Showing papers in "Current Opinion in Rheumatology in 2011"
TL;DR: This review focuses on the novel stress-induced and proinflammatory mechanisms underlying the pathogenesis of osteoarthritis, with particular attention to the role of synovitis and the contributions of other joint tissues to cellular events that lead to the onset and progression of the disease and irreversible cartilage damage.
Abstract: Purpose of review
This review focuses on the novel stress-induced and proinflammatory mechanisms underlying the pathogenesis of osteoarthritis, with particular attention to the role of synovitis and the contributions of other joint tissues to cellular events that lead to the onset and progression of the disease and irreversible cartilage damage.
1,062 citations
TL;DR: Serum IgG4 elevation has convincing diagnostic utility when combined with other disease features although its value in disease monitoring may be limited and its utility in monitoring of therapy or as a marker or predictor of relapse is limited.
Abstract: Purpose of reviewIgG4-related systemic disease (ISD) is a recently recognized syndrome affecting multiple organs. Autoimmune pancreatitis (AIP) is the pancreatic manifestation of ISD and mimics pancreatic cancer. Current data show frequent association with serum IgG4 elevation and other serologic ab
303 citations
TL;DR: IgG4-RSD is an underrecognized condition about which knowledge is now growing rapidly, yet there remain many unknowns with regard to its cause, pathogenesis, various clinical presentations, approach to treatment, disease monitoring, and long-term outcomes.
Abstract: Purpose of reviewTo summarize the existing knowledge of various clinical presentations of IgG4-related systemic disease (IgG4-RSD) and to review the evolving list of organs affected by IgG4-RSD.Recent findingsThe term IgG4-RSD encompasses a variety of clinical entities once regarded as being entirel
295 citations
TL;DR: IgG4 is a unique antibody biologically and structurally that undergoes ‘half-antibody exchange’ in vivo, resulting in recombined antibodies composed of two different binding specificities.
Abstract: Purpose of reviewRecent descriptions of the group of clinical disorders collectively defined as IgG4-related systemic disease (IgG4-RSD) have prompted this review of the unique biology of the IgG4 antibody. This article will discuss IgG4 structure and function, the unique phenomenon of half-antibody
288 citations
TL;DR: Continued progress is being made on characterizing aging-related changes in cartilage as well as supporting a role for the mitochondria in osteoarthritis, including work suggesting changes in energy production.
Abstract: Purpose of reviewOsteoarthritis is strongly linked to aging but the mechanisms for this link are incompletely understood. The recent literature was reviewed to find studies providing new insights into the connection between aging and osteoarthritis.Recent findingsBasic aging studies in nonarticular
233 citations
TL;DR: The natural history and long-term prognosis of IgG4-RSD are not well understood, and large prospective studies and randomized controlled trials of patients with wide spectrum manifestations of Igg4- RSD are required to support better approaches to treatment.
Abstract: Purpose of reviewIgG4-related systemic disease (IgG4-RSD) is a systemic fibroinflammatory condition that can affect any organ system. Prompt recognition and management of this disease process are necessary to prevent sclerosis and permanent organ damage. Here, we review the advances in treatment app
232 citations
TL;DR: IgG4-related systemic disease should be considered in any patient found to have aortitis or periaortitis, and further studies into diagnostic criteria, disease prevalence, prognosis, therapeutic interventions, and differentiating possible localized hypersensitivity reactions from systemic disease are areas of active investigation.
Abstract: Purpose of reviewIn last few years, there have been significant advances in our understanding of a newly recognized condition known as IgG4-related systemic disease. This review will focus on IgG4-related systemic disease as a cause of thoracic aortitis, inflammatory abdominal aortic aneurysm or per
207 citations
TL;DR: Several dietary risk factors for incident gout and gout flares are modifiable and prevention and optimal management of comorbidities are likely to decreased risk of gout.
Abstract: Purpose
Our objective was to perform a systematic review of risk factors and prevention of gout. We searched Medline for fully published reports in English using keywords including but not limited to “gout”, “epidemiology”, “primary prevention”, “secondary prevention”, “risk factors’. Data from relevant articles meeting inclusion criteria was extracted using standardized forms.
203 citations
TL;DR: Because of earlier recognition, aggressive medical treatment, and novel surgical procedures, the morbidity and mortality of large vessel vasculitis in Behçet's disease are improving.
Abstract: Purpose of reviewLarge vessel vasculitis occurs in a subgroup of patients with Behcet's disease who are at high risk for disease-related morbidity and mortality. Recognition of patients at risk, early detection of vasculitis, and aggressive treatment are essential for optimal care of these patients.
168 citations
TL;DR: The mechanism by which Wnt/&bgr;-catenin signaling may modify the response to injury is cell-type and context-dependent, and its sustained activation is associated with fibrogenesis.
Abstract: Purpose of reviewThe Wnt/β-catenin signaling pathway plays a critical role in development and adult tissue homeostasis. Recent investigations implicate Wnt/β-catenin signaling in abnormal wound repair and fibrogenesis. The purpose of this review is to highlight recent key studies that support a role
163 citations
TL;DR: The knowledge of rheumatoid arthritis pathogenesis continues to expand, with some key findings, including the identification of novel, potentially tractable targets for further therapeutic research.
Abstract: Purpose of reviewTo provide a summary of recent advances in the pathophysiology of rheumatoid arthritis.Recent findingsHighlights include further elucidation of the relationship between the shared epitope, smoking and anticitrullinated protein/peptide antibody generation, including identification of
TL;DR: Myopathology can be used to classify IIM and identification of distinctive myopathologic changes in IIM can improve diagnostic and prognostic accuracy and focus treatment, therapeutic trials and studies of pathogenic factors.
Abstract: Purpose of reviewWe discuss pathology-based characterization and classification of acquired immune and inflammatory myopathies (IIMs).Recent findingsSeveral types of IIMs do not fit well into the typical IIM subclassifications: dermatomyositis, polymyositis and inclusion body myositis (IBM). Myopath
TL;DR: Autoimmunity has been considered the most probable pathogenesis of IgG4-related disease, but has not been completely proved so far and a breakthrough study to detect a specific autoantigen, autoantibody, or pathogen is necessary.
Abstract: Purpose of review To review studies that have examined underlying genetic and immunological aspects of IgG4-related disease. Recent findings Genetic studies have suggested that several human leukocyte antigen (HLA) and non-HLA haplotypes/genotypes are associated with susceptibility to IgG4-related disease or to disease relapse after steroid therapy. Among several autoantibodies identified so far, autoantibodies against lactoferrin and carbonic anhydrase II are most frequently detected in serum of IgG4-disease patients. However, it has not been well clarified whether or not those autoantibodies belong to an IgG4 subclass. Studies that have demonstrated molecular mimicry between Helicobacter pylori and constituents of pancreatic epithelial cells suggest that gastric H. pylori infection triggers autoimmune pancreatitis in genetically predisposed individuals through antibody cross-reactivity. Recently, T-helper 2 immune reaction has been suggested to be predominant in IgG4-related disease. Interestingly, regulatory immune reactions are activated in IgG4-related disease, and regulatory cytokines interleukin-10 and transforming growth factor-b have been suggested, respectively, to play important roles in IgG4 class switch and fibroplasia. Summary Autoimmunity has been considered the most probable pathogenesis of IgG4-related disease, but has not been completely proved so far. A breakthrough study to detect a specific autoantigen, autoantibody, or pathogen is necessary.
TL;DR: It is demonstrated that at least two separate lineages of CD4 T cells participate in vascular inflammation in giant cell arteritis, providing an important clue that multiple disease instigators may initiate pathogenic immunity.
Abstract: Purpose of review
Granuloma formation in giant cell arteritis (GCA) emphasizes the role of the adaptive immunity and highlights the role of antigen-specific T cells. Recent data demonstrate that at least two separate lineages of CD4 T-cells participate in vascular inflammation, providing an important clue that multiple disease instigators may initiate pathogenic immunity.
TL;DR: It is important to recognize and distinguish NAM from other causes of myocyte necrosis, because it has the potential of being amenable to treatment, and may provide a useful diagnostic test in the future, to help differentiate immune from nonimmune statin myopathies.
Abstract: PURPOSE OF REVIEW:
Necrotizing autoimmune myopathy (NAM) is a relatively newly recognized subgroup of idiopathic inflammatory myopathies, which despite diverse causes, have the common histopathological features of myocyte necrosis without significant inflammation. Patients present with a subacute severe symmetrical proximal myopathy, associated with a markedly elevated creatine kinase level. These are most likely immune-mediated, as they respond to immunotherapy. The review aims to define this heterogeneous entity and summarize the salient clinical, laboratory, and muscle biopsy findings, in order to facilitate the diagnosis and treatment of this condition.
RECENT FINDINGS:
Statin-associated NAM has been linked with an antibody against the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein, which is up-regulated in regenerating fibres. This finding suggests that NAM is an antibody-mediated disease, and may explain the continuing progression of disease despite cessation of the statin. In addition it may provide a useful diagnostic test in the future, to help differentiate immune from nonimmune statin myopathies.
SUMMARY:
It is important to recognize and distinguish NAM from other causes of myocyte necrosis, because it has the potential of being amenable to treatment.
TL;DR: Emerging data show a body of evidence that IL-17 and Th17 cells may play a role in the pathogenesis of SLE, and the therapeutic implication of targeting this cytokine in SLE is raised.
Abstract: Purpose of reviewThe discovery of T helper (Th)17 cells that produce the proinflammatory cytokine IL-17 has substantially advanced our understanding of T-cell biology and autoimmunity. We will review recent findings on effector T cells, in particular Th17 cells, in lupus.Recent findingsStudies repor
TL;DR: Wegener's granulomatosis is a rare autoimmune disease associated with granuleomatous inflammation and antineutrophil cytoplasmic antibody-associated vessel vasculitis.
Abstract: Purpose of reviewWegener's granulomatosis is a rare autoimmune disease associated with granulomatous inflammation and antineutrophil cytoplasmic antibody-associated vessel vasculitis. Most commonly, upper and lower respiratory tract and kidneys are involved: alveolar hemorrhage and necrotizing glome
TL;DR: Recognition of the fact that IgG4-related systemic disease could involve the vascular lesions offers potential new management of those, however, only 3 years have passed since the first report of IgG 4-related IAAA.
Abstract: Purpose of reviewIgG4-related systemic disease is a recently proposed entity characterized by high serum IgG4 concentrations, sclerosing inflammation containing numerous IgG4-positive plasmacytes, dramatic responsiveness to steroid therapy, and occurrence of multiple organs. This review described th
TL;DR: IgG 4-related sialadenitis belongs to the IgG4-related systemic disease spectrum and shows a swift response to immunosuppression.
Abstract: Purpose of reviewAn enlarged salivary gland or lacrimal gland raises a wide differential diagnosis that includes both benign inflammatory conditions and malignant disorders. This review aims to address the numerous controversies that have arisen regarding inflammatory diseases of the salivary gland
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TL;DR: Most evidence suggests that the ocular and vestibuloauditory manifestations in Cogan's syndrome are not a consequence of vasculitis but rather mediated by other immunologic mechanisms, possibly organ-specific autoimmunity.
Abstract: Cogan’s syndrome is thought to be an autoimmune disease of uncertain etiology which causes inflammation of the eye, most typically interstitial kcratitis, and hearing loss. It typically occurs in the third and fourth decades of life. About half of patients have systemic disease manifestations, including constitutional symptoms of fever and weight loss, arthritis, neuropathy, rash, pericarditis, pleuritis, and vasculitis. The vasculitis typically affects large vessels, particularly the aorta and other large vessels, but may also affect medium and small vessels as well. Vascular complications may lead to limb claudication and aortic aneurysm aortic heart disease and failure of other involved organs. Vasular imaging, which can include angiography using conventional imaging computed tomography, ultrasound, magnetic resonance scanning, and use of positron emission tomography, is required to assess the extent and activity vascular involvement. Treatment is directed to the involved organs, and can include glucocorticosteroids, cytotoxic agents, and vascular repair.
TL;DR: Despite their established clinical utility, the mode of action for antimalarials remains uncertain despite recent advances and still requires further investigation, so their optimal use in the clinical setting can be ensured.
Abstract: Purpose of reviewWhereas antimalarials have been in use to treat rheumatic disease for over 50 years, their exact mechanism of action remains unclear. Over the past decade, new theories have been proposed in this regard both for rheumatic disease, as well as related conditions.Recent findingsWhereas
TL;DR: There is now consistent observational data to suggest a central role for calcium channel blockers in the treatment of microvascular ischemia and prevention of overt LV systolic dysfunction, although randomized controlled trials are lacking.
Abstract: Purpose of review
When present clinically, cardiac involvement in systemic sclerosis (SSc) is a major risk factor for death. It is therefore vitally important to understand the epidemiology, screening, diagnosis, and treatment of the cardiac manifestations of SSc.
TL;DR: Sclerosing lymphoplasmacytic inflammation at almost any site can represent a manifestation of IgG4-RSD, and there are several histologic features that can suggest the diagnosis.
Abstract: Purpose of reviewThe spectrum of IgG4-related systemic disease (IgG4-RSD) continues to widen. At most of the sites involved by this condition, the clinical presentation can mimic neoplasm. Pathologic assessment of small biopsies can be critical to proper management. This review summarizes the histol
TL;DR: Blocking IL-6 with tocilizumab can be a therapeutic option for patients with various IMIDs in which overproduction ofIL-6 plays a pathological role, and future clinical studies investigating the safety and efficacy will elucidate the clinical benefits of IL- 6 blockade therapy for such diseases.
Abstract: Purpose of review Interleukin-6 (IL-6) is a multifunctional cytokine that regulates immune response and induces acute phase response. Despite the important physiological activities of IL-6, dysregulated overproduction of IL-6 is pathologically involved in various immune-mediated inflammatory diseases (IMIDs) including rheumatoid arthritis (RA). A series of clinical studies of tocilizumab, a humanized anti-IL-6 receptor (IL-6R) antibody, for patients with RA refractory to conventional therapy or anti-tumor necrosis factor therapy have demonstrated the clinical benefit of IL-6 blockade in RA. On the other hand, there is now accumulating evidence that tocilizumab is therapeutically effective for patients with a number of IMIDs other than RA. This review focuses on the perspective of IL-6 blockade therapy for such IL-6-related IMIDs outside of RA. Recent findings A considerable number of case reports and preclinical studies have shown the benefit of IL-6 blockade therapy in various IMIDs such as systemic lupus erythematosus, adult-onset Still disease, Takayasu arthritis, polyarteritis nodosa, systemic sclerosis, reactive arthritis, dermatomyositis, and polymyositis. Summary Blocking IL-6 with tocilizumab can be a therapeutic option for patients with various IMIDs in which overproduction of IL-6 plays a pathological role. Future clinical studies investigating the safety and efficacy will elucidate the clinical benefits of IL-6 blockade therapy for such diseases.
TL;DR: Several cell types are involved in the muscle repair process, interacting through multiple signaling molecules and pathways that provide a richness of potential therapeutic targets to reduce fibrosis and facilitate skeletal muscle regeneration.
Abstract: Purpose of reviewThis review evaluates recently published literature examining various muscle tissue cells and their modulators that determine whether injured skeletal muscle will fully regenerate or become fibrotic.Recent findingsMuscle regeneration is a complex process involving several interactin
TL;DR: The issue of large-vessel involvement in chronic periaortitis and its implications in the pathogenesis and nosography of the disease are reviewed to support the notion of a primary inflammatory or immune-mediated disorder.
Abstract: Purpose of review Chronic periaortitis is characterized by a fibro-inflammatory process spreading from the abdominal aorta and the iliac arteries. Originally, chronic periaortitis was considered a localized inflammatory response to severe aortic atherosclerosis. However, subsequent studies have shown that chronic periaortitis may also involve other arteries and present with features of auto-immune diseases. This article reviews the issue of large-vessel involvement in chronic periaortitis and its implications in the pathogenesis and nosography of the disease. Recent findings In many reports, chronic periaortitis has been shown to involve not only the aorto-iliac axis but also other vascular segments such as the thoracic aorta, the proximal epiaortic arteries, the coronary, renal, and mesenteric arteries. Thoracic aorta involvement may manifest as thoracic periaortitis with or without aneurysmal dilatation, or simply as thoracic aorta aneurysm. Thoracic periaortitis can also be a feature of the so-called IgG4-related systemic disease, with which chronic periaortitis may sometimes be associated. Histopathologic studies of chronic periaortitis show adventitial inflammation and fibrosis, vasculitis of vasa vasorum, and adventitial lymphoid follicles with germinal centers, suggesting that chronic periaortitis could be a primary aortitis. Genetic studies have demonstrated an association with HLA-DRB1*03, a marker of auto-immunity, and with the CCR5Δ32 polymorphism, which has been mapped to a Th2 response. Taken together, these findings support the notion of a primary inflammatory or immune-mediated disorder. Summary Chronic periaortitis is an inflammatory or immune-mediated disorder characterized histopathologically by adventitial inflammation and clinically by variable involvement of different arteries, mainly of large caliber. These findings raise the issue of whether chronic periaortitis should be considered a large-vessel vasculitis.
TL;DR: Elucidation of downstream effects of NOD2 mutations could provide valuable clues to mechanisms of arthritis and uveitis in general as well as granulomatous diseases in particular.
Abstract: Purpose of reviewBlau syndrome is a monogenic disease resulting from mutations in nucleotide oligomerization domain 2 (NOD2) and is phenotypically characterized by granulomatous polyarthritis and uveitis. Not only there has been significant progress in disease characterization but also the biologica
TL;DR: It is hoped that those not performing synovial fluid analysis for crystals will be stimulated to acquire or perfect the technique and obtain a compensated polarized microscope to comply with current standards.
Abstract: Purpose of review Describe why this review is timely and relevant. Identifying monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals allows a quick and definitive diagnosis of both gout and CPPD arthritis, and remains the accepted gold standard. These diseases are still often diagnosed on inaccurate clinical grounds. Crystal identification has received little critical attention since its introduction, and it appears necessary to review the technique paying special attention to the possible reasons which deter clinicians. Recent findings Describe the main themes in the literature covered by the article. Synovial fluid analysis for crystals is a simple procedure allowing immediate and definite diagnosis of gout and CPPD arthritis when clinics are fitted with a proper microscope and the rheumatologists appropriately trained. This review also illustrates how crystal analysis in synovial fluid can be initially approached with both the widely available ordinary light microscope and a simple polarized one and with good results. Summary This study describes the implications of the findings for clinical practice or research. We hope that those not performing synovial fluid analysis will be stimulated to acquire or perfect the technique and obtain a compensated polarized microscope to comply with current standards.
TL;DR: PLEX remains a nonselective, expensive therapy with common adverse events, and it is unclear at what severity of renal failure PLEX is beneficial, the optimal PLEx dosing and type and dosing of concomitant medications.
Abstract: Purpose of reviewThe article reviews the use of plasma exchange (PLEX) in the management of the antineutrophil cytoplasm antibody-associated vasculitides (AAV).Recent findingsEarly mortality and end-stage renal disease (ESRD) remain frequent outcomes for AAV patients. Demonstration of the pathogenic
TL;DR: There is an increasing tendency for guidelines to prefer IGRA over TST in IMIDs or to recommend both TST and IGRA to enhance sensitivity, and it is believed the use of either test is acceptable for LTBI screening.
Abstract: Purpose of reviewTo provide a narrative synthesis of evidence on interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in individuals with immune-mediated inflammatory disorders (IMIDs).Recent findingsOnly a few studies have evaluated IGRAs in IMIDs, and m