 levels and a biopsy of affected tissue can help confirm the diagnosis.

Red Flags That May Signal IgG4-Related Disease

Contact an ophthalmologist promptly if you observe any of the following common symptoms:

• Changes in vision, such as blurriness, a decrease in vision, or double vision
• Red eye (with or without pain)
• Light sensitivity
• New floaters (specks or moving spots) appearing suddenly

Lacrimal gland swelling near your eyes may be accompanied by:

• Visible puffiness or a lump in the upper eyelid, often toward the outer corner.
• Tenderness or pain when you touch the swollen spot.
• Changes in tears — one eye might water too much while the other feels dry.
• Redness or warmth around the swollen area.
• Pressure or discomfort that can make it harder to open your eyes fully.
• Worsening eye pain
• Difficulty moving your eye(s)
• Discharge from your eye(s)

What to Ask Your Doctor About Frequent Uveitis

Patients and doctors alike should stay open to exploring causes of eye inflammation beyond the most common ones. Getting the right diagnosis can lead to more effective treatment and help protect long-term vision. With that in mind, if your eye symptoms aren’t improving, here are some questions you might ask your doctor:

• Would it help to consult a rheumatologist or immunologist?

• Should we try a different treatment?

• Should we do additional imaging or consider a biopsy?

• Could something like IgG4-related disease be causing my inflammation?

• Have my IgG4 blood levels been checked?

Frequently Asked Questions (FAQ)

Q: Does having recurring uveitis mean I have IgG4-related disease? A: No. Many different conditions can cause uveitis, including autoimmune diseases and infections. Sometimes doctors cannot find a specific cause. In some persistent or unexplained cases, IgG4-related disease (IgG4-RD) may be a possible explanation, though relatively rare.

Q: Can IgG4-RD cause vision loss? A: Untreated IgG4-RD inflammation may damage tissue permanently and affect your vision. Early diagnosis and treatment help prevent these complications.

Q: Should I ask my doctor about IgG4-RD? A: If you’ve had multiple uveitis flares that don’t respond to treatment or unexplained inflammation elsewhere in your body, you may want to discuss IgG4-RD with your healthcare provider.

Learn More About IgG4-RD

Click here to learn more about the process of getting diagnosed.

This article was made possible with support from Amgen.