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ID PMID Title PublicationDate abstract
16935916 Clinical and immunological characteristics of patients with Sjögren's syndrome in relatio 2007 Mar OBJECTIVES: To analyse the prevalence of alpha-fodrin antibodies in patients with primary (pSS) and secondary Sjögren's syndrome (sSS) and the relation to clinical, serological and immunological features. METHODS: Serum IgA and IgG antibodies to the 120 kDa alpha-fodrin were determined by ELISA technique in 62 pSS patients and 28 sSS patients. Results were correlated with clinical symptoms and laboratory findings as well as with the HLA-DR genotype. Additionally, antibody concentrations were correlated with the numbers of peripheral blood mononuclear cells (PBMCs) secreting interleukin (IL)-6, IL-10, interferon-gamma (INF)-gamma, and tumour necrosis factor-alpha determined by ELISPOT analysis. Lymphocytes and monocytes were examined flow-cytometrically for the expression of activation markers. Healthy age- and sex-matched volunteers served as controls. RESULTS: The sensitivity of IgA and IgG alpha-fodrin antibodies was 35 and 31%, respectively, in pSS patients. In sSS patients, the sensitivity was 29 and 21%, respectively. In pSS patients with IgG antibodies, recurrent parotid swelling was significantly more prevalent. Also the number of INF-gamma secreting PBMCs and the percentage of CD4/CD71+ lymphocytes as well as CD14/HLA-DR+ monocytes were significantly increased in this group compared with alpha-fodrin-negative patients or with controls. Interestingly, these patients also had a shorter disease duration. No association of alpha-fodrin antibodies with the HLA-DR genotype was found. CONCLUSION: Due to the low prevalence, serum antibodies to alpha-fodrin turned out to be of limited diagnostic value in our study. However, our data suggest that IgG antibodies to alpha-fodrin are indicative of clinical and immunological activity in pSS especially in patients with shorter disease duration and may thus serve as a marker of disease activity.
17118334 Effects of autonomic agonists and immunomodulatory cytokines on polymeric immunoglobulin r 2007 May OBJECTIVE: Immunoglobulin A (IgA) is transported across glandular epithelial cells by polymeric immunoglobulin receptor (plgR), with each receptor molecule participating in only one round of transcytosis. Nerve-related stimuli rapidly increase salivary secretion of IgA, while concentrations are increased in the autoimmune disease Sjögren's syndrome. Our aim here was to determine whether autonomic agonists and cytokines present in Sjögren's-affected glands can up-regulate salivary cell plgR expression. METHODS: Cultures of rat parotid acinar cells (PAR C5) and human submandibular gland ductal cells (HSG) were exposed to carbachol or adrenaline for 24 h and to interleukin-4 and/or interferon-gamma for 48 h. The human colonic cell line HT-29 served as a positive control for cytokine response. plgR mRNA was quantified by reverse transcription and real-time PCR and protein expression was examined by immunoblotting. RESULTS: Carbachol increased plgR mRNA levels significantly in all cells but adrenaline did so only with PAR cells (P<0.05). HSG and HT-29 cells both up-regulated plgR gene transcription on exposure to interleukin-4 and interferon-gamma either alone or in combination (P<0.05). By contrast, production of plgR mRNA in PAR cells tended to decrease in response to all cytokine treatments. plgR protein levels rose in line with mRNA expression in cytokine-treated HT-29 cultures (P<0.05). CONCLUSIONS: Autonomimetics can up-regulate plgR transcription in transformed and neoplastic salivary and colonic cells, although intracellular coupling mechanisms require further investigation. Immunomodulatory cytokines increased plgR expression in one of the salivary cell lines, but additional work is needed to establish whether this occurs in Sjögren's patients.
15545270 Autoimmunity against a tissue kallikrein in IQI/Jic Mice: a model for Sjogren's syndrome. 2005 Feb 4 We have recently characterized IQI/Jic mice as a model for Sjogren's syndrome (SS), a chronic autoimmune disease in humans. In SS, local lymphocytic infiltrations into salivary and lacrimal glands frequently develop to the involvement of systemic exocrine and nonexocrine organs, and the mechanism for progression of this disease remains obscure. Herein, we report identification of an autoantigen shared by various target organs in IQI/Jic mice. Polypeptides identified based on immunorecognition by autoantibodies in sera from IQI/Jic mice affected with autoimmune disease (>12 weeks of age) were tissue kallikrein (Klk)-1 and -13 and were cross-reactive to the autoantibodies. Interestingly, Klk-13, but not Klk-1, caused a proliferative response of splenic T cells from IQI/Jic mice from the age of 4 weeks onward. In addition, remarkably enhanced expression of Klk-13 was observed in the salivary glands of the mice in accordance with the development of inflammatory lesions. These results indicate that Klk-13 acts as an autoantigen and may increase T cells responsive to organs commonly expressing Klk-13, playing a pivotal role in the etiology of progression of disease in IQI/Jic mice. Our findings provide insights into the contributions of autoantigens shared by multiple organs in the progress of SS from an organ-specific to a systemic disorder.
23074463 Arthroscopic lavage and debridement for osteoarthritis of the knee: an evidence-based anal 2005 OBJECTIVE: The purpose of this review was to determine the effectiveness and adverse effects of arthroscopic lavage and debridement, with or without lavage, in the treatment of symptoms of osteoarthritis (OA) of the knee, and to conduct an economic analysis if evidence for effectiveness can be established. QUESTIONS ASKED: Does arthroscopic lavage improve motor function and pain associated with OA of the knee?Does arthroscopic debridement improve motor function and pain associated with OA of the knee?If evidence for effectiveness can be established, what is the duration of effect?What are the adverse effects of these procedures?What are the economic considerations if evidence for effectiveness can be established? CLINICAL NEED: Osteoarthritis, the most common rheumatologic musculoskeletal disorder, affects about 10% of the Canadian adult population. Although the natural history of OA is not known, it is a degenerative condition that affects the bone cartilage in the joint. It can be diagnosed at earlier ages, particularly within the sports injuries population, though the prevalence of non-injury-related OA increases with increasing age and varies with gender, with women being twice as likely as men to be diagnosed with this condition. Thus, with an aging population, the impact of OA on the health care system is expected to be considerable. Treatments for OA of the knee include conservative or nonpharmacological therapy, like physiotherapy, weight management and exercise; and more generally, intra-articular injections, arthroscopic surgery and knee replacement surgery. Whereas knee replacement surgery is considered an end-of-line intervention, the less invasive surgical procedures of lavage or debridement may be recommended for earlier and more severe disease. Both arthroscopic lavage and debridement are generally indicated in patients with knee joint pain, with or without mechanical problems, that are refractory to medical therapy. The clinical utility of these procedures is unclear, hence, the assessment of their effectiveness in this review. LAVAGE AND DEBRIDEMENT: Arthroscopic lavage involves the visually guided introduction of saline solution into the knee joint and removal of fluid, with the intent of extracting any excess fluids and loose bodies that may be in the knee joint. Debridement, in comparison, may include the introduction of saline into the joint, in addition to the smoothening of bone surface without any further intervention (less invasive forms of debridement), or the addition of more invasive procedures such as abrasion, partial or full meniscectomy, synovectomy, or osteotomy (referred to as debridement in combination with meniscectomy or other procedures). The focus of this health technology assessment is on the effectiveness of lavage, and debridement (with or without meniscal tear resection). REVIEW STRATEGY: THE MEDICAL ADVISORY SECRETARIAT FOLLOWED ITS STANDARD PROCEDURES AND SEARCHED THESE ELECTRONIC DATABASES: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment. THE KEYWORDS SEARCHED WERE: arthroscopy, debridement, lavage, wound irrigation, or curettage; arthritis, rheumatoid, osteoarthritis; osteoarthritis, knee; knee or knee joint. TIME FRAME: Only 2 previous health technology assessments were identified, one of which was an update of the other, and included 3 of 4 randomized controlled trials (RCTs) from the first report. Therefore, the search period for inclusion of studies in this assessment was January 1, 1995 to April 24, 2005. EXCLUDED WERE: case reports, comments, editorials, and letters. Identified were 335 references, including previously published health technology assessments, and 5 articles located through a manual search of references from published articles and health technology assessments. These were examined against the criteria, as described below, which resulted in the inclusion of 1 health technology assessment and its corresponding update, and 4 articles (2 RCTs and 2 level 4 studies) for arthroscopic lavage and 8 papers (2 RCTs and 6 level 4 studies) for arthroscopic debridement. INCLUSION CRITERIA: English-language articles from PubMed, EMBASE, Cochrane Systematic Reviews, and health technology assessments from January 1, 1995 onwardStudies on OA of the knee with a focus on the outcomes of motor function and painStudies of arthroscopic procedures onlyStudies in which meniscal tear resection/meniscectomy (partial or full) has been conducted in conjunction with lavage or debridement. EXCLUSION CRITERIA: Studies that focus on inflammatory OA, joint tuberculosis, septic joints, psoriatic joints (e.g., psoriatic knee joint synovitis), synovitis, chondropathy of the knee and gonarthrosis (which includes varotic gonarthrosis)Studies that focus on rheumatoid arthritisStudies that focus on meniscal tears from an acute injury (e.g., sports injury)Studies that are based on lavage or debridement for microfracture of the kneeStudies in which other surgical procedures (e.g., high tibial osteotomy, synovectomy, have been conducted in addition to lavage/debridement)Studies based on malalignment of the knee (e.g., varus/valgus arthritic conditions).Studies that compare lavage to lavage plus drug therapyStudies on procedures that are not arthroscopic (i.e., visually guided) (e.g., nonarthroscopic lavage)Studies of OA in children. INTERVENTION: Arthroscopic lavage or debridement, with or without meniscectomy, for the treatment of motor function symptoms and pain associated with OA of the knee. COMPARATORS: Studies in which there was a comparison group of either diseased or healthy subjects or one in which subjects were their own control were included. Comparisons to other treatments included placebo (or sham) arthroscopy. Sham arthroscopy involved making small incisions and manipulating the knee, without the insertion of instruments. SUMMARY OF FINDINGS: IN EARLY OA OF THE KNEE WITH PAIN REFRACTORY TO MEDICAL TREATMENT, THERE IS LEVEL 1B EVIDENCE THAT: Arthroscopic lavage gives rise to a statistically significant, but not clinically meaningful effect in improving pain (WOMAC pain and VAS pain) up to 12 months following surgery. The effect on joint function (WOMAC function) and the primary outcome (WOMAC aggregate) was neither statistically nor clinically significant. IN MODERATE OR SEVERE OA OF THE KNEE WITH PAIN REFRACTORY TO MEDICAL TREATMENT, THERE IS: Level 1b evidence that the effect on pain and function of arthroscopic lavage (10 L saline) and debridement (with 10 L saline lavage) is not statistically significant up to 24 months following surgery.Level 2 evidence that arthroscopic debridement (with 3 L saline lavage) is effective in the control of pain in severe OA of the medial femoral condyle for up to 5 years.For debridement in combination with meniscectomy, there is level 4 evidence that the procedure, as appropriate, might be effective in earlier stages, unicompartmental disease, shorter symptom duration, sudden onset of mechanical symptoms, and preoperative full range of motion. However, as these findings are derived from very poor quality evidence, the identification of subsets of patients that may benefit from this procedure requires further testing.In patients with pain due to a meniscal tear, of the medial compartment in particular, repair of the meniscus results in better pain control at 2 years following surgery than if the pain is attributable to other causes. There is insufficient evidence to comment on the effectiveness of lateral meniscus repair on pain control. CONCLUSIONS: Arthroscopic debridement of the knee has thus far only been found to be effective for medial compartmental OA. All other indications should be reviewed with a view to reducing arthroscopic debridement as an effective therapy. Arthroscopic lavage of the knee is not indicated for any stage of OA. There is very poor quality evidence on the effectiveness of debridement with partial meniscectomy in the case of meniscal tears in OA of the knee.
16259772 The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialys 2005 Nov Inflammation is strongly associated with malnutrition and cardiovascular risk in patients with chronic renal failure on haemodialysis (HD). The acute-phase inflammatory response, defined by the increased synthesis of positive acute-phase proteins, is stimulated by the production of such cytokines as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumour necrosis factor-alpha TNF-alpha The availability of cytokine antagonists allows testing of the hypothesis that suppression of inflammation reverses the malnutrition-inflammation syndrome in HD patients. Etanercept is a soluble TNF-alpha receptor fusion protein used to suppress inflammation in rheumatoid and psoriatic arthritis. Its metabolism in HD patients is unknown. In a study designed to test the safety and pharmacokinetics of etanercept in HD patients, etanercept was administered to six HD patients with albumin levels above 4.2 g dL(-1) and C-reactive protein levels <5 mg L(-1) (five men, one woman, age range 34-59 years). Etanercept (25 mg) was administered subcutaneously twice weekly immediately after dialysis for 13-16 weeks. Etanercept concentrations were measured pre- and post-dialysis by ELISA. Concentrations were compared graphically to assess whether, firstly, dialysis affects etanercept apparent clearance and, secondly, etanercept kinetics were similar between HD patients and the more extensively studied psoriasis population with normal renal function (PS). The second stage examined model-based parameter predictions of the terminal elimination rate constant (k) for HD patients. Steady-state etanercept levels were comparable between HD and PS patients. Treatment with HD had no effect on etanercept levels. When etanercept was discontinued, the terminal rate constant for HD patients was not significantly different from that observed in PS patients. No adverse effects were noted during the 3-month treatment phase and subsequent 6-month follow-up. Albumin and C-reactive protein levels did not change in these non-inflamed patients during the study period. The pharmacokinetics of etanercept in patients with chronic renal failure on HD are similar to patients with normal renal function. It is, therefore, feasible to administer etanercept to HD patients without adjusting the dose.
15860148 [Harms technique of C1-C2 fixation with polyaxial screws and rods]. 2005 PURPOSE OF THE STUDY: The Harms technique of stabilizing C1-C2 by fixation with polyaxial screws and rods is a further option for atlantoaxial fixation from the dorsal approach. Harms and Melcher published this method in 2001, but the operation had first been performed by Harms in August 1997. The aim of this study is to evaluate the first results and try to assign the Harms C1-C2 fixation an appropriate standing in the in broad range of options for stabilization of the atlantoaxial complex. MATERIAL: Between December 2002 and January 2004 we carried out the Harms fixation of C1-C2 on 22 patients admitted to the Department of Spine Surgery, Motol University Hospital, 2nd Medical Faculty in Prague. Out of these, 18 patients were included in this study, 10 men and 8 women between 23 and 84 years of age (average, 55.4 years) followed-up longer than 6 months. In 14 patients we used the Harms technique as a permanent fixation of C1-C2 in order to achieve atlantoaxial arthrodesis and, in four patients, we applied it only for a period of 4 to 6 months without the use of bone grafts or their substitutions. We employed the permanent fixation to treat the following conditions: fracture of the atlas in three patients, type IIA comminuted fracture of the dens base in three patients, fracture of C2 categorized as "other" in two patients, atlantoaxial vertical instability in one patient with rheumatoid arthritis, malunion of the fractured dens in one patient, and complicated trauma to C1-C2 in four patients. The temporary fixation was used for type III displaced fractures of the dens in two and fixed atlantoaxial rotatory dislocations also in two cases. Only one patient showed signs of Frankel C neurological deficit on admission, the rest were without neurological findings. METHODS: All screws were inserted under an image intensifier always in lateral projection. First we retracted the greater occipital nerve in a caudal direction towards C2 with a fine raspatory and, using an awl, marked the entry point in the C1 lateral mass; a pilot hole, reaching through the anterior cortical bone, was made with a 2.5 mm drill. It followed a straight or slightly convergent trajectory in an anterior-posterior direction and parallel to the plane of the C1 posterior arch in the sagittal direction. Individual anatomical variations in the atlantoaxial complex of every patient were respected. The hole was tapped through the entire vertebral body, with the exception of osteoporous bone in which only the posterior cortical bone was treated with a screw tap. At this stage profuse bleeding usually arose from dissection around the epidural venous plexus along the C1-C2 joint. This was effectively controlled by a quick insertion of a screw and compression of the venous plexus with the screw head. To control bleeding by bipolar electrocautery is difficult and is always associated with a risk of nerve injury. Screws 3.5 mm thick, with polyaxial heads, were inserted bicortically into the lateral mass of C1. Subsequently, the intervertebral C2-C3 joint was localized and its medial border in the spinal canal was palpated. The entry point for placement of a C2 pedicle screw was marked with an awl at the point of intersection at a distance of 2 mm from the medial border and 5 mm from the caudal border of the C2 articular process. Under an X-ray intensifier in lateral projection, a hole was drilled approximately parallel to the screws inserted in C1, i. e., at an angle of 20 to 30 degrees cranially, up to and through the anterior cortical bone. In the transversal plane, the screws were situated in a convergent direction at an angle of 20 to 25 degrees. After all screws had been inserted, we reduced the antlantoaxial complex in the correct anatomical position by manipulating the patient's head or by directly adjusting the screws. Connecting 3.0-mm rods were then applied and fastened by cap nuts or inner nuts according to the instrumentation used. RESULTS: Operative time ranged from 35 to 155 min, with an average of 81 min. Intra-operative blood loss ranged from 50 to 1500 ml, with an average of 560 ml. The X-ray intensifier was used for a period of 0.4 to 2.6 min, with an average of 0.9 min. A total of 36 screws were inserted in the atlas; their length ranged from 16 to 34 mm (average, 30.6 mm). All screws were positioned correctly in the C1 lateral mass; two screws did not reach up to the anterior cortical bone and one protruded over it, but without causing clinical problems. Thirty-six screws were inserted in the axis. Their length ranged from 28 to 36 mm (average, 31.7) mm). Twenty-seven screws were correctly applied through the isthmus into the C2 anterior cortical bone, three were too short to reach it and five were placed too close to the vertebral artery canal. Of these, two protruded into the artery canal, but without clinical consequences. One screw inserted too medially passed into the spinal canal, but this also was without clinical response. Of the 36 screws inserted in C2, three (8.3 %) were malpositioned. Bony fusion at C1-C2 was the goal of this operation in 14 patients. At 6 weeks post-operatively, it was achieved in two patients, at 12 weeks in 12 patients and at 6 months in all 14 patients. The C1-C2 segment was stable at 12 weeks in all 18 treated patients. Four patients reported restriction of motion in rotation by 10 to 25 % after removal of the instrumentation. DISCUSSION: Operative time, longer at the beginning than with the Magerl technique, gradually shortened to between 45 and 60 min. Similar trends were seen when intra-operative blood loss and X-ray exposure were evaluated. Using the Harms and Melcher procedure we saved the greater suboccipital nerve. In contrast to these authors, however, we did not resect the atlantoaxial joint. Solid fusion was achieved in all our patients. Of the total of 72 screws inserted, only three (4.2 %) were assessed as malpositioned; however, when related to the 36 screws inserted in C2, this was 8.3 %, which indicates that insertion of screws in C2 was more difficult. We did not observe any clinical consequences in any of these cases. CONCLUSIONS: The Harms fixation of C1-C2 is a very effective technique for stabilizing the atlantoaxial complex. It enables us to provide temporary fixation without damage to atlantoaxial joints and to reduce the vertebrae after the screws and rods had been inserted, which is unique. These advantages compensate for a higher cost of the implant.
16582693 Early rheumatoid arthritis. 2006 May PURPOSE OF REVIEW: This review provides novel and updated information on pathogenesis, referral, and clinical characteristics as well as therapeutic approaches in early rheumatoid arthritis. RECENT FINDINGS: Early referral is important, but new classification criteria for early rheumatoid arthritis need to be elaborated. Predictive markers for rheumatoid arthritis are still confined to autoantibodies; respective algorithms have been presented. Other biomarkers will still have to prove their usefulness. Magnetic resonance imaging and sonography do not appear to sufficiently distinguish between early rheumatoid and nonrheumatoid arthritis. Rheumatoid arthritis has become milder at presentation in recent years. In its very early stages, the cytokine profile reflects T-cell activation and switches to abundant proinflammatory cytokines thereafter. Disease-modifying antirheumatic drugs plus glucocorticoids are highly effective, as is early use of tumor necrosis factor blockers plus methotrexate. Tight control of disease activity and subsequent therapeutic adjustments are highly effective. Disease activity indices that are simple to calculate have been presented and validated. Early intensive therapy may lead to decrease in disability and cost reduction in rheumatoid arthritis. SUMMARY: Understanding of early arthritis is increasing, especially in prognostic and therapeutic respects, and new treatment strategies appear to improve the outcome in patients with early arthritis. Nevertheless, much remains to be studied to better address the issue of early rheumatoid arthritis.
17414956 Early rheumatoid arthritis. 2007 May PURPOSE OF REVIEW: Rheumatoid arthritis is a chronic inflammatory disease in which early aggressive therapy with disease-modifying antirheumatic drugs can improve outcome and prevent joint damage. While such therapy is effective, its application can be limited by diagnostic uncertainty in patients with early inflammatory arthritis and concerns about treatment of patients whose disease would remit spontaneously. The purpose of current research is therefore to identify prognostic markers of early disease and to determine the role of aggressive treatment strategies in inducing remission in such patients. RECENT FINDINGS: Recent research has provided new information on genetic markers predicting rapid progression of joint destruction; the role of serology, in particularly, antibodies to citrullinated peptides in diagnosing rheumatoid arthritis; the utility of radiographic techniques in detecting both early synovitis and bone erosion; and the value of combination therapy in controlling signs, symptoms and radiographic progression. Recent clinical studies support the efficacy of a combination of methotrexate with a biological agent, especially a tumor-necrosis-factor blocker, in reducing disease activity. SUMMARY: While current treatment approaches can produce significant benefits in patients with early arthritis, future investigation is needed to target therapy more selectively and to determine which patients respond best to various agents or combinations.
17540693 Early rheumatoid arthritis. 2007 BACKGROUND: This review outlines current knowledge of diagnosis, assessment, treatment and risk factors for early rheumatoid arthritis (RA). METHODS: Selective review of current literature was obtained by searching the terms 'rheumatoid arthritis' and 'early'. RESULTS: Three issues dominate the current views on early RA. First, its recognition may be difficult. Many experts consider that early inflammatory arthritis should only be classified as RA after several months' of observation. Secondly, there is emphasis on early intensive treatment with conventional disease-modifying drugs or biologics, especially tumour necrosis factor inhibitors. Thirdly, there is a debate on the risk factors with evidence of genetic risks and environmental factors like smoking that may trigger RA. Developing citrullinated proteins followed by anti-cyclic citrullinated peptide antibodies, specific for RA, appears to be a crucial pathogenetic step. DISCUSSION: Early RA needs immediate specialist assessment and review. Early intensive therapy is effective but needs to be focussed on patients mostly at risk of severe progressive disease.
18270677 [Early rheumatoid arthritis]. 2008 Mar This article gives an overview on the clinical features of early rheumatoid arthritis (RA). RA is the most frequent and severe inflammatory joint disease and a serious health burden affecting approximately 1% of the population. The classical image of RA with axial deviations of the fingers, subluxation of the small finger joints and progressive crippling is no big diagnostic challenge since it can easily be distinguished from other rheumatic conditions. However, this picture resembles the end stage disease with irreversible damage and is comparable for instance with renal failure as a consequence of diabetic nephropathy. It is without question that early diagnosis is essential for effective treatment of RA and the only chance to prevent organ damage. Therefore, an effective approach to treat RA as early as possible warrants a detailed knowledge of the specific features of early RA, which not always follows the features of the established disease.
19301780 [Early rheumatoid arthritis]. 2008 Nov This article reviews some key issues of early rheumatoid arthritis such as the dfficulties to recognize this condition during the first months after onset. Therefore, three reference diagnostic criteria have been proposed for any patient presenting with more than three simultaneously inflammed joints, involvement of metacarpophalangeal or proximal interphalangeal joints and morning stiffness lasting more than 30 minutes. Antibodies to cyclic citrullinated peptides are new markers that can be used for diagnosis. The immediate treatment during the "opportunity window" at the onset of inflammation may avoid the erosive joint damage. The use of synthetic or biological disease modifying medications, specially tumor necrosis factor alpha antagonists, also contribute to this purpose. Primary care physicians should be aware of the early signs of the disease to provide an adequate treatment and referral to specialists.
16966022 Rheumatoid arthritis in dermatology. 2006 Sep Rheumatoid arthritis (RA) is a chronic progressive disorder characterized by symmetric inflammatory arthritis in association with systemic symptoms. Although considered a "joint disease," RA is associated with involvement in diverse organ systems, including the skin. Common manifestations include Raynaud phenomenon, rheumatoid nodules, and rheumatoid vasculitis. As with other extra-articular manifestations, dermatologic involvement tends to occur in patients with more severe RA. In addition to manifestations related to the disease, there are also sundry dermatologic reactions related to the medications used to treat RA. Understanding the etiology and therapy for cutaneous manifestations of RA will help optimize patient care.
17952359 [Rheumatoid arthritis and atherosclerosis]. 2007 Sep Rheumatoid arthritis is a systemic inflammatory autoimmune disease characterized by symmetric, erosive and chronic synovitis, especially of minor joints. It is associated with increased prevalence of cardiovascular disease and with high mortality. This occurs because of an accelerated atherogenic process, explained by traditional cardiovascular risk factors such as smoking, hypercholesterolemia, age, diabetes mellitus and systemic arterial hypertension. High levels of hemosedimentation velocity and C-reactive protein are directly correlated with increased cardiovascular events. Pro-inflammatory cytokines contribute with endothelial dysfunction, insulin resistance, dyslipidemia, prothrombotic effects and oxidative stress that are at the basis of the atherogenic process. Recent information about atherosclerosis in rheumatoid arthritis allows for identification of the risk factors involved in atherosclerosis that can be best controlled. This could result in a reduced manifestation of the process and its cutback, with consequent decrease of mortality and morbidity related to rheumatoid arthritis.
16582692 Interleukin-6 in rheumatoid arthritis. 2006 May PURPOSE OF REVIEW: Recent progress in cytokine studies has clarified the pathological roles played by cytokines and provided key evidence that antagonizing their actions can be therapeutic. The pathogenesis of rheumatoid arthritis, an autoimmune inflammatory disease, involves inflammatory cytokines such as tumour necrosis factor-alpha, interleukin-1 and interleukin-6. Anti-tumour necrosis factor-alpha and anti-interleukin-1 therapies have been used successfully to treat rheumatoid arthritis, but they are not consistently effective. We therefore need further therapies for this refractory disease. Interleukin-6 is another target molecule for blockade in the treatment of rheumatoid arthritis. Tocilizumab is a humanized antihuman interleukin-6 receptor monoclonal antibody designed to block the actions of interleukin-6. This review addresses the pathological significance of interleukin-6 and the current status of anti-interleukin-6 therapy for rheumatoid arthritis. RECENT FINDINGS: The safety and efficacy of tocilizumab have been demonstrated in clinical trials conducted in patients with rheumatoid arthritis and other autoimmune inflammatory diseases, such as juvenile idiopathic arthritis and Crohn's disease. SUMMARY: Clinical studies have demonstrated the pathological significance of interleukin-6 and the safety and efficacy of anti-interleukin-6 therapy with tocilizumab. Blockade of interleukin-6 - the second generation of anticytokine therapy - may be a promising treatment for rheumatoid arthritis.
16370926 Tacrolimus in rheumatoid arthritis. 2006 Jan Tacrolimus is an immunosuppressive drug that has been used widely in organ transplantation and topically for atopic dermatitis. Tacrolimus exerts its immunosuppressive effects by the inhibition of calcineurin, leading to interference with T-cell activation. As T-cell activation plays a major role in the pathogenesis of rheumatoid arthritis, there has been an interest in the use of tacrolimus for the treatment of rheumatoid arthritis. The pharmacological properties of tacrolimus have the potential of suppressing the production of inflammatory cytokines, improvement of joint inflammation, improvement of bone and cartilage destruction, improvement of functional status and relief from arthritic pain. This article reviews the pharmacodynamics, pharmacokinetics, clinical efficacy, safety and role of tacrolimus in the treatment of rheumatoid arthritis.
17223742 Adalimumab for rheumatoid arthritis. 2006 Dec In the last few years significant advances have been made in our understanding of the molecular mechanisms underlying rheumatoid arthritis pathogenesis. Pro-inflammatory cytokines, such as TNF-alpha, play a pivotal role in its pathogenesis. Anti-TNF-alpha biological agents are considered a major advance in the treatment of rheumatoid arthritis. Adalimumab is a fully human monoclonal antibody that binds specifically to TNF-alpha, thereby neutralising its activity. It had significant efficacy in well-designed, placebo-controlled trials in patients suffering from rheumatoid arthritis, both as monotherapy and in combination with various disease-modifying antirheumatic drugs, including methotrexate. Adalimumab was generally well tolerated during both concomitant therapy with methotrexate or standard antirheumatic therapy and monotherapy. In addition, the radiographic progression of structural joint damage was significantly inhibited by adalimumab and improved quality of life. This review summarises the recent available data.
16928338 Rheumatoid arthritis and the heart. 2006 Jun The risk of cardiovascular disease is increased in patients with rheumatoid arthritis (RA). Although the pathogenesis of cardiovascular disease in patients with RA is largely unknown, evidence to date indicates that it involves complex interactions between the traditional and nontraditional cardiovascular risk factors as well as various medications commonly used for the treatment of RA patients. This review provides an overview of the clinical studies that demonstrate increased risk of coronary heart disease and heart failure in patients with RA and also discusses the potential role of the various risk factors.
17976416 Rheumatoid arthritis: diagnosis and management. 2007 Nov Accurate diagnosis of rheumatoid arthritis may be difficult early in its course and demands high clinical suspicion, astute examination, and appropriate investigations. Early use of disease-modifying antirheumatic drugs and biologics has improved outcomes but requires close monitoring of disease course and adverse events.
18817644 Rheumatoid arthritis and cardiovascular disease. 2008 Oct An increased risk of cardiovascular events and subclinical atherosclerosis in patients with rheumatoid arthritis (RA) has been attributed to the inflammatory milieu associated with this chronic autoimmune disease and possibly to the independent effects of RA medications on risk. This review provides an update on the most recent epidemiologic studies documenting this relationship and noteworthy publications examining RA-related factors that could influence the role of traditional cardiovascular risk factors and expression of atherosclerotic disease in patients with RA.
19562968 [Elderly onset rheumatoid arthritis]. 2008 Elderly-onset rheumatoid arthritis (EORA), defined as rheumatoid arthritis (RA) with the onset at the age > or =60 differs sligthy at presentation from younger-onset RA (YORA) by a more equal sex distribution, a higher frequency of an acute onset, more frequent involvement of large joints, especially of the shoulder, and higher disease activity. Longitudinal studies have shown greater disease activity, more severe radiographic damage and functional decline in patients with EORA than in those with YORA. These differences were only found in seropositive patients. In seronegative EORA patients a less severe course of the disease and a better outcome have been observed, with the clinical manifestations of polymyalgia rheumatica or remitting seronegative symmetrical synovitis with pitting edema. This article is a review of available data concerning differences between EORA and YORA.