Showing papers in "Current Rheumatology Reviews in 2010"
TL;DR: This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention.
Abstract: The lung is one of the most common extra-muscular targets in idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD) contributes to nearly 80% of the mortality in IIM with a reported prevalence of 65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical and laboratory findings of myositis, overt signs of muscle disease may be absent in the setting of significant lung disease. Understanding the varied scope of presentation of these diseases is essential to providing optimal patient care. This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention.
77 citations
TL;DR: The lessons learned from recent SSc-ILD randomized controlled trials (RCTs) are discussed and outcome measures and recommendations for design of future RCTs for S Sc-ILD are proposed.
Abstract: Pulmonary involvement including interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (scleroderma; SSc). This article reviews the current evidence based medicine regarding available therapies for SSc-ILD ; discusses the lessons learned from recent SSc-ILD randomized controlled trials (RCTs); and proposes outcome measures and recommendations for design of future RCTs for SSc-ILD.
29 citations
TL;DR: The experimental evidence supporting the participation of various growth factors in the pathogenesis of the fibrotic process in SSc and the molecular mechanisms involved will be reviewed.
Abstract: The most severe clinical and pathologic manifestations of systemic sclerosis (SSc) are the result of a fibrotic process characterized by the excessive and often progressive deposition of collagen and other connective tissue macromolecules in skin and numerous internal organs. The mechanisms involved in the initiation and progression of the remarkable fibrotic process in SSc remain largely unknown. Extensive recent studies have indicated that a variety of polypeptide growth factors play a crucial role in this process. The most commonly implicated growth factors include transforming growth factor beta (TGF-β), connective tissue growth factor (CTGF), platelet derived growth factor (PDGF), and vascular endothelial growth factor (VEGF). Here, the experimental evidence supporting the participation of various growth factors in the pathogenesis of the fibrotic process in SSc and the molecular mechanisms involved will be reviewed.
25 citations
TL;DR: In patients with SLE, aPL have been reported to correlate with the markers of lipid peroxidation, suggesting that increased oxidative stress could be a trigger of these antibodies.
Abstract: Publisher Summary
This chapter focuses on the main cardiac and pulmonary features related to the presence of antiphospholipid antibodies (aPL) Patients suffering from systemic lupus erythematosus (SLE) with antiphospholipid antibodies (aPL) show a significantly higher prevalence of valvular defects than from those without these antibodies In addition, almost 89% of patients with SLE and valvular disease have been found to have aPL, compared to 44% of patients without valvular involvement The primary APS valvular lesion consists mainly of superficial or intravalvular fibrin deposits and its subsequent organization such as vascular proliferation, fibroblast infiltration, fibrosis, and calcification Thickening of the valve leaflets is the most common lesion detected by echocardiography in both SLE and primary APS patients The mitral valve is involved most commonly, followed by aortic valve involvement Mitral regurgitation is the most common haemodynamic dysfunction, occurring in 22% and 26% of all patients with primary APS and SLE, respectively and aortic regurgitation is less common, occurring in 6% and 10%, respectively In patients with SLE, aPL have been reported to correlate with the markers of lipid peroxidation, suggesting that increased oxidative stress could be a trigger of these antibodies The prevalence of aCL in patients with myocardial infarction seems to be between 5% and 15% and widespread cardiac dysfunction may be present in some patients with normal valves and coronary arteries
11 citations
TL;DR: The scope, pathogenesis, management, and prognosis, along with the clinical and pathologic features of SLE-associated ILD (SLE-ILD) are discussed.
Abstract: Systemic lupus erythematosus (SLE) is a systemic, inflammatory disorder with a predilection for young women. A wide array of pulmonary manifestations can occur in patients with SLE, including interstitial lung disease. In this review, we will discuss the scope, pathogenesis, management, and prognosis, along with the clinical and pathologic features of SLE-associated ILD (SLE-ILD).
11 citations
TL;DR: The present review summarizes the data on the efficacy of the relevant biochemical factors affecting all the components of the joint and that could be therefore useful targets in treatment of OA.
Abstract: Osteoarthritis (OA) is a complex, age dependent disease in which various factors, including metabolic changes, are all major contributors to its onset and progression. Anatomically, OA embraces the whole joint, i.e. articular cartilage, subchondral bone alterations and joint-lining synovial membrane. Correspondingly, OA development involves elaborate interactions of cartilaginous tissue metabolism and maintenance, osteogenesis, mineralization and inflammation of the synovial membrane. Identification of the molecular pathways and individual factors involved in OA etiology, understanding of mechanisms of their action and interaction are necessary conditions for developing the accurate diagnostic and prognostic tools and for providing OA patients effective treatment. There is a major progress in understanding of the molecular mechanisms of OA appearance and progression, which are pointing out to the network of biochemical factors important for normal functioning of the joints and changes leading to OA. The present review summarizes the data on the efficacy of the relevant biochemical factors affecting all the components of the joint and that could be therefore useful targets in treatment of OA. However, despite the dramatic growth of the knowledge concerning the biochemistry of OA and discovery of a number of useful biomarkers the real breakthrough in this area is still not achieved.
9 citations
TL;DR: The goal of this article is to review histologic patterns and HRCT findings of the IIP as they relate to CTD-associated ILD, and to assess response to therapy.
Abstract: The idiopathic interstitial pneumonias (IIP) are seven fibro-inflammatory interstitial lung diseases of unknown cause, grouped together because of potentially similar clinical features. Each of the seven has a distinct histologic pattern; however, these patterns are not specific to the IIP, and they provide a framework for defining interstitial lung disease (ILD) of known-cause, including ILD associated with underlying connective tissue disease (CTD). With the exception of respiratory bronchiolitis, the histologic patterns corresponding with the other six IIP can be found in association with CTD. Considering all CTD together, the pattern of non-specific interstitial pneumonia is most common. High-resolution computed tomography (HRCT) can hint at the histologic pattern, track changes over time, and assess response to therapy. The goal of this article is to review histologic patterns and HRCT findings of the IIP as they relate to CTD-associated ILD.
7 citations
TL;DR: The proposed methodology that will be utilized to develop core set items for connective tissue disease-associated interstitial lung disease (CTD-ILD) and a core set of outcome measures will be proposed through application of Nominal Group technique.
Abstract: This review article discusses the proposed methodology that will be utilized to develop core set items for connective tissue disease-associated interstitial lung disease (CTD-ILD). CTD-ILD remain an important enigma in clinical medicine. No consensus exists on measurement of disease activity or what constitutes a significant response to therapeutic interventions. Lack of appropriate measures inhibit effective drug development and hamper regulatory evaluation of candidate therapies.An interdisciplinary and international Steering Committee (SC) will oversee the execution of a 3-tier Delphi exercise involving experts in CTD and ILD. In parallel to the Delphi, qualitative information will be gathered from patients with ILD using focus groups. These data will subsequently be used to construct surveys to collect quantitative response from patients with ILD. The final Delphi and Patient Perspective results are to be scrutinized by SC and specialty sub-groups (including patient advocates) for truth, discrimination and feasibility - the OMERACT filters. Through application of Nominal Group technique, a core set of outcome measures will be proposed. Subsequent exercises will evaluate the applicability of a proposed core set to the unique issues posed by individual CTDs in addition to guidelines on screening, prognostication and damage scoring.
6 citations
TL;DR: An approach to the diagnosis and treatment of rheumatoid arthritis associated interstitial lung disease (RA-ILD) including potential biomarkers is discussed, and areas for future research are outlined.
Abstract: Rheumatoid arthritis (RA) affects 1-2% of the general population. Although often thought of as primarily a localized inflammatory disorder with associated joint destruction, it is a diffuse systemic disease. Extra-articular manifestations of rheumatoid arthritis can be demonstrated in almost 50% of patients with RA, and include pulmonary, cardiac, ocular, renal, hematologic, and neurologic involvement. In this article, we review recent studies of interstitial lung disease (ILD) in RA with a focus on clinical and pathological features of rheumatoid arthritis associated interstitial lung disease (RA-ILD). We discuss an approach to the diagnosis and treatment of RA-ILD including potential biomarkers, and conclude by outlining areas for future research.
4 citations
TL;DR: This chapter focuses on various hematological abnormalities in the antiphospholipid syndrome, which is usually mild and clinically benign but in a few number of cases thrombocytopenia may be severe and be tributary of aggressive treatment.
Abstract: Publisher Summary This chapter focuses on various hematological abnormalities in the antiphospholipid syndrome (APS). Thrombocytopenia is frequently found in patients with the antiphospholipid syndrome (APS), which is usually mild and clinically benign. Usually thrombocytopenia in the antiphospholipid syndrome does not require therapeutical intervention. However, in a few number of cases thrombocytopenia may be severe and be tributary of aggressive treatment. This treatment may include high dose corticosteroids, immunomodulating agents, and intravenous immunoglobulin treatment. When steroids or immunosupressive agents are unsuccessful, splenectomy is usually performed to remove the major site of platelet destruction and antibody production. The HELLP syndrome is one of the hypertensive disorders of pregnancy, which also include preeclampsia and eclampsia. Although, most cases of HELLP syndrome are antiphospholipid antibody-negative, in recent years several cases of HELLP syndrome associated with antiphospholipid syndrome have been reported. A recent study reported a frequency of 69% of antiphospholipid antibodies among women with HELLP syndrome. Antiphospholipid antibodies are associated with both thrombocytopenia and hemolytic anemia. These hemocytopenias are mainly due to autoimmune mechanisms as supported by the presence of platelet-associated immunoglobulins for thrombocytopenia and the positive direct Coombs test for hemolytic anemia. Even though these hemocytopenias are rather common manifestations of antiphospholipid syndrome, uncertainties still exist regarding its pathogenesis and management.
4 citations
TL;DR: During the coming years, as additional genetic and functional studies further define the genetic architecture of OA and the underlying molecular mechanisms, additional targets for novel therapies and improved diagnostic and prognostic tests will be identified.
Abstract: Osteoarthritis (OA) is a chronic arthropathy, in which cartilage loss, osteophyte formation, and subchondral bone sclerosis lead to pain, disability, and a reduction in quality of life. OA is a multifactorial disease and OA cases are affected by both genetics and environment to varying degrees. Strong familial aggregation and heritabilities have been reported for OA at the hip, knee, hand and spine. Candidate gene studies and genome-wide linkage studies have identified genes in the bone morphogenetic pathway (e.g. GDF5), the thyroid regulation pathway (DIO2), apoptotic pathways as involved in genetic risk of large joint OA. Genome wide association studies have reported structural genes (COL6A4/DVWA), inflammation related genes (PTGS2/PLA2G4A) and a locus on chr 7q22 associated with knee OA and a gene involved transcriptional regulation (A2BP1) to be associated with hand OA. During the coming years, as additional genetic and functional studies further define the genetic architecture of OA and the underlying molecular mechanisms, additional targets for novel therapies and improved diagnostic and prognostic tests will be identified.
TL;DR: MRI is explored as a disease entity that can be recognised before any radiographic change, and may pose new, yet exciting challenges for the identification and classification of disease, and provide a better understand of the pathogenesis of knee OA.
Abstract: Knee osteoarthritis (OA) is a common and significant cause of disability. Until recently, the major investigation to help establish a diagnosis of knee OA was the joint radiograph. This imaging modality offers only a two-dimensional image of a three-dimensional structure, and can only crudely identify major joint abnormalities at the later stage of disease. Moreover, joint radiographs cannot fully characterise subtle changes in intra and extraarticular structures, such as cartilage and bone marrow abnormalities that are now considered to be part of a whole-organ disease process. The recent advent of Magnetic Resonance Imaging (MRI) has enabled a three-dimensional assessment of the entire joint, thus providing new insights into the natural history of joint arthropathies. It is likely that morphological changes in articular structures caused by the OA process have their origins in the apparently healthy asymptomatic knee joint. MRI has therefore enabled the opportunity to better examine and understand pre-clinical and very subtle early aberrations in joint morphology, prior to the onset of radiographic disease. This discussion seeks to explore knee OA as a disease entity that can be recognised before any radiographic change. This may pose new, yet exciting challenges for the identification and classification of disease, and provide a better understand of the pathogenesis of knee OA.
TL;DR: About three and a half years ago, a causal relation between nephrogenic systemic fibrosis (NSF) and exposure to gadolinium based contrast agents (Gd-CAs) was suggested and all evidence now suggests that low stability Gd- CAs can trigger the development of NSF.
Abstract: About three and a half years ago, a causal relation between nephrogenic systemic fibrosis (NSF) and exposure to gadolinium based contrast agents (Gd-CAs) was suggested. All evidence now suggests that low stability Gd-CAs can trigger the development of NSF. All studies indicate with no exception that macrocyclic Gd-CAs release significantly less free gadolinium than the linear agents, particularly the non-ionic ones which have the highest potential of gadolinium release. The longer the Gd-CA stays in the body the larger the amount of gadolinium that is retained in the body. The magnitude of the NSF problem remains uncertain; the condition seems to be underreported. The demonstration of a link between NSF and low stability Gd-CAs has had major consequences for patients with reduced renal function. Currently, if contrast administration is clinically deemed; necessary the preferred approach is contrast enhanced MRI using a macrocyclic Gd-CA. Contrast enhanced CT is at least as risky if not more as an enhanced MRI with low stability Gd-CAs.
TL;DR: In this paper, the authors have shown that genetic factors play a minor role in SSc development, and that T cells can contribute to fibrosis and vasculopathy through cytokines and autoantibodies.
Abstract: Systemic sclerosis (SSc) is characterized by activation of fibroblasts with extensive deposition of collagen, by small vessel vasculopathy with fibrointimal proliferation, and activation of the immune system, with hyper-γ- globulinaemia and autoantibodies. Twin studies have shown that genetic factors play a minor role in SSc development. Serum autoantibodies and skin lymphocytic infiltrates and small vessel damage occur very early before the appearance of skin fibrosis. T cells can cause fibrosis and vasculopathy through cell-cell contact and cytokines. They produce TH2 cytokines (IL-4, IL13) and TH17 cytokines (IL-17), which are profibrotic. TH2 cells in experimental models also induce pulmonary arterial hypertension. Genetically engineered TGFβ expression in pig arteries causes fibrointimal proliferation. T cells in skin lesions exhibit oligoclonality that persists over time, which indicates an antigen-driven T cell activation, but the antigen(s) responsible are not known. There are known environmental factors that can elicit an immune response and cause a SSc-like disease. T cells also provide help for B cells. B cells can contribute to fibrosis and vasculopathy through cytokines and autoantibodies. Autoantibodies can activate endothelial cells and fibroblasts to a profibrotic phenotype. Finally, treatments directed against T cells and B cells show promising effects in SSc.
TL;DR: Strategies to prevent nephrogenic systemic fibrosis in patients with severe renal dysfunction include administering only single dose GBCA, scheduling MRI for just before the next routine dialysis in dialysis patients, delaying GBCAs in acute renal failure while serum creatinine is rising, and making sure the best technologist is doing the case.
Abstract: Gadolinium based contrast agents (GBCAs) have been linked to nephrogenic systemic fibrosis (NSF) in patients with severe renal dysfunction. This article reviews strategies to prevent this condition in patients at risk. These include administering only single dose GBCA, scheduling MRI for just before the next routine dialysis in dialysis patients, delaying GBCA in acute renal failure while serum creatinine is rising, and making sure the best technologist is doing the case to ensure it will not need repeating. Most MRI centers have implemented at least some these NSF risk reduction strategies and as a result, NSF incidence is markedly decreased.
TL;DR: The methods and limitations of animal pain assessment, rodent models of RA and OA, and how these models have been used to investigate the genesis of pain are discussed, including how the mediators involved in the development of pain may differ between these two arthritic states and during acute and chronic pain.
Abstract: Rheumatoid arthritis (RA) and Osteoarthritis (OA) are both common diseases of the joints. RA is distinguished by inflammation and synovitis leading to joint destruction, whereas OA is typified by degenerative and mostly noninflammatory disease. Although differing in their pathology, both forms can elicit chronic disabling pain in patients. Relief from this pain is an unmet need for many patients, and this has lead to a drive to understand the pain mechanisms occurring in each disease in order to develop new analgesics. This necessitates the use of pre-clinical models. Here we discuss the methods and limitations of animal pain assessment, rodent models of RA and OA, and how these models have been used to investigate the genesis of pain. Specifically, we focus on processes studied in both RA and OA models, and how the mediators involved in the development of pain may differ between these two arthritic states and during acute and chronic pain. From this we have learnt that the key mediators of RA pain include inflammatory cells, inflammatory cytokines, astrocytes, substance P, and CGRP. Endogenous analgesic mediators in RA include β-endorphin, μ-opioid receptor, and various anti-inflammatory cytokines. Less is known of the mediators of OA pain, but important factors include CGRP, TRPV1, NGF, VIP and the μ-opioid receptor. Interestingly, several factors have been found not to play a role in OA pain, including glial cells, neutrophils and TNF. It must be noted that the vast majority of candidate drugs from animal research never reach the human clinic, in part due to false positives from animal models. This may be due to flaws in the models themselves, the methods used to assess pain, the physical properties of the candidate drug, or an inherent difference between animal and human pain pathways. By developing more clinically relevant models, novel diseasespecific analgesics are being developed with the hope of improving the quality of life for sufferers of arthritis pain.
TL;DR: In this article, the authors used functional Magnetic Resonance Imaging (fMRI) to assess how the brain responds to and mediates pain in the presence of arthritic disease.
Abstract: Pain is a major symptom in rheumatic diseases. Understanding the nature of patients pain symptoms in a rheumatology setting is integral to their assessment and optimising care. In recent years we have increasingly come to appreciate that not only is pain dependent on the underlying pathological process, but is also influenced by a number of additional factors that include genetics, the environment of the individual, previous pain experience and psychological status. Although local inflammation in the joint leads to the release of pro-inflammatory mediators including prostaglandins and cytokines that activate nociceptive signals in the joint, recent work has suggested that central activation of the brain is also important in mediating chronic pain in a number of rheumatic conditions including rheumatoid arthritis, fibromyalgia, osteoarthritis and back pain. A number of imaging modalities have been utilized in recent years to gain a deeper understanding of the pathways involved in the perception of pain in the rheumatic diseases. Functional Magnetic Resonance Imaging (fMRI), has been used to assess how the brain responds to and also mediates pain in the presence of arthritic disease. Positron emission tomography (PET) and Single photon emission computed tomography (SPECT) can produce blood flow images of the brain, or with the appropriate choice of radiopharmaceutical can also be used to image metabolic activity or specific neuroreceptors. Magnetoencephalography (MEG) can map cortical brain activity with high temporal resolution. These techniques have shown altered regional cerebral blood flow in areas of the brain in rheumatoid arthritis and fibromyalgia and have been used to determine pathways implicated in the perception of pain in specific conditions including complex regional pain syndrome and fibromyalgia. The information gained from functional imaging studies has improved our understanding of pain perception in rheumatic diseases and so may aid a more effective treatment for pain as will be discussed further in this review.
TL;DR: This chapter focuses on various ophthalmic and otological manifestations in the antiphospholipid syndrome (APS), which includes subjective disturbances as well as objective pathologic findings, some of them considered as potential risk factors for severe ocular or cerebrovascular diseases.
Abstract: Publisher Summary
This chapter focuses on various ophthalmic and otological manifestations in the antiphospholipid syndrome (APS). From the ophthalmological point of view, the APS manifestations include subjective disturbances as well as objective pathologic findings, some of them considered as potential risk factors for severe ocular or cerebrovascular diseases. Ocular involvement in the APS includes various symptoms as well as both anterior and posterior segment signs. There is a high prevalence of transient visual disturbances mostly related to cerebral rather than ocular ischemia. The posterior segment of the eye is usually more severely affected than the anterior one. Amaurosis fugax (episodic and temporary loss of vision in an eye) usually caused by ocular ischemia due to severe stenosis of the extracranial internal carotid artery is frequently described in patients with cerebral, retinal and/or optic nerve ischemic disease as well as in association with anticardiolipin antibodies (aCL), with or without definite APS. Patients with APS may also present with a secondary vasospastic syndrome, which includes both anterior and posterior findings and thrombotic and neovascular glaucoma. There are several reports of aPL associated with thrombosis in patients with infectious diseases, some of which are also documented as causing sensorineural hearing loss (SHL), suggesting a link between infection-induced aPL, thrombosis, and related SHL. In 1994, Moine et al. observed that aCL were detected in 4/35 (11 %) of patients with SHL, suggesting that, theoretically, the use of anticoagulants could provide an effective treatment.
TL;DR: More efforts are needed to improve the management of organ impairment by early detection and prompt treatment, in order to prevent the development of severe complications.
Abstract: Systemic sclerosis (SSc) is a severe autoimmune disease that involves skin and internal organs. Clinical manifestations of SSc are very heterogeneous and derive from microvascular, inflammatory and fibrotic tissue changes. Besides the skin, lung, gastrointestinal tract, heart and kidneys are mainly affected. Over the last years, a progress in the treatment was made, especially in the field of renal involvement and pulmonary hypertension, but prognosis of the disease remains still bad. More efforts are needed to improve the management of organ impairment by early detection and prompt treatment, in order to prevent the development of severe complications.
TL;DR: Conservative care options, perioperative considerations and surgical treatment options for rheumatoid deformity in the foot and ankle are discussed.
Abstract: Rheumatoid arthritis is a common and disabling condition which can be effectively managed through a multidisciplinary approach. A review of the etiology, pathophysiology, clinical presentation, diagnosis and treatment is presented, followed by a discussion focused on the disease presentation and management in the foot and ankle. Conservative care options, perioperative considerations and surgical treatment options for rheumatoid deformity in the foot and ankle are discussed.
TL;DR: Treatment strategies for isolated cartilage lesions of the knee are discussed with a special focus on natural history and evidence of the effectiveness of procedures, and the evidence justifies cartilage repair procedures in patients with symptomatic full-thickness lesions and in Patients with large defects in the weightbearing surface of the knees joint.
Abstract: Articular cartilage defects have poor healing capacity and can lead to osteoarthritis. Treatment strategies for isolated cartilage lesions of the knee are discussed with a special focus on natural history and evidence of the effectiveness of procedures. Many approaches have been undertaken during the last two decades to find treatments for biological repair of the cartilage surface. Surgical techniques include debridement, stimulation by microfracture, mosaicplasty, autologous chondrocyte implantation (ACI) and autologous matrix-induced chondrogenesis (AMIC). Although these treatments are promising and scientifically interesting, there is no evidence for a breakthrough in cartilage repair. The evidence justifies cartilage repair procedures in patients with symptomatic full-thickness lesions and in patients with large defects in the weightbearing surface of the knee joint.