Updated 04-21-2024 There is no single “Sjogren’s test”. SSA is just one of many tests that is used to support a Sjogren’s diagnosis.
If a rheumatologist suspects that a patient has Sjogren's based on their signs and symptoms, they will typically order a blood test for SSA as a first step. If the test comes back positive for SSA, they usually arrive at a diagnosis of Sjogren’s. If the test comes back negative for SSA, some rheumatologists do more testing. Others stop the evaluation and do not arrange for other tests that could help them diagnose Sjogren’s.
A negative SSA does not rule out Sjogren’s (6, 79, 164). SSA-negative (seronegative*) Sjogren’s is real and is just as important to diagnose and treat as SSA-positive Sjogren’s.
At least one third of people with Sjogren’s test negative for SSA (seronegative Sjogren’s*) so it is inappropriate for a clinician to tell you that you do not have Sjogren’s just because you do not have a positive blood test for SSA (6, 20, 118, 139). Some people who present with systemic features of Sjogren’s, especially neurological ones, are more likely to be SSA-negative. Scroll down to the bottom of the page for self-advocacy tools.
Note: This blog post is the comprehensive version of Myth # 2 of MYTHS ABOUT DIAGNOSIS. It goes into detail about the use and misuse of SSA for diagnosing Sjogren’s and why there is so much confusion about this test.
*Seronegative Sjogren’s usually means SSA-negative Sjogren’s when it is used in the medical literature. This is how it is used on Sjogren’s Advocate. Because clinicians use this term inconsistently (see “Seronegative Sjogren’s” in the Glossary), you need to ask your clinician what they mean when they use this term.
Introduction To Diagnosis tells you why it is important to diagnose Sjogren’s.
SSA antibodies are helpful for diagnosing Sjogren’s, but they have some limitations.
SSA (and SSB) are not specific to Sjogren’s.
SSA (and SSB) antibodies are referred to as “Sjogren’s antibodies”. This is a misleading term because SSA (and SSB) may be found in other diseases such as systemic lupus erythematosus (SLE) and myositis and, occasionally, in healthy individuals (6, 84).
Thirty to fifty percent (30-50%) of people with Sjogren’s do not have a positive blood test for SSA.
Some clinicians tell patients that they tested “positive or negative for Sjogren’s”, based on the blood test for SSA. A positive SSA is just one factor that should be considered in a Sjogren’s diagnosis.
“Unfortunately, at the present time, there are no diagnostic tests that have high enough sensitivity and specificity to be used as standalone diagnostic studies in SS. Therefore, a comprehensive evaluation with multiple parameters is recommended.” (79)
SSA and SSB are not the only autoantibodies found in Sjogren’s.
Other autoantibodies and biomarkers (118, 119, 164) are increasingly being recognized in Sjogren’s, which should eventually reduce confusion around diagnosis. More accurate diagnostic tests will be helpful to identify Sjogren’s in people with systemic (non-sicca) presentations, especially neurological, which are less likely to be SSA-positive (184, 202).
The role of SSA in Sjogren’s is unclear, other than as a useful biomarker (indicator) for diagnosis. More research is needed to understand the full role of SSA antibodies and other biomarkers in Sjogren’s. See Do You Have Antibodies? to learn more.
These are the main reasons why rheumatologists over-emphasize the role of SSA in Sjogren’s diagnosis...
1. It is convenient to use only SSA to diagnose Sjogren’s.
SSA is a simple, low-cost blood test. The other standard diagnostic tools for Sjogren’s include tests for eye and oral sicca (dryness), and the lip biopsy. These tests are time-consuming and usually require referrals to specialists. Like every diagnostic test for Sjogren’s, sicca tests and the lip biopsy can have false negative results, especially early in the disease, before glandular damage has progressed enough. Many SSA-negative people with Sjogren’s are never referred for further testing even when they have obvious sicca (79). SSA-negative Sjogren's is real and is important to diagnose.
2. Rheumatologists have historically used SSA (and to a lesser extent, SSB) to diagnose Sjogren’s. It is human nature to favor that which is familiar and/or traditional.
There is a common bias in rheumatology where rheumatologists would rather miss many seronegative cases of a disease than risk misdiagnosing even a few people with it. This is exactly what happens in Sjogren’s. Most people with Sjogren’s are undiagnosed, partially because of this bias. This is especially true of people who are SSA-negative. It is rare to hear stories of people who were mistakenly diagnosed with Sjogren’s when they actually had another condition. I have heard hundreds of stories of extreme delays to diagnosis in Sjogren’s patients, but only one story about someone who was mistakenly diagnosed with Sjogren’s. Seronegative Sjogren’s is readily overlooked by clinicians, partly because they want to see blood tests that “prove” autoimmunity. Using SSA as a single test to rule Sjogren’s in or out is inappropriate because it leaves many people with Sjogren’s undiagnosed (79, 153).
3. There is a misperception among rheumatologists that seronegative (SSA negative) Sjogren’s is uncommon.
Most academic articles state that 30 % (1 in 3) of Sjogren’s patients are SSA negative. Although 30% is a substantial number, it is probably an undercount because it is based on people with Sjogren’s who are fortunate enough to get diagnosed. Because SSA-negative people with Sjogren’s are less likely to be diagnosed, the true number of people with seronegative Sjogren’s (actual prevalence) is underestimated.
4. Many rheumatologists believe that seronegative Sjogren’s is a mild version of the disease, mostly limited to sicca. This outdated idea is not supported by current evidence, as explained on the blog post, DO YOU HAVE ANTIBODIES?
When clinicians do not take seronegative Sjogren’s seriously, they are less likely to diagnose the disease. Some refuse to diagnose seronegative Sjogren’s at all, telling patients that seronegative Sjogren’s is not “real” Sjogren’s, or that it is not important to diagnose because it is the “mild, sicca version” of the disease. Sicca is important, but Sjogren’s Is More Than “Just Sicca”.
5. While some rheumatologists believe that SSA antibodies are essential to the development and progression of Sjogren's disease, there is limited evidence to support this claim. This belief also ignores the many people with Sjogren's who do not have SSA antibodies.
While SSA appears to play a role in the disease process for some patients, it is unclear exactly what it does or how it fits into the multitude of immune system changes that lead to Sjogren’s (118, 243). The underlying causes of Sjogren’s are complex and not fully understood (79, 118, 243). When rheumatologists think that SSA is critical to the development of Sjogren’s, they tend to downplay SSA-negative Sjogren’s, or deny that it even exists. “The positivity for anti-SSA/SSB is genetically determined and a previous study showed that their quantitative levels were not associated with extraglandular involvement.” (118) The role of SSA in Sjogren’s is unclear, other than as a useful biomarker (indicator) for diagnosis.
Self-Advocacy tools
If you are told you can't have Sjogren's because you don't have SSA, there are many tools you can share with your doctor that refute this myths.
1. See Why is it so hard to diagnose Sjogren's? to learn how to use the Sjogren's Foundation Diagnosis handout for self-advocacy.
2. Print "I have anti-SSA (Ro) and anti-SSB (La) antibodies. Does it mean I have Sjogren's Disease?" from Dr. Brandon Law’s website, Beyond Dryness.
Highlight: “Additionally, the absence of these antibodies does not rule out the possibility of Sjögren's Disease. These antibodies can be found in some healthy individuals as well. In order to reach a diagnosis, it is important to note that a positive blood test alone is not sufficient. Additional testing and evaluation by a rheumatologist are necessary.” 3. Print the abstract of “Clinical and serological characteristics of seronegative primary Sjogren’s syndrome: a comparative study” (139) and highlight these sentences: “The current classification criteria for pSS should not be used in the diagnosis of seronegative pSS, as the agreement between the different sets of criteria was low, and some patients fell outside the classification. Further clinical and laboratory studies are needed to identify the features that distinguish seronegative pSS.”
4. If you have neurological features and suspect that you may have Sjogren’s but your SSA test is negative, print “Neuro-Sjogren: Peripheral Neuropathy With Limb Weakness in Sjogren’s Syndrome” (202).
Circle the entire section on page 7 titled, “Diagnostic Tools for Evaluation of Neuro-Sjogren” and highlight:
“Anti-SSA(Ro)-antibodies were present in only 48% of our patients. The other 52% of patients were diagnosed with Sjogren’s’ syndrome based on sufficient sialadenitis on minor salivary gland biopsy. Antibody status alone is therefore no criterion to rule out Sjogren’s syndrome.”
5. DO YOU HAVE ANTIBODIES? has more self-advocacy resources.
6. Print out this page from the Sjogren's Foundation blog post, The Difficult to Diagnose Sjogren's Patient. Circle the second paragraph and highlight these sentences:
“Up to 40% of patients are not positive for anti-SSA and are seen as “seronegative,” making diagnosis harder.” “And all patients, whether “seropositive” or “seronegative”, are at risk for serious disease and deserve quality care!”
7. For more self-advocacy tools, see MYTHS ABOUT SJOGREN'S and MYTHS ABOUT DIAGNOSIS.
