Arthritis News > RA & Subclinical Synovitis
RA Patients in Remission May Still Have Subclinical Synovitis
January 2007 – Jon Giles, M.D.
Radiographic progression has been demonstrated in RA patients with no clinical evidence of synovitis on physical examination. This has raised the question of whether joint damage and destruction can occur in the absence of synovitis. However, physical examination for synovitis is insensitive and some RA remission criteria allow patients with some degree of joint swelling to be classified as “in remission”. Here, Brown et al (Arthritis Rheum 2006; 54(12):3761) use sensitive imaging techniques (MRI and ultrasound) to determine the proportion of RA patients classified as “in remission” who demonstrate subclinical synovitis.
RA patients attending outpatient rheumatology clinic at one site (the Leeds General Infirmary) were selected based on their treating rheumatologists’ subjective determination of disease remission. Subjects with subjective remission underwent radiographs of the hands and feet, gray-scale and power Doppler ultrasound of the hand and wrist for determination of synovitis, hyperemia, and tenosynovitis, and MRI of the hand and wrist for determination of synovitis, bone marrow edema, and tenosynovitis. Qualitative and semiquantitative scoring methods were used for ultrasound and MRI measures. Subjects were further classified based on ACR and EULAR remission criteria, and complete remission, defined as the absence of any joints with active synovitis.
107 subjects were deemed to be in clinical remission by their treating rheumatologist. Sixty-six percent of subjects were female with an average age of 56 years and a median RA disease duration of 7 years. The median duration of remission was 22 months. At baseline, 81% of subjects had evidence of erosive disease on plain radiographs. The majority of subjects (92%) were treated with DMARDS, primarily monotherapy with methotrexate or sulfasalazine. Only 5 subjects were currently treated with biologic DMARDs. Although deemed to be in clinical remission, only 55 % of subjects fulfilled ACR criteria for remission, 57% fulfilled EULAR criteria for remission, and only 29% had no tender or swollen joints. Twenty-five subjects (23%) had a DAS28 score of 3.2 or higher, indicating moderate to high disease activity. Using ultrasound, 84.9% of subjects demonstrated evidence of synovitis and 60.4% demonstrated evidence of hyperemia. Most (82%) of synovitis detected by ultrasound was graded as mild. There was no statistical difference in the proportion of subjects with ultrasound evidence of synovitis between subjects with and without remission based on both EULAR and ACR criteria. The prevalence of ultrasonographic synovitis in subjects with no swollen or tender joints was 73.3% compared to 89.5% in those with any swollen or tender joints (p = 0.037).
However, there was no significant difference in the presence of hyperemia or tenosynovitis, as measured by ultrasound, between subjects with no swollen or tender joints and those with any joint symptoms.
Using MRI, 92.6% of subjects demonstrated evidence of synovitis and 55.2% demonstrated evidence of bone marrow edema. Most (69%) of synovitis detected by MRI was graded as mild. There was no statistical difference in the proportion of subjects with MRI evidence of synovitis between subjects with and without remission based on both EULAR and ACR criteria. Likewise, there was no significant difference in the prevalence of synovitis or bone marrow edema in subjects with no swollen or tender joints compared to those with any active joints. However, there was a significant difference in MRI detected tenosynovitis in subjects with no swollen or tender joints (8.0%) compared to subjects with any active joints (48.5%); p = <0.001).
Seventeen sex-matched control subjects also underwent MRI scanning in the same manner as the RA subjects. Of these, three (18%) demonstrated evidence of synovitis and one subject had evidence of tenosynovitis. None of the control subjects demonstrated evidence of bone marrow edema.
Subclinical synovitis is common in subjects deemed to be in clinical remission, even when the most stringent clinical remission criteria are utilized.
This study highlights the insensitivity of clinical examination for the detection of active RA. Previous anecdotal reports of progressive articular damage despite clinical remission suggested that damage could occur in the absence of synovitis in a subset of RA patients. This study helps to re-establish the premise that damage is unlikely in the absence of synovitis.
Despite the high prevalence of active synovitis observed, it should be noted that, in general, the degree of inflammation detected was mild. Because ultrasound and MRI are very sensitive methods for detecting articular inflammation, it remains to be determined whether there is a threshold level of synovitis that can be tolerated without the risk of subsequent articular damage. This issue will undoubtedly be addressed in follow-up of this prospective cohort. Until then, it is still not clear whether the complete elimination of ultrasound or MRI detected synovitis should be the ultimate goal of RA therapy.
As a final thought, it is interesting to note that the subjective assessment of RA remission within this clinic-based cohort is much less stringent that established criteria, particularly as almost one quarter of subjects referred to the study as in “remission” actually had moderate to high disease activity based on the DAS28 criteria. This should be taken into consideration when interpreting studies in which providers’ assessments of disease activity are used instead of formal disease activity measures.