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

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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.

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