Sjogren's classification criteria serve two main purposes
1.They are used to standardize research populations. In other words, they ensure that everyone enrolled in a study fits the same picture of Sjogren's.
2. They help distinguish similar diseases from each other.
Classification criteria are not diagnostic criteria (77). There are no diagnostic criteria for Sjogren’s.
Because they are strict, people who meet the Classification Criteria are highly likely to have Sjogren's. However, a significant number with Sjogren's will not meet the criteria. When rheumatologists rigidly adhere to the Classification Criteria for making a diagnosis, rather than looking at the entire clinical picture, patients are left undiagnosed and untreated, often for years.
Classification Criteria should not substitute for clinical judgment when diagnosing patients in the clinical setting.
Sjogren’s patients who present with prominent systemic features often do not fulfill the Classification Criteria.
Rheumatologists may be unaware of the limited accuracy of tests and the over-emphasis on sicca features in the Classification Criteria. (36, 77) This leaves many Sjogren’s patients undiagnosed, especially those who present with prominent systemic features (36, 139). It may take years of progression before they meet these criteria.
Many Sjogren's patients do not meet Classification Criteria.
"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
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 examination, 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 (dryness) symptoms may occur without objective measurements of dryness. On the other hand, some patients with measurable dryness may not report feeling dry. Changes in the composition of secretions, inflammation of the salivary and lacrimal glands, and neuropathic pain all contribute to sicca symptoms. These factors are not accounted for in the CC sicca measurements which only measure secretion volume.
About 20% of patients initially present with no obvious sicca manifestations. 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). Better biomarkers are needed that will enable early and accurate diagnosis. The Minor Salivary Gland Biopsy (MSGB), aka "lip biopsy" is the only way to “confirm” a Sjogren's diagnosis in seronegative patients. Yet this test is not always available and requires specialized training for both the procedure and pathology reading. Even in ideal circumstances, it is positive about 80% of the time.
According to Brito-Zeron et al, “Future studies may re-evaluate classification and definition of primary Sjogren’s according to recent evidence about the key role of systemic involvement.” (3)
Each individual test used for Classification Criteria has limitations.
See comments about SS-A (anti-Ro) and the minor salivary gland biopsy (lip biopsy)above.
Unstimulated salivary flow testing is not routinely available in most clinic settings.
Both 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 the severity of sicca. These tests tell you nothing about alterations of the composition of saliva and tears, or the inflammation of the eyes and oral cavity, which are part of Sjogren's sicca.
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.
The ocular staining score (OSS) 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 a normal 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 to 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 often develops slowly. Incomplete presentations are common early in the disease. Sicca may lag behind other manifestations.
Sjogren’s may not be recognized in cases of early organ system or neurological 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 simply because clinicians often assume, incorrectly, that Sjogren’s does not cause systemic disease.
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 SSA, ANA and RF, were all normal. The MSGB (lip biopsy) 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 and did not think I warranted rheumatology care. He reluctantly agreed to follow me when I vehemently insisted.
I soon developed variety of Sjogren's complications, including a parotid gland infection, serositis and increasing painful neuropathy in my feet that I had previously shrugged off. At this point, my rheumatologist labeled me as “Undifferentiated connective tissue disease with features of Sjogren’s.”
2. Diagnosis confirmed by AECG Classification Criteria
In 2009, seven years later, 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 that I no longer had 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 and lip biopsy results.
4. Diagnosis confirmed- yet again. The ACR Classification Criteria were replaced by the 2016 Classification Criteria. Despite no changes in my labs or examination, when the 2016 Criteria replaced the ACR criteria, I once again qualified as a Sjogren’s research subject. I remain seronegative for common autoantibodies to this day.
~ Sarah Schafer, MD and Sjogren's patient
Clinicians, especially rheumatologists, should consider the entire clinical picture, rather than making a diagnosis based on a box-ticking exercise.