Severe Synovitis Research Articles

Degree of synovitis on MRI is correlated with histological and macroscopic features of synovial tissue inflammation in knee osteoarthritis

Background and objectivesSynovitis is often present on MRI of OA knees and is an important determinant of pain. To better understand the nature of synovitis seen on MRI the authors...

Upregulation of tumor necrosis factor receptor-associated factor 6 correlated with synovitis severity in rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Focal bone erosion is due to excess bone resorption of osteoclasts. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the critical mediators both in inflammatory signal pathway and differentiation and resorption activity of osteoclasts. Here we aimed to investigate TRAF6 expression in RA synovium and its correlation with histological synovitis severity and radiological joint destruction in RA.MethodsSynovitis score was determined in needle biopsied synovium from 44 patients with active RA. Synovium from nine patients with osteoarthritis (OA) and seven with orthopedic arthropathies (Orth.A) were enrolled as "less inflamed" disease controls. Serial sections were stained immunohistochemically for TRAF6 as well as CD68 (macrophage), CD3 (T cell), CD20 (B cell), CD38 (plasmocyte), CD79a (B lineage cells from pre-B cell to plasmocyte stage), and CD34 (endothelial cell). Double immunofluorescence staining of TRAF6 and CD68 were tested. Densities of positive staining cells were determined and correlated with histological disease activity (synovitis score) and radiographic joint destruction (Sharp score).ResultsTRAF6 expression was found in the intimal and subintimal area of RA synovium, with intense staining found in the endochylema and nucleus of intimal synoviocytes and subintimal inflammatory cells. Double immunofluorescence staining showed TRAF6 was expressed in most of the intimal cells and obviously expressed in CD68+ cells and some other CD68- cells in subintimal area. Synovial TRAF6 was significantly over-expressed in the RA group compared with the OA and Orth.A group (2.53 ± 0.94 vs. 0.72 ± 0.44 and 0.71 ± 0.49, P < 0.0001). Synovial TRAF6 expression in RA correlated significantly with synovitis score (r = 0.412, P = 0.006), as well as the inflammatory cell infiltration (r = 0.367, P = 0.014). Significant correlation was detected between synovial TRAF6 expression and intimal CD68+ cells, as well as the cell density of subintimal CD68+ cells, CD3+ cells, CD20+ cells, CD38+ cells, and CD79a+ cells (all P < 0.05).ConclusionsElevated synovial TRAF6 expression correlated with synovitis severity and CD68+ cell density in RA. It is, therefore, hypothesized that synovial TRAF6 is involved in the pathogenesis of synovial inflammation and osteoclast differentiation in RA.

Synovitis and bone inflammation in early rheumatoid arthritis: high-resolution multi-pinhole single-photon-emission computed tomography (mph-spect) versus magnetic resonance imaging (mri)

We aimed to assess the relationship between bone inflammation in multi-pinhole single-photon emission computed tomography (MPH-SPECT) and synovitis detected by magnetic resonance imaging (MRI) in early rheumatoid arthritis patients. MPH-SPECT with technetium dicarboxypropanedisphosphonate (Tc-99mDPD) and 3 Tesla MRI were performed in 10 early rheumatoid arthritis patients. Eighty finger joint sites were assessed for increased osteoblastic activity using visual and region-of-interest (ROI) analysis. Presence of joint inflammation in MRI was investigated using the subscores of the rheumatoid arthritis MRI score. Tc-99mDPD uptake was increased in 38 (47.5%) and 22 (27.5%) joint sites as determined by visual and ROI analysis, respectively. A total of 32 (84.2%) sites with increased bone metabolism showed a normal MRI bone signal. The MPH-SPECT uptake ratio was elevated only in the subgroup with severe synovitis (P < 0.001). In early rheumatoid arthritis, molecular imaging with MPH-SPECT detects higher rates of inflammatory bone involvement compared to MRI. Our preliminary data suggest that osteitis is related to severe synovitis.

Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs

IntroductionBiological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.MethodsThe study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months.ResultsBaseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01).ConclusionsCXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.

Enhanced susceptibility to lipopolysaccharide-induced arthritis and endotoxin shock in interleukin-32 alpha transgenic mice through induction of tumor necrosis factor alpha

IntroductionThe present study assessed the potential functions of interleukin (IL)-32α on inflammatory arthritis and endotoxin shock models using IL-32α transgenic (Tg) mice. The potential signaling pathway for the IL-32-tumor necrosis factor (TNF)α axis was analyzed in vitro.MethodsIL-32α Tg mice were generated under control of a ubiquitous promoter. Two disease models were used to examine in vivo effects of overexpressed IL-32α: Toll-like receptor (TLR) ligand-induced arthritis developed using a single injection of lipopolysaccharide (LPS) or zymosan into the knee joints; and endotoxin shock induced with intraperitoneal injection of LPS and D-galactosamine. TNFα antagonist etanercept was administered simultaneously with LPS in some mice. Using RAW264.7 cells, in vitro effects of exogenous IL-32α on TNFα, IL-6 or macrophage inflammatory protein 2 (MIP-2) production were assessed with or without inhibitors for nuclear factor kappa B (NFκB) or mitogen-activated protein kinase (MAPK).ResultsSingle injection of LPS, but not zymosan, resulted in development of severe synovitis with substantial articular cartilage degradation in knees of the Tg mice. The expression of TNFα mRNA in inflamed synovia was highly upregulated in the LPS-injected Tg mice. Moreover, the Tg mice were more susceptive to endotoxin-induced lethality than the wild-type control mice 48 hours after LPS challenge; but blockade of TNFα by etanercept protected from endotoxin lethality. In cultured bone marrow cells derived from the Tg mice, overexpressed IL-32α accelerated production of TNFα upon stimulation with LPS. Of note, exogenously added IL-32α alone stimulated RAW264.7 cells to express TNFα, IL-6, and MIP-2 mRNAs. Particularly, IL-32α -induced TNFα, but not IL-6 or MIP-2, was inhibited by dehydroxymethylepoxyquinomicin (DHMEQ) and U0126, which are specific inhibitors of nuclear factor kappa B (NFκB) and extracellular signal regulated kinase1/2 (ERK1/2), respectively.ConclusionsThese results show that IL-32α contributed to the development of inflammatory arthritis and endotoxin lethality. Stimulation of TLR signaling with LPS appeared indispensable for activating the IL-32α-TNFα axis in vivo. However, IL-32α alone induced TNFα production in RAW264.7 cells through phosphorylation of inhibitor kappa B (IκB) and ERK1/2 MAPK. Further studies on the potential involvement of IL-32α-TNFα axis will be beneficial in better understanding the pathology of autoimmune-related arthritis and infectious immunity.

Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients

ObjectivesInterleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA).MethodsImmunohistochemistry was performed in...

Intra-articular etanercept treatment for severe diffuse pigmented villonodular knee synovitis

Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that require aggressive treatment as surgical synovectomy, eventually followed by radiosynovectomy. Nevertheless, the disease often reoccurs after these treatments. To determine the safety and efficacy of intra-articular (IA) TNFalpha blockade with etanercept (ETN), before extended arthroscopic synovectomy, in severe PVNS of the knee, two patients, (a 26-year-old man with B27+ undifferentiated spondylarthropathy and a 32-year-old femal with seronegative oligoarthritis), affected by diffuse knee PVNS (diagnosis made by histological examination), resistant to IA corticosteroid injections and to repeated arthroscopic synovectomy, were submitted, after protocol approval by human research committee and patient's written informed consent to intra-articular etanercept (IA-ETN) treatment with a different dosage schedule: 12.5 mg weekly IA-ETN injection for 4 weeks, followed by extended arthroscopic synovectomy and of 25 mg IA-ETN injection for 4 weeks, respectively. Previous DMARDs treatment was continued in stable appropriate doses. Any adverse events were recorded throughout the study. The following parameters were considered as clinical endpoints: 1) Knee Joint Index (KJI: range 0-14); 2) Thompson index (THI: range 0-9) At the study entry and at the end of follow-up, high frequency ultrasound grey scale synovial thickening (US-ST) was also assessed. No adverse events were observed due to IA-ETN and to arthroscopic synovectomy. Marked improvement of knee disease activity over time and sustained functional recover was obtained. US-ST evaluation before treatment initiation and at the end of follow-up confirmed the regression of knee joint synovial proliferation.

An ultrasonographic study of metatarsophalangeal joint pain: synovitis, structural pathology and their relationship to symptoms and function

BackgroundPain in the first metatarsophalangeal joint (MTPJ) is common, though the link between pathology and symptoms is poorly understood.ObjectivesTo examine the relationship between pain, function and ultrasound (US)-detected pathology in...

Synovitis in Dogs with Stable Stifle Joints and Incipient Cranial Cruciate Ligament Rupture: A Cross‐Sectional Study

To evaluate stifle joints of dogs for synovitis, before development of joint instability and cranial cruciate ligament rupture (CrCLR). Cross-sectional study. Dogs (n = 16) with CrCLR and stable contralateral stifles; 10 control dogs with intact CrCL. Arthritis and tibial translation were graded radiographically. Synovitis severity and cruciate pathology were assessed arthroscopically. Presence of inflammatory cells in synovial membrane biopsies was scored histologically. CrCLR stifle pairs and control stifles were compared. Radiographic evidence of arthritis, cranial tibial translation, and arthroscopic synovitis were increased in unstable stifles, when compared with stable contralateral stifles in CrCLR dogs (P < .05). Arthroscopic synovitis in both joints of CrCLR dogs was increased compared with controls, was correlated with radiographic arthritis (S(R) = 0.71, P < .05), and was present in all stable contralateral stifles. Arthroscopically, 75% of stable stifle joints had CrCL fiber disruption, which correlated with severity of synovitis (S(R) = 0.56, P < .05). Histologic evidence of synovitis was identified in all CrCLR dogs, but was only significantly correlated with arthroscopic observations in stable stifles (r(2) = 0.57, P < .005). Synovitis is an early feature of the CrCLR arthropathy in dogs before development of joint instability clinically. Severity of synovitis is correlated with radiographic arthritis in joints with minimal to no clinically detectable CrCL damage.

Antigen-induced arthritis in rabbits: a comparative study between high-resolution ultrasound and contrast-enhanced ultrasound and pathologic findings

The objective of this study was to explore the feasibility and value of high-resolution ultrasound and contrast-enhanced ultrasound in evaluation of synovitis in rabbit knee joint in antigen-induced arthritis (AIA). Thirty-six rabbits were divided into three groups, each injected with different doses of ovalbumin (OVA) into the right knee joint. On week 1 and 4, 6 randomly selected in each group were killed. Each knee joint undergone the high-resolution ultrasound to measure capsule thickness and contrast-enhanced ultrasound to measure synovium thickness. The results from the ultrasound examinations were compared with those of pathologic examinations. Different OVA doses resulted in different modeling success rate, different pathological synovitis score, and different capsule and synovium thickness measured by ultrasound. The diagnostic accuracy of synovitis by ultrasound was high. The ultrasound measurement revealed that the capsule thickness on week 4 was lessened than that on week 1, while the synovial thickness on week 4 was greater than that on week 1. Both the joint capsule and synovium thickness measured by ultrasound were significantly and positively correlated to the pathologic synovitis score (P<0.05). The synovial thickness on week 4 is more correlated to the synovitis score than the capsule thickness, rather than that on week 1. Injection of OVA of different doses results in different modeling success rate and synovitis severity. The high-resolution ultrasound and contrast-enhanced ultrasound can be used to determine whether the AIA was made successfully and evaluate the synovitis severity. In chronic inflammatory phase, the contrast-enhanced ultrasound has better effect.

Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study

ObjectivesTo introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI.MethodsMulticenter Osteoarthritis Study (MOST) is a cohort study of people with,...

Efficacy of a single ultrasound-guided injection for the treatment of hip osteoarthritis

BackgroundIntra-articular injection is effective for osteoarthritis, but the best single injection strategy is not known, nor are there established predictors of response. The objectives of this study were to assess...

Caudal Cruciate Ligament Damage in Dogs with Cranial Cruciate Ligament Rupture

To investigate the incidence of caudal cruciate ligament (CaCL) damage in dogs with cranial cruciate ligament rupture (CCLR). Prospective clinical study. Dogs (n=24) admitted for surgical stabilization of the stifle after CCLR and 8 healthy dogs with intact cranial cruciate ligament (CCL) and CaCL studied as controls. Preoperative radiographs and stifle joint images (arthrotomy, 6; arthroscopy, 18) were collected from dogs with CCLR. Severity of arthritis, synovitis, CCL damage, and CaCL damage were assessed using numerical rating scales. The CaCL was probed to determine whether minor fraying or a full thickness defect in the ligament was present. Data collected from the study population were compared with the control population of dogs. The CaCL was damaged in 21/24 (88%) of dogs with CCLR; 6/24 (25%) had a full thickness defect in the CaCL. Severity of stifle synovitis and severity of damage to the CaCL were positively correlated (P<.05). The CaCL is damaged in a high percentage of dogs with CCLR. A significant and positive correlation exists between the degree of synovitis present and the extent of CaCL damage. In dogs with CCLR, cruciate ligament pathology typically involves both the CCL and CaCL. As the severity of synovitis and the extent of CaCL damage are related, this observation supports the hypothesis that stifle synovitis may contribute to CCL and CaCL degeneration and subsequent damage.

288 IMPACT OF HALLUX VALGUS SEVERITY ON GENERAL AND FOOT-SPECIFIC HEALTH-RELATED QUALITY OF LIFE

as follows: 0=none; 1=mild; 2=moderate; 3=severe. Twenty of thirty-four patients underwent Gd-MRI. Synovial membrane inflammation was investigated in 5 ROIs. Thickening of the inflamed synovial membrane was determined in each ROI and grade on a 4-point scale. A correlation analysis was conducted by Spearman’s correlation coefficient. Results: The synovitis of the knee joint was evaluated by a histological analysis and Gd-MRI. A statistically significant correlation was observed between the total composite score of synovitis by the histological analysis and the synovitis score evaluated by Gd-MRI in patients of this study (r=0.88, p<0.01). Next, the possible correlation between synovial inflammation and the symptoms and the disability of the patients was assessed. The pain VAS score of patients was not correlated with either the mean total synovitis score evaluated by the histological analysis nor that evaluated by Gd-MRI (r=0.25, p=0.18 and r=0.08, p=0.75, respectively). On the other hand, the total JKOM score of the patients showed a significant positive correlation with both the mean total synovitis score evaluated by the histological analysis and that evaluated by Gd-MRI (r=0.55, p<0.01 and r=0.71, p<0.01, respectively). To further examine whether the WOMAC could obtain a similar result, fourteen of thirty-four patients were evaluated for any disability by both the JKOM and WOMAC. The WOMAC of the fourteen patients did not show a significant correlation with either the mean total synovitis score evaluated by the histological analysis or that evaluated by Gd-MRI. Conclusions: The present study revealed the disability of Japanese patients with knee OA who required TKA using JKOM showed a significant correlation with the severity of synovitis in affected knee joint. This study further confirmed the superiority of the JKOM for evaluating the disability of Japanese patients with knee OA. Synovitis may play a crucial role, not only in the progression of disease, but also in the current functional impairment and disability in patients with end-stage knee OA who required TKA.

287 CORRELATION BETWEEN SYNOVITIS DETECTED ON ENHANCED-MAGNETIC RESONANCE IMAGING AND A HISTOLOGICAL ANALYSIS WITH A PATIENT-ORIENTED OUTCOME MEASURE FOR JAPANESE PATIENTS WITH END-STAGE KNEE OSTEOARTHRITIS RECEIVING JOINT REPLACEMENT SURGERY

Osteoarthritis (OA) is a disease that primarily results in the degeneration and destruction of the articular cartilage. However, synovitis that occurs secondarily by this primary phenomenon is crucial for both the structural and symptomatic progression of the disease. The Japanese Knee Osteoarthritis Measure (JKOM) was created as an outcome measure for Japanese patients with knee OA. This study was conducted to determine whether synovitis in knee OA correlates with the current disability of patients with knee OA who required total knee arthroplasty (TKA). Thirty-four Japanese patients with end-stage knee OA who required TKA were included in this study. The visual analog scale (VAS, 0–100) for pain and the JKOM score, as well as the Western Ontario and McMaster Universities Arthritis Index (WOMAC), were examined before the operation. Synovial samples were taken at the time of the operation. A histological analysis and gadolinium-enhanced magnetic resonance imaging (Gd-MRI) were conducted to evaluate synovitis. Correlations between the synovitis score evaluated by histological analysis and Gd-MRI with either the pain VAS score or the JKOM score were examined using Spearman’s rank correlation coefficient. Neither the synovitis scores evaluated by the histological analysis nor those by a Gd-MRI correlated with the pain VAS score (n = 34, r = 0.25, p = 0.18 and r = 0.08, p = 0.75, respectively) and WOMAC (n = 14, r = 0.35, p = 0.22 and r = 0.45, p = 0.16, respectively) of the patients. However, they significantly correlated with the JKOM score of the patients (n = 34, r = 0.55, p = 0.001 and r = 0.71, p = 0.001, respectively). The severity of synovitis in OA was closely correlated with the current functional impairment and disability of the patients receiving TKA with end-stage knee OA.

Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis?

It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR ( n = 51) and healthy dogs with normal stifles ( n = 9). Arthritis was assessed radiographically in CCLR dogs. Bacterial load was assessed using qPCR and broad-ranging 16S rRNA primers. qRT-PCR was used to estimate expression of the T lymphocyte antigen receptor (TCR Vβ), CD3ɛ, tartrate-resistant acid phosphatase (TRAP), IL-4, IL-17, and TNF-α genes. Severity of synovitis was assessed histologically. Bacterial load was increased in arthritic stifles, when compared with healthy stifles. Histologic synovitis in arthritic stifles was mononuclear and was significantly correlated with bacterial load (1 of 2 primer sets) ( S R = 0.49, p < 0.001). In arthritic stifles, expression of TRAP in synovium was increased relative to healthy stifles. Expression of pro-inflammatory genes was not correlated with bacterial load, histologic inflammation, or radiographic arthritis. Translocation of bacterial material to the canine stifle is related to the presence of joint inflammation. The lack of a strong positive correlation suggests that bacterial load is unlikely to be a primary pro-inflammatory factor. However, dysregulation of immune responses within synovial tissues may be dependent upon an environmental microbial trigger.

Correlation between synovitis detected on enhanced-magnetic resonance imaging and a histological analysis with a patient-oriented outcome measure for Japanese patients with end-stage knee osteoarthritis receiving joint replacement surgery

Osteoarthritis (OA) is a disease that primarily results in the degeneration and destruction of the articular cartilage. However, synovitis that occurs secondarily by this primary phenomenon is crucial for both the structural and symptomatic progression of the disease. The Japanese Knee Osteoarthritis Measure (JKOM) was created as an outcome measure for Japanese patients with knee OA. This study was conducted to determine whether synovitis in knee OA correlates with the current disability of patients with knee OA who required total knee arthroplasty (TKA). Thirty-four Japanese patients with end-stage knee OA who required TKA were included in this study. The visual analog scale (VAS, 0-100) for pain and the JKOM score, as well as the Western Ontario and McMaster Universities Arthritis Index (WOMAC), were examined before the operation. Synovial samples were taken at the time of the operation. A histological analysis and gadolinium-enhanced magnetic resonance imaging (Gd-MRI) were conducted to evaluate synovitis. Correlations between the synovitis score evaluated by histological analysis and Gd-MRI with either the pain VAS score or the JKOM score were examined using Spearman's rank correlation coefficient. Neither the synovitis scores evaluated by the histological analysis nor those by a Gd-MRI correlated with the pain VAS score (n = 34, r = 0.25, p = 0.18 and r = 0.08, p = 0.75, respectively) and WOMAC (n = 14, r = 0.35, p = 0.22 and r = 0.45, p = 0.16, respectively) of the patients. However, they significantly correlated with the JKOM score of the patients (n = 34, r = 0.55, p = 0.001 and r = 0.71, p = 0.001, respectively). The severity of synovitis in OA was closely correlated with the current functional impairment and disability of the patients receiving TKA with end-stage knee OA.

PET assessment of disease activity in children with juvenile idiopathic arthritis

The degree of 18-fluorodeoxyglucose (FDG) uptake is previously reported to correlate with physical examination and laboratory tests for evaluating disease activity in patients with rheumatoid arthritis. The clinical validity of (18)F-FDG positron emission tomography (PET) has not been evaluated in juvenile idiopathic arthritis (JIA). To assess the relationship between (18)F-FDG PET uptake and disease activity in children with JIA. A total of 560 joints in 28 children (mean age, 5.4 years; range, 1-16 years) with JIA who had undergone whole-body (18)F-FDG PET before treatment were retrospectively assessed clinically, biochemically and radiographically. PET images were assessed independently by two readers. We investigated the relationships between the degree of synovial (18)F-FDG uptake and radiographic and clinical symptoms and laboratory findings. Joint tenderness and swelling had a positive association with abnormal (18)F-FDG uptake in the joint [odds ratio (OR) 5.37, 7.12, respectively]. The standardized uptake value (SUV) max correlated with the neutrophil count, plasma C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and matrix metalloproteinase (MMP) 3. Joint erosion (OR, 6.17), soft-tissue swelling (OR, 3.77), major joints involvement (OR, 3.50), tenderness (OR, 5.22), and CRP concentration in plasma (OR, 1.81) were positively associated with SUVmax. The degree of (18)F-FDG uptake may be associated with the severity of synovitis in children with JIA.

Relation of synovitis to knee pain using contrast-enhanced MRIs

BackgroundIt has been suggested that synovitis causes joint pain. On non-contrast-enhanced MRIs synovial thickening cannot be assessed and on these images synovitis has been inconsistently associated with pain.ObjectiveTo assess synovial...

Reversible severe synovitis associated with everolimus

Inhibitors of mammalian target of rapamycin (mTOR) are immunosuppressants with less nephrotoxicity than calcineurin inhibitors and have anti-proliferative effects.1 However, clinical use of mTOR inhibitors can be associated with a number of adverse events. We report a case of everolimus-associated severe synovitis in a heart transplant recipient with a targeted trough blood level, who was successfully treated by drug withdrawal.