"Published classification criteria are designed for use in clinical trials and not for diagnosing patients in a clinic for general management and treatment. As such, they are very strict so that there is absolutely no doubt that a patient has Sjögren’s, something that is important to prove for participating in a clinical trial. Patients that do not meet these criteria can still have Sjögren’s." ~ The Sjogren's Foundation
Many Sjogren's patients do not meet Classification Criteria.
Classification Criteria are an important tool for standardizing research populations. A significant number of Sjogren’s patients do not meet the 2016 Classification Criteria due to the limitations discussed below. Sjogren’s expert Dr. Frederick Vivino states in his excellent 2017 review article, “Until we have better tests, 'the gold standard' for diagnosis still remains the clinician’s expert opinion.”(2)
+ “lip” biopsy 3
+ SS-A (Ro) 3
+ OSS (ocular staining score) 1
+ Unstimulated salivary flow 1
+ Schirmer’s test 1
2016 Sjogren's Classification Criteria
Total Score ≥ 4 to Classify as Primary Sjogren’s. For detailed exclusions and inclusions, see Criswell, Shiboski, et al. (4)
General Limitations of the 2016 Classification Criteria (CC)
Sjogren’s is a systemic disease with widespread manifestations. The CC are heavily weighted toward sicca, reinforcing the misperception that Sjogren’s is mostly a dryness disease. The CC do not take into account history and physical exam, which often provide important clues to diagnosis. The 2016 criteria are the best we have to date. When interpreting research studies, it is important to keep in mind that they (necessarily) select for a subset of Sjogren’s patients that do not represent all Sjogren's patients.
Sicca symptoms may occur without objective measurements of dryness. On the other hand, some patients with measurable dryness my not report feeling dry. Changes in the composition of secretions, inflammation of the salivary and lacrimal glands, and neuropathic pain also contribute to sicca symptoms. These factors are not accounted for in the CC sicca measurements which only measure secretion volume.
Initial presentation of Sjogren's in about 20 % of patients occurs without sicca symptoms. This is sometimes referred to as “occult Sjogren’s.” Patients in this group often do not meet the Classification Criteria. (3)
The classic Sjogren’s antibody, SS-A, is the only measurement of systemic disease activity included in the 2016 criteria. Yet SS-A is absent in 30 % of Sjogren’s patients, possibly more. (5, 6, 7) Complicating matters further, SS-A can be positive in other autoimmune diseases and in healthy people. (6, 7) We need better biomarkers to diagnose Sjogren’s early and accurately. The Minor Salivary Gland Biopsy (MSGB) is the only way to “confirm” the diagnosis in seronegative patients. Yet this test is not always available, requires specialized training, and is not positive in 10-20% of Sjogren’s patients.
Each individual test used for Classification Criteria has limitations.
See comments about SS-A (anti-Ro) above.
Minor salivary gland biopsy (lip biopsy), is often considered the "gold standard" for diagnosis. It is not always accurate, for a number of reasons that you can read about in the MSGB page.
Unstimulated salivary flow is not routinely available in most clinic settings.
The Schirmer’s test and the unstimulated salivary flow test measure the volume of secretions at a single point in time, as opposed to the amount of tears and saliva produced throughout the day. Patients are typically driest in the evening, not during clinic hours. The amount of secretions may not reflect severity of sicca, which also involves inflammation and changes in the composition of saliva and tears.
Many patients cannot tolerate abstaining from artificial tears prior to their clinic appointment. Recent instillation of these or other eye drops invalidates the Schirmer’s test.
OSS: The ocular staining score measures corneal damage. Milder corneal erosions may heal with newer treatments such as autologous serum eye drops and scleral lenses. Sometimes the cornea heals enough to produce normal a OSS on follow-up, despite an initial positive result. This does not mean that Sjogren's went into remission!
The REAL WORLD IMPACT – What happens when Classification Criteria are used exclusively for diagnosis?
Seronegative patients (usually meaning SS-A negative) tend to have especially long delays in diagnosis, or may never be diagnosed.
Patients who present with an incomplete clinical picture may progress for decades before a Sjogren’s diagnosis is suspected.
Sjogren’s may not be recognized in cases of early organ system or neurologic involvement. Many of these patients have no obvious sicca manifestations early on. They are often misclassified as having other autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus due to the mistaken assumption that Sjogren’s is not serious. Early organ system manifestations are associated with poorer prognosis. For these patients, the stakes are very high. They need Sjogren’s-specific care as early as possible. (3, 23, 36 )
My own story illustrates the problem of relying solely on Classification Criteria for diagnosis:
1. Non-diagnosis despite full blown clinical Sjogren’s
In 2002, despite severe classic symptoms, my initial blood tests, including SS-A, ANA and RF, were all normal. The MSGB showed inflammation, but did not have the correct focus score. Without laboratory confirmation, my rheumatologist did not think I had Sjogren’s or any other autoimmune disease. He suggested a diagnosis of Chronic Fatigue Syndrome.
I soon developed variety of Sjogren's complications, including a parotid gland infection, serositis, and painful neuropathy in my feet. At this point, my rheumatologist treated me for “Undifferentiated connective tissue disease with features of Sjogren’s.”
2. Diagnosis confirmed by AECG Classification Criteria
In 2009, I enrolled in the international SICCA study at UCSF. Sjogren’s was officially confirmed with a positive MSGB, OSS and unstimulated salivary flow.
3. Diagnosis revoked by a Sjogren’s eye researcher
A few years after my official diagnosis, a research optometrist at UCSF declared me free of Sjogren’s based on a normal OSS that day. She insisted that the ACR Classification Criteria currently in use ruled out Sjogren’s, even though she admitted that my autologous serum eye drops probably contributed to my improvement. My rheumatologist agreed that this was absurd given my clinical manifestations.
4. Diagnosis confirmed- yet again. The ACR Classification Criteria were replaced by the 2016 Classification Criteria. Once again, I qualified as a Sjogren’s research subject. I remain seronegative for common autoantibodies to this day.
~ Sarah Schafer
Endnote: Sjogren’s often develops slowly. Incomplete presentations are common early in the disease. Sicca may lag behind other manifestations. Oral sicca may lag ocular sicca, resulting in a negative MSGB despite severe disease. We need tests that can diagnose Sjogren’s early and accurately.
Clinicians, especially rheumatologists, should consider the entire clinical picture, rather than making a diagnosis based on a box-ticking exercise.