Determinants of physical function in rheumatoid arthritis: association with the disease process

Rheumatoid arthritis (RA) is a chronic, debilitating disease that follows a progressive course characterized by persistent inflammation and erosive joint damage leading to functional disability. The Health Assessment Questionnaire is now viewed as a key instrument to measure physical function, based on its reliability and ease of use. It has been demonstrated that multiple variables affect physical function, of which those most frequently indicated are disease activity, joint damage and the psychosocial characteristics of the patient. When these variables are pooled together the variation observed in a patient's physical function over the long term can be explained mainly by disease activity, partially by joint damage and additionally by psychosocial factors. Therefore, to maintain or improve physical function in long-standing RA, it is imperative to control disease activity and joint damage by early initiation of treatment.     

Disability in patients with early inflammatory polyarthritis cannot be "tracked" from year to year: an examination of the hypothesis underlying percentile reference charts

OBJECTIVE: To determine whether disability in patients with early inflammatory polyarthritis (IP) can be charted or "tracked" over time. The disability score was also adjusted in an attempt to exclude the influence of current disease activity, with the aim of ascertaining that component of disability relating to other factors such as psychosocial factors and joint damage. METHODS: Four hundred thirty-three patients with early IP referred to the Norfolk Arthritis Register (NOAR) were followed annually using the Health Assessment Questionnaire (HAQ) for 5 years. HAQ scores at each year were divided into quartiles. The number of patients remaining in the same quartile from year to year was examined. The relationship between disease activity, assessed by swollen and tender joint counts, and HAQ was modelled, with the residual HAQ attributed to psychosocial factors and joint damage. RESULTS: From year to year, there was considerable within-individual variation in quartile, with only 48-65% of patients remaining in the same quartile. With increasing time, a greater proportion of patients remained in the same quartile. A statistically valid activity-adjusted HAQ score could not be computed. CONCLUSION: Disability in patients with early IP cannot be easily tracked over time. It is therefore not appropriate to construct longitudinal reference charts for disability in the early years, although it may be feasible for more established disease.     

ACPA (anti-citrullinated protein antibodies) and rheumatoid arthritis

It has recently been discovered that anti-citrullinated protein antibodies (ACPA) are present in 50% of patients with early rheumatoid arthritis (RA). Assays for detecting ACPA have been shown to have very good diagnostic and predictive characteristics, and they may facilitate the identification of patients with early arthritis who need aggressive treatment. In addition to their diagnostic and predictive properties, ACPA have also provided new insights into the pathophysiology of RA. The specific association of certain genetic and environmental risk factors with ACPA-positive but not with ACPA-negative RA, has led to new concepts of the underlying pathogenetic mechanisms. The fact that ACPA-positive patients have a more severe disease course with greater joint destruction has also fueled the hypothesis that ACPA themselves may be pathogenic. Although there is no direct proof for this intriguing theory so far, it is clear that ACPA allow the classification of RA patients into two different disease subsets that are associated with distinct pathophysiological mechanisms and clinical outcomes. Rheumatoid arthritis (RA) is a chronic, potentially destructive, arthritis which has a large impact on patients' quality of life(1). It has become clear that in order to be able to prevent disease progression and joint destruction, RA needs to be diagnosed early, which requires diagnostic markers which can reliably predict disease development and progression(2). Some of the most attractive diagnostic markers are autoantibodies. Rheumatoid factor (RF) has long been known to be a marker of future RA development(3), but more recently, a better diagnostic and predictive marker has emerged in the form of anti-citrullinated protein antibodies (ACPA).     

Pathogenesis of lentivirus-induced arthritis

Summary While it has been known for some years that there is an association between lentiviruses and slowly progressive joint diseases in ruminants, the realization that the human immunodeficiency virus, the cause of AIDS, is a lentivirus has made this group of virus the focus of a considerable research effort. The manifestations of lentivirus infection in animals are discussed and reference is made to the possibility of using them as models for human rheumatoid arthritis and for AIDS.     

Quantitative ECG analysis in diagnosing ischemic heart disease: a comparison with coronary angiographic data

By collating the results of qualitative and quantitative analysis of the ECG with the findings of selective coronary angiography obtained from 32 patients with coronary heart disease, considerable informative value of the planimetric method of the quantitative analysis of the ECG has been proved. It is concluded that the quantitative interpretation of changes in the areas of the initial and end fragments of the ventricular complex of the ECG contributes to early diagnosis of coronary heart disease and in some cases it helps to specify the localization of coronary impairments.     

Strategies to control disease in rheumatoid arthritis with tumor necrosis factor antagonists-an opportunity to improve outcomes

Recent data have shown that disability and joint destruction in rheumatoid arthritis (RA) occur early on in the course of the disease and progress rapidly. It has been shown that in the early stages of RA, disability is attributed to increased disease activity, whereas later in the course of the disease, disability results from irreversible joint damage. These findings support the need to develop treatment strategies that will rapidly bring the disease under control, with the ultimate goal of alleviating symptoms and halting progressive joint damage. A number of such strategies have been evaluated, including the early administration of a biologic agent alone or in combination with high-dose methotrexate. Other, more recent treatment strategies include the tight control of disease activity by targeting specific outcomes necessary for decision making; the use of biologic agents for the treatment of moderate disease; and the induction of remission with a biologic agent early in the course of disease, followed by maintenance therapy using a conventional disease-modifying antirheumatic drug. The substantial positive effect these strategies have on patient outcomes supports the concept that the optimal management of RA involves aggressive early therapy combined with close monitoring of disease progression and modification of ineffective therapeutic strategies.     

Biochemical markers of osteoarthritis

The recent attempts to discover markers of early degenerative joint disease need to be considered from several viewpoints. 1. Our basic understanding of events in joint disease has increased considerably as a result of these studies, and the information gained will collectively contribute to future developments. 2. It should be clearly stated that at present, no marker has been found in biologic fluids that can be used for diagnosing and monitoring degenerative joint disease. 3. Current data provide optimism that the analysis of biologic fluids, perhaps by using more than one marker or fluid, will in the future offer clinically useful information allowing an earlier diagnosis and more appropriate monitoring of the disease. 4. Genetic markers will provide information on subpopulations of patients susceptible to disease development, which should allow early intervention in disease activity and progression in these patients.     

Cor pulmonale (pulmonary heart disease): present-day status.

In reviewing the present-day status of cor pulmonale, it is clear that considerable progress has been made in almost all instances of the disease. It is clearly a preventable form of heart disease in most cases and it is treatable and curable in its most common form, i. e., in COPD. One must agree with Petty, that today we have effective means of caring for the majority of respiratory cripples. Therapy for lung disease now appears even to have reduced the expected rate of pulmonary function deterioration in some patients. Surely with improved gas exchange and early detection of respiratory insufficiency the outlook for patients with respiratory diseases leading to cor pulmonale is better today than it was 30 years ago.     

Pathogenesis of haemophilic synovitis: experimental studies on blood-induced joint damage

Summary.  Hemarthrosis is a common manifestation of haemophilia, and joint arthropathy remains a frequent complication. Even though the exact mechanisms related to blood-induced joint disease have not yet been fully elucidated, it is likely that iron deposition in the synovium induces an inflammatory response that causes not only immune system activation but also stimulates angiogenesis. This process ultimately results in cartilage and bone destruction. Investigating the processes that occur in the early stages of blood-induced joint disease in humans has been very limited. Therefore, the use of haemophilic animal models is critical to augment the understanding of this phenomenon. This article discusses three cellular regulators (p53, p21 and TRAIL) induced in synovial tissue that are important for iron metabolism. A cartilage remodelling programme induced by the release of cytokines and growth factors that result in articular damage is also discussed. Full elucidation of the pathogenesis of haemophilic joint disease is required to identify new avenues for prevention and therapy.     

Imaging in rheumatoid arthritis

The optimal management of rheumatoid arthritis (RA) requires tools that allow early and accurate disease diagnosis, prediction of poor prognosis and responsive monitoring of therapeutic outcomes. Conventional radiography has been widely used in both clinical and research settings to assess RA joint damage due to its feasibility, but it has limitations in early disease detection and difficulty distinguishing between active treatments in modern trials. Imaging modalities such as magnetic resonance imaging (MRI) and ultrasound (US) have the advantage of detecting both joint inflammation and damage and hence they can provide additional and unique information. This can be especially useful in the context of early and/or undifferentiated joint disease when detection of soft tissue and bone marrow abnormalities is desirable. This review focusses on the recent literature concerning modern imaging, and provides clinicians with an insight into the role of imaging in modern RA diagnosis, prognosis and monitoring.     

The role of echocardiography in evaluation of the cardiac transplant recipient

Echocardiography is an important tool in the management of cardiac transplant recipients. It provides comprehensive information about allograft structure and function without exposing the recipient to the risks associated with invasive investigations. Imaging can be performed in the early in-hospital phase and easily repeated during follow-up for the purposes of screening or for assessing the progression of specific pathology. When interpreting studies it is important to be aware that characteristic normal findings may be quite different from the non-transplant population. Endomyocar-dial biopsy remains the gold standard for the detection of acute allograft rejection. Doppler echocardiography has traditionally formed the basis for non-invasive diagnosis of this important complication but has recognised limitations. Advances in echocardiographic techniques indicate a potential important role for the reliable detection of rejection by this modality in the future. A range of other complications can be evaluated by echocardiography. There has been considerable recent interest in assessment of cardiac allograft vasculopathy by stress-imaging methods.     

Septic arthritis of the sterno-clavicular joint as a cause of dysphagia: a report of two cases and review of literature

Septic arthritis of sterno-clavicular joint is a rare entity which is often associated with predisposing conditions like intravenous drug abuse and diabetes. Its prevalence in healthy subjects with absence of medical co-morbidities has been sporadically reported. Due to the rarity of the condition, diagnosis is often delayed predisposing the patients to serious complications. Clinical suspicion supported by haematological and radiological investigations is needed for early diagnosis. Dysphagia as a complication of sterno-clavicular joint infection has not been reported. In this study, we report a case of sterno-clavicular joint infection causing dysphagia and review the literature with regards to aetiology, predisposing factors and treatment options. The aim of this study is to highlight the importance of early diagnosis in suspected cases of septic arthritis of sterno-clavicular joint and institution of intravenous antibiotics.     

Lateral subcutaneous internal sphincterotomy for chronic anal fissure,an outpatient procedure

Summary We have adapted the lateral internal sphincterotomy technique for the repair of chronic anal fissure to a strictly office or outpatient procedure. The early cure rate in this review of our first 200 patients was very good—well in excess of 98 per cent. Complication were exceedingly minor, the considerable cost to the patient of hospitalization and time off from work has been saved, and patient acceptance has been excellent. Submitted to the joint meeting of the Section of Proctology, Royal Society of Medicine, the Section of Colonic and Rectal Surgery, Royal Australasian College of Surgeons, and the American Society of Colon and Rectal Surgeons, Washington, D.C., May 22 to 25, 1974.     

Mast cells in the pathogenesis of fibrosis

It has been appreciated for quite some time that a "round Cell" inflammatory infiltrate is present in the dermis during the early stages of scleroderma. Considerable research has emanated from this basic observation, with the assumption that interactions between immune cells and fibroblasts are paramount in the genesis of fibrosis. The large number of mast cells that accumulate early in involved tissues has been less appreciated in recent studies. The purpose of this update is to demonstrate how mast cells interact with fibroblasts in a manner that leads to fibroblast activation and subsequent extracellular fibrosis. Furthermore, the notion that myofibroblasts represent a critical fibroblast phenotype in sclerosing disorders, such as scleroderma, has also gained considerable support. The relationship of tissue mast cells to the generation of a myofibroblast phenotype has been the focus of several recent reports and will also be discussed.     

What are the costs to society and the potential benefits from the effective management of early rheumatoid arthritis?

Rheumatoid arthritis is a chronic disabling condition associated with a significant long-term loss of function and a significant socio-economic impact on individual sufferers and their families, as well as on society as a whole. There is a suggestion that the incidence and severity of the disease may be abating slightly, which has been attributed to the trend to 'invert the pyramid' and to diagnose and treat rheumatoid disease earlier and more aggressively. Studies have confirmed that the erosions, which lead to subsequent joint damage, occur early in the course of the disease. Ongoing disease activity, both clinically and serologically, has now been linked to increasing morbidity, loss of function and mortality. New agents have been developed and, together with combinations of old and new agents, have been shown to be more effective if used earlier in the course of the disease. The better the early control of the disease, the better the long-term outcome. Early and more vigorous treatment, particularly of those patients with a high joint count, early loss of function and an elevated titre of inflammatory markers, has potential to reduce the twofold increase in mortality seen among rheumatoid arthritis patients. The scene is set to have a greater impact on the long-term disability and associated cost to the individual and society by treating early and treating often. Combination therapy and the new 'biologicals' are, however, far more expensive than the previously available agents, and the direct medical costs associated with medication, as well as the monitoring costs for rheumatoid arthritis, are increasing. It is difficult to value the long-term prevention of pain and suffering, and the maintenance of productivity. However, if the disease were effectively controlled early, there would be long-term benefits to be offset against the higher treatment cost. It behooves the rheumatological community to use the new agents wisely to gain the greatest advantage for all patients as well as to monitor the long-term benefits and drawbacks so that cost-effectiveness can be comprehensively evaluated.     

Therapiestrategien bei rheumatoider Arthritis

Rheumatoid arthritis is the most common chronic inflammatory-rheumatic joint disease. If untreated, patients develop radiologically detectable progressive joint destruction. Rheumatoid arthritis has considerable socioeconomic importance, since a majority of patients are affected at employable age and can be significantly disabled over the course of the disease. Therefore, an appropriate early intervention with disease modifying anti-rheumatic drugs as well as ergo- and physiotherapy plays an important role for the prognosis. In the past few years, the introduction of novel drugs has improved the treatment opportunities markedly. This progress was the basis for new treatment strategies of tight disease control with the goal of disease remission.     

Prophylaxis for severe hemophilia: experience from Europe and the United States

Since the late 1950s, prophylactic therapy has been used in patients with severe hemophilia in order to convert their phenotype into the phenotype of moderate hemophilia. In the early years, prophylaxis was mostly started after the development of arthropathy. This secondary prophylaxis decreased the number of bleeds but did not halt the development of arthropathy. With the start of primary prophylaxis, however, it was shown that both joint bleeds and arthropathy could be prevented. Although its benefits have been proved, prophylaxis has been used as standard treatment for children in only few countries. There are now favorable results with prophylaxis on bleeding and arthropathy with more than 25 years of follow-up. In general, the strategies used for prophylaxis can be divided into those that are targeted at preinfusion clotting factor levels of > 1% and those that are guided by clinical bleeding patterns of individual patients. In both types of strategies, treatment should be started early, before the start of joint damage. However, clotting factor consumption in the first group of strategies is expected to be higher, whereas bleeding frequencies are expected to be slightly lower. The differences in long-term outcome between both strategies may only become apparent after more than two decades. In addition, some patients may be able to stop taking prophylaxis in adulthood while maintaining a low bleeding frequency. In conclusion, although the optimal prophylactic regimen is still under debate, it is well established that prophylaxis reduces or even prevents joint bleeds and hemophilic arthropathy. Therefore, prophylaxis should be offered to all children with severe hemophilia, at least until adulthood.     

Bakteriell septische Arthritis als rheumatologischer Notfall

Septic arthritis has always been a challenge to rheumatologists and surgeons. Treatment according to the current classification needs to be stage-adapted and has to be initiated rapidly as the time factor constitutes the key prognostic criterion. Failure to treat and late treatment initiation result in irreversible joint damage, functional impairment and increasing mortality. Particularly in cases of acute joint infection, clinical findings, laboratory markers of inflammation and synovial analysis lead to a rapid diagnosis of empyema in most cases. However, chronic septic arthritis may be associated with considerable diagnostic problems. In these cases further diagnostic methods, e.g. magnetic resonance imaging (MRI), computed tomography (CT) and skeletal scintigraphy may be needed. Consideration of prior treatment, extent of the infection and of the degree of joint damage is of high clinical relevance. After an optional initial antibiotic pretreatment, definitive surgical treatment is always necessary either arthroscopically or using open techniques, depending on the stage of infection. Both surgical techniques have comparable treatment success rates. Surgical radicality in removing the infected tissue is of high importance. Local and systemic antibiotic treatment is of adjuvant and supportive value. An intensive physical therapy should be initiated early to avoid functional deficits.     

Early juvenile idiopathic arthritis

Early juvenile idiopathic arthritis (JIA) is important to recognize as timely diagnosis and treatment improves prognosis. It is a misconception that complications of JIA arise only from long-standing disease and that children will outgrow it. Early aggressive treatment is the paradigm as early disease activity has long-term consequences. There are predictors of persistent disease and joint erosions that may identify patients at higher risk. Control of disease activity within the first 6 months of onset confers improved clinical course and outcomes. The treatment perspective is thus one of early aggressive treatment for induction of disease control and ultimately remission.     

Remodeling the pyramid--a concept whose time has come

It is clear that the traditional treatment program, as illustrated by the pyramid, does not suppress inflammation in most patients with RA to an extent sufficient to prevent joint damage. There is no basis for the concept that slow acting drugs are uniquely disease modifying. Disease modification correlates best with control of inflammation. Contrary to popular wisdom, this has been best demonstrated with prednisone. The arbitrary concept of a drug being either antiinflammatory or disease modifying serves no useful purpose and should be dropped. Many medications provide incomplete or temporary suppression of inflammation, presumably by differing mechanisms of action. Based on this rationale, a therapeutic program is proposed, employing a combination of drugs to control inflammation in the critical early stages of RA. With this step-down bridge concept, medications are sequentially withdrawn in contrast to the traditional pyramid, in which they have been sequentially added. Our early experience with patients indicates that toxicity is no greater problem with combined drugs than with the same drugs used individually. Time and comparative observations will be needed to show the optimum combination of drugs and whether the step-down bridge concept will achieve the sought-for and presently unobtained goal of early and sustained control of inflammation, improved quality of life, and prevention of bone and joint damage.