Ablation of synovial pannus using microbubble-mediated ultrasonic cavitation in antigen-induced arthritis in rabbits

To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US)?+?microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1?h and 14?days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound?+?microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.     

Contrast medium in power Doppler ultrasound for assessment of synovial vascularity: comparison with arthroscopy

OBJECTIVE: To evaluate the reliability of contrast-unenhanced power Doppler (CUPD) and contrast-enhanced power Doppler (CEPD) ultrasound (US) assessment of synovial vascularity of knee joint synovitis by prospective comparison with the "gold standard," arthroscopy. METHODS: A total of 18 knees of 17 patients with refractory rheumatoid and psoriatic knee joint synovitis were examined by US. Recognition of PD synovial vessel flow and its spatial arrangement in relation to the pannus/cartilage interface (P/CI) or fluid/synovium interface (F/SI) were studied by CUPD- and CEPD-US after a single intravenous bolus of galactosel palmitic acid (Levovist). Arthroscopy video recordings were reanalyzed by computer image analysis to assess synovial vascular marking. CUPD and CEPD flow signal scores were compared with each other and with corresponding vascular marking scores. Using villous vascular marking as reference, CUPD and CEPD sensitivity and specificity were measured. Interobserver variability was evaluated. RESULTS: Compared with the unenhanced PD method, contrast administration increased the PD flow signal score in 13/18 knees (72.2%), allowing increased detection of F/SI PD flow signal configuration (p < 0.018) and of the coexistence of P/CI and F/SI PD imaging (p < 0.0078). With arthroscopy as reference, contrast-enhanced PD was found to be more useful than the unenhanced method, showing more reproducible PD signal scores (p = 0.05 vs p = nonsignificant), as well as higher sensitivity (80% vs 30%), but lower specificity (62% vs 87%), in the recognition of increased vascularity of synovial villi. Interobserver agreement was 100%. CONCLUSION: The prospective comparison with arthroscopy showed the reliability of the CEPD method in synovial vessel recognition and its potential clinical usefulness in assessment of knee joint synovitis.     

Experimental synovitis induced by intraarticular administration of alpha 2-macroglobulin-proteinase complexes

Rheumatoid synovial collagenase was prepared from tissue cultures from rheumatoid arthritis patients, obtained after synovectomy. Alpha 2-macroglobulin was isolated from human plasma and complexed with collagenase or trypsin. Formation of both types of complexes was proven by sodium dodecyl sulfate and rate electrophoresis. Normal rabbits were injected intraarticularly into the right knee, on days 0, 3, and 6, with either alpha 2-macroglobulin-collagenase or alpha 2-macroglobulin-trypsin complexes. Control injections of alpha 2-macroglobulin, trypsin, or rheumatoid synovial collagenase were applied to the left knee joint cavity. Groups of rabbits were killed 18 hours, 1 week, or 3 weeks after the last injection, and cellular exudation into synovial fluid and morphologic alterations of synovium were investigated. Joints injected with alpha 2-macroglobulin showed no synovitis, while joints injected with collagenase showed an experimental synovitis. Alpha 2-macroglobulin-proteinase complexes, however, induced a synovitis, which was more severe than that occurring after injection of proteinases only. In the early stages, synovium showed perivascular accumulation of inflammatory cells, infiltration with neutrophils, proliferation of synovial cells, and exudation of inflammatory cells into synovial fluid. Later stages were characterized by infiltration with mononuclear cells and fibroplasia.     

Prevalence of cartilage shards in synovium and their association with synovitis in patients with early and endstage osteoarthritis.

It has been suggested that incorporation of shards of fibrillated cartilage into the synovium is a cause of synovitis in osteoarthritis (OA). We examined the prevalence with which fragments of cartilage are seen in synovium, and their association with synovitis, in patients with endstage OA and early OA of the knee. Samples of synovium were obtained from 12 patients with endstage OA who were undergoing knee joint replacement and 30 with only mild/moderate radiographic changes of OA who exhibited articular cartilage changes of OA at arthroscopy. The presence of cartilage shards was sought in synovium from the medial and lateral tibiofemoral compartments and the suprapatellar pouch of each patient. Comparable volumes of the synovial lining from patients with endstage and early OA were examined, and tissue mononuclear cell infiltration was graded as an indicator of synovitis. Cartilage shards were seen in synovium from 7 of 12 patients with endstage OA, all of whom had synovitis. No topographic relationship was found between shards and mononuclear cell infiltration. In contrast, cartilage fragments were not seen in synovium from any of the 30 patients with early OA, although 9 of them had full thickness cartilage ulcers and 17 had evidence of synovitis.     

Power Doppler ultrasonography and synovitis: correlating ultrasound imaging with histopathological findings and evaluating the performance of ultrasound equipments

OBJECTIVES: To examine the validity of power Doppler ultrasound imaging to identify synovitis, using histopathology as gold standard, and to assess the performance of ultrasound equipments. METHODS: 44 synovial sites in small and large joints, bursae and tendon sheaths were depicted with ultrasound. A synovial biopsy was performed on the site depicted and a synovial sample was taken for histopathological evaluation. The performance of three ultrasound devices was tested using flow phantoms. RESULTS: A positive Doppler signal was detected in 29 of 35 (83%) of the patients with active histological inflammation. In eight additional samples, histological examination showed other pathological synovial findings and a Doppler signal was detected in five of them. No significant correlation was found between the amount of Doppler signal and histological synovitis score (r = 0.239, p = NS). The amount of subsynovial infiltration of polymorphonuclear leucocytes and surface fibrin correlated significantly with the amount of power Doppler signal: r = 0.397 (p<0.01) and 0.328 (p<0.05), respectively. The ultrasound devices differed in showing the smallest detectable flow. CONCLUSIONS: A negative Doppler signal does not exclude the possibility of synovitis. A positive Doppler signal in the synovium is an indicator of an active synovial inflammation in patients. A Doppler signal does not correlate with the extent of the inflammation and it can also be seen in other synovial reactions. It is important that the quality measurements of ultrasound devices are reported, because the results should be evaluated against the quality of the device used.     

Experimental synovitis induced by intraarticular administration of α2-macroglobulin-proteinase complexes

Rheumatoid synovial collagenase was prepared from tissue cultures from rheumatoid arthritis patients, obtained after synovectomy. Alpha₂-macroglobulin was isolated from human plasma and complexed with collagenase or trypsin. Formation of both types of complexes was proven by sodium dodecyl sulfate and rate electro-phoresis. Normal rabbits were injected intraarticularly into the right knee, on days 0, 3, and 6, with either α₂-macroglobulin-collagenase or α₂-macroglobulin-trypsin complexes. Control injections of α₂-macroglobu-lin, trypsin, or rheumatoid synovial collagenase were applied to the left knee joint cavity. Groups of rabbits were killed 18 hours, 1 week, or 3 weeks after the last injection, and cellular exudation into synovial fluid and morphologic alterations of synovium were investigated. Joints injected with collagenase showed no synovitis, while joints injected with collagenase showed an experimental synovitis. Alpha₂-macroglobulin-proteinase complexes, however, induced a synovitis, which was more severe than that occurring after injection of proteinases only. In the early stages, synovium showed perivascular accumulation of inflammatory cells, infiltration with neutrophils, proliferation of synovial cells, and exudation of inflammatory cells into synovial fluid. Later stages were characterized by infiltration with mononuclear cells and fibroplasia.     

Synovial inflammation in patients with early osteoarthritis of the knee

While synovitis is common in advanced osteoarthritis (OA), its prevalence and severity in patients with early or mild OA are uncertain. In our study synovial biopsies from patients with arthroscopic evidence of OA whose radiographs were normal, or showed only mild/moderate changes of OA, were examined to determine the prevalence and severity of lining cell proliferation and mononuclear cell infiltration. Synovitis was present in only 16 of 29 patients (55%) who underwent arthroscopy because of chronic knee pain and were found to have OA; no synovium from 50% of the 22 patients in this group with full thickness cartilage ulceration showed infiltration with mononuclear cells. Similarly, no evidence of synovitis was seen in biopsies from 7 of 14 additional patients with OA who did not have knee pain but who underwent arthroscopy to evaluate joint instability. An association was seen between synovial mononuclear cell infiltration and thickness of the synovial lining cell layer (p less than 0.03), but lining cell hyperplasia was found in samples from only 12% of the patients with OA in our series. The severity of OA cartilage lesions was unrelated to severity of synovitis and no topographic relationship was found between cartilage ulceration and synovitis.     

Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis

OBJECTIVE: To determine the role of vascular endothelial growth factor B (VEGF-B) in 2 mouse models of arthritis, antigen-induced arthritis (AIA) and collagen-induced arthritis (CIA). METHODS: For AIA studies, monarticular AIA was induced by methylated bovine serum albumin (mBSA) priming of Vegfb gene knockout (Vegfb(-/-)) and wild-type (Vegfb(+/+)) mice, followed by intraarticular injection of mBSA or saline control 8 days later. CIA was induced in Vegfb(-/-) and Vegfb(+/+) mice by intradermal injection of chick type II collagen in adjuvant. Arthritis was monitored in both models using defined criteria (clinical and histologic). Angiogenesis was measured by synovial vessel density in diseased and control joints. RESULTS: In AIA studies, Vegfb(+/+) mice displayed significant knee joint swelling and synovial inflammation 7 days after intraarticular injection of antigen. Synovial inflammation was associated with angiogenesis, since vessel density in AIA synovium was significantly higher in arthritic than in control joints from the same animal. Knee joint swelling, synovial inflammation, and inflammation-associated vessel density in arthritic joints were reduced in Vegfb(-/-) mice compared with arthritic joints from Vegfb(+/+) mice. Similarly, in CIA, both disease incidence and mean clinical severity scores were significantly reduced in Vegfb(-/-) mice compared with Vegfb(+/+) mice. Mean histologic severity scores and mean synovial vessel density were reduced in diseased joints from Vegfb(-/-) mice when compared with diseased joints from Vegfb(+/+) mice. CONCLUSION: The reduction in inflammation-associated synovial angiogenesis in Vegfb(-/-) mice implicates VEGF-B in pathologic vascular remodeling in inflammatory arthritis. VEGF-B may be an attractive target in the design of anti-angiogenic therapies for rheumatoid arthritis.     

Intraarticular factor IX protein or gene replacement protects against development of hemophilic synovitis in the absence of circulating factor IX

Hemophilic bleeding into joints causes synovial and microvascular proliferation and inflammation (hemophilic synovitis) that contribute to end-stage joint degeneration (hemophilic arthropathy), the major morbidity of hemophilia. New therapies are needed for joint deterioration that progresses despite standard intravenous (IV) clotting factor replacement. To test whether factor IX within the joint space can protect joints from hemophilic synovitis, we established a hemophilia B mouse model of synovitis. Factor IX knockout (FIX(-/-)) mice received a puncture of the knee joint capsule with a needle to induce hemarthrosis; human factor IX (hFIX) was either injected through the needle into the joint space (intraarticularly) or immediately delivered IV. FIX(-/-) mice receiving intraarticular FIX protein were protected from synovitis compared with mice receiving same or greater doses of hFIX IV. Next, adeno-associated virus (AAV) gene transfer vectors expressing hFIX were injected into knee joints of FIX(-/-) mice. Joints treated with 10(10) vector genomes (vg)/joint AAV2-, AAV5-, or AAV8-hFIX or 2.5 x 10(9) vg/joint AAV5-hFIX developed significantly fewer pathologic changes 2 weeks after injury compared with the pathology of control injured contralateral hind limbs. Extravascular factor activity and joint-directed gene transfer may ameliorate hemophilic joint destruction, even in the absence of circulating FIX.     

Synovial permeability in rheumatoid arthritis.

In patients with rheumatoid arthritis, as well as in persons with other kinds of synovitis, proteins enter the knee joint more rapidly than in normal individuals (P less than 0.001). The rheumatoid synovium, however, is less permeable to small molecules (tritiated water, P less than 0.02; urate, P less than 0.05; and glucose, P less than 0.002) than is the normal joint lining. This difference is explained if rheumatoid microvascular changes enhance synovial permeability to proteins while coexisting interstitial changes diminish synovial permeability to smaller molecules.     

Assessing rheumatoid arthritis disease activity with ultrasound

In practice, composite indices are used for rheumatoid arthritis (RA) disease activity evaluation. Despite valid and widely used, not rarely composite indices miss accuracy. Ultrasound (US) is more precise than clinical examination in synovitis appraisal. US-based disease activity estimation depends on the detection of synovitis. The most common synovitis abnormalities are proliferation, effusion, and neoangiogenesis. Gray scale ultrasound identifies synovial hypertrophy and effusion with its good soft tissue contrast. Additionally, power Doppler ultrasound depicts neoangiogenesis within synovia, remarking local inflammation. Several studies have combined local US findings to develop a patient level disease activity index. Most of them summed selected joint scores in an overall score of disease activity and evaluated its correlation with clinical composite indexes. To be incorporated into clinical practice, an overall US score must have some fundamental characteristics such as reproducibility, viability, and sensitivity to change over time. In global US score development, finding the joints that truly estimate individual disease activity is highly challenging. This article presents an up-to-date literature review on assessing RA disease activity with US and depicts the challenges in finding the perfect global US score.     

LONG-TERM SONOGRAPHIC FOLLOW-UP OF RHEUMATOID AND PSORIATIC PROLIFERATIVE KNEE JOINT SYNOVITIS

The potential role of sonography in evaluating the responseto therapy of persistent knee joint synovitis (KJS) was assessedin a longitudinal study in pre- and post-arthroscopic (AS) synovectomyin rheumatoid and psoriatic patients. At entry to the study,ultrasound (US) detection of synovial proliferation was comparedwith arthroscopic visualization as the ‘gold standard’reference. US joint effusion and synovial thickness measuresand predominant patterns of synovial proliferation were recordedby comparing clinical and US indices before and at 2, 6 and12 months after AS synovectomy, or after KJS relapse up to 24months. A 12 month survival analysis of clinical and US outcomesof arthroscopic synovectomy was also performed. US detectionof morphology and degree of synovial proliferation was correlatedwith AS macroscopic evaluation. After AS synovectomy, the clinicalindex and both US joint effusion and synovial thickness weresignificantly reduced, whereas US patterns of synovial proliferationdid not show significant changes. US and clinical indices weresignificantly correlated in all follow-up measurements and USjoint effusion was significantly increased in the relapsed comparedwith the non-relapsed KJS group. The probability at 12 monthsof reaching maximum improvement in US joint effusion and synovialthickness outcomes was 99 and 58%, respectively; that for clinicalremission of KJS was 72%. Ultrasound evaluation has proven reliableand accurate by the arthroscopic gold standard in detectingchanges of rheumatoid arthritis and psoriatic arthritis kneejoint synovitis. The correlation of US with clinical findingsin pre- and post-synovectomy patients suggests that sonographycan be used as an objective method in monitoring the responseto therapy of inflammatory knee joint disease. KEY WORDS: Knee joint synovitis, Arthroscopic synovectomy, Sonographic follow-up     

Analysis of knee arthroscopic findings in rheumatic diseases

46 patients with knee joint arthritis were subjected to arthroscopic examination. The results were analyzed and its clinical significance was discussed. The postoperative diagnoses were rheumatoid arthritis in 19 cases, Sj?gren syndrome in one, seronegative spondyloarthropathy in 4, gouty arthritis in one, tuberculous arthritis in one, pigmented villous nodular synovitis in two, undefined synovitis in 5, osteoarthritis in 8 and nonsynovitis conditions in 5. The most important indication of arthroscopic examination is for differential diagnosis of arthritis of unknown cause, such as rheumatoid arthritis with single knee joint involvement, osteoarthritis with symmetric large and small joints involvement as well as crystal induced arthritis. These conditions showed under arthroscope their special features in synovium both grossly, microscopically and immuno-pathologically. The synovial damage as observed through arthroscopic examination correlated to certain extent with the X-ray film changes of the knee joint, but direct visualization with the former is better than indirect imaging with the latter.     

Role of TNF alpha in the induction of antigen induced arthritis in the rabbit and the anti-arthritic effect of species specific TNF alpha neutralising monoclonal antibodies.

OBJECTIVE--To investigate the role of tumour necrosis factor alpha (TNF alpha) in the development of antigen induced arthritis (AIA) in rabbits. METHODS--Monoclonal antibodies to rabbit TNF alpha were developed in rats and were used to detect TNF alpha in synovial fluid by enzyme linked immunosorbent assay and to localise it in tissue sections of synovium and cartilage from rabbits up to 21 days after induction of AIA. An antibody which neutralised TNF alpha activity in vitro was injected into rabbits to block TNF alpha action in vivo in AIA. Joint swelling, leucocyte infiltration into synovium and proteoglycan loss from cartilage were measured and compared with a control group, which were injected with sterile saline. RESULTS--Monoclonal antibodies to purified rabbit TNF alpha were prepared in rats and two were selected which were able to neutralise rabbit TNF alpha in a cytotoxicity bioassay. TNF alpha was detected in significant concentrations (21.7 (SE 0.5) pg/ml) in the arthritic joint fluid of rabbits with AIA only at one day after induction and it was then also sparsely localised in cells of the synovium, but from day 3 onwards it was localised more strongly in the deep zone of articular cartilage. Injection of anti-TNF monoclonal antibody R6 over three days into rabbits with AIA reduced joint swelling and leucocyte infiltration into joint fluid and decreased the expression of CD11b and CD18 on cells in the joint fluid. However, there was no significant reduction in the loss of proteoglycan from articular cartilage, although the joint fluid at three days contained a lower glycosaminoglycan content. The antibody R6 gave most effect at a dose of 0.6 mg/kg and there was no increase in its effectiveness at a fivefold greater dose (3.0 mg/kg). Treatment over 10 days gave a more complete suppression of joint swelling, but did not result in any less proteoglycan loss from cartilage. Treatment for five days with a 16 day follow up gave a significant reduction in swelling for several days beyond the treatment, but the swelling then slowly returned, until by day 21 there was no significant difference in joint swelling and there was also no recovery of cartilage proteoglycan content. A rabbit anti-rat immunoglobulin response was detected at 21 days, which may have limited the long term effectiveness of the antibody. CONCLUSIONS--In AIA in rabbits, TNF alpha was only detected in synovial fluid at one day after induction and there was only limited cellular localisation of TNF alpha in synovium and cartilage from three days. However, neutralising TNF alpha with a monoclonal antibody was effective in suppressing inflammatory changes in the joint during the acute onset of AIA, but it had little effect on the loss of proteoglycan from cartilage. The results suggest that blocking inflammation and synovitis with anti-TNF alpha may be more easily achieved than preventing damage to articular cartilage.     

Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis

Objective

To examine the relationship between longitudinal fluctuations in synovitis with change in pain and cartilage in knee osteoarthritis.

Methods

Study subjects were patients 45 years of age and older with symptomatic knee osteoarthritis from the Boston Osteoarthritis of the Knee Study. Baseline and follow‐up assessments at 15 and 30 months included knee magnetic resonance imaging (MRI), BMI and pain assessment (VAS) over the last week. Synovitis was scored at 3 locations (infrapatellar fat pad, suprapatellar and intercondylar regions) using a semiquantitative scale (0–3) at all 3 time points on MRI. Scores at each site were added to give a summary synovitis score (0–9).

Results

We assessed 270 subjects whose mean (SD) age was 66.7 (9.2) years, BMI 31.5 (5.7) kg/m²; 42% were female. There was no correlation of baseline synovitis with baseline pain score (r = 0.09, p = 0.17). The change in summary synovitis score was correlated with the change in pain (r = 0.21, p = 0.0003). An increase of one unit in summary synovitis score resulted in a 3.15‐mm increase in VAS pain score (0–100 scale). Effusion change was not associated with pain change. Of the 3 locations for synovitis, changes in the infrapatellar fat pad were most strongly related to pain change. Despite cartilage loss occurring in over 50% of knees, synovitis was not associated with cartilage loss in either tibiofemoral or patellofemoral compartment.

Conclusions

Change in synovitis was correlated with change in knee pain, but not loss of cartilage. Treatment of pain in knee osteoarthritis (OA) needs to consider treatment of synovitis.The cause of pain in knee osteoarthritis remains elusive as the primary site of pathology in OA, cartilage, has no pain fibres.¹ Many other structures around the knee such as the periosteum, subchondral bone, the fat pad, capsule and, inconsistently, the synovium have been shown to contain nociceptive fibres.¹ In addition, inflammation itself appears to play a role in increasing input from peripheral nociceptors.² Biopsies of patients with both early and late knee OA have shown low‐grade chronic synovitis with production of pro‐inflammatory cytokines.^3,4Magnetic resonance imaging (MRI) allows evaluation of multiple structures within the knee, including synovium, cartilage, menisci, bone marrow lesions and effusion. In cross‐sectional studies of MRI in knee osteoarthritis (OA), bone‐marrow lesions, periarticular lesions, knee effusions and synovitis have been shown to be more often present in persons with knee pain than in persons with a comparable amount of radiographic knee osteoarthritis but without pain.^5,6,7,8 Fernandez‐Madrid et al demonstrated that synovial thickening seen on non‐contrast enhanced MRI in the infrapatellar region of knees with OA showed low‐grade synovial inflammation on biopsy. This feature was present in 73% of knees with early OA.⁹We have previously shown that this synovial thickening is present in persons with knee pain and OA much more often than in persons with OA but without pain.⁷ Among those with pain, the presence of MRI synovial thickening identified those with more severe pain. While this evidence suggests that synovial thickening may affect pain, these data are cross‐sectional, making it impossible to evaluate the temporal relation of pain with synovial thickening. More persuasive evidence would emanate from a longitudinal study in which fluctuations in synovial thickening could be tied to fluctuations in the severity of knee pain. Herein, we provide such evidence. Our aims were to study the association between baseline and longitudinal changes in MRI‐detected synovitis and changes in knee pain, and also to study the association between baseline and longitudinal changes in synovitis and cartilage loss in patients with symptomatic knee OA.     

EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: prevalence of inflammation in osteoarthritis

Objectives: To assess the prevalence of inflammation in subjects with chronic painful knee osteoarthritis (OA), as determined by the presence of synovitis or joint effusion at ultrasonography (US); and to evaluate the correlation between synovitis, effusion, and clinical parameters. Methods: A cross sectional, multicentre, European study was conducted under the umbrella of EULAR-ESCISIT. Subjects had primary chronic knee OA (ACR criteria) with pain during physical activity ?30 mm for at least 48 hours. Clinical parameters were collected by a rheumatologist and an US examination of the painful knee was performed by a radiologist or rheumatologist within 72 hours of the clinical examination. Ultrasonographic synovitis was defined as synovial thickness ?4 mm and diffuse or nodular appearance, and a joint effusion was defined as effusion depth ?4 mm. Results: 600 patients with painful knee OA were analysed. At US 16 (2.7%) had synovitis alone, 85 (14.2%) had both synovitis and effusion, 177 (29.5%) had joint effusion alone, and 322 (53.7%) had no inflammation according to the definitions employed. Multivariate analysis showed that inflammation seen by US correlated statistically with advanced radiographic disease (Kellgren-Lawrence grade ?3; odds ratio (OR) = 2.20 and 1.91 for synovitis and joint effusion, respectively), and with clinical signs and symptoms suggestive of an inflammatory "flare", such as joint effusion on clinical examination (OR = 1.97 and 2.70 for synovitis and joint effusion, respectively) or sudden aggravation of knee pain (OR = 1.77 for joint effusion). Conclusion: US can detect synovial inflammation and effusion in painful knee OA, which correlate significantly with knee synovitis, effusion, and clinical parameters suggestive of an inflammatory "flare".     

Inflammatory synovitis due to underlying lipoma arborescens (gadolinium-enhanced MRI features): report of two cases

Lipoma arborescens (synovial lipomatosis) is a rare, benign intra-articular lesion of unknown etiology. It is a very rare primary benign tumour of the synovium, which usually affects the knee joint and can lead to slowly progressive chronically swollen knee. In this report we described two cases with this rare entity with initial presentation of inflammatory synovitis. We also described the Gadolinium (Gd-DTPA)-enhanced MRI features.To the best of our knowledge, this is the first report that described inflammatory synovitis in association with this rare entity.     

Protoporphyrin IX photodynamic therapy for synovitis

OBJECTIVE: To determine the conditions for synovial accumulation of protoporphyrin IX (PpIX) and photodynamic therapy (PDT)-induced synovial cytotoxicity in vitro and in vivo. METHODS: Synovial tissues were obtained from mice with antigen-induced arthritis (AIA) and incubated with different concentrations of 5-aminolevulinic acid hexyl ester (h-ALA), a PpIX precursor. Following photoexcitation, cell death in synovial tissues was evaluated by Sytox green fluorescence. PDT was performed after intraarticular injection of h-ALA into the knee joints of mice with AIA, and its effect on joint inflammation was assessed by technetium scintigraphy and histology. Synovial biopsy samples were obtained from patients with osteoarthritis (OA; n = 9) and rheumatoid arthritis (RA; n = 7) and studied for PDT-induced cytotoxicity in vitro. RESULTS: Conversion of h-ALA to PpIX was observed in inflamed synovium in mice and humans. Cytotoxicity was confirmed by Sytox green staining in samples subjected to PDT. In the AIA model, injection of affected knees with h-ALA prior to PDT led to a statistically significant reduction of joint damage in the irradiated joints. The preferential transformation of h-ALA to PpIX in inflammatory tissues was confirmed in human synovial biopsy tissues, where RA samples showed higher tissue concentrations of PpIX following incubation with h-ALA than did OA samples. Fluorescence microscopy showed that PpIX was localized to the synovial lining layer, endothelial cells, and macrophages and induced cell death after PDT. CONCLUSION: Our findings suggest that PDT based on the accumulation of PpIX in the synovial membrane may be a rational basis for photodynamic synovectomy in arthritic diseases.     

Doppler ultrasound measurements of knee joint synovitis in rheumatoid arthritis patients treated with infliximab

Doppler ultrasound measurements were done for the thickness of synovial effusion and synovial proliferation (pannus), and diameter of the flow signals using digital calipers as well as flow signal grades and vascular resistance in the knee joint synovitis of patients with rheumatoid arthritis (RA) treated with infliximab. Forty knee joints of 20 RA patients were assessed before and after three injections of infliximab. The flow signals in the pannus were classified into the superficial and the deep signals and the joints were classified into the superficial signal pattern and the deep signal pattern. After treatment, the number of joints with superficial signal pattern reduced from 23 to 11, whereas the number of joints with deep signal pattern increased from 17 to 29 (P=0.0066), with a significant reduction of the superficial signal grades (P=0.0003). The mean cortical (posterior) pannus thickness increased significantly in the joints with superficial signal pattern (P=0.022) and in the total joints (superficial plus deep signal pattern) (P=0.031) but not in the joints with deep signal pattern. After 6 weeks of treatment with infliximab, the hyperemia in the superficial layer of the pannus developed into proliferation of the cortical pannus in the knee joints.     

Synovialitis-Score: Wertigkeit histopathologischer Diagnostik bei unklaren Arthritiden

Histopathological assessment of synovial biopsies has an established value. The value for inflammatory joint diseases without standardized rating mechanisms was, however, unknown until recently. The exemplary use of the synovitis score in four cases all including recurrent bruises of the knee joint portrays its value for diagnosis and therapy.Usage of the score includes assessing the enlargement of the lining layer, cellular density of synovial stroma and leucocyte infiltration by giving each a score of 0-3 points and adding them. Presence of high-grade synovitis (>or=4 points) in all cases displayed the reason for the joint bruises within a primarily inflammatory, rheumatoid circle.In this report we show the broad variety of uses for the synovitis score dealing with cases of Lyme arthritis, rheumatoid arthritis, seronegative monarthritis and HLA-B27-positive peripheral arthritis.