Sjögren's disease, which you might know as Sjögren's syndrome, often features sicca symptoms such as mouth (xerostomia) and ocular (keratoconjunctivitis) dryness. But it may extend far beyond dryness.^1,2

Beyond sicca, inflammation or damage can also occur in the joints, skin, lymph nodes, lungs, brain, or other organ systems.^2-4 

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

When examining patients with Sjögren's disease, it’s important to recognize that not all signs of disease activity will appear during the physical exam. Critical indicators of disease can lie beneath the surface, requiring deeper, more comprehensive assessment.^5-7

Therefore, patients with either Sjögren's disease suspicion or diagnosis need to be referred to a rheumatologist as early as possible.

Learn more about signs of systemic involvement

Historically, primary Sjögren's disease referred to cases when clinical manifestations occurred alone, while secondary Sjögren's disease was used when it was associated with another systemic autoimmune disease. 

While these terms are still recognized, current medical practice often refers to primary Sjögren's disease simply as Sjögren's disease, and secondary Sjögren's disease as Sjögren's disease with overlap or associated Sjögren’s disease.^8,9

Sjögren's is a serious, systemic disease that can be progressive and may extend far beyond dryness.^1,5,10-12 It is believed that hyperactivation of B cells in Sjögren's disease can lead to chronic inflammation and target self-tissues, specifically the lacrimal and salivary glands, which may lead to tissue damage.^13-15

Did you know Sjögren’s disease is believed to be a B-cell–driven disease?

Sjögren's disease is believed to be a B-cell–driven autoimmune disease in which the perpetual activation of B cells results in a pathological cycle of immune activation, leading to chronic inflammation and irreversible tissue destruction.^13,14,16,17

Environmental factors may trigger epithelial and immune cells to release cytokines and chemokines, including B-cell activating factor (BAFF).^18-20

Elevated levels of BAFF support survival and B-cell hyperactivity, further advancing disease progression.^19,20

Hyperactive B cells are responsible for the production of immunoglobulin G autoantibodies that attack lacrimal and salivary glands, contributing to inflammation and activation of other signaling pathways.^13,16,17

Did you know Sjögren’s disease is believed to be a B-cell–driven disease?

Certain biomarkers and clinical factors can help you better understand the extent of a patient's systemic disease activity and signs of disease progression. Examples include: ESSDAI ≥5, indicating moderate or high disease activity; skin involvement; prolonged inflammation in the salivary glands; cytopenias.^{7,10,12,21-26} 

Laboratory testing can also help assess subclinical systemic disease activity. IgG level, blood cell counts (of autoimmune origin only), cryoglobulin, and complement levels are key blood tests to help assess disease activity.^22,27

What could be indicators of underlying disease activity?

Sjögren's disease, which you might know as Sjögren's syndrome, often features sicca symptoms such as mouth (xerostomia) and ocular (keratoconjunctivitis) dryness. But it may extend far beyond dryness.^1,2

Beyond sicca, inflammation or damage can also occur in the joints, skin, lymph nodes, lungs, brain, or other organ systems.^2-4

EULAR Sjögren's syndrome disease activity index (ESSDAI) is the gold standard in clinical trials for assessing disease activity across 12 domains.²²

Could your patients be experiencing manifestations beyond their dryness symptoms?

Renal involvement is a recognized systemic manifestation of Sjögren’s disease. It may present with changes in urine characteristics or fluid retention. Symptoms such as changes in urine color or swelling in the legs or feet may raise concern for potential renal involvement and warrant further clinical evaluation. Patients should be monitored as part of a broader systemic assessment using disease activity tools such as ESSDAI. If you have patients like this, the sicca plus approach could help you assess if they may benefit from biologics.²²

Questions to uncover deeper manifestations

Pulmonary involvement is a recognized systemic manifestation of Sjögren's disease. It may present with persistent cough, shortness of breath, or radiographic abnormalities, like interstitial lung disease (ILD). 

Prompt pulmonary referral is recommended for Sjögren's patients reporting any respiratory complaints. These symptoms warrant a comprehensive evaluation, including a clinical exam, radiographic imaging, and pulmonary function testing, as early identification and treatment are important.

Patients should also be routinely monitored for respiratory symptoms as part of a broader systemic assessment, using disease activity tools such as ESSDAI. The sicca plus approach could help you assess if they may benefit from biologics.²⁸

Questions to uncover deeper manifestations

Neurologic involvement is a recognized systemic manifestation of Sjögren’s disease and includes both the peripheral and central nervous systems. Peripheral symptoms may include numbness, tingling, or burning sensations in the extremities, while central symptoms may include headaches, dizziness, or cognitive impairment. These symptoms may raise concern for potential neurologic involvement and warrant further clinical evaluation. Patients should be monitored as part of a broader systemic assessment using disease activity tools such as ESSDAI. If you have patients like this, the sicca plus approach could help you assess if they may benefit from biologics.²²

Questions to uncover deeper manifestations

Patients with Sjögren’s disease have a significantly increased risk of developing lymphoma, compared with the general population. Clinical features that have been associated with increased lymphoma risk include lymphadenopathy, persistent salivary gland swelling, cytopenias, cryoglobulinemia, and complement abnormalities.^25,29

Generally, these findings should prompt further evaluation when they occur in patients with Sjögren's disease. Experts recommend monitoring patients with low systemic disease activity every 6 to 12 months, and more frequently in patients with high systemic disease activity.^5,25,29

What could be indicators of underlying disease activity?

Your sicca plus patients—those with sicca symptoms plus involvement of 1 or more organs or systems—may be candidates for biologic therapy. This simple, practical framework (located within the link below) helps guide comprehensive patient assessment, uncovering those who may be biologic ready and enabling timely, targeted intervention.

Blood testing for biomarkers can help you determine if a patient has subclinical systemic disease activity.²²

Identify sicca plus patients in your practice

Your sicca plus patients—those with sicca symptoms plus involvement of 1 or more organs or systems—may be candidates for biologic therapy. This simple, practical framework (located within the link below) helps guide comprehensive patient assessment, uncovering those who may be biologic ready and enabling timely, targeted intervention.

Blood testing for biomarkers can help you determine if a patient has subclinical systemic disease activity.²²

Identify sicca plus patients in your practice

At present, there are no FDA-approved therapies targeting the underlying pathogenesis of SjD or slowing disease progression.^1,30

In the absence of Sjögren's-specific disease-modifying therapies, EULAR guidelines* describe a targeted treatment flow based on specific organ involvement, increasing clinical complexity.⁵

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

Why symptomatic treatment may not be enough

Progression is highly variable—it may be slow in some patients whose disease remains relatively stable, while others may experience worsening symptoms or develop new systemic manifestations of disease. A subset of patients may develop severe symptoms and/or lymphoma.^10,19

What could be the indicators of underlying disease activity?

ESSDAI measures systemic disease activity in SjD. Each individual domain is divided into 3 to 4 levels of activity (no, low, moderate, or high activity), and the corresponding scores are multiplied by the domain weight (a scale of 1 to 6, depending on domain). The sum of individual domains is the ESSDAI score, with a maximum score of 123.³¹

Review patient cases to see how ESSDAI scores pair with symptom severity