Recognizing Sjögren's disease as serious and systemic Q&A with Dr. Ghaith Noaiseh

Dr Ghaith Noaiseh:
Hello, I'm Dr Ghaith Noaiseh. Today I'll be answering frequently asked questions about Sjögren's disease to dive deeper into the systemic autoimmune disease that can be serious and progressive. While Sjögren's disease is characterized by the development of dry eyes and dry mouth, or what is referred to as the sicca syndrome, patients with Sjögren's disease may experience much more than just dryness. From joint pain and salivary gland enlargement to interstitial nephritis, vasculitic neuropathy, and interstitial lung disease, we'll explore the many ways Sjögren's can impact patients’ lives—often in ways that are overlooked. Let's take a closer look at how Sjögren's disease may be affecting your patients so you can better recognize potential organ involvement and uncover the heterogeneity of the systemic autoimmune disease.

What are the most common systemic organ manifestations, and how are they assessed and monitored?

Dr Ghaith Noaiseh:
I think that's a great question. It's important to recognize that systemic organ manifestations of Sjögren's disease can virtually affect any body organ and significantly contribute to the clinical picture. Beyond sicca syndrome, inflammation or damage can also occur in the joints, skin, kidney, lungs, nerves, brain, and other organ systems. In clinical trials, it's the gold standard to use the EULAR Sjögren's Syndrome Disease Activity Index, known as the ESSDAI, which assesses systemic manifestations in 12 different domains: biological, articular, glandular, hematological, pulmonary, constitutional, cutaneous, lymphadenopathy, peripheral nervous system, renal, muscular, and central nervous system. While this score is mostly used in research, I find that it's a great resource to recognize the multisystem nature of Sjögren's disease and collaborate closely with other specialties to ensure comprehensive monitoring and care. Staying alert to signs of organ involvement is key to allow for early recognition and facilitate early therapy to improve symptoms and potentially prevent irreversible damage.

Beyond sicca, which symptoms are most disruptive to quality of life?

Dr Ghaith Noaiseh:
I think this is a very important point to highlight. Dryness-related symptoms are the most common reason patients seek care, yet up to 40% experience systemic manifestations. This high systemic disease activity has been associated with reduced quality of life. Many patients experience articular symptoms, such as joint pain, stiffness, and arthritis, which can limit mobility and interfere with everyday activities. Glandular involvement, particularly enlargement of the salivary glands, often leads to discomfort and visible swelling. Peripheral neuropathy is also a common manifestation, with symptoms including numbness, tingling, burning sensations, and, in some cases, motor deficits leading to limb weakness. Therefore, in my practice, I conduct a comprehensive patient assessment by systematically exploring the various domains of the ESSDAI tool, ensuring a thorough evaluation of the diverse systemic manifestations of the disease.

What are some of the potential complications of Sjögren's disease?

Dr Ghaith Noaiseh:
This is truly an excellent question. My patients frequently seek insights into the potential trajectory of their condition. Even in cases where symptoms appear mild, Sjögren's disease may progress slowly over time and lead to severe systemic complications. These manifestations can significantly impact long-term outcomes and can be life-threatening, particularly in those with certain risk factors, such as vasculitis, interstitial lung disease (ILD), hypocomplementemia, or cryoglobulinemia. A particularly serious complication is the development of lymphoma, with epidemiological studies indicating a 10-to 44-fold increased risk in Sjögren's patients compared with healthy individuals. Persistent parotid swelling, vasculitis, and elevated rheumatoid factor are some of the key clinical indicators that warrant close surveillance and further evaluation. Interstitial lung disease represents another severe, potentially life-threatening manifestation, contributing to increased mortality and diminished quality of life. Therefore, in my practice, I proactively manage my patients including regular follow-up, timely imaging, and multidisciplinary care approach, all of which are essential to facilitate early detection and improved patient outcomes.

How does Sjögren's disease affect daily life for patients?

Dr Ghaith Noaiseh:
I love this question. Living with Sjögren's disease can be a daily challenge, affecting many aspects of life. Alongside constant symptoms, nearly half of patients report a disruption in their sex life, social activities, or ability to work. The impact goes beyond physical discomfort and often extends to affect emotional and social well-being too. In conclusion, Sjögren's disease is far more than dry eyes and mouth—it is a complex and multifaceted condition with multiorgan involvement that can lead to serious complications. Recognizing the broader impact of the disease is essential to providing the comprehensive care, monitoring, and support these patients truly need. While progress is being made in understanding Sjögren's disease, there are currently no FDA-approved therapies to address the systemic nature of the disease and, as a result, a more comprehensive approach to patient care is needed to encompass additional systemic manifestations beyond dryness. Additionally, 97% of patients reported wanting more treatment options. As health care professionals, recognizing the impact of this wide-ranging disease is our opportunity to advance care and improve the quality of life for patients with Sjögren's disease. Explore our other videos to learn more about the underlying pathogenesis of Sjögren's disease and how to assess the systemic manifestations your patients may be experiencing.

For additional expert insights and resources on Sjögren's disease, please visit SjogrensSjoutsHCP.com

Dr Teja Kapoor: 
Welcome to our video series on Sjögren's disease, where we look beyond dryness to the full impact of this complex condition. In each episode, my colleagues and I share our insights to help fellow health care professionals recognize and manage Sjögren's disease with clarity and confidence.

In this video, we examine Sjögren's disease as more than sicca symptoms, highlighting its systemic involvement, patient variability, and the importance of early recognition.

Hi, my name is Dr Teja Kapoor. I'm a rheumatologist and director of the Columbia Sjögren's Center in New York City. I am joined by my colleagues today to discuss Sjögren's disease, a condition we each have extensive experience managing in our own practices.

Dr Adam Doré: 
Hello, I'm Dr Adam Doré, a rheumatologist at Allegheny Health Network in Pittsburgh, Pennsylvania, and I'm happy to be here.

Erin Siceloff: 
And I'm Erin Siceloff, a physician assistant specializing in rheumatology, including Sjögren's disease, at AOCC in Charlotte, North Carolina. Thank you for having me.

Dr Teja Kapoor: 
Dr Doré, will you start us off?

Dr Adam Doré: 
You may already be familiar with how Sjögren's disease is typically characterized. Sjögren's disease often features sicca symptoms such as dry mouth, or xerostomia, and ocular dryness, or keratoconjunctivitis.

But it's important to recognize that Sjögren's disease may extend far beyond dryness. It is a serious systemic autoimmune disease that can be progressive and affect multiple organs, including the joints, skin, and more.

As you may know, Sjögren's disease affects up to 4 million people in the US, with a prevalence between 0.5% and 1% of the population. It predominantly affects women, with a female to male ratio of 9:1, and symptoms usually begin to appear between the ages of 45 and 55 years. We've talked about the prevalence, but statistics are only 1 part of the story. Erin, can you walk us through the manifestations patients may experience?

Erin Siceloff: 
Of course. Looking at these data, it's clear that patients carry a large symptom burden. This comes from the Living with Sjögren's patient survey conducted by the Harris Poll on behalf of the Sjögren's Foundation.

The survey questioned adult patients with Sjögren's about the variety and severity of the symptoms that they had experienced in the last 12 months. It included 3622 self-reported respondents, not verified by a physician, 97% of whom were female, with an average age at diagnosis of 49.7 years. While it's no surprise that dryness symptoms are at the top, there are many more symptoms that patients may experience. In fact, 36 symptoms were experienced by 30% or more of patients, and 21 symptoms were experienced by more than half of patients in the past 12 months.

As I mentioned, these findings highlight the breadth of symptoms and burden endured by patients with Sjögren's.

Here are a few examples of how patients may present when they first come to a rheumatologist's office.

Dr Kapoor, does this reflect what you typically see in your own practice when patients first come to see you?

Dr Teja Kapoor: 
Absolutely. From what I've seen in my practice, no 2 patients present with the same manifestations. These represent typical clinical presentations observed at a patient's initial rheumatology consult. While some experience classic sicca symptoms, others show significant systemic involvement—ranging from joint inflammation to neuropathy and vasculitis.

And this variability underscores the importance of a comprehensive, individualized approach to evaluation and management—looking beyond dryness to identify systemic disease and inform appropriate therapy.

Let's look at a couple of examples. Emma is experiencing severe sicca and fatigue complaints but has no obvious systemic involvement. In contrast, patients like Rebecca report mild dry eyes, reminding us that dryness is not always the chief symptom.

Dryness symptoms are one of the top reasons my patients seek care, and while most patients with Sjögren's disease experience dry mouth and eyes, early detection of Sjögren's can be challenging due to the high prevalence of other conditions that can also cause dryness. That's why asking targeted screening questions is critical, since patients often underestimate or adapt to their symptoms.

Dr Adam Doré:
That's a great point. When I see a patient who may meet the criteria for Sjögren's disease but doesn't report sicca symptoms, I ask specific questions to assess for subjective dryness. Conversely, when patients report dryness, it's crucial to evaluate whether these symptoms are related to Sjögren's.

Some of these questions include 

• Is your mouth dry when eating a meal?

• Can you eat a cracker without drinking a fluid or liquid?

• How often do you have excessive tearing?

• Are you able to produce tears?

Erin Siceloff:
To build upon that, I've found that these few questions can reveal both oral and ocular dryness that patients might not mention otherwise or they may have normalized over time. The questions are quick to ask during a visit and can serve as an early signal that further evaluation for Sjögren's may be warranted—especially when dryness is accompanied by fatigue, pain, or systemic signs.

This review reminds us that every patient's experience with Sjögren's is unique, making it vital to look beyond dryness and recognize the broader impact of the disease.

That's all for this video. Thank you for joining us and we invite you to explore the other videos.

Look beyond dryness and explore the full spectrum of Sjögren's disease at SjogrensSjoutsHCP.com.

Dr Teja Kapoor: 
Welcome to our video series on Sjögren's disease, where we look beyond dryness to the full impact of this complex condition. In each episode, my colleagues and I share our insights to help fellow health care professionals recognize and manage Sjögren's disease with clarity and confidence.

In this video, we look beyond sicca symptoms to explore the significant disease burden of Sjögren's disease and how ESSDAI-based questions can help uncover systemic manifestations.

My name is Dr Teja Kapoor, a rheumatologist and director of the Columbia Sjögren's center in New York City. I'm joined by my colleague today to discuss Sjögren's disease, a condition we each have extensive experience managing in our own practices.

Dr Adam Doré: 
Hello, I'm Dr Adam Doré, a rheumatologist at Allegheny Health network in Pittsburgh, Pennsylvania. Thank you for having me.

Dr Teja Kapoor: 
Dr Doré, will you start us off?

Dr Adam Doré: 
You may already be familiar with how Sjögren's disease is typically characterized. Sjögren's disease often features sicca symptoms such as dry mouth, or xerostomia, and ocular dryness, or keratoconjunctivitis.

But it's important to recognize that Sjögren's disease may extend far beyond dryness. It is a serious, systemic autoimmune disease that can be progressive and affect multiple organs, and including the joints, skin, and more.

In fact, 30 to 40% of patients experience systemic manifestations beyond dryness, which underscores the complexity of this condition.

Now, let's take a closer look at systemic manifestations across 12 clinical domains and the clinical index used to assess them—the EULAR Sjögren's syndrome disease activity index, or ESSDAI. It is used as a gold standard to measure disease activity in clinical studies. ESSDAI assesses disease activity across the 12 domains shown here.

Each domain is divided into 3 to 4 levels of activity, each of which has a score based on domain weight. The sum of each individual domain score gives you the total ESSDAI score, which tells you whether the disease activity is low, moderate, or high.

ESSDAI was developed for use in patients diagnosed with Sjögren's disease, and only Sjögren's disease- associated signs and symptoms should be scored. Any features that have been stable for at least 12 months are not scored.

While we recognize that not every rheumatologist can use the ESSDAI for all their Sjögren's patients in the clinic, we can base our assessment and questions on this index.

Let's take a look at a few examples of how asking ESSDAI-based questions can be used to foster patient conversation and help uncover the full burden of disease. We will focus on a few domains to show you examples of how they are scored within the ESSDAI.

Dr Teja Kapoor: 
For example, to assess glandular involvement, you might ask your patient, “Have you noticed any swelling in your face or neck?”

If the patient were to answer yes, then there is potential involvement in this domain. If we were scoring the domain with the ESSDAI, this table shows the scoring criteria based on the size and location of the patient's glandular swelling.

Next, let's look into the articular domain.

To probe for articular involvement, consider asking: 

• “Have you had pain in your hands, wrists, ankles, or feet in the past 4 weeks?”

• “Have you noticed any stiffness in the morning lasting for at least 30 minutes?”

As rheumatologists, we know that joint pain is a common symptom across many rheumatic diseases. But in Sjögren's, it should be recognized as a sign of systemic involvement.

As shown in the table, the ESSDAI scoring criteria assigns a score based on the presence of joint pain and morning stiffness and the number of joints affected by synovitis. In a retrospective study of 419 patients with Sjögren's disease, 45% presented with articular manifestations. Interestingly, those with articular manifestations had twice the number of involved organs compared with those without articular manifestations, as assessed after a mean follow-up period of 73 months.

Now, let's look into the cutaneous domain.

To evaluate cutaneous involvement, try asking: 

• “Have you noticed any changes in skin color or texture?”

• “Have you noticed any skin rashes or lesions?”

The ESSDAI scoring criteria takes cutaneous vasculitis into consideration.

Let's look at one more domain—lymphadenopathy.

To evaluate lymphadenopathy, you could ask your patient, “Have you noticed any swollen lymph nodes?”

For this domain, the ESSDAI scoring criteria factors in the size and location of lymphadenopathy.

The domains that we've already covered are the most common ones that rheumatologists can identify in the office. Beyond that, the ESSDAI also evaluates involvement across 8 other domains. These manifestations are important to keep in mind because they may be affecting your patients with Sjögren's disease.

Although we've seen how Sjögren's can impact a wide range of organs, patients also face risks for more serious systemic complications that can significantly impact long-term health—and in some cases can be irreversible.

Notably, patients have a 10-to 44-fold increased risk of lymphoma compared with healthy individuals. Additionally, up to 20% of patients develop interstitial lung disease, or ILD, and 61% of ILD cases exhibit a nonspecific interstitial pneumonia pattern.

Overall, patients with Sjögren's have a 50% increased risk of mortality compared with the general population. Greater mortality was found to be associated with certain demographic, systemic, and immunologic factors.

Dr Adam Doré: 
Taken together, these findings highlight just how serious and systemic Sjögren's can be—underscoring the urgent need for ways to manage disease activity and long-term health. The reality is, though, that there are no FDA-approved therapies targeting the underlying pathogenesis of Sjögren's disease or slowing disease progression.

Because of this limitation, our only option is to rely on “borrowed” immunosuppressive treatments not approved for systemic manifestations of Sjögren's disease.

To address this, Novartis has expanded its commitment to rheumatology by partnering with experts and universities to explore new ways to target B-cell hyperactivity and BAFF.

Given the seriousness of this systemic disease and limited treatment options, it's essential to assess patients comprehensively. I found ESSDAI-based questions valuable for uncovering domain involvement and understanding the full scope of burden.

That's all for this video. Thank you for joining us, and we invite you to explore the other videos.

Discover patient questions that can help uncover the systemic impact of Sjögren's disease at SjogrensSjoutsHCP.com

Eric Anderson, MD, RhMSUS

Patients with Sjögren's disease may initially present with dryness symptoms, but for many patients, it's much more than that. Sjögren's is a systemic autoimmune disease and can be serious and progressive, and looking beyond dryness is key to identifying systemic involvement early. I'm Dr Eric Anderson, and I'm a rheumatologist with the West Suburban Center for Arthritis in Brookfield, Wisconsin.

In this video, we'll explore key clinical considerations for examining patients with Sjögren's disease.

Before we dive into how we can optimize initial patient assessments, I want to acknowledge that this can be challenging. No 2 patients present with the same manifestations. Existing symptoms can worsen, and new manifestations can emerge. The disease's heterogeneity often makes progression unpredictable.

While dryness is a common symptom reported by patients, it is important to take a more holistic approach in our assessments. Let's start with the initial Sjögren's diagnosis.

At the first visit, a thorough medical history is gathered to provide insight into the presence, extent, and duration of dryness and other symptoms. During this conversation, questions about oral symptoms are asked, such as…

…"Is your mouth dry when eating a meal? Can you eat a cracker without drinking fluid or liquid?" And questions about ocular dryness, such as, "How often do you have excessive tearing?" and "Are you able to produce tears?"

Based on the answers to these questions or other reported symptoms of dryness, objective assessments can help identify and evaluate potential salivary and lacrimal gland dysfunction.

Oral dryness is assessed using a salivary flow test that may be either unstimulated or stimulated, while ocular dryness can be evaluated with a Schirmer's test.

The Schirmer's test, performed without anesthesia, measures tear production by the length of a moistened area on the Schirmer's test strip.

Normal tear production…

…typically exceeds 15 millimeters, whereas less than 5 millimeters indicates reduced tear production, suggesting lacrimal gland dysfunction. These results can help determine whether additional diagnostic evaluation may be appropriate.

The stimulated or unstimulated salivary flow test can be used to measure how much saliva a patient produces.

Collected saliva is measured to determine the flow rate.

A flow rate of lower than or equal to 0.1 milliliters per minute for the unstimulated test—or lower than or equal to 0.7 milliliters per minute for the stimulated test—can indicate hyposalivation, which is often seen in Sjögren's disease.

Hyposalivation may suggest salivary gland dysfunction and has been associated with more active or advanced disease. Reduced salivary flow can also raise concern for potentially irreversible gland damage, so these results should be interpreted in the context of other findings. Together, this information can help guide early treatment decisions aimed at helping to prevent irreversible damage.

Both the Schirmer's test and the salivary flow testing take only 5 minutes and can be performed together. A positive result on the Schirmer's test or the unstimulated whole salivary flow test, together with the SSA/Ro antibody positivity, can support the diagnosis of Sjögren's.

For patients who are seronegative but are still suspected of having Sjögren's disease…

…additional options include labial salivary gland biopsy and/or salivary gland ultrasound to help assess disease activity.

To learn more about these tests, you can view additional videos at sjogrenssjoutshcp.com.

In addition to objective assessments of dryness and gland dysfunction, a physical exam is important to evaluate signs of systemic disease, including the patient's glands, lymph nodes, skin, and joints.

Along with a physical exam, I typically order several laboratory tests, including autoantibody screening, a complete blood count with differential, protein and immunoglobulin levels, complement levels, inflammatory markers, and renal and urinary assessments. These lab results can help confirm a diagnosis, provide insight into underlying disease activity, and offer a better sense of how the disease may be progressing.

In addition to labs and dryness assessments, it's important to assess patients holistically. Framing questions around the ESSDAI domains can help pick up on other signs of systemic disease activity that may not be obvious at first. ESSDAI stands for the EULAR Sjögren's syndrome disease activity index…

…and it looks at disease activity across 12 different organ-specific domains, including central nervous system, biological, lymphadenopathy, renal, articular, peripheral nervous system, constitutional, glandular, pulmonary, cutaneous, hematological, and muscular.

ESSDAI is considered the gold standard in clinical trials for assessing systemic involvement.

Each domain is weighted and scored based on severity, and those scores are added together to give a disease activity score. Whereas the formal ESSDAI score is especially important in clinical research and trials, using it more qualitatively in daily practice can help guide our approach to managing Sjögren's disease in patients.

For example, to identify signs of lymphadenopathy, I may ask, "Have you noticed any swollen lymph nodes?"

To assess for cutaneous involvement, I may ask, "Have you experienced any changes in skin color or texture?" If the patient answers yes to either of these questions, additional follow-up questions and a more focused physical evaluation may help further assess these findings. This type of questioning can be continued to cover additional domains of ESSDAI.

Even after a diagnosis of Sjögren's disease is established at the initial visit, ongoing monitoring of disease activity is essential, as it can be a progressive condition. In my experience…

…patients with low disease activity can often be followed every 6 to 12 months, while those with high disease activity may need more frequent monitoring.

During routine visits, it's important to keep an eye on any worsening of existing symptoms as well as the appearance of new symptoms or systemic manifestations, as these can signal early disease progression. Asking about new symptoms and using questions guided by the ESSDAI domains, as in the initial visit, is also a key part of the assessment.

Additionally, it's also important to screen for signs of lymphoma at these visits, given that patients with Sjögren's disease have an approximately 10- to 44-fold increased risk compared with healthy individuals.

There are several independent risk factors for lymphoma in patients with Sjögren's disease...

…such as swollen lymph nodes and salivary glands…

…and cutaneous involvement.

As the risk of non-Hodgkin lymphoma increases with the number of risk factors, incorporating lymphoma screening into follow-up visits is a crucial aspect of ongoing assessment.

Another factor to consider is that disease progression in Sjögren's is highly variable—it may be slow in some patients whose disease remains relatively stable, while in others you may observe worsening symptoms or new systemic manifestations of the disease.

We do have some clues about which patients may be at higher risk for disease progression.

Factors like being male; having a higher focus score, which is determined from a salivary gland biopsy; the presence of germinal centers; being a rheumatoid factor carrier; having cryoglobulinemia; or low C3/C4 levels have been associated with a higher risk of developing systemic disease. Taken together, these biomarkers and clinical features can give you a clearer picture of a patient's systemic disease activity and whether there is a higher risk for disease progression.

That's why regular, ongoing monitoring is very important for patients with Sjögren's disease.

As we wrap up, I want to reemphasize that Sjögren's is a serious, systemic autoimmune disease. It can be progressive, it can affect multiple organs, and no 2 patients look the same…

…which is why ongoing, comprehensive assessment really matters. When you're evaluating a patient with Sjögren's disease, keep in mind that not everything shows up on a physical exam. That's why it's important to assess biomarkers and clinical features. And always ask clear, targeted questions, because some of the most important signs of disease activity can be subtle or hidden, and they require a deeper look.

Ultimately, reducing disease activity is an essential goal for our patients, and I hope the perspective I've shared today helps support your own approach to assessing and managing patients with Sjögren's disease.

For additional expert insights and resources, please visit sjogrenssjoutshcp.com.

Dana DiRenzo, MD, MHS

As many of us have seen in practice, Sjögren's disease is a systemic, heterogeneous autoimmune disease that can be progressive, making it difficult to assess and manage. Salivary gland ultrasonography is a noninvasive tool that may provide useful information when evaluating salivary gland abnormalities, including those seen in Sjögren's disease. Although this technique has been available for decades, it may still be underused in the clinical evaluation of Sjögren's disease.

Hi, my name is Dr Dana DiRenzo and I'm a rheumatologist and assistant professor of clinical medicine at the University of Pennsylvania. In this video, I'll review the role of salivary gland ultrasound in Sjögren's disease, including its value in assessing glandular involvement and key findings and considerations.

In patients with Sjögren's disease, pathogenic B cells, along with T cells and other immune cells, infiltrate glandular tissues, resulting in inflammation that can cause tissue damage and reduce gland function. A decrease in saliva and tear production is why we see characteristic oral and ocular dryness in patients with Sjögren's disease.

Glandular tissue damage resulting from immune cell infiltration can be objectively assessed by ultrasound.

Major salivary gland ultrasonography focuses on the parotid and submandibular glands.

The parotid gland is the largest of the major salivary glands. It's made up of a superficial lobe, which accounts for about 80% of the gland, and a small deeper lobe.

The submandibular gland is the second largest and is responsible for producing about 60% to 70% of our saliva. Like the parotid gland, it also has a larger superficial lobe and a smaller deeper lobe.

The glands can be assessed using both longitudinal and transverse ultrasound views to capture images and evaluate for signs of structural damage to the salivary glands.

On ultrasound that can present as inhomogeneity of the gland parenchyma. Instead of a smooth, uniform appearance, the gland may show focal hypoechoic or anechoic areas.

There are a few different scoring systems used to grade the extent of salivary gland involvement on ultrasound. One of the most commonly used is the OMERACT, or Outcome Measures in Rheumatology, ultrasound scoring system for Sjögren's disease, which grades glands on a scale of 0 to 3.

Grade 0 reflects a normal gland, while grade 3 represents more severe changes consistent with advanced tissue damage. Across grades 0 to 3, ultrasound helps visualize a spectrum from normal glandular structure to progressive inflammatory changes, tissue damage, fibrosis, and fatty infiltration.

Using the OMERACT scoring system, a score of 2 or more in at least 1 gland has been associated with findings suggestive of Sjögren's disease. One study demonstrated that this OMERACT score cutoff provided 72% sensitivity and 91% specificity when compared with the ACR/EULAR criteria for a Sjögren's diagnosis.

Studies exploring the role of salivary gland ultrasound findings combined with antibody testing suggest that these results can help inform decisions about whether a biopsy is needed. Concordant findings in ultrasound and anti-Ro/SSA antibody testing may suggest that Sjögren's disease is likely.

It is important to keep in mind that ultrasound is not intended to replace biopsy or other standard-of-care practices used to evaluate patients for possible Sjögren's disease. For instance, patients in the early stages of the disease who test seropositive may still exhibit normal ultrasound results. Conversely, seronegative patients may present ultrasound findings indicative of Sjögren's disease.

Therefore, ultrasound findings should be evaluated within the broader clinical context and in conjunction with other diagnostic results.

Ultrasound can also play a valuable role in ongoing monitoring. Higher salivary gland ultrasound scores have been associated with more systemic disease and an increased risk of lymphoma, suggesting it may help stratify patients early into lower- and higher-risk groups. In turn, this may help guide decisions around closer follow-up for those at greater risk—highlighting its potential value beyond the initial assessment of salivary gland involvement.

In summary, salivary gland ultrasound is a simple, noninvasive imaging technique that can provide insight into salivary gland involvement in patients with Sjögren's disease. In my practice, when interpreted alongside other clinical assessments and measures, it has been a useful tool for evaluating disease severity and identifying signs that may indicate risk of progression.

For additional expert insights and resources, please visit sjogrenssjoutshcp.com.

Sara McCoy, MD, PhD

Salivary gland biopsy plays an important role in the assessment of Sjögren's disease—particularly in seronegative patients—by providing highly specific histopathologic evidence to help support diagnosis, aid in disease categorization, and potentially help assess disease severity and associated risks.

Hi, my name is Dr Sara McCoy. I'm an assistant professor of rheumatology and the director of the University of Wisconsin Health Sjögren's Disease Clinic. In this video, I will review the value of labial salivary gland biopsy in the diagnosis and management of patients with Sjögren's disease.

Sjögren's is a serious, systemic autoimmune condition that can be progressive. No 2 patients present with the same systemic manifestations, and the variability in how it manifests across individuals can make assessing and managing this disease challenging.

Sjögren's disease can present with a wide range of symptoms. Most commonly, patients report dryness of the eyes and mouth—often referred to as sicca symptoms—which affects more than 90% of individuals, based on a patient survey.

That said, a subset of patients have significant sicca symptoms but still do not meet the 2016 ACR/EULAR classification criteria, which require a total weighted score of ≥4 for classification…

…often because they lack key serologic markers such as anti-SSA or Ro antibodies.

This can create a real diagnostic challenge, leaving seronegative patients in a clinical gray area and at risk of being overlooked, under-recognized, or misclassified—even when their symptoms may be consistent with Sjögren's disease.

This means that Sjögren's disease diagnosis in seronegative patients can be missed unless additional evaluation is pursued.

A labial minor salivary gland biopsy is a highly specific, minimally invasive diagnostic test that is generally safe and associated with few local adverse effects.

With the appropriate skills and training, the procedure is relatively straightforward and can typically be performed in a standard exam room under local anesthesia in about 10 to 15 minutes.

The biopsy findings can help distinguish immune‑mediated sicca from other causes of dry eyes or mouth, and they often add clarity when making management decisions—especially given the potential for serious extraglandular manifestations in Sjögren's disease.

To ensure accurate interpretation, clear communication between the rheumatologist and pathologist is essential.

The pathologist looks for focal lymphocytic sialadenitis, a characteristic feature of Sjögren's disease, defined by dense aggregates of 50 or more lymphocytes clustered around ducts or blood vessels within the salivary gland.

The focal lymphocytic infiltration reflects chronic, antigen-driven immune activation within the gland, influenced by epithelial cell signaling and abnormal activation of B cells and T cells.

The pathologist may also identify atrophy, fibrosis, and findings suggestive of other conditions in the differential diagnosis of Sjögren's disease, such as sarcoidosis, amyloidosis, or IgG4-related disease. Features like lymphoepithelial lesions, ectopic germinal centers, and the focus score may help evaluate a patient's risk for developing glandular and extraglandular manifestations of Sjögren's disease.

The focus score is defined as the number of mononuclear cell infiltrates containing at least 50 lymphocytes per 4 square millimeters of glandular tissue. This metric is especially important because it is incorporated into the ACR/EULAR classification criteria for Sjögren's disease.

Beyond confirming a diagnosis, the histopathological evaluation of salivary glands may offer valuable insights into the severity of Sjögren's disease and the potential for systemic involvement.

In one study, higher focus scores were seen in patients with systemic disease. Therefore, a salivary gland biopsy may be a useful tool in clinical practice, even after a diagnosis has been established.

Given the clinical importance of histopathology, focus scores should be assessed using standardized methods. Although the SICCA protocol is widely used, variability can occur across alternative methods and in pathologist interpretation.

Thank you for watching. I hope I've been able to show you why this simple procedure and proper interpretation of the results can make a real difference in assessing Sjögren's disease—not just in confirming a diagnosis, but also in guiding a more comprehensive and personalized approach to management.

Labial salivary gland biopsy is a critical tool that may help us understand prognosis, anticipate risks, and make informed treatment decisions.

For additional expert insights and resources, please visit sjogrenssjoutshcp.com.

Dr Teja Kapoor:
Welcome to our video series on Sjögren's disease, where we look beyond dryness to the full impact of this complex condition. In each episode, my colleagues and I share our insights to help fellow healthcare professionals recognize and manage Sjögren's disease with clarity and confidence.

In this video, we'll discuss the underlying pathogenesis of Sjögren's disease and the unmet treatment needs.

Hi, my name is Dr Teja Kapoor. I'm a rheumatologist and director of the Columbia Sjögren's Center in New York City. I am joined by my colleagues today to discuss Sjögren's disease, a condition we each have extensive experience managing in our own practices.

Dr Adam Doré: 
Hello, I'm Dr Adam Doré, a rheumatologist at Allegheny Health Network in Pittsburgh, Pennsylvania. Thank you for having me.

Dr Teja Kapoor: 
Dr Doré, will you start us off?

Dr Adam Doré: 
The reality is there are no FDA-approved therapies targeting the underlying pathogenesis of Sjögren's disease or slowing disease progression.

Because of this limitation, our only option is to rely on “borrowed” immunosuppressive treatments not approved for systemic manifestations of Sjögren's disease.

The shortcomings of current treatment options highlight an opportunity to advance the standard of care, which may include biologic therapy. But how do you know when it's the right time to consider starting biologic therapy?

"Sicca plus" is a simple framework based on treatment guidelines that can help you identify patients with Sjögren's disease who may be eligible for biologic therapy.

If a patient with sicca symptoms such as dry eyes, dry mouth, or other dryness is also experiencing 1 or more signs of organ involvement, including swollen glands, lymphadenopathy, cutaneous involvement, or inflammatory joint pain or stiffness, it may be time to consider a biologic therapy.

When you think about your own patients, you've probably seen that many patients have "sicca plus" at least 1 sign of organ or system involvement.

Let's take a look at a few patient examples.

These cases illustrate the spectrum of what "sicca plus" can look like in practice—from those with obvious systemic involvement, to those who may need a closer look to uncover it.

Ava does meet the qualifications of "sicca plus" due to sicca symptoms plus lymphadenopathy and PNS involvement. Rebecca also qualifies for "sicca plus" due to sicca symptoms plus constitutional and articular involvement. Emma, on the other hand, does not meet the qualifications of "sicca plus" because there is no obvious systemic involvement. However, her rheumatologists should ask her the ESSDAI-based questions to determine whether she has any systemic involvement.

James clearly meets the qualification of "sicca plus" due to sicca symptoms plus glandular, biological, and cutaneous involvement. And Grace does meet the qualification of "sicca plus" due to sicca symptoms plus glandular involvement, which we have seen earlier. And while our understanding continues to evolve, there's still a significant unmet need. Based on the “Living Sjögren's disease” survey of 2961 adult patients, 97% of patients report wanting more treatment options.

Dr Teja Kapoor: 
Current B-cell–targeted approaches have failed to demonstrate significant outcomes in Sjögren's disease, and that's why several novel therapies for effective and sustained B-cell depletion are currently under investigation.

Looking ahead, a deeper understanding of the critical role of B cells in Sjögren's disease pathogenesis may pave the way for targeted therapies that address the unmet needs of patients living with this complex autoimmune condition. Now let's turn our attention to what are believed to be the drivers of this disease, the underlying pathogenesis and the critical role of B cells.

Let's take a look at the underlying pathogenesis. So, epithelial cells form the first line of defense against external pathogens, and they play a crucial role in immunity. But when an environmental trigger, such as a virus, activates epithelial and immune cells, it can initiate a cascade of immune events.

The initial immune response takes place in the salivary glands.

Let's zoom in on what's happening. Once activated, epithelial and immune cells release proinflammatory cytokines and chemokines. The initial immune response takes place in the salivary glands and can later affect additional organ and tissues, including the skin, joints, and lymph nodes. This initiates an autoimmune response. B-cell activating factor, or BAFF, is a proinflammatory cytokine that still stimulates B cells, promoting their proliferation, survival, and differentiation. Elevated levels of BAFF can allow autoreactive B cells to survive, contributing to immune responses.

Activated epithelial cells also release autoantigens that trigger an autoimmune response in potentially any organ tissue or system.

As you can see, the BAFF receptor is expressed on the cell surface throughout B-cell maturation from the immature B-cell stage through the plasmablast.

Elevated levels of BAFF activate BAFF receptor, on the surface of B cells to advance disease progression by supporting the maturation, survival, and hyperactivity of B cells.

As a result, hyperactive B cells produce a constant supply of autoantibodies, which can contribute to epithelial cell damage and inflammation.

And this constant activation of B cells and autoantibody production leads to chronic inflammation and further immune activation, potentially resulting in irreversible tissue damage. Pathogenic autoimmune B cells may infiltrate target tissues, resulting in a range of symptoms, including swollen glands, dry eyes, lung involvement, cutaneous vasculitis, and kidney involvement.

So, this summarizes the whole self-perpetuating cycle of systemic inflammation underlying Sjögren's disease, beginning with epithelial and immune cell activation. This triggers the initiation of an autoimmune response and release of autoantigens, leading to elevated levels of BAFF, B-cell hyperactivity, and autoantibody production. As a result, elevated levels of BAFF and hyperactive B cells further reinforces this autoimmune cycle.

Dr Adam Doré: 
I'm hopeful about future therapies, but the reality today is quite different. Despite growing insights into the immunopathology of Sjögren's disease, there are currently no approved therapies that target the underlying mechanisms or slow disease progression.

To address this, Novartis has expanded its commitment to rheumatology by partnering with experts and universities to explore new ways to target B-cell hyperactivity and BAFF.

That's all for this video. Thank you for joining us, and we invite you to explore the other videos. Learn more about the role of B cells in Sjögren's disease at SjogrensSjoutsHCP.com.

For those of us caring for patients with Sjögren's disease, we know it's a systemic autoimmune disease that can affect multiple organs. It is believed that B-cell hyperactivity and B-cell activating factor, or BAFF, contribute to a self-perpetuating cycle of inflammation that can lead to the systemic manifestations we see in our patients.

Hello, I'm Dr Al Kim, a rheumatologist at Washington University School of Medicine, where I manage patients with Sjögren's disease.

Today we'll take a closer look at immune cell activity involved and discuss how a deeper understanding of the critical role of B cells in Sjögren's disease pathogenesis can inform the development of novel therapies. Sjögren's disease may extend far beyond eye and mouth dryness. It's a serious systemic autoimmune disease that can be progressive and affect multiple organs, including the joints, skin, lymph nodes, various glands, lungs, and kidneys.

Clinical presentation varies widely, beyond the typical oral and ocular sicca symptoms that characterize Sjögren's disease. Disease heterogeneity often leads to underdiagnosis, which may have serious consequences, including the potential to develop organ damage. Sjögren's disease is believed to be a B-cell driven autoimmune disease in which hyperactivation of BAFF receptors on B cells results in a pathological cycle of immune activation. This may lead to chronic inflammation and potential irreversible tissue destruction if left undertreated, or worse, untreated. A possible inciting event is an environmental trigger such as a virus infection, which activates epithelial and immune cells and can initiate an inflammatory cascade induced by the cells of the innate immune system.

This epithelial cell layer is found in nearly all glandular organs, including the salivary glands. Normally, epithelial cells protect the organs they surround, secreting bioactive products to maintain normal function, and absorbing environmental cues. However, a wide array of common viruses can infect the salivary epithelium. In patients with Sjögren's disease, this results in injury and the release of autoantigens, such as Ro/SSA and La/SSB, that trigger an autoimmune response.

So, what makes these patients susceptible to this autoimmune response? A core issue in Sjögren's disease is excessive B-cell survival, which is largely driven by elevated levels of BAFF, driving significant and detrimental impacts on patients with Sjögren's disease. The primary role of BAFF is to promote B-cell development and differentiation by enhancing B-cell survival. Therefore, elevated levels of BAFF in the bone marrow, where B-cell development takes place, can interfere with the negative selection process responsible for the normal elimination of autoreactive B cells through apoptosis. This results in the survival and release of too many autoreactive B cells into the bloodstream.

Another consequence of elevated levels of BAFF occurs during the B-cell differentiation process in the lymph nodes. BAFF engages BAFF receptors, which are expressed on the cell surface throughout the B-cell lineage from immature B cells to plasmablasts, supporting B-cell differentiation, survival, and activation. Since BAFF regulates these downstream B-cell functions, which occur in germinal centers within lymph nodes, excessive BAFF levels then can lead to excessive numbers of B cells that are activated. When excess BAFF is present in both the bone marrow and lymph nodes, it can lead to pathogenic autoimmunity.

Overproduction of autoreactive B cells along with their activation in the lymph nodes result in the B-cell hyperactivity underlying Sjögren's disease. The salivary gland is a key example of where B-cell–mediated injury can manifest in Sjögren's disease. Excess BAFF leads to the formation of autoreactive B cells that produce characteristic autoantibodies—most notably, anti-SSA/Ro, and anti-SSB/La IgG. These autoantibodies can form immune complexes with these autoantigens, SSA and SSB, that infiltrate the salivary gland, causing inflammation. This chronic inflammation results in additional BAFF production locally within the tissue, further activating B cells and T cells, perpetuating the vicious cycle of immune system activation. As more tissue is damaged, more immune activation occurs, creating a positive feedback loop that amplifies inflammation and may lead to tissue destruction in salivary glands and in other organs or systems.

Infiltration of pathogenic B cells results in a wide range of symptoms including swollen glands, dry eyes, lung involvement, cutaneous vasculitis, kidney involvement, and other systemic manifestations characteristic of Sjögren's disease. To put it all together, the self-perpetuating cycle of systemic inflammation is thought to result from B-cell hyperactivity and autoantibody production, driven by elevated levels of BAFF.

These factors, along with others such as virus infections, contribute to the activation of epithelial and immune cells, triggering a cascade of immune events that reinforce the autoimmune cycle and exacerbate tissue damage and immune responses. Despite our growing understanding of Sjögren's disease, there are currently no FDA-approved therapies that target the underlying pathogenesis of Sjögren's disease or slow disease progression. So, the only options patients have is to rely on “borrowed” immunosuppressive treatments not approved for systemic manifestations of Sjögren's disease. This remains a significant unmet need—evidenced by the 97% of patients who want better treatment options. Current B-cell targeted approaches have not demonstrated statistically significant outcomes in Sjögren's disease; however, several novel therapies for effective and sustained B-cell depletion are currently under investigation.

I'm optimistic about these future therapies. Strategies aimed at sustained B-cell depletion may offer renewed hope for addressing the systemic nature of Sjögren's disease. For its part, Novartis has expanded its commitment to rheumatology by partnering with experts and universities to explore a new way to target B-cell hyperactivity and BAFF. Explore our other videos to learn more about Sjögren's disease—its clinical impact, and how to assess systemic manifestations in your patients.

For additional expert insights and resources on Sjögren's disease, please visit SjogrensSjoutsHCP.com.

As you might have seen in your practice, Sjögren's disease is more than dryness. Up to 40% of patients also experience systemic manifestations. But like me, you may have asked yourself: Is there a right time to start biologic therapy?

Hello, I'm Dr Tara Rizvi, I'm a rheumatologist at Texas Arthritis and Rheumatology Associates, in Houston, and I specialize in managing patients with Sjögren's disease. In this video, I'm excited to share the "Sicca Plus" framework. It's a simple tool informed by expert recommendations to identify patients who may be eligible for biologic therapy. It's something you can start using in your practice today.

I find that applying the "Sicca Plus" framework in my clinical practice helps offer a more holistic approach, guide ongoing monitoring, and inform treatment decisions regarding the use of biologic therapy. The "Sicca Plus" framework is built on the learnings from the EULAR Sjögren's Syndrome Disease Activity Index, also called the ESSDAI score and the latest EULAR recommendations. The ESSDAI score is designed to measure systemic disease activity across 12 domains. And it is considered the gold standard to measure disease activity in clinical studies. While ESSDAI was developed for clinical research, it may have limitations in daily practice. And that's why the "Sicca Plus" framework was created to help clinicians like you and me.

Using this framework and asking patients key questions based on the ESSDAI domains can prompt further evaluation of systemic manifestations that may otherwise go unrecognized. It also helps identify patients who may be eligible to start a biologic.

For example, when I'm checking for glandular involvement, I ask my patients, “Have you noticed any swelling in the salivary glands around your face or neck?” For articular involvement, I typically ask, “In the past 4 weeks, have you had joint pain, swelling, or stiffness lasting more than 30 minutes in your hands, wrists, ankles, or feet?” To evaluate lymphadenopathy, I make it a point to ask, “Have you noticed any swollen lymph nodes?” And for cutaneous involvement, I ask questions like, “Have you experienced any new or persistent rashes?”

In my experience, these questions help prompt further evaluation of some domain involvement and identify patients experiencing "Sicca Plus" who may be eligible for biologic therapy.

I encourage you also to use these questions in your practice. Ready to put the "Sicca Plus" framework in action? Visit SjogrensSjoutsHCP.com to learn more.

Erin Siceloff:
Welcome to our video series on Sjögren’s disease, where we look beyond dryness to the full impact of this complex condition. In each episode, my colleagues and I share our insights to help fellow health care professionals recognize and manage Sjögren’s disease with clarity and confidence.

In this video, we’ll explore the serious and systemic nature of Sjögren’s disease through the case of Laura, a patient in her late 40s who progressed from mild sicca symptoms to systemic manifestations. We’ll also examine how the "sicca plus" framework can help identify the full impact of Sjögren’s disease.

Dr Teja Kapoor: 
Hi, my name is Dr Teja Kapoor. I’m a rheumatologist and director of the Columbia Sjögren’s Center in New York City. I am joined by my colleagues today to discuss Sjögren’s disease, a condition we each have extensive experience managing in our own practices.

Dr Adam Doré: 
Hello, I’m Dr Adam Doré, a rheumatologist at Allegheny Health Network in Pittsburgh, Pennsylvania, and I’m happy to be here.

Erin Siceloff: 
And I’m Erin Siceloff, a physician assistant specializing in rheumatology, including Sjögren’s disease, at AOCC in Charlotte, North Carolina. Thank you for having me.

Dr Doré, will you introduce us to our patient?

Dr Adam Doré: 
Laura is in her late 40s, began experiencing mild sicca symptoms—dry eyes and dry mouth—approximately 5 years ago but did not seek medical evaluation at that time.

Two years ago, she developed a rash on her ankles. Initial treatment with topical corticosteroids by her primary care provider was ineffective, and the rash progressed to involve her shins. She was then referred to dermatology, where a short course of systemic corticosteroids led to temporary improvement, but the rash recurred upon treatment discontinuation.

Approximately 10 months ago, she began to show signs of inflammatory joint involvement, reporting pain in her knees, ankles, and wrists. Her primary care provider subsequently referred her to a rheumatologist for further evaluation.

As Laura’s case shows, Sjögren’s disease can extend beyond dryness. In fact, 30 to 40% of patients experience systemic manifestations.

Dr Teja Kapoor: 
Patients also face the risk for more serious systemic complications that can significantly impact long-term health—and in some cases can be irreversible.

Notably, patients have a 10- to 44-fold increased risk of lymphoma compared with healthy individuals. Additionally, up to 20% of patients develop interstitial lung disease, or ILD, and 61% of ILD cases exhibit a nonspecific interstitial pneumonia pattern. Overall, patients with Sjögren’s have a 50% increased risk of mortality compared with the general population. Greater mortality was found to be associated with certain demographic, systemic, and immunologic factors.

Erin Siceloff: 
As we assess this patient, it’s important to recognize the broader impact her symptoms are having on daily functioning and quality of life. She used to be an active runner, but knee pain forced her to stop—a significant shift for someone who relied on exercise as both a physical and mental outlet. She’s also scaled back on activities, doesn’t join family events as much as she used to, and has even skipped a few work trips, all of which may point to increasing fatigue, joint discomfort, or even emotional distress related to her condition. These changes underscore the importance of evaluating not only physical symptoms but also the personal and professional burden of disease when developing a management plan.

What’s striking about Sjögren’s disease is its constant presence, bringing daily challenges that impact quality of life. It can affect physical, emotional, and social well-being. Approximately 50% of patients report disruption in their sex life, social activities, or ability to work. About one-third report an impaired ability to enjoy food or a need to make dietary adjustments.

The dryness that patients experience is also associated with poor or worsening quality of life. Dry mouth is associated with the risk of caries, tooth loss, periodontal disease, and fungal oral infections. Similarly, dry eye is associated with photosensitivity and corneal melt or perforation.

Dr Adam Doré: 
Now, going back to our patient, Laura. She underwent a comprehensive evaluation, including both serologic testing and objective assessments of glandular function. She tested positive for anti-SSA antibodies and had a positive ANA, both of which support an autoimmune etiology. She tested negative for rheumatoid factor, but cryoglobulins were present in the blood.

Objective testing confirmed glandular involvement. Schirmer’s test showed reduced tear production at 4 mm over 5 minutes, and her unstimulated whole salivary flow rate was significantly low at <0.2 milliliters per minute, well below the normal threshold.

Additional lab findings revealed systemic involvement, including hypocomplementemia (low C3 and C4), elevated ESR and CRP indicating active inflammation, and hypergammaglobulinemia with elevated IgG levels.

Taken together, these findings supported a diagnosis of Sjögren’s disease. Given her systemic involvement—particularly the vasculitis and inflammatory arthritis—the rheumatologist initiated treatment with azathioprine.

Despite being on azathioprine, she continues to experience joint pain and stiffness and has now developed palpable purpura on her feet, raising concern for persistent or worsening cutaneous vasculitis despite immunosuppressive therapy. Many of us have likely seen this in our own practice, where our patients experience residual or refractory symptoms despite being on treatment.

We need to consider a few things. Is her therapy sufficient or does she require escalation? Could another immunosuppressant or a biologic for joint pain be appropriate? Are there disease-modifying approaches that could better control systemic activity? Do we need to reevaluate for other contributors—such as infection, drug reaction, or overlapping autoimmune disease?

I’m sure you all share the same concerns that I do. The reality is there are no FDA-approved therapies targeting the underlying pathogenesis of Sjögren’s disease or slowing disease progression.

Erin Siceloff: 
Because of this limitation, our only option is to rely on “borrowed” immunosuppressive treatments not approved for systemic manifestations of Sjögren’s disease.

Dr Adam Doré: 
The shortcomings of current treatment options highlight an opportunity to advance the standard of care, which may include biologic therapy. But how do you know when it’s the right time to consider starting biologic therapy?

"Sicca plus" is a simple framework based on treatment guidelines that can help you identify patients with Sjögren’s disease who may be eligible for biologic therapy.

If a patient with sicca symptoms such as dry eyes, dry mouth, or other dryness is also experiencing 1 or more signs of organ involvement, including swollen glands, lymphadenopathy, cutaneous involvement, or inflammatory joint pain or stiffness, it may be time to consider a biologic therapy.

When you think about your own patients, you’ve probably seen that many patients have "sicca plus" at least 1 sign of organ or system involvement.

Let’s take a look at a few patient examples.

These cases illustrate the spectrum of what "sicca plus" can look like in practice—from those with obvious systemic involvement, to those who may need a closer look to uncover it.

Ava does meet the qualifications of "sicca plus" due to sicca symptoms plus lymphadenopathy and PNS involvement. Rebecca also qualifies for "sicca plus" due to sicca symptoms plus constitutional and articular involvement. Emma, on the other hand, does not meet the qualifications of "sicca plus" because there is no obvious systemic involvement. However, her rheumatologists should ask her the ESSDAI-based questions to determine whether she has any systemic involvement.

James clearly meets the qualification of "sicca plus" due to sicca symptoms plus glandular, biological, and cutaneous involvement. And Grace does meet the qualification of "sicca plus" due to sicca symptoms plus glandular involvement, which we have seen earlier.

And while our understanding continues to evolve, there’s still a significant unmet need.

Based on the “Living with Sjögren’s disease” survey of 2961 adult patients, 97% of patients report wanting more treatment options.

Dr Teja Kapoor: 
We’ve just seen the far-reaching impact of Sjögren’s disease and how it remains a constant presence in our patients’ lives. Current B-cell–targeted approaches have failed to demonstrate significant outcomes in Sjögren’s disease. And that’s why several novel therapies for effective and sustained B-cell depletion are currently under investigation.

Looking ahead, a deeper understanding of the critical role of B cells in Sjögren’s disease pathogenesis may pave the way for targeted therapies that address the unmet needs of patients living with this complex autoimmune condition.

Erin Siceloff: 
To address this, Novartis has expanded its commitment to rheumatology by partnering with experts and universities to explore new ways to target B-cell hyperactivity and BAFF.

Dr Teja Kapoor: 
That’s all for this video. Thank you for joining us, and we invite you to explore the other videos.

Discover the many ways Sjögren’s disease can manifest in each patient at SjogrensSjoutsHCP.com.

Cindy Johnston, MD

When it comes to Sjögren's disease, no two patients present the same way. While most report ocular and/or oral dryness, some may develop systemic involvement affecting the joints, skin, lungs, nervous system, and more.

Cindy Johnston, MD

Up to 40% of patients may experience systemic manifestations that may impact long-term outcomes and survival.

Cindy Johnston, MD

I'm Cindy Johnston, a rheumatologist at Sarasota Arthritis Center.

Chadwick R. Johr, MD

And I'm Chadwick R. Johr, a rheumatologist at University of Pennsylvania.

Cindy Johnston, MD

Today we're going to walk through Jessica's case, inspired by real experiences of individuals with Sjögren's disease. She is in her early 30s with persistent symptoms despite treatment. This case reflects common challenges in evaluating systemic involvement and guiding management decisions.

Chadwick R. Johr, MD

This is a patient profile many of us recognize—sicca symptoms with inflammatory and systemic features. The key question becomes: How do we fully assess her disease and optimize treatment?

Cindy Johnston, MD

Let's get to know Jessica. She's in her early 30s with severe dry eyes and mouth, along with synovitis, myalgia, and cytopenia. She also has hypertension and hyperlipidemia.

Cindy Johnston, MD

In her late 20s, she managed symptoms with artificial tears and by increasing her water intake.

Cindy Johnston, MD

Three years later, her PCP prescribed naproxen and light exercise for her synovitis and myalgia. After no improvement, she was referred to a rheumatologist and diagnosed with Sjögren's disease.

Cindy Johnston, MD

Her rheumatologist initiated hydroxychloroquine. As there are no approved therapies for Sjögren's disease, he had to rely on immunosuppressive therapies that aren't specifically approved for Sjögren's. But after 1 year, Jessica continued to experience significant symptoms, suggesting an incomplete response.

Chadwick R. Johr, MD

This presentation tracks with what I see clinically. Severe dry eye and mouth dryness are classic sicca symptoms, and synovitis occurs in up to one third of my patients. Cytopenia is also common and reflects systemic disease activity.

Cindy Johnston, MD

I would say 99% of my patients with sicca symptoms have had them for a long time, with chronic fatigue. These patients tend to dismiss them, or their providers have dismissed them as other symptoms related to perimenopause or menopause, other disorders, or medication side effects. It's important to remember that although some of these may be present, we cannot, as providers, rule out Sjögren's disease.

Chadwick R. Johr, MD

I agree, fatigue is one of the biggest problems for patients with Sjögren's disease. These patients report feeling like they're in their 80s when they're just in their 30s, and we as clinicians can support our patients in finding ways to optimize diet and sleep and by reviewing medication lists to further manage symptoms.

Cindy Johnston, MD

Even without severe organ involvement like vasculitis, Jessica has clinically significant disease burden. She reports that her dryness is affecting her sleep, and her arthritis is impacting her ability to function—clear signs that her disease is not adequately controlled.

Chadwick R. Johr, MD

To better quantify Jessica's experience, we can use patient-reported outcomes like ESSPRI, PROMIS, or RAPID3. While objective findings guide treatment decisions, these tools help capture the patient's lived experience and support shared decision-making.

Chadwick R. Johr, MD

Now that we've established her symptom burden, let's look at her labs and physical exam. Jessica has 6 tender and 6 swollen joints, indicating active inflammatory arthritis. Her test results are SSA-positive and rheumatoid factor–positive, with a negative CCP. Her ANC of 750 reflects neutropenia, which is consistent with systemic Sjögren's. Her Schirmer's test and salivary flow confirm significant glandular dysfunction.

Cindy Johnston, MD

These findings—particularly synovitis and seropositivity—are high-risk features when stratifying disease activity.

Chadwick R. Johr, MD

Exactly. With this degree of joint involvement and RF positivity, overlap with rheumatoid arthritis should be considered. Imaging is important here to further evaluate her joints—erosions would support a more aggressive treatment approach.

Cindy Johnston, MD

At baseline, I would expand testing to include IgG levels, complement levels, and urinalysis with protein-to-creatinine ratio to assess for systemic involvement, particularly renal disease. I would also screen for hepatitis B and C, HIV, and TB in anticipation of potential immunosuppressive therapy.

Chadwick R. Johr, MD

Yes, I would also add serum protein electrophoresis to evaluate for monoclonal gammopathy or hypergammaglobulinemia, which can signal B-cell activation or lymphoma risk. Complement levels—C3 and C4—can reflect immune complex activity and disease severity. And we should also evaluate for alternative causes, such as hypothyroidism, which can contribute to fatigue and dryness and is readily treatable.

Cindy Johnston, MD

After reviewing Jessica's labs, we can better characterize her systemic involvement. She has both hematologic abnormalities and inflammatory arthritis, indicating more disease activity beyond glandular symptoms. Her SSA and rheumatoid factor positivity further increase concern for systemic progression, reinforcing the need for close monitoring and potential treatment escalation.

Chadwick R. Johr, MD

We need to systematically assess for additional organ involvement. I approach this by going through the 12 domains of the validated EULAR Sjögren's syndrome disease activity index, or ESSDAI, asking about things like persistent cough or shortness of breath, numbness or tingling, weakness, weight loss, or night sweats. These questions help prompt the need for further evaluation of systemic manifestations. That structured review helps ensure we're not missing pulmonary, neurologic, constitutional, or other systemic features.

Chadwick R. Johr, MD

For Jessica, her active domains are articular, hematologic, and we can calculate her total ESSDAI score: it's a 10, which corresponds to moderate systemic disease activity because it's above a score of 5.

Cindy Johnston, MD

Given her sicca symptoms plus systemic involvement, she classifies as a patient with active systemic disease in addition to her dryness symptoms—you may think of this patient as a sicca plus patient and she may be eligible for biologic therapy.

Cindy Johnston, MD

To learn more about the sicca plus framework, visit sjogrenssjoutshcp.com.

Cindy Johnston, MD

Now that we've established moderate disease activity, this directly informs management. Patients like Jessica may require closer monitoring than every 6 months, and the ESSDAI can help track treatment response over time.

Chadwick R. Johr, MD

She's currently on systemic treatment and continues to express discomfort in her daily life. I would offer treatment escalation in a patient like this.

Cindy Johnston, MD

After initiating escalating treatment, I reassess within 4 to 6 weeks to evaluate tolerability, then adjust therapy and monitor every few months once stable.

Chadwick R. Johr, MD

My primary target is reduction in swollen and tender joint count, as this is the most objective marker of improvement. Cytopenias are more variable and require longitudinal monitoring.

Cindy Johnston, MD

I also incorporate patient goals into decision-making. While some patients prefer conservative approaches initially, it's important to explain that systemic involvement and abnormal labs indicate active systemic disease that may require an escalated treatment approach.

Chadwick R. Johr, MD

Exactly. We're not just treating current symptoms—we're also considering progression. Different emerging therapies may change management.

Cindy Johnston, MD

Targeted therapies may provide additional options for patients with systemic disease in the future.

Chadwick R. Johr, MD

Jessica's case highlights that Sjögren's is far more than dryness. She has objective systemic involvement placing her in the moderate disease activity range.

Cindy Johnston, MD

It highlights the importance of structured assessment using tools like ESSDAI to help guide treatment decisions. Moderate disease activity—especially in young patients—warrants timely treatment and close follow-up.

Chadwick R. Johr, MD

Progression in Sjögren's disease is unpredictable and can vary widely between patients. Some patients may remain relatively stable, while others develop worsening symptoms, systemic manifestations, or progressive organ involvement. Because not all signs of disease activity are visible on physical exam, thorough assessment is essential.

Effective management requires early identification of systemic disease, assessment of progression risk, appropriate risk stratification, and ongoing partnership with patients to align treatment goals. We hope our review of Jessica's case was helpful in supporting your own approach in assessing and managing Sjögren's disease in your patients.

Cindy Johnston, MD

Uncover more patient cases and expert-led resources on Sjögren's disease at sjogrenssjoutshcp.com.

Sebastian Wilk, MD

Sjögren's disease is more than just dryness—it's a serious, autoimmune disease that can be progressive and can affect the whole body. While many patients notice dry eyes or dry mouth, also known as sicca symptoms, there can be much more going on beneath the surface. Focusing on only dryness can mean missing signs of systemic involvement, which can have significant consequences.

Sebastian Wilk, MD

Hi, my name is Sebastian Wilk, and I'm a rheumatologist with Buffalo Rheumatology and Medicine in Orchard Park, New York.

Sebastian Wilk, MD

I'm joined here today with Lindsay Tom, a physician assistant, who practices at Northern Virginia Center for Arthritis.

Sebastian Wilk, MD

In this video, we'll dive into a patient case inspired by real experiences of individuals with Sjögren's disease. We'll follow Lynn's journey, exploring her symptoms and how they impact her day-to-day life, her management plan, and other clinical considerations. Our goal is to take a comprehensive approach to supporting those living with Sjögren's and enhancing their quality of life.

Sebastian Wilk, MD

With that in mind, Lindsay, why don't you introduce Lynn?

Lindsay Tom, PA-C

Sure, let's get started.

Lindsay Tom, PA-C

Lynn is a woman in her mid-40s, experiencing severe eye dryness, mild mouth dryness, moderate vaginal dryness, swollen bilateral parotid glands, and cytopenia.

Lindsay Tom, PA-C

Three years ago, she began using artificial tears... ...and xylitol chewing gum for mild dry eyes and dry mouth.

Lindsay Tom, PA-C

A year ago,... ...she sought help from her gynecologist for discomfort during intercourse and soon noticed swelling in her parotid glands, prompting an ENT evaluation.

Lindsay Tom, PA-C

She received a 2-week course of prednisone after ductal obstruction was ruled out, but the swelling recurred twice more, leading to a referral to rheumatology, where her initial diagnosis of Sjögren's disease was made.

Lindsay Tom, PA-C

I often see patient journeys like Lynn in my practice. Dr Wilk, do you find this typical in your experience too?

Sebastian Wilk, MD

Absolutely, it's quite typical to see patient journeys like Lynn's. In my practice, we receive referrals from primary care physicians—who often spot initial symptoms—and from specialists such as ENT, dental, pulmonary, or gynecology, who may see various manifestations of the disease.

Sebastian Wilk, MD

And to that point, referrals from other specialists may be more likely to lead to a Sjögren's diagnosis, as patients may already be showing signs of organ involvement. Regardless of symptom severity, a comprehensive exam is essential to ensure no early signs or complications are missed.

Sebastian Wilk, MD

Let's return to Lynn's case. After being referred by the ENT, Lynn is now under the care of a rheumatologist, who ordered lab work and performed a physical exam.

Sebastian Wilk, MD

This revealed swollen parotid glands measuring 1.5 × 2 cm, and an ultrasound confirmed parotid involvement.

Sebastian Wilk, MD

Her ANA is negative, but she tested positive for anti-SSA or Ro antibodies.

Sebastian Wilk, MD

A Schirmer's test indicates reduced tear production, measuring between 2 to 3 millimeters over 5 minutes.

Sebastian Wilk, MD

And her unstimulated salivary flow rate is 0.3 mL/min, which is at the lower end of normal.

Sebastian Wilk, MD

Her immunoglobulin G and complement levels are within normal ranges, but the absolute neutrophil count is notably low at 920 cells/mm³.

Sebastian Wilk, MD

Lastly, her hepatitis B and C virus test results are negative.

Sebastian Wilk, MD

So, Lindsay, there are several findings from her labs and physical assessment that support a diagnosis of Sjögren's disease. What else do you usually consider when evaluating a new patient for suspected Sjögren's disease?

Lindsay Tom, PA-C

When I evaluate a new patient for suspected Sjögren's disease, it's important I differentiate the disease from other autoimmune conditions due to overlapping serologic markers.

Lindsay Tom, PA-C

Additionally, monitoring for other autoimmune and rheumatic diseases is crucial, as they can occur concomitantly in patients with Sjögren's. And immune-related comorbidities can develop throughout the disease course, so ongoing reassessment is helpful.

Lindsay Tom, PA-C

In addition to that, ultrasound may be a valuable tool for monitoring this disease. It's noninvasive, and it may help us assess glandular involvement and track changes to follow disease progression.

Lindsay Tom, PA-C

In a patient like Lynn, where she shows ultrasound evidence of parotid involvement, ultrasound can help us make more informed decisions about treatment adjustments and prognostic evaluations as we follow her disease progression over time.

Lindsay Tom, PA-C

The way Lynn is feeling is similar to what we see in other patients. We can see that the constant presence of her disease leads to daily challenges that impact her quality of life.

Lindsay Tom, PA-C

The swelling of her parotid glands has also made it difficult for her to enjoy some of her favorite foods, further reducing her overall quality of life.

Lindsay Tom, PA-C

Additionally, Lynn's symptoms extend to her intimate relationships—as vaginal dryness has made intimacy more challenging.

Lindsay Tom, PA-C

Lynn's experience highlights the broad impact of Sjögren's beyond dryness, affecting patients physically, emotionally, and socially.

Lindsay Tom, PA-C

Many patients may delay mentioning symptoms, attributing them to stress, aging, or hormonal changes, until they become more disruptive or visible, like swollen glands.

Lindsay Tom, PA-C

That's why it's important to ask proactively about patients' daily functioning and quality of life, while also keeping systemic involvement on the radar.

Sebastian Wilk, MD

ESSDAI, also known as the EULAR Sjögren's disease activity index, is the gold standard in clinical trials for assessing systemic disease activity across 12 domains...with individual domain scores based on the presence and severity of involvement, resulting in an overall score categorized as low, moderate, or high disease activity.

Sebastian Wilk, MD

While you may not use it directly in your practice, asking questions based on ESSDAI may be useful to help prompt further evaluation.

Lindsay Tom, PA-C

As Dr Wilk mentioned, using the ESSDAI domains during a review of systems can help guide more comprehensive questioning.

Lindsay Tom, PA-C

For example, I may ask about shortness of breath or a persistent cough in the pulmonary domain, and numbness, tingling, or burning in the hands or feet in the peripheral nervous system domain.

Lindsay Tom, PA-C

I also revisit these ESSDAI-based questions at follow-up visits, as Sjögren's can evolve over time. These targeted questions can help guide additional evaluation or monitoring. After completing Lynn's ESSDAI assessment, her total score was calculated to be 6, indicating moderate disease activity.

Lindsay Tom, PA-C

With her sicca symptoms and additional organ-system involvement—specifically glandular and hematologic involvement—Lynn would be classified as having active systemic disease in addition to her dryness symptoms. You may consider her a sicca plus patient, and she may, therefore, be eligible for biologic therapy.

Lindsay Tom, PA-C

To learn more about the sicca plus framework and ESSDAI scoring, visit sjogrenssjoutshcp.com.

Sebastian Wilk, MD

So, once the diagnosis is established, we start thinking about a management plan. Current Sjögren's disease management is based on the treatment of dryness symptoms with secretagogues and the use of immunosuppressants for systemic features.

Sebastian Wilk, MD

For Lynn, she had already been using artificial tears and xylitol gum to help with her sicca symptoms. And she was prescribed hydroxychloroquine after being diagnosed with Sjögren's but had to discontinue due to side effects.

Sebastian Wilk, MD

Dr Wilk, what are some challenges you face in managing Sjögren's disease in patients similar to Lynn?

Sebastian Wilk, MD

A major challenge is the lack of an approved therapy for Sjögren's disease. As you mentioned, management focuses on relieving dryness symptoms and addressing systemic manifestations with immunosuppressive therapies that are not specifically approved for Sjögren's.

Sebastian Wilk, MD

This can be frustrating for both clinicians and patients, especially when patients are unable to tolerate therapies. For example, Lynn discontinued hydroxychloroquine, which is among the limited options we currently have, due to side effects. Another important consideration is how a patient's risk factors can shape management decisions.

Sebastian Wilk, MD

In Lynn's case, she presents with moderate disease activity, prolonged glandular swelling, and cytopenia, which are clinical factors that have shown to increase the risk associated with systemic disease activity in Sjögren's.

Sebastian Wilk, MD

So, I'd follow her more closely to catch any signs of progression early and adjust her management plan as needed.

Lindsay Tom, PA-C

Alongside closer monitoring, clear communication and building trust with the patient are crucial. I focus on transparency, explaining the diagnosis, why specific symptoms and labs are monitored, and what changes might prompt a plan adjustment.

Lindsay Tom, PA-C

When patients understand the reasoning behind follow-up and treatment, it sets expectation and makes care manageable and collaborative. Regular check-ins and availability for questions can also be very reassuring, especially for patients with Sjögren's disease, where the disease course can be unpredictable.

Lindsay Tom, PA-C

I agree, and I tailor the conversations to the patient's education level and readiness, so I don't overwhelm them in the first visit.

Lindsay Tom, PA-C

Connective tissue diseases are complex. I describe it as the immune system becoming overactive and that treatment aims to "turn down the volume" rather than completely shut it off. And this can involve some trial and error to find what works best for the patient.

Sebastian Wilk, MD

And to that point, despite the current limitations, we are optimistic about future treatments in development for Sjögren's, with several novel therapies being investigated in clinical trials.

Sebastian Wilk, MD

An FDA-approved, target therapy specifically for Sjögren's would be a meaningful step forward and would give clinicians clear guidance and may offer patients a treatment that targets the underlying disease biology, not just the symptoms.

Sebastian Wilk, MD

Caring for patients with Sjögren's means looking beyond dryness and taking a holistic approach to assess systemic manifestations and help prevent complications.

Sebastian Wilk, MD

We hope Lynn's case was helpful in supporting your approach to assessing and managing Sjögren's in your patients.

Sebastian Wilk, MD

Uncover more patient cases and expert-led resources on Sjögren's disease at sjogrenssjoutshcp.com.

Chadwick R. Johr, MD

Patients with Sjögren's disease experience daily challenges that impact their quality of life. The most common symptoms of Sjögren's disease, including excessive dryness, severe fatigue, chronic pain, can be debilitating.

Beyond symptoms, up to 40% of patients may face systemic manifestations that can significantly impact their long-term health.

I'm Dr Chadwick R. Johr, a rheumatologist at the University of Pennsylvania.

Cindy Johnston, MD

And I'm Dr Cindy Johnston, a rheumatologist at Sarasota Arthritis Center in Sarasota, Florida.

Chadwick R. Johr, MD

We're going to discuss a case focused on Melissa, inspired by real experiences with individuals with Sjögren's disease. She is a female in her 40s with high systemic disease activity. A patient like Melissa prompts us to think carefully about systemic involvement, risk stratification, and how aggressively we should intervene.

Cindy Johnston, MD

Yes, I think this case is important because Melissa is a woman in her 40s who has had symptoms for years that were easy to dismiss. Mild dryness and fatigue get attributed to hormones or just getting older. But over time, we start to see systemic features emerge. And that's really where the urgency changes, because while progression is highly variable, a subset of patients may develop severe symptoms and potentially lymphoma.

Chadwick R. Johr, MD

Okay, let's get to know Melissa. She presents with severe eye dryness, moderate mouth dryness, synovitis in her right knee and wrist, palpable purpura, elevated IgG, low complement, elevated inflammatory markers, and mild night sweats.

5 years ago, she had mild dryness and fatigue and didn't seek care. That makes sense. If symptoms aren't too bad, people won't seek help. And dryness in a woman in her 40s will often be explained away.

But now we're seeing immune activation with elevated IgG and low complement, plus inflammatory arthritis and vasculitis. That changes the conversation.

Cindy Johnston, MD

I completely agree. Sicca symptoms are often ignored and dismissed, especially early on. By the time patients feel dryness symptoms, they may have already lost 50% of glandular function. So, we're often seeing them later in the disease course than we'd like.

Chadwick R. Johr, MD

Now that we've outlined Melissa's clinical presentation, the next step is to understand how this level of disease activity is affecting her day-to-day life. She stopped running because of knee pain. She scaled back involvement at home. She has had to skip work trips as her symptoms have progressed. That's real functional decline. I only have a handful of patients with Sjögren's like this, many have a lower activity level. But when these patients show up, I pay attention.

Cindy Johnston, MD

Exactly. And what's tricky is that dryness alone doesn't always drive urgency, but when you layer in systemic inflammation, arthritis, and vasculitis, that translates into functional decline and signals a need to escalate care.

Chadwick R. Johr, MD

So, given this level of disease burden, the next step is to evaluate Melissa's labs and physical exam findings to better define the extent of her systemic disease. Looking at her lab results—SSA positive, ANA positive, low complement levels, elevated sed rate and CRP, elevated IgG—these values tell me the immune system is overactive. The combination of purpura and low complement levels is particularly concerning for vasculitis. That's why I would check cryoglobulins, rheumatoid factor, SPEP, and possibly do a salivary gland ultrasound. And with systemic synovitis in the knee and wrist, I would broaden the differential to rule out overlap disease or alternative diagnoses, which is why I'd check anti-CCP for RA, double stranded DNA and Smith antibodies for lupus.

Cindy Johnston, MD

And on exam, this is someone who needs a comprehensive head-to-toe assessment, because we're specifically looking for signs of organ involvement that may not yet be clinically obvious. For example, screening for neuropathy, renal involvement, or subtle vasculitic findings helps ensure we're not missing early organ disease that would further increase urgency. With Melissa, I see palpable purpura and low complement levels, so I'm already thinking we need to control this disease activity.

Chadwick R. Johr, MD

Initially, we want to broaden the differential and avoid being biased.

Cindy Johnston, MD

I agree, a head-to-toe review of systems is important. We need to screen for vasculitis and neurological involvement. Red flags that shift urgency are purpura plus low complement levels. We need to make sure nothing subtle is missed on exam.

Chadwick R. Johr, MD

Systemic manifestations began to appear for Melissa about 2 years ago. She developed a rash on her ankles, which prompted her to see her primary care physician, who prescribed topical triamcinolone. However, Melissa didn't see any improvement; in fact, the rash spread to her shins, so she was referred to a dermatologist. The dermatologist prescribed a short course of prednisone, which provided temporary relief, but the rash returned after treatment ended, ultimately necessitating the persistent use of systemic corticosteroids.

Then, about 10 months ago, Melissa developed synovitis with pain in her right knee and wrist, prompting a referral to a rheumatologist. After the rheumatologist diagnosed her with Sjögren's disease, he initiated methotrexate, titrated up to 25 mg weekly. Despite this, Melissa continues to have joint symptoms and now presents with palpable purpura due to vasculitis on her feet. Additionally, she has been experiencing mild, intermittent night sweats.

Cindy Johnston, MD

So, now that we've reviewed her clinical course and objective findings, the next step is to formally quantify Melissa's disease activity using a validated tool, such as the EULAR Sjögren's syndrome disease activity index, or ESSDAI.

Chadwick R. Johr, MD

In Melissa's case, her active domains include biological, cutaneous, articular, and constitutional involvement.

And after calculating those domains her total ESSDAI score is 14, which puts her in the "high disease activity" category. This provides an objective confirmation of what we're already seeing clinically and reinforces the need for treatment escalation.

Cindy Johnston, MD

With her sicca symptoms and involvement of 1 or more organ systems, Melissa qualifies as a patient with active systemic disease in addition to her dryness symptoms—you may think of this patient as a sicca plus patient—and she may be eligible for biologic therapy.

To learn more about the sicca plus framework, visit sjogrenssjoutshcp.com.

This is not a "watch and wait" situation. Vasculitis in a relatively young woman needs intervention. The systemic involvement is what changes the urgency.

Chadwick R. Johr, MD

I agree. Melissa needs careful monitoring because these features—particularly low complement level, purpura, and possible cryoglobulinemia—are established risk factors that can signal higher likelihood of lymphoproliferative disease over time. Baseline lymphoma risk in Sjögren's may be around 5% to 10%, depending on the study. But certain risk factors, such as SSA positivity, low C4 levels, cryoglobulins, rheumatoid factor status, and purpura, can increase the risk. If multiple of those are present, the risk climbs based on published models. So Melissa needs a careful lymph node exam, parotid exam, abdominal exam for splenomegaly, and close lab surveillance.

Now that we've established that Melissa has high systemic disease activity, the key question becomes: How do we treat her? There are currently no FDA-approved treatments specifically for systemic Sjögren's. Melissa is already on methotrexate at 25 mg weekly, which is appropriate for her inflammatory arthritis. If her treatment response has plateaued and her symptoms are still active, I would escalate. I would also add hydroxychloroquine because it's low risk, but I don't have a lot of confidence that it will help treat her vasculitis. For Melissa, I would strongly consider a B-cell–directed therapy to treat synovitis and vasculitis.

Cindy Johnston, MD

That's my approach as well. Systemic vasculitis is believed to be B-cell driven, and that's the rationale for treatment selection. I'd follow up within a month to ensure therapy was initiated and tolerated, and then monitor closely.

Chadwick R. Johr, MD

Right now, all we have are "borrowed" treatments. We treat the manifestations that are in front of us, like the vasculitis or synovitis. So, we use the therapies that are approved and available to us for other rheumatic diseases for those manifestations.

Cindy Johnston, MD

That's right, we use evidence from similar systemic vasculitis and categorize patients as having mild, moderate, or severe systemic involvement. Then we set realistic expectations with the patient.

Chadwick R. Johr, MD

Stepping back from Melissa's treatment plan, it's also important to consider what her case tells us more broadly about disease progression. We're not just talking about dryness anymore. Between the synovitis, the purpura, the abnormal labs, and a high disease activity score, this is a patient with significant inflammatory activity. And when you see vasculitis, low complement levels, and ongoing inflammation despite methotrexate, that's the signal to escalate.

Cindy Johnston, MD

And, looking at the broader picture, the real opportunity arises in catching patients with Sjögren's symptoms earlier. The 40-year-old with dryness and serologic positivity before they develop vasculitis—that's where we want to intervene more proactively in the future.

Chadwick R. Johr, MD

Melissa represents high systemic disease activity in Sjögren's. And while no two patients present with the same manifestations, you're likely to have a few patients like her.

Cindy Johnston, MD

Melissa's case also highlights how Sjögren's can evolve from subtle dryness to clear systemic disease with high activity over the course of a few years. Recognizing progression is critical, because it changes how aggressively we need to manage the disease.

Chadwick R. Johr, MD

Exactly. With a patient like Melissa, you move decisively, monitor carefully, and involve the patient in shared decision-making, because while we don't have all the answers, we do know that high systemic activity requires action.

We hope our review of Melissa's case was helpful in supporting your own approach to assessing and managing patients with Sjögren's disease.

Cindy Johnston, MD

Uncover more patient cases and expert-led resources on Sjögren's disease at sjogrenssjoutshcp.com.

Lindsay Tom, PA-C

Every patient's experience with Sjögren's disease is unique. Therefore, it is important to regularly assess each patient comprehensively and tailor their disease management approach…

Lindsay Tom, PA-C

…according to individual symptom burden, clinical factors, and risk profile.

Lindsay Tom, PA-C

Hi, my name is Lindsay Tom, and I'm a physician assistant practicing at Northern Virginia Center for Arthritis.

Lindsay Tom, PA-C

I'm excited to be joined today by Dr Sebastian Wilk from Buffalo Rheumatology and Medicine.

Lindsay Tom, PA-C

In this video, we'll explore a patient case inspired by real experiences with Sjögren's disease. We'll follow Judith's journey, examine how her symptoms impact daily life, review her treatment and management plan, and highlight key clinical considerations and decisions that can enhance her quality of life. Dr Wilk, can you get us started by introducing Judith?

Sebastian Wilk, MD

Sure, let's start by getting to know Judith.

Sebastian Wilk, MD

She's in her late-50s and is experiencing severe eye and mouth dryness. She also shows signs of lymphadenopathy and her lab findings show some abnormalities.

Sebastian Wilk, MD

About a decade ago, she developed moderate mouth and eye dryness and saw an ophthalmologist, who prescribed topical cyclosporine A for her dry eyes.

Sebastian Wilk, MD

Seven years later, she consulted her primary care physician for persistent mouth dryness, and was advised to stay hydrated,

Sebastian Wilk, MD

…and was referred to a rheumatologist for further evaluation.

Sebastian Wilk, MD

Judith was diagnosed with Sjögren's disease by her rheumatologist and was started on symptomatic management. Unfortunately, a year has passed, and she has shown only….

Sebastian Wilk, MD

…minimal improvement in her dryness and has developed swollen submandibular lymph nodes. Lindsay, do you have any thoughts on her patient journey and history leading up to her diagnosis?

Lindsay Tom, PA-C

So, Judith's journey exemplifies a common issue in diagnosing Sjögren's disease. The 7-year gap between symptom onset and diagnosis highlights a few key points regarding symptom perception and awareness. Initially, many patients like Judith may perceive sicca symptoms as mild or even normal, attributing them to aging or hormonal changes, like menopause.

Lindsay Tom, PA-C

Because these symptoms are often underestimated, patients may delay seeing their provider. Additionally, many are unaware of Sjögren's itself and might not realize that what they consider "mild" symptoms can be linked to a systemic autoimmune disease.

Sebastian Wilk, MD

Now, let's take a look at Judith's labs and physical exam.

Sebastian Wilk, MD

On exam, she has swollen cervical lymph nodes, with submandibular nodes measuring approximately 1.8 × 2.2 cm. Her labs are positive for SSA antibodies, rheumatoid factor, and ANA, with low complement levels and elevated ESR. Her immunoglobulin G level is also elevated at 19 g/dL. Schirmer's test measures 8 mm over 5 minutes, consistent with moderate dry eyes, and her unstimulated whole salivary flow rate is <0.1 mL/min, indicating severe hyposalivation.

Sebastian Wilk, MD

Based on her lab results and physical exam findings, what are the key things you would want to keep in mind early when you're evaluating for suspected Sjögren's disease?

Lindsay Tom, PA-C

The key thing to keep in mind is that the diagnosis of Sjögren's does not rely on lab results alone. Common but nonspecific labs may overlap with lupus or other rheumatic diseases, so results should be interpreted alongside clinical findings.

Lindsay Tom, PA-C

What's interesting about Judith's case is that she hasn't improved much over time and continues to experience dryness.

Lindsay Tom, PA-C

She started on topical cyclosporine A for dry eyes long before her Sjögren's diagnosis, and even after the diagnosis, the focus remained on symptom management, which included serum eye drops, plus lozenges and pilocarpine. However, her labs suggest a potential for disease progression.

Sebastian Wilk, MD

That's a great point. A patient can look "stable" from a symptom standpoint, but their lab profile may tell you more. That's why I emphasize the prognostic value of routine labs, not just at diagnosis but longitudinally. For me, I like to follow clonal immunoglobulins, complement levels, and cryoglobulins over time.

Sebastian Wilk, MD

And again, I don't view these labs as one-time checkboxes—I look at trends. For example, someone who is rheumatoid factor-negative at onset and later becomes rheumatoid factor-positive may be giving you a clue about the underlying immune activity. Additionally, anti-Ro52 antibodies and rheumatoid factor may be useful to help stratify patients, guide monitoring, and prompt earlier evaluation for potential systemic features.

Sebastian Wilk, MD

So in Judith's situation, even though the care has understandably focused on symptom relief, her labs—like low complements and positive rheumatoid factor—are telling us that she may be at risk for progression.

Lindsay Tom, PA-C

Based on her labs and symptoms, she may have underlying systemic disease activity that's impacting her quality of life.

Lindsay Tom, PA-C

She has trouble swallowing and speaking, especially in the mornings, and a constant gritty eye sensation that makes driving uncomfortable. She now completes only 1 to 2 chores before needing to rest and relies on frequent naps, reflecting a significant decline in her overall quality of life.

Lindsay Tom, PA-C

Dr Wilk, how do you factor symptom burden into your overall management approach?

Sebastian Wilk, MD

It's important to balance what the patient is feeling with what you're seeing clinically.

Sebastian Wilk, MD

I try to make symptom impact measurable using structured tools—like patient-reported symptom scales and quality-of-life measures. That said, these tools don't capture everything, like underlying systemic disease activity.

Sebastian Wilk, MD

Which is why asking thorough, targeted questions can help build the full clinical picture. ESSDAI is the gold standard in clinical trials for assessing systemic disease activity across 12 domains…

Sebastian Wilk, MD

…with individual domain scores based on the presence and severity of involvement, resulting in an overall score categorized as low, moderate, or high disease activity. While you may not use it directly in your practice, asking questions based on ESSDAI may be useful to help prompt further evaluation, and can help ensure we're not focused only on sicca symptoms, but also on screening for organ-system involvement patients may not connect to Sjögren's.

Lindsay Tom, PA-C

As Dr Wilk just mentioned, ESSDAI-based questions can help uncover symptoms people may normalize or forget to mention—like shortness of breath with mild activity, night sweats, or unexplained weight loss.

Lindsay Tom, PA-C

Many patients assume only current symptoms matter, so they won't volunteer past issues unless prompted—but if you ask directly, they might recall things like a chest X-ray last year or intermittent breathing problems.

Lindsay Tom, PA-C

After completing Judith's ESSDAI assessment, her total score was calculated to be 9, indicating moderate disease activity.

Lindsay Tom, PA-C

With her sicca symptoms and additional organ-system involvement—specifically lymph node and biological involvement—Judith would be classified as having active systemic disease in addition to her dryness symptoms. You may consider her a sicca plus patient, and she may, therefore, be eligible for biologic therapy.

Lindsay Tom, PA-C

To learn more about the sicca plus framework and ESSDAI scoring, visit sjogrenssjoutshcp.com.

Sebastian Wilk, MD

One aspect of Judith's presentation that raises a red flag for ongoing immune overactivity is her persistent lymphadenopathy. It raises concern not only for "more active disease," but also for the long-term risk of progression to lymphoma—a risk that's relatively distinctive and higher in Sjögren's than many other autoimmune diseases.

Sebastian Wilk, MD

In patients with higher disease activity, I monitor more closely and reassess for evolving systemic involvement to avoid missing complications that require closer surveillance. For patients with low disease activity, I typically follow up more frequently, for example, every 6 to 12 months.

Sebastian Wilk, MD

Another challenge in managing Sjögren's disease is the limited treatment options.

Sebastian Wilk, MD

Management is largely focused on relieving dryness symptoms with secretagogues, and using immunosuppressive therapies that are not specifically approved for systemic manifestations of Sjögren's disease.

Lindsay Tom, PA-C

That is why individualized management is so important—to help prevent disease progression and reduce the risk of long-term, potentially irreversible complications.

Lindsay Tom, PA-C

Early identification of systemic disease activity can make a meaningful difference—for both you and your patients—in managing the disease and preventing complications.

Sebastian Wilk, MD

We hope today's review of Judith's case highlighted how careful assessment and timely intervention can make a significant difference for patients with Sjögren's disease, especially those with underlying systemic disease activity and risk of progression.

Lindsay Tom, PA-C

Uncover more patient cases and expert-led resources on Sjögren's disease at sjogrenssjoutshcp.com.