The American College of Rheumatology (ACR), in partnership with the European League Against Rheumatism (EULAR), has released its first ever official classification criteria for Sjogren syndrome. The multisystem autoimmune disease has no cure, but can often be treated to improve systems and prevent complications.
There were 11 diagnostic and classification criteria sets developed for Sjögren syndrome between 1965 and 2002, but none of them has received the endorsement of the ACR or EULAR. “The need for international consensus on classification criteria has recently been recognized by the [Sjögren syndrome] scientific community,” wrote the investigators, led by Dr. Caroline Shiboski from the University of California, San Francisco.1
“Well-defined entry criteria and end points that allow measurement of the effect of new treatments are needed for the development of new therapies,” the researchers added.
The working group tasked with developing the new criteria used recently developed and validated disease activity indices for Sjögren syndrome end points: the EULAR SS Patient Reported Index and EULAR SS Disease Activity Index (ESSDAI).2-5 The group used methods for development and validation that closely followed those from previous ACR/EULAR criteria and classification. The objective, the authors noted, was to combine features of previously developed criteria using methods consistent with those accepted by ACR/EULAR.6-9
“Consistent with our goal of producing criteria to aid in recruitment for clinical trials, we focused on primary rather than secondary [Sjögren syndrome],” the investigators wrote. “Patients with the latter,” they added, “would typically not be eligible for experimental treatments for [Sjogren syndrome].”
A total of 52 clinician-experts in Sjögren syndrome participated in surveys to develop a criteria list and weighting for classification of primary Sjögren syndrome. The end result of the working group’s efforts yielded a set of classification criteria for primary Sjögren syndrome “applicable to any patient with at least 1 symptom of ocular or oral dryness (based on American-European Consensus Group [AECG] questions)10 or suspicion of Sjögren syndrome due to systemic features derived from the EULAR ESSDAI measure4 with at least 1 positive domain item.”
Summary and Clinical Applicability
The new ACR/EULAR classification criteria for Sjögren syndrome are based on 5 objective tests/items, with individuals having a score ≥4 being classified as having primary Sjögren syndrome. Classification scoring is outlined in the following table.
Table: ACR/EULAR Classification Criteria: Primary Sjögren Syndrome
The ACR/EULAR classification of primary Sjögren syndrome applies to any individual who: meets the inclusion criteria,* does nothave any conditions listed as exclusion criteria,† and has a score of ≥4 when the weights from the 5 following criteria items aresummed:
|Labial salivary gland with focal lymphocytic sialadenitis and focus score of ≥1 foci/4 mm2‡||3|
|Ocular Staining Score ≥5 (or van Bijsterveld score ≥4) in at least 1 eye§¶||1|
|Schirmer’s test ≤5 mm/5 min in at least 1 eye§||1|
|Unstimulated whole saliva flow rate ≤0.1 mL/min§**||1|
|*Inclusion criteria are applicable to any patient with at least 1 symptom of ocular or oral dryness, defined as a positive response to at least 1 of the following: (1) Have you had daily, persistent, troublesome dry eyes for more than 3 months? (2) Do you have a recurrent sensation of sand or gravel in the eyes? (3) Do you use tear substitutes more than 3 times a day? (4) Have you had a daily feeling of dry mouth for more than 3 months? (5) Do you frequently drink liquids to aid in swallowing dry food? or in whom there is suspicion of Sjögren syndrome from the European League Against Rheumatism SS Disease Activity Index questionnaire (at least 1 domain with a positive item).|
|†Exclusion criteria include prior diagnosis of any of the following, which would exclude diagnosis of Sjögren syndrome and participation in Sjögren syndrome studies or therapeutic trials because of overlapping clinical features or interference with criteria tests: (1) history of head and neck radiation treatment, (2) active hepatitis C infection (with confirmation by PCR), (3) AIDS, (4) sarcoidosis, (5) amyloidosis, (6) graft-versus-host disease, (7) IgG4-related disease.|
|‡Histopathologic examination should be performed by a pathologist with expertise in the diagnosis of focal lymphocytic ialadenitis and focus score count, using the protocol described by Daniels et al.11|
|§Patients who are normally taking anticholinergic drugs should be evaluated for objective signs of salivary hypofunction and ocular dryness after a sufficient interval without these medications in order for these components to be a valid measure of oral and ocular dryness.|
|¶Ocular Staining Score described by Whitcher et al12; van Bijsterveld score described by van Bijsterveld.13|
|**Unstimulated whole saliva flow rate measurement described by Navazesh and Kumar.14|
- The study used expert clinical judgement to define the disease in the absence of an objective gold standard. This limitation “is common to criteria for many rheumatic diseases” the investigators noted, and leads to “the associated effect of the resulting ‘circularity’ on measured performance of criteria sets.”
Dr. Caroline Shiboski has received consulting fees from the Pasteur Institute. Dr. Stephen Shiboski has received royalties from Springer Publishing. Dr. Labetoulle has received consulting fees from Alcon, Allergan, MSD, Sanofi, Santen, and Thea. Dr. Scofield has received consulting fees from UCB and Eli Lilly. Dr. Bowman has received consulting fees from Celgene, Eli Lilly, Glenmark, GlaxoSmithKline, MedImmune, Novartis, Ono, Pfizer, Roche, Takeda, and UCB.
- Shiboski CH, Shiboski SC, Seror R, et al; International Sjögren’s Syndrome Criteria Working Group. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren’s syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017;76(1):9-16. doi: 10.1136/annrheumdis-2016-210571.
- Seror R, Gottenberg JE, Devauchelle-Pensec V, et al. European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index and European League Against Rheumatism Sjögren’s Syndrome Patient-Reported Index: a complete picture of primary Sjögren’s syndrome patients. Arthritis Care Res. 2013;65:1358-1364.
- Seror R, Mariette X, Bowman S, et al. Accurate detection of changes in disease activity in primary Sjögren’s syndrome by the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index. Arthritis Care Res. 2010;62:551-558.
- Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjögren’s Syndrome Disease Activity Index: development of a consensus systemic disease activity index for primary Sjögren’s syndrome. Ann Rheum Dis. 2010;69:1103-1109.
- Seror R, Ravaud P, Mariette X, et al. EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjögren’s syndrome. Ann Rheum Dis. 2011;70:968-972.
- Aletaha D, Neogi T, Silman AJ, III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69:1580-1588.
- Aletaha D, Neogi T, Silman AJ, III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-2581.
- Van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65:2737-2747.
- Van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2013;72:1747-1755.
- Vitali C, Bombardieri S, Jonsson R, et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554-558.
- Daniels TE, Cox D, Shiboski CH, et al. Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjögren’s syndrome among 1,726 registry participants. Arthritis Rheum. 2011;63:2021-2030.
- Whitcher JP, Shiboski CH, Shiboski SC, et al. A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjögren’s Syndrome International Registry. Am J Ophthalmol. 2010;149:405-415.
- Van Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol. 1969;82:10-14.
- Navazesh M, Kumar SK, University of Southern California School of Dentistry. Measuring salivary flow: challenges and opportunities. J Am Dent Assoc. 2008;139(Suppl):35S-40S.