When Sjögren’s Isn’t the Full Story: Could IgG4-Related Disease Be the Missing Diagnosis?

Dry eyes. Fatigue. Swollen glands. If you’ve been diagnosed with Sjögren’s disease, these symptoms probably sound familiar.¹

But what if your diagnosis doesn’t fully explain everything you’re going through? For some people, the question becomes whether their symptoms fit Sjögren’s disease alone — or whether they might point to something else, such as IgG4-related disease vs Sjögren’s.

What Is Sjögren’s Disease — and How Does It Compare to IgG4-Related Disease?

Sjögren’s disease is a chronic autoimmune condition in which the body’s immune system mistakenly attacks its own moisture-producing glands. This is why one of the most common symptoms is dry eyes and dry mouth, also known as sicca symptoms, caused by inflammation of the tear (lacrimal) and saliva (salivary) glands. People living with Sjögren’s often describe the sensation as feeling like sand in their eyes. Additionally, they may struggle to swallow dry foods, need to sip water frequently, or develop oral health problems such as dental cavities. These symptoms often overlap with those seen in IgG4-related disease vs Sjögren’s, which can make diagnosis more complicated.

Because the disease is systemic, about half of all people with Sjögren’s experience inflammation beyond the glands. This extra-glandular involvement can affect the joints, skin, lungs, digestive system, nervous system, and kidneys.

Sjögren’s can occur on its own (primary Sjögren’s) or appear alongside other autoimmune conditions like rheumatoid arthritis (RA) or lupus (secondary Sjögren’s).

Treatment generally focuses on relieving dryness symptoms and calming the immune system, both within the glands and throughout the rest of the body.

What Is IgG4-Related Disease — and Why Is It Sometimes Confused With Sjögren’s?

IgG4-related disease (IgG4-RD) is a rare, immune-mediated condition, meaning the immune system is not working the way it should. Understanding IgG4-related disease vs Sjögren’s is essential because the two conditions often appear similar at first. The immune system becomes overactive and mistakenly attacks healthy tissue, leading to swelling, thickening, and sometimes scarring in different organs, including the glands, pancreas, kidneys, lungs, and tissue around the brain and eyes.

How Can IgG4-RD Affect the Body?

Many parts of the body can be affected, including the tear (lacrimal) glands near your eyes, the salivary glands in your cheeks and jaw, the pancreas, bile ducts, kidneys, and more. It is called “IgG4-related” because many people with this condition have high levels of a type of antibody in their blood called IgG4.

Doctors can also see a buildup of IgG4-producing immune cells when they look at affected tissue under the microscope. Because the disease can appear differently depending on which organ it affects, people may experience a wide range of symptoms — from swelling or lumps in glands to abdominal pain or even organ damage if left untreated. As a result, doctors may confuse IgG4-related disease with autoimmune conditions like Sjögren’s disease, especially when symptoms overlap. However, there are some important differences.

Is it IgG4-Related Disease or Sjögren’s? 

We spoke with Mahsa Pazokifard, 34, from California, who shared with us her journey to an IgG4-RD diagnosis to help us understand the patient experience better. It was a long and complicated pathway to diagnosis, starting in childhood with persistent ear, nose, and throat infections, swollen glands, bronchial asthma, and Raynaud’s phenomenon, all unexplained. In her early twenties, she had her gallbladder removed due to severe gastrointestinal issues, and radiology testing revealed biliary cholangitis and pancreatic involvement. Her health deteriorated rapidly after a COVID-19 infection, marked by severe fatigue, stiffness, visual problems, and near-fainting episodes.  

In 2022, she woke up with her eyes “puffed shut,” prompting medical tests. A PET CT scan showed widespread multi-glandular inflammation, mainly on the left side of her face. This led to referrals to ophthalmologists and biopsy discussions. Mahsa researched her symptoms, which initially suggested Mikulicz’s disease. 

An ophthalmologist suggested she might have Sjögren’s disease. She had a lip biopsy that involved removing tissue from 10 glands, nine of which showed inflammation. An immune-ophthalmologist then ordered a lacrimal gland biopsy, confirming IgG4-related Mikulicz disease despite normal blood IgG4 levels. Later, a second lip biopsy confirmed the diagnosis. Mikulicz disease is a rare condition characterized by painless, symmetrical swelling of the salivary and tear glands, now recognized as part of IgG4-related disease. 

“Every time I had a pathology result come in, it just confirmed to me that I was right,” recalls Mahsa, who felt both relief and confusion with her new diagnosis. 

She couldn’t help but question how the two conditions – Sjogren’s and IgG4-Related Mikulicz’s – might be connected. On her hardest days, she couldn’t walk or stand for long, and she experienced episodes of near-fainting and uncontrollable shaking. To find answers and community, she joined a support group on Facebook, hoping to connect with others who understood the challenges she was facing. Over time, speaking up gave her a sense of being heard and validated in a way that medical appointments alone could not provide. 

How Mikulicz’s Disease Is Related to IgG4-Related Disease 

Mikulicz’s disease is now understood to be part of a larger condition called IgG4-related disease (IgG4-RD).² When IgG4-RD affects the lacrimal glands (glands above the eyes) and the major salivary glands (like the parotid or submandibular glands), it causes long-lasting swelling in those areas. In the past, this specific pattern of gland swelling was called Mikulicz’s disease.

Today, doctors know that in most cases, Mikulicz’s disease is not a separate illness, but actually one of the ways IgG4-RD can appear in the body. Doctors prefer to now say “IgG4-related dacryoadenitis and sialadenitis” (IgG4-DS) rather than Mikulicz’s disease, since it more accurately describes the condition and its link to IgG4-RD. 

Because IgG4-RD can involve multiple organs over time, even if the swelling starts only in your tear or salivary glands, your doctor will usually check for inflammation in other parts of your body and may order blood tests or biopsies to confirm the diagnosis. Treating the underlying IgG4-RD (often with steroids or other immune therapies) usually improves the gland swelling as well. 

Real Stories of Perseverance and Self-Advocacy

Understanding the differences between Sjögren’s disease and IgG4-related Mikulicz’s disease is important, but disease facts and lab tests are only part of the story. In reality, the path to a correct diagnosis isn’t straightforward for many people — it’s a winding road filled with uncertainty, missteps, and persistence.

Behind every diagnosis is a person who had to recognize when something wasn’t right, speak up about their symptoms, and keep asking questions until they found answers.

To gain a fuller picture, we listened to the experiences of people living with Sjögren’s disease. They faced delays, confusion, and sometimes disbelief, yet refused to give up. Ultimately, their journeys show the power of self-advocacy, the value of listening to your body, and the importance of having healthcare providers who truly listen in return.

Cristina’s Story: “I Learned to Cope, Even When It Didn’t Make Sense” 

Cristina Montoya, a registered dietitian, first showed signs of Sjögren’s disease at age 8 while she was growing up in rural Colombia. Over time, her salivary glands would swell, her mouth was always dry, and by 10 years old, she no longer produced tears. However, despite visiting multiple doctors and even discussing exploratory surgery on her glands, a diagnosis didn’t come until much later.

Years later, Cristina developed rheumatoid arthritis and finally saw a rheumatologist who diagnosed her with Sjögren’s. After moving to Canada, the dry climate worsened her symptoms, and she now lives with chronic fatigue, dizziness, and difficulty swallowing. She’s seen specialists, tried medications, and even developed her own meticulous self-care routine with custom eye drops, oral rinses, and a strict diet.

Still, Cristina wonders if something has been missed. “There’s no real criterion for a Sjögren’s flare,” she explains. “You have to show your doctors the impact of your symptoms — not just say ‘dry eyes,’ but explain how it disrupts your life.”

Cristina was the featured guest on the Health Advocates podcast, sharing what it’s like to live with Sjögren’s and why better treatments can’t come soon enough. 

Cassia’s Story: “Nothing Is Black and White” 

Cassia was diagnosed with Sjögren’s disease (formerly known as Sjögren’s syndrome) in 2018 after decades of unexplained health issues — including fertility challenges, fatigue, and incontinence. When a nephrologist noticed a skin rash and concerning symptoms, she was referred to a rheumatologist, who confirmed the diagnosis. Still, not everything made sense. Cassia has trained for and completed triathlons, including Ironman races, but her symptoms have caused her to significantly change her activity levels and routines, including needing to monitor her kidney function daily.  

“I still don’t think I have a full answer,” she says. IgG4-RD has never been discussed by her care team, and she’s left wondering if there’s more to the story. 

Stacy’s Story: “I Had to Keep Pushing for Answers” 

Getting the right diagnosis and treatment isn’t always straightforward. Doctors may not immediately connect the dots, and symptoms can change over time. So, that’s why speaking up, asking questions, and pushing for answers when something doesn’t feel right is so important. Stacy’s experience shows just how critical self-advocacy can be.

Later, Stacy’s health declined after contracting COVID-19 in 2020. Then, her symptoms continued to evolve as she developed fevers, joint pain, dry eyes, and fatigue. She was first diagnosed with seronegative rheumatoid arthritis, but her symptoms continued to evolve — including facial rashes, sinus infections, and blurry vision. Eventually, in 2022, a blood test finally confirmed Sjögren’s disease. After that, her condition worsened, and an allergist discovered IgG subclass deficiency, which increased her risk of sinus infections, bronchitis, and pneumonia. Today, she receives SCIG infusions at home to help manage her immune system.

Looking back, she says, “I was lucky my primary care doctor kept digging. Otherwise, I might not have even considered the possibility that this could be something other than Sjögren’s.” She faced challenges with rheumatologists who didn’t listen and had to advocate repeatedly to change treatments.

Ultimately, Stacy’s journey illustrates how persistence and self-advocacy helped uncover answers that might have otherwise been missed.

Why It’s Easy to Miss IgG4-RD 

Because IgG4-RD and Sjögren’s disease share so many overlapping symptoms — dry eyes, fatigue, swollen glands — doctors may misattribute new or worsening symptoms to an existing autoimmune condition. But if medications aren’t working, or new signs like organ swelling, sinus infections, or nerve pain appear, it may be time to look deeper. 

Signs That It Might Not Just Be Sjögren’s: 

• Frequent or unusual infections (e.g. repeated sinus infections) 

• Swelling in unexpected places (jaw, pancreas, lymph nodes) 

• Poor response to standard Sjögren’s treatments 

• Imaging or biopsy showing IgG4-positive cells 

• Improvement with corticosteroids 

Questions to Ask Your Doctor About IgG4-RD or Sjögren’s

If you have been diagnosed with Sjögren’s disease and your current treatment isn’t helping or you’re starting to feel like your diagnosis isn’t the full story, bring up the possibility of IgG4-related disease. Consider asking: 

• Should I be referred to a specialist in rare autoimmune conditions? 

• Could IgG4-related disease explain some of my symptoms? 

• Have my IgG4 levels ever been tested? 

• Would a biopsy or imaging scan provide more clarity? 

• Should I try a short course of corticosteroids to see how I respond? 

Don’t Settle for Unanswered Questions 

If you’ve been diagnosed with Sjögren’s disease but your symptoms aren’t improving — or new ones keep appearing — you’re not alone, and you’re not imagining it. Mahsa, Cassia, Cristina, and Stacy all know what it’s like to live in limbo, trying to connect the dots. And for some—like Mahsa—the answer may be IgG4-related disease. 

Stacy offers some advice to those seeking answers: “Not every corner of the internet is helpful, but doing your own research and finding the right doctor can make all the difference.” 

You deserve to feel heard, supported, and properly diagnosed. If your treatment isn’t working, it’s okay to speak up and keep looking for answers. Patients are often their own best advocates. Trusting your instincts, raising concerns, and pressing for more information can make a real difference when your health changes.

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.