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  • Writer's pictureSarah Schafer, MD

Sjogren's and Inflammation - Part I

Updated: Jan 20

Has a doctor told you that Sjogren’s does not cause systemic inflammation? That having a normal C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) means that your inflammation is low, your Sjogren’s is inactive, or you don’t need treatment? These are common misperceptions about Sjogren’s.

This 2-part blog post explains why Sjogren’s is a systemic inflammatory disease, even if your CRP and ESR are normal. It also highlights a recent study about inflammation and fatigue, with a surprising twist. See Sjogren's and Inflammation - Part II to learn about the uses and limitations of CRP and ESR in Sjogren's.

Although we still have much to learn about the immune system, the regulation of inflammation is thought to be central to how autoimmune diseases start and progress.

At the end of the blog post you will find self-advocacy tools to counter misperceptions related to inflammation in Sjogren's.


Sjogren’s is a systemic inflammatory disease.  What does this mean?

Systemic diseases impact multiple areas of the body.   Sjogren’s is a systemic disease because it impacts multiple organs and systems. Lung disease, joint pain, neuropathies, low blood counts, and Raynaud’s’ are examples of common systemic manifestations of Sjogren's. Although sicca (dryness) may affect a variety of exocrine glands and is technically, therefore, systemic, the convention among Sjogren’s experts is to refer only to the non-sicca parts of Sjogren’s as “systemic manifestations”.

Sjogren’s is part of a family of diseases called autoimmune rheumatic diseases (AIRDs) that are systemic inflammatory diseases. Other AIRDs include rheumatoid arthritis (RA), systemic sclerosis, and systemic lupus erythematosus (lupus / SLE). RA is more than just a joint disease and systemic sclerosis is more than just a skin disease, although this is how they were originally described. These diseases may also impact the lungs, kidneys, nerves and more. Sjogren’s is more than “just sicca. If and when you look for them, systemic manifestations can be found in nearly every person with Sjogren’s.

Sjogren’s and systemic lupus (SLE) are even more variable in the body systems they affect than RA and systemic sclerosis. While rheumatoid arthritis has more predictable and easily recognizable signs and symptoms in almost everyone with the disease, 2 people with Sjogren's or 2 people with lupus may have very different organ systems affected by the respective diseases. This is one reason that Sjogren’s and SLE are especially challenging to diagnose, monitor, and manage.  Learn more about systemic manifestations of Sjogren’s. Inflammation plays a major role in autoimmune diseases.   Not all inflammation is bad. Inflammation is necessary for responding to infections and healing wounds. Even exercise, which reduces chronic inflammation, temporarily increases muscle inflammation to stimulate healing. When inflammation is excessive or out of balance, it can lead to disease, including autoimmune disease. 

The immune system is in charge of fine-tuning inflammation. This complex system includes multiple types of white blood cells and cytokines. Cytokines are proteins that function as chemical messengers.  Cytokines that increase inflammation are proinflammatory.  Cytokines that decrease inflammation are anti-inflammatory.  We are still learning how the immune system works and why the body sometimes turns against itself.  

Learn Immune system basics by watching these short Immune System Videos.

Cytokines may play a significant role in fatigue caused by Sjogren's.

Fatigue, often profound, impacts 70-80% of people with Sjogren’s (26, 240). Despite fatigue being a top patient concern, few studies have looked at what causes it. Common laboratory markers such as SSA, ESR, CRP, IgG, and hemoglobin do not corelate with fatigue. Disease activity, as measured by the ESSDAI, does not either (152, 204).

Fortunately, research on Sjogren’s fatigue has increased in recent years. We now have convincing evidence that Sjogren’s fatigue is biologically based (88, 152). Sjogren's is not caused by sicca and should not be misattributed to psychological or functional disorders. Fatigue is common in systemic autoimmune diseases, suggesting it could be related to inflammation. Davies et al have identified distinct proinflammatory cytokines that are elevated in Sjogren’s. These cytokines vary with fatigue severity, in a counterintuitive way, as described in the article (204) and immediately below.

The fatigue surprise It is logical to expect that inflammatory cytokines would be increased in Sjogren’s patients with severe fatigue. Research by Davies et al showed the opposite. Inflammatory cytokines were measured in Sjogren’s patients with minimal, mild, moderate, and severe fatigue. The inflammatory cytokines were lowest in the severe fatigue group and highest in the minimal fatigue group (204). The mild and moderate groups landed in the middle, as expected. What does this mean? Could anti-inflammatory processes cause or trigger fatigue? A better understanding of inflammation in Sjogren's could lead to better treatments for fatigue.  

Self-Advocacy Tools

1. Your rheumatologist tells you that Sjogren’s is not an inflammatory disease.

Print the article, Fatigue in primary Sjogren’s syndrome is associated with lower levels of proinflammatory cytokines: a validation study (204).    Circle these sentences in page 1868 (the second page and highlight the last part as illustrated.    “Considering the role cytokines play in the development of the initial inflammatory response, our group postulated that a potentially maladaptive immune response may contribute to the maintenance of persistent fatigue in a chronic inflammatory state as observed in conditions such as Sjogren’s".

2. “Your rheumatologist tells you that Sjogren’s does not cause fatigue, or that it is caused by depression, anxiety, being overweight, fibromyalgia, or functional disorders. Print the article, Fatigue in primary Sjogren’s syndrome is associated with lower levels of proinflammatory cytokines: a validation study (204).   Highlight the 1-paragraph conclusion on page 1871. 


Please read the Handouts for Clinicians page to learn how to share Sjogren’s information with your doctors.

See MYTHS ABOUT SJOGREN’S for other self-advocacy tools.


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