Classification criteria are created in an attempt to produce a homogenous group of subjects with rheumatoid arthritis (RA) who can be used for clinical and basic research. The 1987 revised criteria lead to improved performance and more confidence in correct classification compared with the 1958 criteria. As therapies were introduced and early, aggressive approaches to RA management became common, there was a growing need for clinical trials focusing on early RA. The 2010 criteria were created to facilitate study of subjects at earlier stages in the disease. This article reviews the diagnostic performance of the 2010 criteria.
The classification criteria for rheumatoid arthritis (RA) have undergone a substantial evolution since the 1950s.
The 1987 revised criteria for rheumatoid arthritis (RA) lead to improved performance and more confidence in correct classification compared with the 1958 criteria.
The 2010 criteria were created with a focus to facilitate study of subjects at earlier stages in the disease.
The data show that the new 2010 American College of Rheumatology-European League Against Rheumatism criteria identify patients with RA at an earlier point in their disease course.
The new 2010 criteria create a more heterogeneous group of patients now classified as having RA, including patients with self-limiting disease or other arthritides, and can lead to overtreatment.
Introduction and historical perspective
In the past two decades the identification and management of rheumatoid arthritis (RA) has changed multiple times. Gone are the days of managing end-stage joints and long-term prednisone use complications. Now, early, almost subclinical, identification of RA is sought out and aggressive combination therapy is the norm. RA is a chronic systemic autoimmune disorder that leads to synovial inflammation, progressive joint erosions, and eventual disability. The American Rheumatism Association (ARA), the precursor to the American College of Rheumatology (ACR), first proposed classification criteria for RA in 1956. Eleven criteria with 19 exclusions were proposed and resulted in three categories: definite, probable, and possible RA. Two years later, in an effort to increase specificity, the ARA added the category classic RA, further complicating matters. These criteria were developed from the experiences of five committee members, review of recent epidemiologic data at that time, and analysis of 332 cases provided by interested physicians from around the United States and Canada. In 1966, the New York Criteria were developed at the Third International Symposium on Populations Studies of the Rheumatic Disease. The New York Criteria were more specific; however, they were also more cumbersome and never gained wide acceptance. The 1956 classification criteria were used for almost 30 years, standardizing the vocabulary and allowing research results to be more easily compared. The criteria helped foster better communication between physicians and enabled more effective teaching. The use of the 1956 classification criteria was generally supported; however, there were some observed problems. In practice there was little difference between definite and classic RA and many patients who were labeled probable RA were ultimately found to have a different disease. The various exclusions were though to be burdensome and three of the criteria required invasive procedures, such as mucin clot, nodule biopsy, and synovial biopsy.
Almost 30 years later, the clinical and biochemical knowledge of RA has expanded exponentially. The shortcomings of the 1956 diagnostic criteria became apparent and the criteria were viewed as old-fashioned. The ARA again appointed a subcommittee of the Diagnostic and Therapeutic Criteria to review and revise the criteria. Subjects with RA, as well as subjects without RA (controls), were studied and the then-current ARA classification criteria were dissected. Numerous disease discriminators were studied, such as morning stiffness, pain and swelling of various joints, nodules, and laboratory and radiographic findings, and their sensitivity and specificity were calculated. Shortly thereafter, the 1987 revised criteria were established. The revisions kept five of the original 1958 ARA criteria and provided more precise definitions for several others ( Table 1 ). The explicit definitions of criteria that were provided lead to improved performance and ultimately more confidence in a correct classification. These new criteria performed better than both the 1958 ARA and the New York Criteria and simplified classification because it eliminated the need for extensive radiographs and invasive procedures. The classification subcategories were dropped and definite and classic RA were relabeled as simply RA. The term probable RA was exchanged for terms such as undifferentiated polyarthritis, undifferentiated oligoarthritis, or undifferentiated monoarthritis, and the lengthy list of exclusions, previously part of the 1958 criteria, was dropped. Although it was debated that this might lead to misclassification of patients with other diseases, such as systemic lupus erythematosus, polymyalgia rheumatica, Sjögren syndrome, and HLA-B27–associated spondyloarthropathy, the advantage to eliminating this onerous list was felt to outweigh this possible risk.
|Morning stiffness in and around joints for at least 1 h||Morning stiffness|
|Soft tissue joint swelling observed by physician in at least 3/14 joint groups (Right or left: MCP, PIP, wrist, elbow, knee, ankle, MTP)||Swelling of a joint|
|Symmetric swelling of one joint area||Swelling of another joint|
|Rheumatoid nodule||Pain on movement or tenderness in a joint|
|Rheumatoid factor by method positive in <5% normal population||Symmetric swelling|
|Radiographic changes in wrist or hands: erosions or juxtaarticular osteoporosis||Rheumatoid nodule|
|RA: 4/7||Classical RA: 7/11 |
Definite RA: 5/11
Probable RA: 3/11
A new age
Another 20 years passed and, again, rheumatologists found themselves dealing with out-of-date classification criteria. Although the 1987 criteria were not meant to be used for diagnosis, in the rheumatology community these criteria were largely deemed the gold standard for the diagnosis of RA. In the past two decades, rheumatologists again had an exponential growth in their knowledge of RA. Studies emerged, highlighting the effectiveness of early, aggressive, combination therapy. For the first time, remission of disease was a realistic therapeutic goal and the need to uniformly identify patients in the earliest stage became imperative. Korpela and colleagues with the FIN-RACo (Finnish Rheumatoid Arthritis Combination Therapy) Trial Group found that aggressive initial treatment with methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone resulted in more rates of remission and less peripheral joint radiographic damage when compared with disease-modifying antirheumatic drug (DMARD) monotherapy. This group found that aggressive treatment early in a subject’s course was key. Verstappen and colleagues confirmed this idea with the CAMERA (Computer Assisted Management in Early Rheumatoid Arthritis) trial. This group demonstrated intensive treatment in early RA (<1 year) resulted in higher rates of remission when compared with more conventional treatment. Verstappen and colleagues used frequent visits and standardized criteria to aggressively titrate medications early in the disease course and found this resulted in lower inflammatory markers and decreased morning stiffness and tender and swollen joints. The BeST (Behandel-Strategieën) Study challenged previous paradigms of treatment algorithms by evaluating the effectiveness of four different treatment strategies: sequential DMARD monotherapy, step-up combination therapy, initial combination therapy with tapered high-dose prednisone, and initial combination therapy with the tumor necrosis factor antagonist infliximab. Goekoop-Ruiterman and colleagues found that initial combination therapy, with either prednisolone or infliximab, was superior to monotherapy and the step-up combination treatment strategy in function and Health Assessment Questionnaire scores. These studies, and others, emphasized the idea of a window of opportunity to drastically alter the course of the disease for a patient with aggressive, early therapy.
As in 1983, at the beginning of the new millennium the pitfalls of the 1987 ARA classification criteria were becoming apparent. One pitfall was that early disease was often not appropriately identified. From France, Saraux and colleagues evaluated at the ability of the 1987 criteria to correctly predict the diagnosis of RA in a cohort of subjects with arthritis followed for 2 years. Using the opinion of a panel of five rheumatologists as the gold standard of an RA diagnosis, they evaluated the specificity and sensitivity of the 1987 criteria at a subject’s initial visit as well as 2 years later. They found that the 1987 criteria were not as effective at predicting a diagnosis of RA 2 years later, thus making these criteria limited in identifying early disease. They further evaluated each criterion and how well it performed ( Table 2 ). Not surprisingly, criteria such as rheumatoid nodules and radiographic changes had a low sensitivity but high specificity for the diagnosis of RA at the initial visit. This was not unexpected because many patients do not exhibit these findings early in their disease course.
|Classification criteria for RA (score-based algorithm: add score of categories A-D; a score of ≥6/10 is needed for classification of a patient as having definite RA) c||—|
|A. Joint involvement d|
|1 large joint e||0|
|2−10 large joints||1|
|1−3 small joints (with or without involvement of large joints) f||2|
|4−10 small joints (with or without involvement of large joints)||3|
|>10 joints (at least 1 small joint) g||5|
|B. Serology (at least 1 test result is needed for classification) h|
|Negative RF and negative ACPA||0|
|Low-positive RF or low-positive ACPA||2|
|High-positive RF or high-positive ACPA||3|
|C. Acute-phase reactants (at least 1 test result is needed for classification) i|
|Normal CRP and normal ESR 0||0|
|Abnormal CRP or normal ESR 1||1|
|D. Duration of symptoms j|
a The criteria are aimed at classification of newly presenting patients. In addition, patients with erosive disease typical of RA with a history compatible with prior fulfillment of the 2010 criteria should be classified as having RA. Patients with long-standing disease, including those whose disease is inactive (with or without treatment) who, based on retrospectively available data, have previously fulfilled the 2010 criteria should be classified as having RA.
b Differential diagnoses differ in patients with different presentations, but may include conditions such as systemic lupus erythematosus, psoriatic arthritis, and gout. If it is unclear about the relevant differential diagnoses to consider, an expert rheumatologist should be consulted.
c Although patients with a score of less than 6 out of 10 are not classifiable as having RA, their status can be reassessed and the criteria might be fulfilled cumulatively over time.
d Any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis. Distal interphalangeal joints, first carpometacarpal joints and first metatarsophalangeal joints are excluded from assessment. Categories of joint distribution are classified according to the location and number of involved joints, with placement into the highest category possible based on the pattern of joint involvement.
e Shoulders, elbows, hips, knees and ankles.
f The metacarpophalangeal joints, proximal interphalangeal joints, second to fifth metatarsophalangeal joints, thumb interphalangeal joints and wrists.
g At least one of the involved joints must be a small joint; the other joints can include any combination of large and additional small joints, as well as other joints not specifically listed elsewhere (eg, temporomandibular, acromioclavicular, sternoclavicular).
h International unit (IU) values that are less than or equal to the upper limit of normal (ULN) for the laboratory and assay. Low-positive are IU values that are higher than the ULN but three or less times the ULN for the laboratory and assay. High positive are IU values that are more than three times the ULN for the laboratory and assay. When rheumatoid factor (RF) information is only available as positive or negative, a positive result should be scored as low-positive for RF.
i Normal or abnormal is determined by local laboratory standards.
j Patient self-report of the duration of signs or symptoms of synovitis (eg, pain, swelling, tenderness) of joints that are clinically involved at the time of assessment, regardless of treatment status.