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ID PMID Title PublicationDate abstract
20849666 Strongyloides stercoralis hyperinfection in a patient with rheumatoid arthritis and bronch 2010 Sep 20 OBJECTIVE: Strongyloides stercoralis is a soil-transmitted intestinal nematode that has been estimated to infect at least 60 million people, especially in tropical and subtropical regions. Strongyloides infection has been described in immunosupressed patients with lymphoma, rheumatoid arthritis, diabetes mellitus etc. Our case who has rheumatoid arthritis (RA) and bronchial asthma was treated with low dose steroids and methotrexate. METHODS: A 68 year old woman has bronchial asthma for 55 years and also diagnosed RA 7 years ago. She received immunusupressive agents including methotrexate and steroids. On admission at hospital, she was on deflazacort 5 mg/day and methotrexate 15 mg/week. On her physical examination, she was afebrile, had rhonchi and mild epigastric tenderness. She had joint deformities at metacarpophalengeal joints and phalanges but no active arthritis finding. RESULTS: Oesophagogastroduodenoscopy was performed and it showed hemorrhagic focus at bulbus. Gastric biopsy obtained and showed evidence of S.Stercoralis infection. Stool and sputum parasitological examinations were also all positive for S.stercoralis larvae. Chest radiography result had no pathologic finding. Albendazole 400 mg/day was started for 23 days. After the ivermectin was retrieved, patient was treated with oral ivermectin 200 μg once a day for 3 days. On her outpatient control at 15th day, stool and sputum samples were all negative for parasites. CONCLUSION: S.stercoralis may cause mortal diseases in patients. Immunosupression frequently causes disseminated infections. Many infected patients are completely asymptomatic. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. In immunosupressed patients, to detect S.stercoralis might help to have the patient survived and constitute the exact therapy.
20153319 Role of matrix metalloproteinases in recurrent corneal melting. 2010 May The aim of this study was to compare the presence and activity of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9 and 13 in human melted and cadaverous corneas. Twelve melted corneal specimens from three patients with rheumatoid arthritis, one patient with ocular cicatricial pemphigoid and one patient with melting attributed to spastic entropion and ten control corneal buttons were used. The presence of MMPs was detected using indirect enzyme immunohistochemistry. The active forms of MMP-2 and -9 and MMP-3 and -7 were examined by gelatin and casein zymography, respectively. The concentrations of active MMP-1 and -3 were measured using activity assays. Increased immunostaining intensity for MMP-1 and -9 was seen in the corneal epithelium and the anterior stroma of all, and for MMP-2, -3, -7 and -8 of almost all, melted corneas compared to the negative or slightly positive staining of the controls. The posterior stroma showed the presence of MMP-1, -2, -3 and -9 in almost all and of MMP-7 and -8 in half of all melted specimens. A markedly higher level of active MMP-2 was detected in six and active MMP-9 in all of eleven pathologic specimens compared to control specimens, using gelatin zymography. The proenzymes of MMP-3 and -7 and the MMP-7 intermediate cleavage product were detected only in melted corneas using casein zymography. Significantly increased MMP-1 and -3 activity was also found in the melted corneas using activity assays. The markedly increased immunostaining for MMP-1, -2, -3, -7, -8 and -9 as well as the elevated levels of the active forms of MMP-1, -2, -3 and -9 in melted corneal specimens from patients with various diagnoses suggest that although different stimuli may trigger the pathways that lead to the destruction of the extracellular matrix, these enzymes could play a subsequent role in this process.
19543730 Macrophagic myofascitis associated with rheumatoid arthritis. 2010 May Macrophagic myofascitis (MMF) is an unusual inflammatory myopathy characterized by muscle infiltration by macrophages and lymphocytes. Here, we describe a case of MMF which is associated with rheumatoid arthritis. A 53-year-old Japanese rheumatoid arthritis (RA) patient presented with focal tenderness of lower extremities. Magnetic resonance imaging showed evidence of myofascitis involving fascias of anterior tibialis muscle. Muscle biopsy showed a unique pathological pattern of MMF. MMF is known to be associated with vaccination containing aluminum. However, our case was not related to aluminum containing vaccinations and etiologies are unknown. The possible link needs to be discussed.
19773290 EULAR evidence-based recommendations for cardiovascular risk management in patients with r 2010 Feb OBJECTIVES: To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. RESULTS: Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. CONCLUSIONS: Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.
20064207 Risk of incident or recurrent malignancies among patients with rheumatoid arthritis expose 2010 INTRODUCTION: We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs). METHODS: The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis). RESULTS: A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFalpha agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFalpha: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFalpha agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFalpha vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFalpha agents (P = 1.0). CONCLUSIONS: No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.
20661469 Identification of the rheumatoid arthritis shared epitope binding site on calreticulin. 2010 Jul 22 BACKGROUND: The rheumatoid arthritis (RA) shared epitope (SE), a major risk factor for severe disease, is a five amino acid motif in the third allelic hypervariable region of the HLA-DRbeta chain. The molecular mechanisms by which the SE affects susceptibility to--and severity of--RA are unknown. We have recently demonstrated that the SE acts as a ligand that interacts with cell surface calreticulin (CRT) and activates innate immune signaling. In order to better understand the molecular basis of SE-RA association, here we have undertaken to map the SE binding site on CRT. PRINCIPAL FINDINGS: Surface plasmon resonance (SPR) experiments with domain deletion mutants suggested that the SE binding site is located in the P-domain of CRT. The role of this domain as a SE-binding region was further confirmed by a sulfosuccinimidyl-2-[6-(biotinamido)-2-(p-azido-benzamido) hexanoamido] ethyl-1,3-dithiopropionate (sulfo-SBED) photoactive cross-linking method. In silico analysis of docking interactions between a conformationally intact SE ligand and the CRT P-domain predicted the region within amino acid residues 217-224 as a potential SE binding site. Site-directed mutagenesis demonstrated involvement of residues Glu(217) and Glu(223)--and to a lesser extent residue Asp(220)--in cell-free SPR-based binding and signal transduction assays. SIGNIFICANCE: We have characterized here the molecular basis of a novel ligand-receptor interaction between the SE and CRT. The interaction represents a structurally and functionally well-defined example of cross talk between the adaptive and innate immune systems that could advance our understanding of the pathogenesis of autoimmunity.
20879879 An oral spleen tyrosine kinase (Syk) inhibitor for rheumatoid arthritis. 2010 Sep 30 BACKGROUND: Spleen tyrosine kinase (Syk) is an important modulator of immune signaling. The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy. METHODS: We enrolled 457 patients who had active rheumatoid arthritis despite long-term methotrexate therapy in a 6-month, double-blind, placebo-controlled trial. The primary outcome was the American College of Rheumatology (ACR) 20 response (which indicates at least a 20% reduction in the number of both tender and swollen joints and improvement in at least three of five other criteria) at month 6. RESULTS: R788, at a dose of 100 mg twice daily and at a dose of 150 mg once daily, was significantly superior to placebo at month 6 (ACR 20 response rates of 67% and 57%, respectively, vs. 35%; P<0.001 for the comparison of both doses with placebo). It was also significantly superior with respect to ACR 50, which indicates at least a 50% improvement (43% and 32% vs. 19%; P<0.001 for the comparison of the 100-mg dose with placebo, P=0.007 for the comparison of the 150-mg dose with placebo) and ACR 70 (28% and 14% vs. 10%; P<0.001 for the comparison of the 100-mg dose with placebo, P=0.34 for the comparison of the 150-mg dose with placebo). A clinically significant effect was noted by the end of the first week of treatment. Adverse effects included diarrhea (in 19% of subjects taking the 100-mg dose of R788 vs. 3% of those taking placebo), upper respiratory infections (14% vs. 7%), and neutropenia (6% vs. 1%). R788 was associated with an increase in systolic blood pressure of approximately 3 mm Hg between baseline and month 1, as compared with a decrease of 2 mm Hg with placebo; 23% of the patients taking R788 vs. 7% of the patients receiving placebo required the initiation of or a change in antihypertensive therapy. CONCLUSIONS: In this phase 2 study, a Syk inhibitor reduced disease activity in patients with rheumatoid arthritis; adverse events included diarrhea, hypertension, and neutropenia. Additional studies will be needed to further assess the safety and efficacy of Syk-inhibition therapy in patients with rheumatoid arthritis. (Funded by Rigel; ClinicalTrials.gov number, NCT00665925.)
21120562 Effectiveness of radiation synovectomy with Yttrium-90 and Samarium-153 particulate hydrox 2011 Jan The aim of the present study was to investigate the long-term effectiveness of and tolerance to Yttrium-90 and Samarium-153-particulate hydroxyapatite radiation synovectomy in patients with rheumatoid arthritis (RA) and chronic knee synovitis. Eight-four patients (90 knees) with chronic knee synovitis and RA (according to the American College of Rheumatology criteria) participated in a controlled, double-blinded trial. Patients were randomized to receive an intra-articular injection with either 5 mCi Yttrium-90 plus 40 mg of triamcinolone hexacetonide (Y/TH Group), 15 mCi Samarium-153 hydroxyapatite plus 40 mg of triamcinolone hexacetonide (Sm/TH Group), or 40 mg triamcinolone hexacetonide alone (Control Group). Blinded examination at baseline, 1, 4, 12, 32, and 48 weeks post-intervention included a visual analog scale for joint pain and swelling, morning stiffness, range of motion, knee circumference, Likert scale, percentage of improvement, Stanford Health Assessment Questionnaire, Lequesne index, use of non-steroidal anti-inflammatory drugs and corticosteroids, events and adverse effects, calls to the physician, and hospital visits. There were three withdrawals prior to the injections. Regarding the pain, there was a significantly better response in the Y/TH Group versus the Sm/TH Group at T1 (p = 0.025) and versus TH alone at T48 (p = 0.026). The Sm/TH group had more adverse effects (p = 0.042), but these were mild and transitory. For the pain parameter alone, Yttrium-90 radiosynovectomy associated to TH proved superior to Samarium-153 hydroxyapatite radiosynovectomy associated to TH at T1 and to synovectomy with TH at T48. No other statistically significant inter-group differences were detected.
19452100 Are glucocorticoids a consistent risk factor for infections in rheumatoid arthritis patien 2009 OBJECTIVE: To evaluate the incidence of infections in subjects with rheumatoid arthritis (RA), treated with an anti-TNFalpha blocker during one year follow-up. The aim of the study was focused to evaluate the number of infectious episodes in two groups of patients treated with etanercept (ETN) plus methotrexate (MTX) or ETN plus MTX and glucocorticoid drugs (GCs/prednisone) for a 12 months period. MATERIALS AND METHODS: Sixty-nine out of 122 RA patients treated with an anti-TNFalpha drug (ETN) were included in an outpatient control system within the Immunology Department Sapienza-University of Rome-II; School of Medicine. RA patients were studied during the first year after ETN introduction. Particularly 20 RA patients have been included in a subgroup. For these 20 patients infections have been monitored for 2 years: 12 months before and 12 months after ETN treatment starting. RESULTS: According to drugs administration protocols, after a careful screening aiming to exclude latent tuberculosis infection, 20 patients have been treated with ETN (10 of them received treatment in association to MTX, while 10 were given a GCs therapy plus MTX). During the one-year ETN treatment period, 7 infections have been described in the group treated with ETN, MTX and GCs and no infection in the group treated with ETN and MTX. After analysing the infection number in the two groups of patients, in the year preceding biological treatment no significant change arose. CONCLUSIONS: The risk of infections in subjects treated with the biological drug ETN is well known. Our data show that after one year therapy the [ETN+MTX+GCs] group is marked by a greater frequency of infectious episodes compared to the subjects treated with ETN plus MTX. Therefore, the additional infectious risk appears to be related to steroid therapy itself, though infections were not serious.
20096537 Iliopsoas tendonitis caused by overhang of a collared femoral prosthesis. 2011 Apr Pain after total hip arthroplasty can be due to a variety of causes, one of the less common being iliopsoas tendonitis. We report an unusual case of iliopsoas tendonitis caused by overhang of the femoral calcar by a collared femoral prosthesis resulting in impingement on the iliopsoas tendon. An ultrasound-guided corticosteroid and local anesthetic diagnostic injection to the site of impingement confirmed the diagnosis with temporary symptom relief. Revision of the femoral stem to a collarless prosthesis resulted in immediate and complete resolution of symptoms.
20663638 Influence of prosthetic design on squeaking after ceramic-on-ceramic total hip arthroplast 2010 Sep Squeaky ceramic-on-ceramic (COC) total hips have received much recent publicity, and implant design may be implicated. We reviewed 270 consecutive COC total hip arthroplasties in 233 patients comparing 4 implant combinations representing 4 manufacturers. A cohort (n = 45) of Stryker Trident acetabular cups paired with Stryker Accolade femoral stems showed a dramatically higher incidence of "problem squeaking"--defined as always audible to others and occurring at least once per week--with a 35.6% incidence of squeaking and 11.1% incidence of problem squeaking. The 3 non-Stryker designs (n = 225) revealed 3.6% squeaking (P < .0001) and 0.44% problem squeaking (P = .006). The Stryker system has a unique design and metallurgy. Our results suggest that although the genesis of squeaking in COC total hips is multifactorial, prosthetic design plays a key role.
20580552 NF-kappaB inducing kinase (NIK) inhibitors: identification of new scaffolds using virtual 2010 Aug 1 As a wide variety of pro-inflammatory cytokines are involved in the development of rheumatoid arthritis (RA), there is an urgent need for the discovery of novel therapeutic strategies. Among these, the inhibition of the NF-kappaB inducing kinase (NIK), a key enzyme of the NF-kappaB alternative pathway activation, represents a potential interesting approach. In fact, NIK is involved downstream of many tumor necrosis factor receptors (TNFR) like CD40, RANK or LTbetaR, implicated in the pathogenesis of RA. But, up to now, the number of reported putative NIK inhibitors is extremely limited. In this work, we report a virtual screening (VS) study combining various filters including high-throughput docking using a 3D-homology model and ranking by using different scoring functions. This work led to the identification of two molecular fragments, 4H-isoquinoline-1,3-dione (5) and 2,7-naphthydrine-1,3,6,8-tetrone (6) which inhibit NIK with an IC(50) value of 51 and 90 microM, respectively. This study opens new perspectives in the field of the NF-kappaB alternative pathway inhibition.
20152870 Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and impr 2010 Jun 1 Macrophages play key roles in inflammatory disorders. Therefore, they are targets of treatments aiming at their local destruction in inflammation sites. However, injection of low molecular mass therapeutics, including photosensitizers, in inflamed joints results in their rapid efflux out of the joints, and poor therapeutic index. To improve selective uptake and increase retention of therapeutics in inflamed tissues, hydrophilic nanogels based on chitosan, of which surface was decorated with hyaluronate and which were loaded with one of three different anionic photosensitizers were developed. Optimal uptake of these functionalized nanogels by murine RAW 264.7 or human THP-1 macrophages as models was achieved after <4h incubation, whereas only negligible uptake by murine fibroblasts used as control cells was observed. The uptake by cells and the intracellular localization of the photosensitizers, of the fluorescein-tagged chitosan and of the rhodamine-tagged hyaluronate were confirmed by fluorescence microscopy. Photodynamic experiments revealed good cell photocytotoxicity of the photosensitizers entrapped in the nanogels. In a mouse model of rheumatoid arthritis, injection of free photosensitizers resulted in their rapid clearance from the joints, while nanogel-encapsulated photosensitizers were retained in the inflamed joints over a longer period of time. The photodynamic treatment of the inflamed joints resulted in a reduction of inflammation comparable to a standard corticoid treatment. Thus, hyaluronate-chitosan nanogels encapsulating therapeutic agents are promising materials for the targeted delivery to macrophages and long-term retention of therapeutics in leaky inflamed articular joints.
19915943 Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients wit 2010 Apr P-glycoprotein (P-gp) on activated lymphocytes is an adenosine triphosphate (ATP)-binding cassette transporter that causes drug resistance by exclusion of intracellular drugs in patients with active rheumatoid arthritis (RA). However, infliximab with methotrexate (MTX) can overcome P-gp-mediated drug resistance. We encounter patients who cannot continue infliximab or MTX. Here we tested how etanercept affected P-gp-mediated drug resistance in such intractable RA patients. Peripheral lymphocytes of 11 RA patients (3 switched from infliximab and 8 who could not be treated with MTX) were analyzed for P-gp expression by flow cytometry and for drug exclusion using radioisotope-labeled dexamethasone. Activated lymphocytes of RA patients overexpressed P-gp and coexpressed CD69. Incubation of these lymphocytes with dexamethasone in vitro reduced intracellular dexamethasone levels. Two-week etanercept therapy significantly reduced P-gp expression and eliminated such P-gp- and CD69-high-expressing subgroup. The reduction in P-gp resulted in recovery of intracellular dexamethasone levels in lymphocytes and improvement of disease activity, thus allowing tapering of corticosteroids. None of the patients experienced any severe adverse effects. Etanercept is useful for overcoming P-gp-mediated treatment resistance in intractable RA patients who have to discontinue infliximab or are intolerant to MTX.
19706737 Benefit of anti-TNF therapy in rheumatoid arthritis patients with moderate disease activit 2009 Oct OBJECTIVES: Anti-TNF therapy has improved outcomes for patients with highly active RA. Less is known about its effectiveness in patients with lower disease activity. The aim of this analysis is to compare the response to anti-TNF therapy between RA patients with high (DAS28 > 5.1) and moderate (DAS28 > 3.2-5.1) disease activity. METHODS: A total of 4687 anti-TNF and 344 DMARD patients with high disease activity despite treatment with two standard DMARDs (including MTX) and 224 anti-TNF- and 300 DMARD-treated patients with moderate disease activity were selected from the British Society For Rheumatology Biologics Register. Mean change in HAQ over the first 12 months of enrolment was compared first between anti-TNF-treated and untreated patients in each DAS28 group, and then between anti-TNF-treated patients in the moderate and high DAS28 groups, using doubly robust estimates, adjusting for age, gender, disease duration, baseline HAQ and DAS28 score, number of previous DMARDs and steroid use. RESULTS: Compared with anti-TNF-untreated patients within each DAS group, treated patients were younger, had higher DAS28 and HAQ and had failed a higher number of previous DMARDs. The mean adjusted change in HAQ over 12 months was similar in anti-TNF-treated patients with moderate and high disease activity at baseline: moderate -0.26 (95% CI -0.35, -0.16), high -0.28 (95% CI -0.34, -0.23) and mean difference -0.03 (95% CI -0.14, 0.08). CONCLUSIONS: Improvement in HAQ score 12 months after start of anti-TNF therapy was not dependent on baseline DAS28 scores, suggesting that substantial benefits may also be gained by treating those with moderately active disease despite standard DMARD therapy.
20233177 Co-administration of the JAK inhibitor CP-690,550 and methotrexate is well tolerated in pa 2010 Feb AIMS: To investigate the effects of methotrexate (MTX) on the pharmacokinetics (PK) of CP-690,550, a novel Janus kinase (JAK) inhibitor in development as a therapy for rheumatoid arthritis (RA), to determine the effects of multiple doses of CP-690,550 on the PK of MTX, and to evaluate the short-term safety and tolerability of co-administration of CP-690,550 and MTX. METHODS: This was a fixed-dose drug-drug interaction study. Twelve patients diagnosed with RA for at least 6 months were enrolled in a Phase I, open-label study of the PK of multiple doses of CP-690,550 (30 mg b.i.d.) and single doses of MTX (15-25 mg per week). RESULTS: All patients completed the study and were evaluated for PK and safety. CP-690,550 exposure was not affected by co-administration with MTX; AUC(12) ratio (CP-690,550 + MTX/CP-690,550) was 103.06% [90% confidence interval (CI) 99.00, 107.29]. MTX exposure decreased by 10%; AUC(12) ratio (CP-690,550 + MTX/MTX) was 89.53% (90% CI 77.38, 103.57), which was not considered clinically significant. Co-administration of CP-690,550 and MTX was safe and well tolerated. There were no serious adverse events or withdrawals from the study and there was no trend in the incidence or severity of adverse events across treatments. CONCLUSIONS: Co-administration of CP-690,550 and MTX was safe and well tolerated. There was no clinically significant effect on the PK profile of either drug. Therefore, dose adjustments should not be required when co-administering CP-690,550 and MTX.
19728013 Risk factors for the development of gastric mucosal lesions in rheumatoid arthritis patien 2009 The objective of this study was to investigate the prevalence of gastric mucosal injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA). Upper gastrointestinal endoscopy was performed on 100 RA patients treated with NSAIDs. Patient factors potentially contributing to the development of NSAID-induced gastric mucosal injury were identified by logistic regression analysis; gastric mucosal injury and ulcers were used as objective variables. Gastric mucosal injury was detected in 62 of 100 patients, and eight of these patients had ulcers. Previous history of ulcers, lifestyle, NSAID dosage, and body mass index were associated with the development of gastric mucosal injury,and the use of diclofenac and steroid dose were associated with the development of ulcers. Disease-modifying antirheumatic drugs (DMARDs) did not appear to influence the risk of NSAID-induced gastric mucosal injury. RA patients treated for long periods with NSAIDs for RA symptoms should be controlled with DMARDs, without consideration of increased doses of steroids, in terms of risk for NSAID-induced gastric mucosal injury. Simultaneously, concomitant use of histamine-2 receptor antagonists (H2RA) such as famotidine should be considered.
20823656 Rheumatoid leptomeningitis: radiological alteration of cerebral hypoperfusion and subarach 2010 A 56-year-old man with rheumatoid arthritis developed emotional lability and myoclonic seizure in the left arm, followed by fever and generalized convulsion. Brain magnetic resonance imaging (MRI) revealed leptomeningeal lesions with abnormal enhancement. MRI lesions were localized predominantly in the right cerebral subarachnoid spaces. Electroencephalogram showed epileptogenic focus at the right frontal and central points. After administration of valproate sodium improved convulsion and myoclonus, single photon emission computed tomography (SPECT) using N-isopropyl-p-(123)I-iodoamphetamine was performed. Brain SPECT displayed hypoperfusion predominantly in the right cerebral hemisphere. Cerebrospinal fluid (CSF) disclosed mild pleocytosis and marked elevations of interleukin-6 levels. Repeated CSF analyses showed cytology of class I and negative results for infectious pathogens. Methylprednisolone pulse therapy (1 g for 3 days, iv) and subsequent prednisolone administration (daily 50 mg, po) ameliorated neurological symptoms dramatically. Prednisolone was tapered to 20 mg/day for 5 months. Leptomeningeal MRI lesions were attenuated gradually followed by restoration of cerebral hypoperfusion on SPECT. He was diagnosed as rheumatoid leptomeningitis (RLM). Although clinical features of RLM exhibited variable deficits of the central nervous system (CNS), MRI failed to detect the corresponding CNS lesions. We first highlighted neuroradiological changes of cerebral hypoperfusion and leptomeningeal lesions in RLM. These neuroimages of our patient supported that leptomeningeal inflammation and the adjacent cerebrocortical ischemia could cause encephalitis-like symptoms in RLM patients.
20628268 Synovial fluid of patients with rheumatoid arthritis induces alpha-smooth muscle actin in 2010 Aug 31 Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-beta1 (TGF-beta1) is a secreted protein that promotes differentiation of synovial fibroblasts to alpha-smooth muscle actin (alpha-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of alpha-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced alpha-SMA expression was abrogated by immunodepletion of TGF-beta1 from RA-SF with anti-TGF-beta1 antibody. Furthermore, pretreatment of hASCs with the TGF-beta type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-beta type I receptor expression in hASCs blocked RA-SF-induced alpha-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated alpha-SMA expression. These results suggest that TGF-beta1 plays a pivotal role in RA-SF-induced differentiation of hASCs to alpha-SMA-positive cells.
19755507 Benefits of ultrasonography in the management of early arthritis: a cross-sectional study 2009 Dec OBJECTIVE: To assess ultrasonography's (US) performance to detect the structural damage in the initial evaluation of early arthritis (EA) using the Etude et Suivides Polyarthrites Indifférenciées Récentes (ESPOIR) cohort. METHODS: ESPOIR is a French, multi-centric EA cohort. Four centres assessed the structural damage by both X-ray and US examination at baseline. X-rays of hands and feet were read first by the centre's local investigator (usual reading), then in the X-ray coordinating centre (central reading). Four trained examiners performed US blindly from clinical data to detect erosions on the second and fifth MCP (MCP2 and 5) and the fifth MTP (MTP5) joints bilaterally. RESULTS: Patients' characteristics (n = 126) were: female 78%; mean age 50.3 years; disease duration 103 days; disease activity score on 28 joints 5; CRP level 22.7 mg/l; and 79.4% of the patients fulfilling RA ACR criteria. Twelve patients had missing data for X-rays. US revealed 42 (36.8%) patients with erosive disease, whereas radiography revealed only 30 (26%) with central reading and only 11% with usual reading. US missed erosive disease present in X-rays in 10 (8.8%) patients. Combined technique of both revealed 52 (45.6%) patients with erosive diseases. On the targeted joints, US detected erosion on 75 (11%) joints vs X-rays on only 11 (1.5%). Only three joints with erosion(s) detected on X-rays were missed on US. At baseline, the presence of PD activity was not associated with joint erosions. CONCLUSIONS: US on six joints detected 1.4-fold more patients with erosions (3.3-fold more with the usual reading). In clinical practice, US combined with X-rays is of helpful diagnostic value in EA.