This blog post explains why Sjogren’s patients should be monitored for C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and why these inflammatory markers are frequently misinterpreted in Sjogren’s.
CRP and ESR are non-specific biomarkers for inflammation that can be measured with a blood test. An elevated CRP or ESR means there is inflammation somewhere in the body; it can be localized or generalized. In Sjogren’s, CRP and ESR do not rise and fall with disease activity or overall inflammation (152) like they often do in rheumatoid arthritis. If you have Sjogren’s, low levels of CRP and/or ESR do not mean that your disease is mild or does not need treatment. As explained in Part I, people with Sjogren’s have systemic inflammation even when CRP and ESR are normal.
CRP and/or ESR levels do not tell you how sick you are. The only way to determine the extent and severity of Sjogren’s is through ongoing monitoring of multiple organs and systems in the body. This should be done in EVERY Sjogren’s patient, regardless of symptoms, CRP levels, ESR levels, or SSA/SSB status.
ESR and CRP levels should not be used as a general guide to Sjogren’s treatment, such as deciding whether to use hydroxychloroquine, methotrexate, or other systemic treatments because: 1. decreased or normal CRP or ESR do not mean your Sjogren’s is mild or in remission, 2. people with Sjogren’s can have high disease activity or inflammation with a normal CRP or ESR, and 3. people with Sjogren’s can have serious systemic manifestations despite having a normal CRP and ESR. For example, I have never had elevated CRP or ESR despite having debilitating systemic Sjogren’s manifestations such as longstanding small fiber neuropathy, dysautonomia (POTS), extreme fatigue, and inflammatory arthritis (not osteoarthritis). Special Considerations
CRP and ESR levels are usually elevated in vasculitis (214, p. 355) and systemic eye disease (unrelated to dry eye) (156), which are uncommon, but serious systemic manifestations of Sjogren's. Doctors use multiple tools, including ESR and CRP, to diagnose and monitor treatment of these conditions.
ESR may be elevated in people with other systemic manifestations such as interstitial lung disease or kidney disease, but this test does not play a central role in diagnosing or monitoring these conditions.
C-Reactive Protein (CRP)
What is CRP and how is it related to Sjogren’s? CRP is a protein in the blood that is elevated when an inflammatory process is occurring in your body. It does not indicate what that process is or where it is happening. In Sjogren's, myositis, and systemic lupus erythematosus, CRP is not an indicator of systemic inflammation triggered by these specific diseases, even though it often reflects such processes in other rheumatic diseases (261).
Why should CRP be a part of routine monitoring in Sjogren’s? 1. An elevated CRP usually indicates that another disease is present. This should trigger investigation for other causes, such as infection or a second rheumatic/ inflammatory disease (42). 2. People with Sjogren’s often have immune comorbidities that may be associated with elevated CRP, such as rheumatoid arthritis, polymyalgia rheumatica, and spondylitis.
MYTHS ABOUT CRP and Sjogren’s CRP Myth 1: A normal CRP level indicates low Sjogren’s disease activity and inflammation.
Reality: CRP levels do not reflect overall inflammation caused by Sjogren’s.
There is no association of CRP with disease activity (261) or fatigue (152). CRP Myth 2: A high CRP level indicates high Sjogren’s disease activity and inflammation.
Reality: A high CRP rarely indicates high Sjogren’s disease activity and inflammation.
A high CRP should trigger investigation for other causes of inflammation such as infection or a second rheumatic/inflammatory disease.
Self-advocacy tool for CRP Myths 1 and 2
Print the article, The Complex Role of C-Reactive Protein in Systemic Lupus Erythematosus (261). Highlight this sentence in the abstract to show that CRP does not correlate with inflammation in Sjogren’s, “Autoimmune diseases characterized by the Type I interferon gene signature (e.g., systemic lupus erythematosus, primary Sjogren’s syndrome and inflammatory myopathies) represent exceptions to the general rule that the concentration of CRP correlates with the extent and severity of inflammation.” (261)
Erythrocyte Sedimentation Rate (ESR)
What is ESR and how is it related to Sjogren’s?
Unlike CRP, 20%-40% of people with Sjogren’s have an elevated ESR caused by Sjogren’s- related immune system dysfunction. However, just like CRP, ESR does not reflect overall disease activity or inflammation. Elevated ESR in Sjogren’s is usually caused by overactive B cells producing excessive antibodies, causing a high ESR (24, 214, p. 174). These antibodies (immune globulins) are measured using blood tests such as IgG levels.
Why should ESR be a part of routine monitoring in Sjogren’s?
1. An elevated ESR should prompt testing for immune globulin levels. High immune globulin levels are one of several risk factors for severe systemic disease.
2. An elevated ESR may indicate that another disease is present. Like CRP, a high ESR may indicate infection, a second rheumatic or inflammatory disease, or other diseases.
MYTHS about ESR and Sjogren’s
Unfortunately, the only scientific papers/clinical studies I could find for Sjogren’s and ESR that were suitable for use as self-advocacy tools were behind a paywall or too technical and complex for most readers.
ESR Myth 1: A normal ESR indicates low Sjogren’s disease activity and inflammation.
Reality: There is no association of ESR with overall disease activity or fatigue (152) in Sjogren’s.
Normal or falling ESR levels do not mean you are in remission. People with Sjogren’s can have high disease activity with a normal ESR. In fact, people with systemic Sjogren’s manifestations such as lung disease, inflammatory arthritis, Raynaud’s, and peripheral neuropathies often have a normal ESR.
ESR Myth 2: An elevated ESR level indicates high Sjogren’s disease activity and inflammation.
Reality: An elevated high ESR in Sjogren’s is usually associated specifically with high immune globulin levels, not overall inflammation.
Increased ESR levels do not mean you are having a flare of your Sjogren’s overall. However, increasing ESR levels should prompt further investigation for infection, a second immune/inflammatory disease, or other conditions, in addition to checking for high IgG levels.
