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Abstract
OBJECTIVES By repeated magnetic resonance imaging (MRI) to study synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) and other (non-RA) causes of persistent knee joint synovitis.
METHODS Contrast enhanced MRI was performed in 15 knees (nine RA, six non-RA) before and one day, seven days, two months, and 12 months after arthroscopic synovectomy. Synovial membrane volumes, joint effusion volumes, and cartilage and bone destruction were assessed on each MRI set. Baseline microscopic and macroscopic assessments of synovitis and baseline and follow up standard clinical and biochemical examinations were available.
RESULTS Synovial membrane and joint fluid volumes were significantly reduced two and 12 months after synovectomy. However, MRI signs of recurrent synovitis were already present in most knees at two months. No significant differences between volumes in RA and non-RA knees were seen. Synovial membrane volumes at two months were significantly inversely correlated with the duration of clinical remission, for all knees considered together (Spearman's correlationr s=−0.67; p<0.05), for RA knees (r s=−0.76; p<0.05), and for non-RA knees (r s=−0.83; p<0.05). Baseline volumes were not significantly correlated with clinical outcome. Only three knees (all RA) showed erosive progression. The rate of erosive progression was not correlated with MRI volumes or with clinical or biochemical parameters.
CONCLUSION The synovial membrane had regenerated two months after arthroscopic knee joint synovectomy and despite significant volume reductions compared with baseline it often showed signs of recurrent synovitis. MRI seems to be valuable as a marker of inflammation, destruction and, perhaps, as a predictor of therapeutic outcome in arthritis.
- magnetic resonance imaging
- synovitis
- arthroscopy
- rheumatoid arthritis
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Arthroscopic synovectomy is an accepted therapeutic option in knee joint synovitis resistant to treatment. Clinical efficacy data vary, but are generally encouraging, with clinical remission or marked improvement in most patients after two years.1-7
However, longitudinal studies, which with sensitive methods follow the regeneration of the synovium and analyse the timing and frequency of recurrent synovial inflammation and its relation to progressive bone destruction, are lacking, probably mainly owing to the lack of non-invasive follow up methods.
Magnetic resonance imaging (MRI) allows reliable estimation of volumes of inflamed synovial membrane in arthritic knee joints.8-11 Furthermore, MRI visualises destructive bone changes better than conventional radiography.12-15
The aim of the present investigation was, by performing repeated MRI, to study synovial regeneration and the recurrence of synovitis after arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) and other (non-RA) causes of persistent knee joint synovitis. Furthermore, we attempted to assess whether MRI signs of synovitis were related to subsequent erosive progression or clinical outcome, or both.
Material and methods
PATIENTS
Fifteen knees of 12 patients scheduled for arthroscopic synovectomy were included. The underlying disease was RA (American College of Rheumatology 1987 criteria16) in nine knees (seven patients), while six knees (five patients) had other (non-RA) causes of persistent arthritis (juvenile RA: two knees (one patient), unspecified monarthritis: three knees; osteoarthritis: one knee). Table1 shows baseline patient characteristics.
Baseline data. Values are medians (ranges in parentheses). NS indicates no significant difference
CLINICAL PROCEDURE
MRI, standard blood tests (including serum C reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), and a clinical examination (including assessment of swelling and tenderness of the treated joint and swollen and tender joint counts) were obtained before surgery, and one day, seven days, two months, and 12 months after surgery. Clinical relapse was diagnosed, if clinical knee joint swelling recurred.
SURGICAL PROCEDURE
Firstly, at four preselected sites, macroscopic signs of synovitis were graded (grade 0–3: none, mild, moderate, severe) and synovial biopsy specimens were obtained. The synovial membrane biopsy specimens were graded similarly by a histopathologist for histological signs of synovitis. Details of the methods for macroscopic and histological grading of synovitis are described by Østergaardet al.11 Secondly, as much synovium as possible was removed by a synovial resector, equipped with a suction device, through three to four portals (anteromedially, anterolaterally, and one to two portals in the suprapatellar recess).
MRI
Continuous transversal and sagittal T1 weighted spin echo MR images (TR/TE/slice thickness = 500–750 ms/15–17 ms/5 mm) were obtained on a 1.5 Tesla Siemens (Erlangen, Germany) Magnetom before and after intravenous injection of 0.05 mmol gadolinium-DTPA (Schering, Berlin, Germany)/kg body weight (fig 1).
Transversal T1 weighted spin echo magnetic resonance images through the suprapatellar recess. (A, B) Before arthroscopic synovectomy, (A) before and (B) after intravenous injection of Gd-DTPA. After intravenous Gd-DTPA the signal intensity of the synovial membrane (outlined) has increased markedly, while the joint fluid remains dark grey. MRI determined synovial membrane and joint fluid volumes were 177 cm3 and 173 cm3, respectively. (C, D) Corresponding images two months after arthroscopic synovectomy, showing regeneration of the synovial membrane and, despite markedly decreased signs of joint inflammation, some synovitis and joint effusion (volumes 45 cm3 and 12 cm3, respectively).
MRI ASSESSMENT OF SYNOVIAL MEMBRANE AND JOINT FLUID VOLUMES
By means of image processing software, the synovial membrane and the joint fluid of each transverse MRI slice were outlined and the areas automatically calculated. Total volumes of synovial membrane and joint fluid were calculated by summation of slices. Methodological details have been described by Østergaardet al.9 ,11
MRI ASSESSMENT OF CARTILAGE AND BONE EROSIONS
Each of six regions was graded as follows: 0 = no erosions; 1 = non-penetrating pannus-induced cartilage erosions; 2 = penetrating pannus-induced cartilage erosions; 3 = presence of bone erosions. An erosion score, calculated as the sum of the gradings, was calculated. Methodological details have been described by Østergaardet al.15 ,17
STATISTICAL METHODS
Non-parametric methods were used for statistical analysis. The Mann-Whitney test (two sample rank sum test) was used to analyse differences between groups of patients and the Wilcoxon-Pratt test (one sample signed rank sum test) to analyse changes within the patient. Analysis of statistical correlation was performed by the Spearman test of rank correlation.
Results
Table 1 shows baseline data. MR images obtained at one and seven days after surgery were characterised by massive amounts of intra-articular debris, effusion, and bleeding, and diffuse enhancement from the periphery of the joint cavity was seen. As a consequence, only results from baseline and months 2 and 12 are reported.
At baseline, median synovial membrane volumes were 59 cm3(range 46–128) in RA knees and 66 cm3 (range 21–177) in non-RA knees. Volumes of membrane and fluid were significantly reduced after two months and 12 months, compared with baseline (table2). However, considerable amounts of synovium (two months: median 49 cm3 (range 18–86)) and effusion (two months: median 18 cm3 (range 3–49)) were still present. No significant differences between volumes in RA and non-RA knees were seen at any time.
Synovial membrane and joint fluid volumes after arthroscopic synovectomy. Values are medians (ranges in parentheses). NS indicates no significant difference
Synovial membrane volumes at month 2 were significantly inversely correlated with the duration of clinical remission for all knees considered together (r s=−0.67; p<0.05), RA knees (r s=−0.76; p<0.05), and non-RA knees (r s=−0.83; p<0.05). Baseline volumes were not significantly correlated with clinical outcome.
Only three knees (two patients, both with RA) showed erosive progression. The rate of erosive progression was not statistically correlated with synovial membrane or effusion volumes or with clinical or biochemical parameters.
Discussion
This study introduces follow up of synovial regeneration, recurrence of synovitis, and erosive progression after arthroscopic synovectomy in arthritic knees by means of the best currently available non-invasive technique, MRI.
Volumes of synovium and joint fluid decreased after arthroscopic synovectomy, in accordance with a study by Fioccoet al,18 which reported reduced synovial membrane thickness and joint effusion two months after knee joint arthroscopic synovectomy, when assessed by ultrasonography. On the other hand, a considerable amount of inflamed synovium was found in many knees at both two and 12 months after synovectomy (table 2), indicating that the synovium quickly regenerates and that recurrence of some degree of synovitis after a few months is common.
Images from days 1 and 7 could not be properly interpreted owing to post-surgical changes. Thus no imaging evidence of the completeness of synovectomies was available. However, at least in the most accessible areas such as the suprapatellar and parapatellar recesses, there is no doubt that all the synovium was removed. Also, in these areas, synovitis was commonly found at two months, verifying the occurrence of regeneration of synovium and recurrence of synovitis.
An inverse correlation between synovial membrane volumes at month 2 and the duration of clinical remission was found, suggesting a prognostic value of MRI for treatment outcome. A previous study showed a correlation between pretreatment synovial membrane volumes determined by MRI and the duration of clinical remission in RA knees treated with intra-articular corticosteroid.17 A relation between pretreatment MRI signs of synovitis and the rate of subsequent erosive progression during treatment with disease modifying antirheumatic drugs, non-steroidal antirheumatic drugs, and/or prednisolone has been described in the wrists of patients with established19 and early20 RA. No correlation between pretreatment MRI signs of synovitis and erosive progression was found in the present study. The character of the treatment (surgery), the small number of patients, and the few new erosions are probable main causes.
In summary, the synovial membrane had regenerated two months after arthroscopic knee joint synovectomy and it often showed signs of recurrent synovitis. However, compared with pretreatment values, synovial membrane and joint fluid volumes were significantly reduced both two and 12 months after synovectomy. Synovial membrane volumes two months after arthroscopic synovectomy were inversely correlated with the duration of clinical remission. In addition to sensitive assessment of joint inflammation and destruction, MRI may have a value as predictor of long term therapeutical effect in arthritis.
Acknowledgments
The authors thank nurse Brigitta Pedersen-Zbinden for clinical management of the patients and Jens Arnth Jensen and Poul Ring for development of image processing software. We acknowledge the Foundation of 17–12–81, the University of Copenhagen, the Thomas and Elisabeth Frølund Nielsen Foundation, the Danish Rheumatism Association, the Danish Medical Research Council, Johann and Hanne Weimann born Seedorf's grant, Karen Marie Jørgensen and Datters grant and the Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands, and Greenland for financial support. Schering Diagnostika, Denmark, is acknowledged for providing the contrast agent.